ABSTRACTS OF THE ANNUAL MEETING ON BURULI ULCER
14–17 March 2005
WHO headquarters Geneva, Switzerland
1 ABSTRACTS OF THE ANNUAL MEETING ON BURULI ULCER
14–17 March 2005
WHO headquarters Geneva, Switzerland
i © World Health Organization 2006
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ii CONTENTS
General Information ...... 1
Buruli ulcer prevalence survey in the northern departments of Benin (Presenter: Dr C. Johnson)...... 3
Preliminary findings of the national survey on Buruli ulcer in the Democratic Republic of the Congo: lessons learnt (Presenter: Dr A. Kibadi Kapay) ...... 7
Preliminary results of a national survey on Buruli ulcer in Cameroon (Presenter: Dr A. Um Boock) ..8
Mycobacterium ulcerans infection in French Guyana, 2004 (Presenter: Dr P. Couppié) ...... 11
Noteworthy action by ANESVAD in 2004 as part of the Buruli ulcer control effort (Presenter: Ms Verónica Malda) ...... 13
Surgical and POD training supported by American Leprosy Missions in Ashanti Region, Ghana: conclusions from a recent evaluation (Presenter: Dr P. Saunderson)...... 16
The Association Française Raoul Follereau: 10 years’ partnership in Buruli ulcer control, 1995–2005 (Presenter: Mr J.-M. Rondot) ...... 17
Contribution made by the Swiss Leprosy Relief Association to the Buruli ulcer control effort in Cameroon since 2002 (Presenter: Dr A. Um Boock)...... 19
Implementation of experimental hyperbaric oxygen therapy as treatment for Buruli ulcer at the Allada hospital in Benin (Presenter: Dr F. Poggio) ...... 22
Health-seeking determinants of patients with Buruli ulcer in Benin (Presenter: Ms A. A. Mulder)...... 23
Buruli ulcer: village follow-up of treated patients in rural Benin (Presenter: Prof. F. Portaels) ...... 24
Treatment of Buruli ulcer with the combination of rifampicin and streptomycin in Benin (Presenter: Dr A. Chauty) ...... 25
Economic burden of Buruli ulcer In Ghana, 2001-2003 (Presenter: Mr G. Mumma) ...... 26
Buruli ulcer laboratory network: How a diagnostic system operates in Ghana (Presenter: Dr G. Bretzel)...... 28 The ecology of Mycobacterium ulcerans: aquatic food webs and water quality relationships (Presenter: Prof. R. Merritt)...... 31
The complete genome sequence of Mycobacterium ulcerans strain Agy99 (Presenter: Dr T. Stinear) ...... 32
Report on Buruli ulcer control activities for the year 2004 and outlook for 2005 in Benin (Presenter: Dr C. Johnson) ...... 34
The Buruli ulcer situation in Burkina Faso (Presenter: Dr C. Kafando)...... 42
The Buruli ulcer control situation in Cameroon (Presenter: Dr C. Nsom Mba) ...... 44
The Buruli ulcer situation in the Republic of the Congo (Presenter: Dr D. Obvala)...... 46
Buruli ulcer control in Côte d’Ivoire (Presenter: Dr M. Diabaté) ...... 49
Epidemiological situation in the Democratic Republic of the Congo (Presenter: Dr A. Kibadi Kapay) ...... 53
The Buruli ulcer situation in Gabon (Presenter: Dr L. Bayonne Manou) ...... 55
iii Report on Buruli ulcer control activities in Ghana in 2004 (Presenter: Dr E. Ampadu)...... 58
Overview of Buruli ulcer control in Guinea in 2004 (Presenter: Dr A. M. Bangoura)...... 60
Mycobacterium ulcerans in Papua New Guinea in 2004 (Presenter: Sister Joseph)...... 67
Summary of Buruli ulcer planned activities in South Sudan (Presenter: Dr I. Sindani)...... 71
Prevalence of Buruli ulcer disease in Adjumani District, Uganda, in 2004 (Presenter: Dr H. Wabinga) ...... 73
How to evaluate the efficacy of hyperbaric oxygen therapy (HOT) in Mycobacterium ulcerans disease: The HOT project in the CDTUB of Allada, Benin (Presenter: Dr G. Leigheb) ...... 75
Telepathology: support for the HOT (hyperbaric oxygen therapy) project in the Allada Hospital of Benin (Presenter: Dr C. Clemente)...... 76
Vacutex™: a capillary dressing to improve the treatment of Buruli ulcer patients (Presenter: Mrs A. Doran) ...... 77
The role of surgical missions in the management of Buruli ulcer in Côte d'Ivoire (Presenter: Prof. H. Assé) ...... 78
The role of volunteer surgeons in Buruli ulcer control (Presenter: Dr R. Zilliox)...... 82
Basic plastic surgery skills for district/community doctors to manage Buruli ulcer patients in Ghana (Presenter: Dr P. Agbernorku) ...... 85
WHO essential surgical care rraining tools linked to Buruli ulcer (Presenter: Dr M. Nathan Cherian) ...... 86
Training modules on the management of Buruli ulcer control programme at the health district level..... (Presenter: Dr A. Tiendrebeogo) ...... 87 Interactive web-based learning courses on Mycobacterium ulcerans infection (Presenter: Dr S. Deepak) ...... 90
Training of doctors from endemic countries in basic plastic surgery to manage Buruli ulcer (Presenter: Prof. H. Assé) ...... 91
The role of training in the prevention of disabilities from Buruli ulcer (Presenter: Ms V. Simonet) .....92
Prevention of disability in people with Buruli ulcer: the development of a manual for field use (Presenter: Mrs L. Lehman) ...... 93
Presentation of a handbook illustrated by photographs on Buruli ulcer prevention and rehabilitation techniques (Presenter: Mr F. Bonifacio)...... 95
Willingness-to-pay for a hypothetical drug for treating Buruli ulcer, Ghana, 2003 (Presenter: Dr G. Mumma)...... 97
A framework for measuring quality of life in Buruli ulcer patients (Presenter: Mr F. Dadzie) ...... 98
Strengthening Buruli ulcer surveillance: evaluating the efficacy of educational materials (Presenter: Dr C. Dykewicz)...... 102
Standardized recording and reporting system using the BU 02 form and HealthMapper (Presenter: Dr G. Sopoh) ...... 103
Mycobacterium ulcerans toxic macrolide, mycolactone modulates the host immune response and cellular location of M. ulcerans in vitro and in vivo (Presenter: Dr P. Small) ...... 104
iv High rates of apoptosis in Mycobacterium ulcerans culture positive lesions of Buruli ulcer (Presenter: Dr D. Walsh)...... 105
Local and systemic immune response to M. ulcerans infection and correlations with histopathology (Presenter: Dr R. Phillips)...... 106
Susceptibility to develop Buruli ulcer is associated with natural resistance-associated macrophage protein 1 polymorphisms (Presenter: Dr T. van der Werf)...... 108
Nerve damage by bacteria causing Buruli ulcer – ultrastructure of mouse inoculated with Mycobacterium ulcerans (Presenter: Dr M. Goto)...... 109 Vaccine optimalization by experimental mouse model for Mycobacterium ulcerans footpads infection (Presenter: Dr A. Tanghe) ...... 111
Construction of mycolactone-negative mutants of Mycobacterium ulcerans may contribute to the development of vaccine candidates against Buruli ulcer (Presenter: Dr A. Mve-Obiang) ...... 112
New laboratory tools for studying Mycobacterium ulcerans infection (Presenter: Dr G. Pluschke) ..113 Sensitivity of PCR for IS2404 insertion sequence of Mycobacterium ulcerans in diagnosis of Buruli ulcer from punch biopsies (Presenter: Dr R. Phillips) ...... 114
Genotyping Mycobacterium ulcerans, Mycobacterium marinum and related species using mycobacterial interspersed repetitive units (Presenter: Prof. F. Portaels) ...... 115
Study of the M. ulcerans proteome (Mr L. Marsollier)...... 116 Identification of Mycobacterium ulcerans in the environment by PCR: Limitations of IS2404 as proof for M. ulcerans in the environment, and development of a mycolactone-specific probe (Presenter: Ms H. Williamson) ...... 117
Buruli ulcer control integration model for public health establishments: pilot project to improve awareness of and treat Buruli ulcer patients in Taabo, Côte d’Ivoire (Dr J. Aké Aké) ...... 118
Annex 1: Resolution WHA57.1 – Surveillance and control of Mycobacterium ulcerans disease (Buruli ulcer) 122 Annex 2: List of participants ...... 124
v GENERAL INFORMATION
Background
Buruli ulcer is a devastating skin disease caused by Mycobacterium ulcerans, a pathogen belonging to the same family as the organisms that cause tuberculosis and leprosy. Unlike these conditions, however, Buruli ulcer is a poorly understood disease that has emerged dramatically since the 1980s. The causative agent has unique features and its exact mode of transmission remains unknown. Rapid diagnostic tests are lacking, and surveillance and reporting are poor. Currently, surgery is the principal treatment, but there is increasing evidence that specific antibiotics would play an important role in the management of the disease. Early interventions to prevent disabilities are essential in the overall management of the disease. Although it has a low mortality rate, Buruli ulcer frequently causes disabilities, and the costs of treatment and rehabilitation are prohibitive in the most severely affected areas.
In early 1998, WHO responded to the growing spread and impact of the disease by launching the Global Buruli Ulcer Initiative, uniting multiple partners through common goals, technical strategies and agreed principles of action. Concerned about the inadequate control of a disease that has such a significant social and economic impact on poor communities, the Fifty-seventh World Health Assembly (WHA) adopted Resolution WHA57.1 on Buruli ulcer in May 2004 (Annex 2). This resolution called for increased surveillance and control of Buruli ulcer and intensified research to develop tools to diagnose, treat and prevent the disease.
Every March, WHO organizes a meeting in Geneva that brings together representatives from the ministries of health of affected countries, nongovernmental organizations and researchers currently involved in Buruli ulcer activities (Annex 2). This meeting is a very important part of global advocacy efforts and provides a forum to share and disseminate new information and coordinate efforts among all partners. Participation in this meeting has grown annually, and more than 120 people attended the 2004 meeting. In accordance with Resolution WHA57.1, WHO will continue to organize this meeting in order to continue to foster technical cooperation among countries and partners as a means of strengthening surveillance, control and rehabilitation activities and promoting research on better diagnostic, treatment and preventive tools.
Objectives
To share information on progress of control, prevention of disability and research activities.
To review and discuss national action plans and research projects for the year.
To develop strategies for implementing Resolution WHA57.1.
To make recommendations to improve control and research activities.
To promote increased awareness of Buruli ulcer during the annual meeting.
Control and surveillance
Discussions on control and surveillance included:
early detection of cases;
1 standardized case management (surgery, antibiotics and prevention of disability);
laboratory confirmation of cases;
institutional strengthening through the provision of essential equipment, medicines and dressings;
training of health workers, schoolteachers and village volunteers;
teaching of Buruli ulcer in medical and paramedical schools;
standardized recording and reporting system using BU 01 and 02 forms and the HealthMapper;
monitoring and evaluation of control activities.
Research
Discussions on research included:
mode of transmission;
development of methods for early diagnosis;
drug treatment and new treatment modalities;
immunology and vaccine development;
results and use of the information from the genome sequencing project.
2 BURULI ULCER PREVALENCE SURVEY IN THE NORTHERN DEPARTMENTS OF BENIN
Dr Christian Johnson
Introduction
Buruli ulcer is known to be widespread in localized foci in 8 out of 12 of Benin’s geographical departments.
The number of cases detected passively has reached 24.2 per 100 000 population in some departments where the condition is endemic.
However, there are no data that would enable us to confirm an absence of cases in the four northern departments.
In so doing, and in the absence of a properly conducted survey, the fact that there are no data does not mean that there are no cases.
The hitherto existing figures on the prevalence of the condition are fragmentary and cannot be extrapolated to the entire country.
This survey has therefore been set in motion to fill the present gap.
Objectives
Overall objective
To document Buruli ulcer in the 4 northern departments of the Republic of Benin.
Specific objective
To confirm whether Buruli ulcer exists in northern Benin.
To determine the prevalence of Buruli ulcer in the four northern departments of Benin.
To provide training on Buruli ulcer to social and health workers in the departments concerned.
Case definitions
Probable indigenous case:
Any person residing in the area surveyed for more than two years, who has not previously lived in an endemic area but has presented with at least one of the under-mentioned lesions: nodule, plaque, oedema, or ulcer that has been active for less than a year.
Clinically confirmed indigenous case:
Any person presenting with the above-mentioned characteristics and whose lesion has been validated by a suitably trained specialist.
Biologically confirmed indigenous case:
3 Any person meeting the above-mentioned characteristics and in whom Ziehl-Neelson staining, culture, or PCR have proved positive.
Method
Preliminary training of survey team members;
Family-to-family, door-to-door census;
Notification: only cases fulfilling the definition of a probable indigenous case are to be notified;
Repeat visit by a priority validation team being made to areas where there is a great deal of water in the ecosystem.
Provisional results
Number of probably indigenous cases reported: 652
Breakdown by department:
Alibori 108 17% Atacora 41 6% Borgou 404 62% Donga 99 15%
Figure 1: Breakdown of probable indigenous cases by patient age-group
300
250 200
150 100
50 0 less than 15 to 49 49 yrs and Not stated 15 yrs yrs over
4 Figure 2: Breakdown of probable indigenous cases in northern Benin, by geographical department
Figure 3: Breakdown of probable indigenous cases traced in northern Benin, by commune (local district)
5 Figure 4: Local districts where some cases test positive in Ziel-Neelsen smear tests
Comments
Buruli ulcer is present in the northern departments of Benin.
The disease is less widespread in the north than in the south of the country.
Cases have been notified to northern Ghana.
All social and health personnel in the northern departments have been briefed on Buruli ulcer.
Conclusions
The north of Benin should be included in any surveillance system set up.
Acknowledgements to WHO for funding the survey.
Thanks to the entire social and health teams of the departments visited.
6 PRELIMINARY FINDINGS OF THE NATIONAL SURVEY ON BURULI ULCER IN THE DEMOCRATIC REPUBLIC OF THE CONGO: LESSONS LEARNT
Dr Anatole Kibadi Kapay, Deputy Director, PNLUB, Democratic Republic of the Congo
Summary
In 2004, we carried out a rapid analysis of Buruli ulcer in the 11 provinces of the Democratic Republic of the Congo in order to document the situation of the disease and to define a control strategy.
The purpose of the study was to determine the prevalence of Buruli ulcer cases and to identify the main foci in the country. The study was conducted in all of the country’s provinces through the provincial coordinating offices for tuberculosis and Buruli ulcer control.
The findings allowed three types of foci to be identified:
Foci in which the disease is highly endemic: Bas Congo province (cases reported (CR) 110, confirmed cases (CC) 10; Bandundu (CR: 7, CC: 7); Kinshasa (CR: 8, CC: 8); Maniema (CR.46, CC: 4)
Foci in which the disease is endemic: Orientale province (CR: 140, CC: 0); Katanga (CR: 60, CC: 1); Equateur (CR: 40, CC: 0); Sud Kivu (CR: 12, CC: 4).
Foci in which the disease is less likely to be endemic: Nord Kivu (CR: 36, CC: 0); Kasaï occidental (CR: 12, CC: 0); Kasaï oriental (CR: 16, CC: 0).
A total of 487 cases of Buruli ulcer were reported in 2004 during this national survey, 34 of which were confirmed on the spot. Partial results of confirmation by the Institute of Tropical Medicine in Antwerp give 20 confirmed cases out of 101 already analysed.
This first national survey shows that it is possible to determine the prevalence of Buruli ulcer in the Democratic Republic of the Congo, that the disease is still endemic there and that old foci are still active.
7 PRELIMINARY RESULTS OF A NATIONAL SURVEY ON BURULI ULCER IN CAMEROON
Dr Alphonse Um Boock, Dr Charles Nsom Mba
Buruli ulcer is an infectious disease caused by Mycobacterium ulcerans. After tuberculosis and leprosy, it is the third most common mycobacterial infection. The pathogen was first described by MacCallum et al. in Australia in 1948, although it had probably already been described by Sir Robert Cook in Uganda in 1887.
Endemic foci have been reported in rural areas in more than 30 tropical countries in Africa, Asia, Australia, Mexico, Oceania and South America.
In Cameroon, the disease was first described by Ravisse et al. in 1975 and byBoisvert in 1977 in a focus limited to the Nyong valley between the villages of Ayos and Akonolinga (Centre province).
In 2001, an epidemiological survey carried out in the Nyong basin under the supervision of the Swiss Leprosy Relief Association (Aide aux Lépreux Emmaüs-Suisse (ALES)) led to Cameroon being classified among endemic countries in Africa and to recognition of the disease as a public health problem.
Since then, several partners, including ALES, Médecins Sans Frontières Switzerland and the Centre Pasteur in Cameroon, have committed themselves to providing the country with technical and financial support for case management, which is limited to the districts of Ayos and Akonolinga in Centre province.
However, health workers have continued intermittently to report suspect cases of Buruli ulcer in different regions of the country, including in the provinces of Extrême Nord, Sud-Ouest and Centre; there has been no confirmation of these reports by diagnosis.
These observations persuaded ALES and the Ministry of Health of Cameroon, with the assistance of the Swiss Tropical Institute, to carry out a national survey, which was conducted between March and November 2004. The first phase of the survey involved identifying areas in which the disease was suspected. Investigation of suspect cases was based on a questionnaire that was administered in 64% (N = 98) of health districts through the leprosy network, which is the most extensive and organized within the health system. The results of the first phase showed that there are suspect cases in all of the country’s 10 provinces.
The second phase of the survey, which was designed to identify other foci besides Ayos and Akonolinga, made it possible to determine the prevalence of the disease in certain suspect areas, thanks to biological and clinical confirmation of Buruli ulcer cases.
The present prospective study covered all the areas that proved suspect during the first phase; other villages were identified when patients were examined. A workplan was predetermined in agreement with the district leprosy controllers, the village and health centre chiefs and served as a basis for organizing work in the field. The population was informed of the arrival of the investigators at least 24 hours in advance. Activities always began with a health education session focusing on Buruli ulcer, once the purpose of our presence in the village had been explained.
All patients corresponding to our case definition were included in the study as Buruli ulcer cases, and their samples were subjected to laboratory examination for Mycobacterium ulcerans. The patients were questioned and underwent a clinical examination. A form designed for the study was completed for each case; the form contained the following information: patient’s identity, presence or absence of other Buruli ulcer cases in the family, level of exposure to risk factors and history of BCG vaccination based on the presence of the vaccination scar on the inside of the left arm or proof of vaccination (vaccination
8 certificate). After they had been measured and weighed, each patient underwent a detailed skin examination to identify and describe, in particular, characteristic Buruli ulcer lesions.
The description and location of lesions, together with any sequelae, were recorded on the form. The location of the lesions was also indicated on a body diagram. The clinical form of Buruli ulcer, classified as active or inactive, was recorded in accordance with WHO recommendations.
Swab samples were taken from all patients with an active ulcer. The samples were taken from the undermined edges of the ulcer. A smear was systematically produced after each swab to detect AFB using Ziehl-Neelsen staining at the Centre Pasteur in Yaoundé. Two swabs per patient were systematically kept at at a temperature of 4 °C and sent to the Centre Pasteur in Yaoundé, the reference laboratory, for bacteriological confirmation using PCR, which uses IS2404 published primers (MU5 and MU6) to detect M. ulcerans DNA and by culture of DNA using the otagene extraction kit.
Suspect nodules were systematically excised; one fragment was conserved for pathology and another for bacteriological confirmation.
A dressing was made of any ulcers, and the patients were also given supplies for minor dressings.
Data entry and analysis used EpiInfo 6.0. The Chi-square test was used to determine associations between dichotomous variables. Continuous variables were analysed using the student’s T test.
A total of 1525 patients living in 167 villages were examined. A total of 705 cases of Buruli ulcer (active and inactive cases) were registered, of which 84% (N = 590) were active and 16% (N = 115) inactive.
The presence of the disease was confirmed in 6 provinces (Adamaoua, Centre, Sud, Sud-Ouest, Est and Extrême Nord). There were no cases in Nord, Littoral, Ouest and Nord-Ouest provinces. Mbalmayo health district, in Centre province, is also a major focus of the disease.
With the exception of the Ayos and Akonolinga health districts, Centre province has the highest level of endemicity, with 49% (N = 342) of all cases registered; it is followed by Est province with 32% (N = 229) and Sud-Ouest province with 11% (N = 76).
The difference between the 0–15-year age group (N = 346) and the above-15-years age group (N = 359) is not statistically significant (P >0.05). There are significantly more cases among men (52%) than women (48%).
More than 75% (N = 443) of the lesions detected were at the ulcerative stage, and some 5% (N = 30) had developed bone involvement. Early stages and nodules accounted for only 2% (N = 12).
The study showed that 52% (N = 369) of lesions are sited on a lower limb. There are no significant variations in distribution between men and women (P >0.05).
The average length of time the lesions had evolved since they appeared was 10.3 months (an interval of from 3 months to 5 years), the median period being 5 months – a sign of the chronic nature of the lesions.
Approximately 93% (N = 549) of patients with active lesions had resorted at least once to traditional medicine, in comparison with 21% (N = 124) who had made use of modern medicine.
A BCG vaccination scar was apparent on only 50% (N = 295) of patients with active lesions.
We did not think it worthwhile to carry out the study in Ayos and Akonolinga health districts because their populations are quite well informed about the disease and biomedical case management is well organized. In addition, these foci have been in existence for a long time. However, we did include cases confirmed (N = 225) and registered in these districts during 2004 in the data for national prevalence.
If Ayos and Akonolinga districts are included, prevalence of the disease is 930 cases, 73% (N = 676) of which are active forms.
9 It is likely that prevalence has been underestimated because of the limited resources and because certain potentially endemic areas were inaccessible during the rainy season. Additional factors were the poor collaboration of traditional healers, the bans imposed on some patients by healers and the population’s scepticism about modern medicine, which they consider ineffective.
Although the characteristics of the foci found in Centre province are similar to those described in the literature – swampy areas liable to flooding – the same is not true of the areas in Adamaoua province, and this calls for a clarification.
As regards inactive cases, Buruli ulcer is a major cause of mobility deficits and is very often responsible for more or less significant disabilities. In most cases, the causes of these disabilities are linked to lack of proper rehabilitation. Most of them are attributable to lack of mobilization and/or incorrect positioning throughout the healing and scarring process.
Contractures and skin adhesions are the leading cause of mobility deficits.
Almost 80% of functional disorders were associated with skin problems. In the absence of re-education, success in restoring the functions of the upper limbs is just as mediocre after surgery as after spontaneous healing or treatment by a traditional healer.
Efforts to limit skin contractures call for specific rehabilitation similar to that required for major burn victims.
The limits of this preliminary study mean that more precisely focused regional studies are required in order to determine the actual prevalence of the disease in Cameroon. However, these data provide a sound basis on which to develop the national programme for control of the disease.
10 MYCOBACTERIUM ULCERANS INFECTION IN FRENCH GUYANA, 2004
Dr Pierre Couppié, Department of Dermatology, Centre Hospitalier de Cayenne, French Guyana
Surveillance
In 2004, Buruli ulcer was diagnosed in 17 new cases. No relapses were reported. The average age of the patients was 34 years. The sex ratio was 0.89. Patients were from all geographical origins and social classes. Of the 17 patients, 5 were from Brazil. Most cases (14/17) were inhabitants of Cayenne region; 2 children from the same family developed the disease. In 2 patients, the lesion was a nodule, in 5 patients an ulcer without undermined edges and in 10 patients an ulcer with undermined edges. There were no cases of bone involvement. As regards diagnosis: PCR + in 16/16; Ziehl + in 12/16; pathology + (Ziehl and/or necrosis) 8/17; Culture + in 5/17.
Special clinical forms
One case concerned an HIV-positive patient in whom Buruli ulcer was diagnosed in 2002 (multiple subcutaneous nodules on a leg); 5 months’ treatment with rifabutin-clarithromycin, apparent cure after 1 year.
Diagnosis
PCR is now routinely offered by the Pasteur Institute in Guyana. Since June 2004, culture has been carried out in the country (B. Maubert, Institut Pasteur, Guyana).
Epidemiology
Two studies are under way:
Two case control studies: 30 cases and 60 controls, matched by sex, age and period of consultation. Subjected to univariate analysis, association between the risk of developing M. ulcerans infection and habitat, activity or leisure in the vicinity of: a river (OR=3.33 [1.06– 10.46]); swamp (OR=3.67 [1.31–10.23]); farm (OR=4.40 [1.43–13.54]) or zone liable to flooding (OR=28.0 [3.05–256.7]).
One study to isolate M. ulcerans in the environment; a study is being carried out in the region of Mana (O. Quéré, B. Maubert).
Research projects
Discussions are under way with the Institute for Research and Development to determine the contribution of remote sensing by satellite in order to understand the very sharp variations in the incidence rate from one year to the next in Guyana. A study to compare case incidence with geographical elements and a dynamic study of variations of incidence in time and in relation to flooding could be carried out.
11 ACTIVITIES OF NONGOVERNMENTAL ORGANIZATIONS
12 NOTEWORTHY ACTION BY ANESVAD IN 2004 AS PART OF THE BURULI ULCER CONTROL EFFORT
Verónica Malda
1. Campaign to inform the Spanish public about the disease
2. Projects in the countries affected by the disease
1. Existe.org campaign
Introduction
Informing the Spanish public
The main Spanish NGO engaged in Buruli ulcer control
The only organization to provide information through the mass media. Seventh information campaign (to be confirmed)
Objectives
To provide information on Buruli ulcer.
To disseminate the video produced by WHO.
To collect funds for implementing development projects to counter the disease.
Communication strategy
In 2004, WHO produced a documentary on Buruli ulcer that was financed in part by ANESVAD. The purpose of the documentary was to inform the international community about the disease.
In order to publicize the documentary, ANESVAD organized an information campaign about the disease, together with concrete actions targeting its members and collaborators, the general public and the mass media.
Buruli ulcer receives little attention in the mass media. The very harsh reality of the disease posed a problem when it came to creating information material. There is a risk in showing things as they really are, and it is occasionally counterproductive.
The solution lay in not showing Buruli ulcer itself but rather the effect the disease produces in the eyes of those who see it, thus making it possible for anyone who wants more information to ask for it.
13 Creative concept
The campaign was intended as a programme to raise awareness by providing Spanish society with information on Buruli ulcer. To achieve this, a web site was set up within the www.existe.org domain. The site offered both key information about the disease (its causes, consequences, course, diagnosis and treatment and countries concerned) and allowed users to request the WHO documentary. The campaign was an active one because it encouraged users to contact ANESVAD for more information or to request the documentary.
The second step was to draw attention to this web page by a TV advertising campaign. A number of TV advertisements were designed showing the reactions of different men and women when they watched scenes in the WHO documentary showing Buruli ulcer. In order to arouse the curiosity of viewers, there was no mention of ANESVAD in the sequences; an internet address simply appeared at the end: www.existe.org. In the final stage of the campaign, the adverts carried ANESVAD’s signature.
The TV commercials were broadcast for two months (October and November 2004).
The information campaign was bolstered by press and radio advertisements, a banner campaign on the Internet and another direct marketing campaign targeting 1 300 000 people, together with 4200 displays in the main Spanish banks.
Results
Difficulties: the disease is very remote for the Spanish public and this means that it is difficult to capture the attention of the mass media.
A total of 6500 WHO documentaries were distributed.
There were 720 495 hits on the www.existe.org site, with an average of 8.65 pages being visited by each user.
There were 36 interviews and media appearances.
The campaign had a domino effect through people learning about the campaign and contacting us to organize activities to explain the disease to their immediate circle (leaflets in educational establishments, projections of the documentary).
Quantification of the results is difficult because of the absence of concrete indicators for measuring greater awareness. In ANESVAD’s opinion, this information campaign has had a beneficial effect.
2. Projects in the countries affected
A short presentation of ANESVAD’s action in the main areas of its control strategy: a. Direct care for patients
b. Early detection campaigns
c. Training
d. Help with schooling for hospitalized patients
14 e. Awareness raising, information, education and communication (IEC) material f. Disability prevention and physiotherapy The implementation of our pilot campaign for disability prevention and physiotherapy in Côte d’Ivoire and Benin should be highlighted.
Future plans in this field.
15 SURGICAL AND POD TRAINING SUPPORTED BY AMERICAN LEPROSY MISSIONS IN ASHANTI REGION, GHANA: CONCLUSIONS FROM A RECENT EVALUATION
Dr Paul Saunderson
Central Ghana is one of the most endemic areas for Buruli ulcer in west Africa. The number of new cases of the disease reported in Ashanti Region is increasing steadily, although this is presumably mainly a consequence of better reporting; 435 cases were reported in 2004, of which 40% presented as nodules and 60% as ulcerative cases; only 224 cases were reported in 2003 and 154 cases in 2002.
After discussions with Dr Pius Agbenorku, a plastic surgeon based in Ashanti Region, and officials from both church and government, American Leprosy Missions (ALM) began to fund a programme to train staff at district level in the management of the disease. The training focused on teaching doctors to carry out debridement and skin grafting. The project started in 2001 and this evaluation was conducted after 3 years of work. The main objective of the programme is “to train doctors and paramedics at the district and community health institutions to manage effectively Buruli ulcer patients in their own health institutions”. Prevention of disability (POD) activities were added to the training in 2003.
The training programme has been effective, in that the number of centers managing Buruli ulcer cases has doubled and the quality of care has improved everywhere. Policies and activities aimed at POD are being slowly implemented. The programme has made significant progress towards its goal. Recommendations
ALM should continue to support this very worthwhile programme.
There should be a gradual move away from formal courses to structured on-the-job training during supervision visits.
The concepts and strategies of POD should be an integral part of all training.
ALM’s POD Consultant should target the training of local POD facilitators.
16 THE ASSOCIATION FRANÇAISE RAOUL FOLLEREAU: 10 YEARS’ PARTNERSHIP IN BURULI ULCER CONTROL, 1995– 2005
Mr Jehan-Michel Rondot
The Association Française Raoul Follereau (AFRF), a major player in leprosy control – its principal activity – has a high profile in the field and is deeply attentive to the needs voiced by health officials of countries where it is present. In 1995, it was asked by Benin and Côte d’Ivoire to help support national projects to provide treatment for Buruli ulcer patients.
In 1998, AFRF helped to organize and finance the Yamoussoukro conference and was one of the signatories of the final declaration, the founding act of the initiatives that were to follow.
In spite of strong political resolve, there was still uncertainty about the underlying facts of the health situation. Specialized knowledge of this “re-emerging” disease was extremely limited and understanding of Mycobacterium ulcerans was poor. However, we rapidly found ourselves having to deal with a growing number of new cases in areas in which the disease had been declared endemic. These are poor regions, without any health facilities capable of providing case management for barely solvent patients who are unable to meet the high cost of surgery, which is the only treatment.
AFRF and its Scientific and Medical Commission adopted a clear and pragmatic strategy with three complementary objectives: assistance with case management, support for research and awareness.
Its operational support focused on two countries, both of them longstanding partners, Benin and Côte d’Ivoire, where, depending on the circumstances, it provides support for private or state centres.
In Benin, starting in 1995 and regularly for 10 years, AFRF has provided its support to the Gbémontin Centre in Zou, in the form of medicines and medical supplies (€38 000 earmarked for 2005). This centre, which is run by Sister Julia, was the first to provide treatment for Buruli ulcer patients in Benin. Sister Julia, a brave and pioneering Spanish nun, now appears as a precursor; today, Buruli-ulcer related activities are still an important part of the centre’s work. In 2004, 400 patients were treated there.
The Madeleine and Raoul Follereau Buruli Ulcer Detection and Treatment Centre (BUDTC) was officially inaugurated at Pobè in April 2004. This major project marks the response to a request from the Ministry of Public Health and is part of the strategy developed by the national Buruli ulcer control programme. The centre has four wards (26 beds), an outpatient consulting room, an operating theatre and a laboratory. As well as building the centre, AFRF has completely equipped it and covers its running costs. Management of the centre is in the hands of Docteur Annick Chauty, who has been at work in Pobè since the beginning of 2003. In 2004, the budget amounted to €310 000; for 2005, €365 000 have been set aside, including amortization.
Since 1 January 2005, at the request of the Benin Ministry of Public Health, AFRF has contributed €68 000 to the running costs of the Lalo BUDTC, located in Mono Couffo. This centre has 40 beds for patients and treats 100 patients each year.
In Côte d’Ivoire, assistance from AFRF is directed to the Raoul Follereau Institute in Adzopé, a public hospital run by the Ministry of Health. In 1999, AFRF entered into an agreement to provide case management for 200 patients each year. Since then, its annual contribution has ranged from €100 000 to €115 000. However, activities have been considerably disturbed by the crisis besetting Côte d’Ivoire since 2003.
17 AFRF is very active in the Congo, where for many years it has been the partner of the National Leprosy Control Programme; it has been asked to support the activities of the recently created National Buruli Ulcer Control Programme. This new partnership will take shape in 2005.
The second major thrust is support for research programmes: since 1995, the aim of the projects selected has been prevention and treatment of the disease thanks to a better understanding of Mycobacterium ulcerans; examples of this are the “M. ulcerans ecology study” and the “Therapeutic trial of clinical lesions of M. ulcerans infections using combined aminoglycoside–rifampicin” by Professor Carbonnelle and Mr Laurent Marsollier of the Angers Medical Faculty (2002–2003) and the “Analysis of the M. ulcerans genome” by Professor Stewart Cole of the Pasteur Institute in Paris. The research budgets for 2004 and 2005 amounted respectively to €154 000 and €229 000. For the same purpose, AFRF also awards fellowships to young researchers investigating the disease.
Dissemination of information and raising awareness: this complementary element of the strategy adopted is designed to bring this “mystery” disease to the attention of the general public and to ensure health workers have the information they need. To this end, AFRF has provided €60 000 towards the French versions of several publications: Diagnosis of M. ulcerans disease and Management of M. ulcerans disease. It has also jointly produced with WHO a video, The mystery disease. Apart from this, for 10 years AFRF has informed and drawn the attention of the French and French-speaking public: its publications and congresses are an opportunity to put out messages which are taken up by the media. The Bulletin de l’Association des léprologues de langue française (Bulletin of the Association of French- speaking leprologists) – ALLF, which it funds, has published articles on M. ulcerans. As a whole, these efforts have unquestionably helped to develop national and international awareness and improved our understanding of Mycobacterium ulcerans disease.
In this way, a grand total of over €2 500 000 has been invested since 1995 and testifies to the commitment of AFRF to Buruli ulcer control in Africa.
The annual meeting at Geneva in April 2005 is an opportunity to show that significant progress has been made internationally, although we must still show caution as uncertainties remain. Even though research is flourishing and shows promise, much about Mycobacterium ulcerans remains unknown, and our understanding of the disease’s epidemiology is still incomplete. Documentation of the social consequences of the disease and physical rehabilitation is also scant. AFRF sincerely hopes that in 2005 it will be possible to optimize both scientific and operational synergies, which guarantee the effectiveness and relevance of efforts in the respective fields. The Association is prepared to contribute to that effort by helping to galvanize exchange within the network of partners committed to Buruli ulcer control.
18 CONTRIBUTION MADE BY THE SWISS LEPROSY RELIEF ASSOCIATION TO THE BURULI ULCER CONTROL EFFORT IN CAMEROON SINCE 2002
Dr Um Boock Alphonse, Mr René Stäheli
Introduction
The Swiss Leprosy Relief Association (Aide aux Lépreux Emmaüs-Suisse – ALES) has been a valuable partner in the field of health in Cameroon for almost half a century. Collaboration between ALES and the Ministry of Pubic Health dates back almost 50 years.
Together with its local partners, ALES has succeeded in developing a very effective leprosy control network in Cameroon, thanks to which the leprosy elimination threshold was attained almost 3 years ago in Cameroon.
Until 2000, ALES had limited its action to leprosy and tuberculosis; after 2000, it extended it to include Buruli ulcer, starting with the study carried out in the Nyong river basin.
Justification
Study carried out in 2000 in the Nyong river basin under the leadership of ALES in collaboration with Médecins Sans Frontières Switzerland (MSF-CH).
In 2000, Buruli ulcer was recognized as a public health problem in Cameroon.
Buruli ulcer is caused by a mycobacterium similar to that responsible for leprosy.
Buruli is a neglected disease.
The disease is present in the area of a project supported by ALES.
A request was received from the Ministry of Public health.
Overall objective
To ease the suffering caused by Buruli ulcer at Ayos and Akonolinga.
Specific objectives
To organize treatment for the cases detected.
To support the development of a national Buruli ulcer control programme.
To set up a research programme.
To provide rehabilitation for patients.
19 Funding
Significant financial support from ALES for the programme since 2002.
FCFA 354 566 007 mobilized over 3 years to organize case management of the disease:
. Year 1 (CFA 9,176,674)
. Year 2 (CFA 234,626,157)
. Year 3 (CFA 110,763,176)
Achievements
Thanks to the funds mobilized, it was possible to attain the above objectives:
Renovation and equipment, provision of a food programme, staff training, transport for patients, educating the populations and research and rehabilitation activities.
Impact of the achievements
Improvement of hospital attendance by patients; a sign of greater confidence.
A marked improvement in the quality of case management.
Health is considered in terms of the classical definition as “a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity”.
A stimulating working environment for staff.
Overall enhancement of the health system.
Conclusion
The support of ALES has been decisive in organizing case management in Cameroon.
The Ayos and Akonolinga pilot centres provide a valuable opportunity to extend and organize case management to other sites.
The support of donors is essential because of the programme’s high operating cost.
It would be worthwhile to spread the expertise developed at Ayos to other disease foci.
Prospects
The Ayos pilot project is to be transformed into a regional training centre.
Management tools are to be developed for the programme.
Research activities to improve knowledge of the disease and its treatment are to be developed.
20 An effort will be made to educate populations about the disease.
Staff from other sites will be trained.
Efforts will be made to improve the equipment used for case management.
21 IMPLEMENTATION OF EXPERIMENTAL HYPERBARIC OXYGEN THERAPY AS TREATMENT FOR BURULI ULCER AT THE ALLADA HOSPITAL IN BENIN
Dr Franco Poggio
At the fourth meeting here in Geneva in 2001, I presented the donation made by my Rotary Club, Milan Aquileia, for a hyperbaric oxygen therapy chamber which was intended to speed up cure and to improve treatment outcomes.
At the time, I said that “it should be done in an African hospital where there is a medical and surgical team specialized in treating Buruli ulcer, possessing a well-equipped laboratory for analysis, and if possible, a telemedicine link”.
This wish has been fulfilled by the Buruli Ulcer Screening and Treatment Centre (CDT/BU) at Allada.
The hyperbaric oxygen treatment chamber was installed at the hospital, and the Raoul Follereau Foundation of Luxembourg completed the building thanks to the intervention of Professor Kiniffo and Doctor Kohll. Telemedicine facilities are even available at the site.
This has all been made possible by the contributions of the Rotary Club of North Bergamo (whose Chairman, Mr Civettini participated personally on the spot), the San Sirino Rotary Club of Milan and the Rotary clubs of Meda, Novare and of New York.
The Italian Navy’s health services, under the command of Admiral Dr Vincenzo Martines, took part in the project by training three Beninese: a physician, a technician and a nurse at the Consubin diving school in La Spezia. We should also like to express our thanks to three Beninese physicians, Dr Roch Christian Johnson, Dr Ghislain Emmanuel Sopoh and Dr Ange Dossou for their helpfulness.
Two members of the International Scientific Committee who visited Allada last August, Professor Giorgio Leigheb and Dr Claudio Clemente, both of whom are Rotarians, will now describe the programme that has been set up with the agreement of the Beninese health authorities and the participation of WHO, represented by Dr Kingsley Asiedu.
We are committed to participating in the experiment by sending physicians from the Navy (which has already sent two naval physicians on mission) specialized in hyperbaric treatment together with volunteer physicians who are Rotarians, to collaborate with the team of Beninese physicians.
22 HEALTH-SEEKING DETERMINANTS OF PATIENTS WITH BURULI ULCER IN BENIN
A.A. Mulder1, R. P. Boerma1, Y. Stienstra1, C. Zinsou2, T.S. van der Werf 1, C. Bovi, R.C. Johnson3
1 Groningen University Hospital, Department of Internal Medicine, Groningen, The Netherlands 2 Centre Sanitaire et Nutritionnel, Gbemoten, Zagnanado, Benin 3 Programme Nationale de Lutte contre l’Ulcère de Buruli, Cotonou, Benin
Few studies have shown why patients present late to the hospital after developing Buruli ulcer. Therefore, health-seeking behaviour determinants and stigma were studied by in-depth interviews in patients treated in the hospital, patients treated traditionally or with active disease and healthy community control subjects. Witchcraft was the most common attributed cause of the disease. Other causes mentioned were hygiene, drinking-water and the environment. Self medication and traditional medicine are sought before presenting at the treatment centre. A model is shown in which internal and external factors on decision- making are described. With increasing severity, extent and duration of Buruli ulcer, a shift appears to occur in health-seeking behaviour. Confidence in the hospital and advice of others are important factors. Factors causing delay were the use of traditional medicine before presenting at the treatment centre; the costs and duration of admission; the disease as considered not serious enough; witchcraft as a perceived cause of disease; and fear of treatment effects. Patients expected amputation as treatment in the hospital. Stigma among Buruli ulcer patients is huge, with fear of contamination an important contributing factor. This study shows the importance of traditional healing in society. To shorten delay, the hospital should be promoted as a treatment centre for Buruli ulcer independent of attributed cause. Involving traditional healers in health-seeking behaviour should be considered.
23 BURULI ULCER: VILLAGE FOLLOW-UP OF TREATED PATIENTS IN RURAL BENIN
M. Debacker1, J. Aguiar2, C. Steunou BSc2, C. Zinsou1,2, W.M. Meyers3, F. Portaels1
1 Institue of Tropical Medicine, Antwerp, Belgium 2 Centre Sanitaire et Nutritionnel Gbemoten, Zagnanado, Benin 3 Armed forces Institute of Pathology, Washington, DC, USA
Summary
Buruli ulcer is a recognized public health problem in west Africa. In Benin, between 1989 and 2001, the Centre Sanitaire et Nutritionnel Gbemoten (CSNG) treated more than 2500 Buruli ulcer patients. Between March 2000 and February 2001, field trips were conducted in the Zou and Atlantique regions. The choice of the two regions was based on the distance from the CSNG and on villages with the highest number of patients treated at the CSNG. A total of 66 out of 150 former patients (44.0%) treated at the CSNG were located in the visited villages. The recurrence rate of CSNG-treated patients after up to 7 years follow-up was low (6.1%, CI 95%: 2.0–15.6). We attribute this low rate to the high quality of treatment for Buruli ulcer at an accessible regional center (CSNG).
The WHO definition of a recurrent case of Buruli ulcer should be revised to include a follow-up period longer than one year.
Debacker M et al. Buruli ulcer: village follow-up of treated patients in rural Benin. Emerging Infectious Diseases, 2005.
24 TREATMENT OF BURULI ULCER WITH THE COMBINATION OF RIFAMPICIN AND STREPTOMYCIN IN BENIN
Annick Chauty
Until recently, surgical excision was the only available treatment for Mycobacterium ulcerans disease. Following the discovery that treatment with the antibiotic combination rifampicin and streptomycin kills M. ulcerans in early lesions of the human disease after 4 weeks, the role of antibiotics either alone or in combination with surgery for management of all forms of the disease was evaluated in 224 patients. All patients were treated with rifampicin (10 mg/kg body weight by mouth daily) and streptomycin (15 mg/kg body weight by intramuscular injection daily) for at least 4 weeks on an ambulatory basis under direct supervision of 12 health centres located in Ouémé and Plateau departments of Benin. Two groups were defined at week 4: those in whom lesions were healing who continued with antibiotics alone for another 4 weeks, and those thought to require surgical excision who were referred for surgery while continuing antibiotic treatment for another 4 weeks. The lesions of 99 patients (44.2%) were healed exclusively by antibiotics for a total of 8 weeks, while in 112 patients (50%) referred for surgery the extent of surgical excision was reduced after antibiotics. A large proportion of the patients (211/224: 94.2%) were cured with antibiotics for 8 weeks. Interestingly, 31 patients treated for less than 8 weeks were cured with antibiotics only, despite their weak compliance. Among 124 cured patients followed up for at least 12 months after treatment completion, 2 cases of recurrence were observed with the use of antibiotics only and another one after antibiotics and surgery. This prospective observational study suggests that treatment with rifampicin and streptomycin for 8 weeks, as recommended in WHO guidelines, can cure a large proportion of patients with Buruli ulcers. If antibiotic treatment is recommended for 8 weeks, the optimal duration of therapy is yet to be determined in order to prevent recurrence.
(Work supported by the Association Française Raoul Follereau with the national programme against Buruli ulcer in Benin.)
25 ECONOMIC BURDEN OF BURULI ULCER IN GHANA, 2001- 2003
Mumma GA,1 Whitney EAS,1,2 Dadzie F,1 Asiedu K,3 Addo BO,4 Adomako J,4 Etuaful S,4 Ampadu E,4 Klutse E,4 Appah B,4 and Ashford DA1
1 United States Centers for Disease Control and Prevention, Atlanta, GA 2 Emory University, Atlanta, GA 3 World Health Organization 4 Ministry of Health of Ghana
Introduction
Buruli ulcer is caused by Mycobacterium ulcerans. If left untreated, the disease can cause serious skin destruction, scarring, joint contractures and permanent disability. Rarely, amputations and death may result. Since it is associated with prolonged and expensive treatment and long term disability, Buruli ulcer is suspected to have a large economic impact on the victims, their households and entire communities. However, the total societal costs of Buruli ulcer for Ghana are unknown, and the proportion of Buruli ulcer-related costs that are subsidized through the health care system is uncertain.
Methods
In October 2003, we used a survey to retrospectively collect data about socioeconomic, demographic, disease-specific, resource use and disease management characteristics from households affected by Buruli ulcer from 1998 to 2003 in three endemic districts of Ghana, Amansie West, Upper Denkyira and Atwima. The survey population included all households in which a household member had been reported to have Buruli ulcer from 1998 to 2003. A household was defined as a basic social and economic unit where the residents ate from the same pot. We used a cost-of-illness approach to assess the median annual costs per Buruli ulcer patient by stage of disease to affected households in Ghana. All calculations were converted from Cedis, the local currency, to US$ in 2003. Costs incurred in 2003 were annualized by a constant weight of 4/3, and costs incurred before 2003 were adjusted for time preference using a 3% discount rate. Data were entered into Microsoft Access and t-test comparisons for equality of means of the annual total costs by year were performed using STATA.
Results
We enrolled and interviewed people from 390 households in which 468 Buruli ulcer patients resided. Of these 468 patients, 57 were excluded from analysis because of incomplete survey responses and 2 were excluded based on outlying responses. From the 409 patients included in the analysis, 53% were aged ≤15 years, 55% were females, 71% had less than secondary school education and 44% were students. The median duration of illness was 3 years; the mean duration of illness for 2003 was 11.3 months (95% CI: 11.04–11.52 months).
26 For 2001–2003, the median annual total costs of Buruli ulcer to a household by stage of disease ranged from US$ 76.20 (N = 81) per patient with a nodule to US$ 428 (N = 11) per amputee. Statistically significant differences in the median annual total costs of Buruli ulcer were seen among the specific disease stages. Based on an average opportunity cost of US$ 2.04 per 6-hour workday for this population, affected households lost between 37.4 (16% of a work-year) and 210 (89% of a work-year) whole work- days per year for a patient with a nodule and amputation, respectively.
Conclusions
Treatment interventions targeting the very early stages of Buruli ulcer would result in lower costs and considerable cost savings to households affected by the disease.
27 BURULI ULCER LABORATORY NETWORK: HOW A DIAGNOSTIC SYSTEM OPERATES IN GHANA
Ohene Adjei, Vera Siegmund, Gisela Bretzel
The Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR) as a Buruli ulcer reference centre
In order to support active case-finding, to allow rapid on-site laboratory diagnosis of Mycobacterium ulcerans disease and to provide accurate laboratory-confirmed incidence and prevalence data, diagnostic laboratory networks consisting of different level laboratories that collaborate closely with clinical staff and provide training are required in endemic areas.
Presently, the KCCR in Kumasi, Ghana, acts as reference centre for the northern zone including the Ashanti region.
Village health workers (volunteers) from Upper Denkyira and Asante Akim North District have been trained in active early case-finding. The efficiency of case-finding activities in the respective regions has been monitored on a regular basis by KCCR/BNITM staff. Hospital Buruli ulcer teams from Agogo Presbyterian Hospital, Dunkwa Governmental Hospital and St. Martin’s Hospital, Agroyesum (Amansie West District), have received on-site training in specimen collection according to a standardized system developed by KCCR/BNITM staff in collaboration with local surgeons and laboratory staff. Specimens and corresponding data forms (designed for the ongoing study) have been collected from the treatment centres on average twice a month (depending on the availability of patients) by two KCCR graduate students assigned to the Buruli ulcer research group. Diagnostic tests (Ziehl-Neelson, culture, DRB-PCR) have been carried out at KCCR laboratory facilities, quality assurance (Ziehl-Neelson , standard reference PCR) and histopathological analysis for differential diagnosis have been conducted at BNITM. Diagnostic results have been reported to the hospitals and the Ghanaian Buruli ulcer control programme in due course. Laboratory staff from St. Martin’s Hospital has received refresher training in ZN microscopy and basic culture techniques at KCCR.
Decentralization of advanced diagnostic tools, i.e. DRB-PCR, in selected laboratories of major treatment centres at district level, allows rapid pre-surgical on-site diagnosis of Buruli ulcer, thus ensuring adequate treatment of laboratory-confirmed disease in the majority of cases. The implementation of DRB-PCR laboratories for on-site diagnosis in three treatment centres at district level is scheduled for 2005. Hospital teams (hospital and laboratory staff) from the respective treatment units will receive on-site training in surgical techniques, specimen and data collection, and diagnostic laboratory methods. Following the implementation of diagnostic methods at district level, KCCR will take over quality assurance for the respective laboratories. Expansion of training activities to additional settings is planned according to the requirements and recommendations of the Ghanaian Buruli ulcer control programme. In addition, to achieve technology transfer to other endemic countries, “training for trainers” workshops in diagnostic laboratory techniques for laboratory staff from the Democratic Republic of the Congo and Benin will take place at KCCR.
28 Three-step approach to the laboratory diagnosis of Buruli ulcer
Preliminary results from an ongoing study on the DRB-PCR laboratory confirmation of clinically diagnosed cases supported by a grant from the Volkswagen foundation suggest the need to revise the current approach to the laboratory diagnosis of Buruli ulcer.
The comparison of the diagnostic sensitivity of DRB-PCR analysis of swab and tissue specimens suggests that testing of diagnostic swabs renders a positive diagnosis in over 70% of early ulcerative forms of M. ulcerans disease, whereas the analysis of tissue specimens provided only an additional 10% of positive diagnostic results. Thus, we conclude that in the majority of early ulcerative cases analysis of non- invasive diagnostic swabs is sufficient to establish the laboratory diagnosis.
Furthermore, based on our previous work, we can safely assume that 30% to 40% of the ulcerative cases can already be diagnosed by swab smear microscopy. In an additional 30% to 40% swab DRB-PCR renders a positive diagnostic result. Thus, DRB-PCR laboratory confirmation of tissue specimens obtained during surgery shall be required in the remaining approximately 20% to 30% of the cases only.
We also assume that, contrary to the current WHO standards, only one positive diagnostic test is sufficient for a positive laboratory diagnosis of Buruli ulcer.
Based on these considerations, a novel three-step approach focusing on non-invasive diagnostic tests for the optimized, timely, practicable and cost-effective laboratory diagnosis of Buruli ulcer is being evaluated in Ghana (Figure 1).
For optimum quality of diagnostic specimens, standardized procedures of specimen collection, including transport and storage media, have been established as a prerequisite.
Two diagnostic swabs per patient are collected either by village health workers in the field, or by hospital staff from patients already presenting at the treatment units.
First, one diagnostic swab is subjected to microscopy in microscopy units at district level, and microscopically-positive patients shall subsequently be referred to treatment.
Second, if microscopically negative, the second diagnostic swab is DRB-PCR-tested in hospital DRB- PCR laboratories to be installed in major Buruli ulcer treatment centres. Positive patients are referred to surgery.
Third, if pre-surgical laboratory tests cannot confirm Buruli ulcer, patients are operated on according to the surgeon’s indication, and tissue specimens are tested for retrospective laboratory confirmation. Bacteriologically negative specimens may be subjected to histopathology to determine the differential diagnosis.
29 Pre-surgery: diagnosis Post-surgery: laboratory confirmation Hospital Field or Hospital (hospital staff) (village health worker) (hospital staff)
Diagnosticswab I Diagnosticswab II Tissue specimen
All ulcerative forms Swab MIC and DRB-PCR negative ulcers All non-ulcerative forms
1. Smear MIC (peripheral level or hospital laboratory)
2. Swab DRB- + – PCR (hospital laboratory) 3. Tissue DRB-PCR + – Laboratory confirmation (hospital)
Differential diagnosis + –
Treatment
Figure 1: Three-step approach to the laboratory diagnosis of Buruli ulcer: swab smear microscopy (MIC), swab DRB-PCR, tissue DRB-PCR
30 THE ECOLOGY OF MYCOBACTERIUM ULCERANS: AQUATIC FOOD WEBS AND WATER QUALITY RELATIONSHIPS
Richard W. Merritt, M. Eric Benbow, R. Kimbirauskas
Mycobacterium ulcerans infection is commonly called Buruli ulcer, a rapidly emerging skin disease that is often disfiguring and causes severe and lasting morbidity in communities of developing nations. Outbreaks of the disease are nearly always associated with slow-flowing aquatic habitats, which many times are affected by, or created from, human-made changes to the landscape. PCR evidence suggests that the organism is present in water, biofilm of aquatic plants, detritus, snails, fish and invertebrates. However, the organism has rarely been cultured from the environment. We have proposed a “trophic transmission hypothesis” as a possible transmission scenario for M. ulcerans. With this background, we are trying to determine landscape factors that influence aquatic food web structure and M. ulcerans distribution within and among aquatic habitats of Ghana, Africa. By integrating molecular diagnostic tools (PCR), GIS and remote sensing technologies with established ecological sampling and water quality bioassessment techniques, we hope to determine the ecological distribution and potential factors influencing environmental conditions conducive for M. ulcerans occurrence and distribution at three hierarchical spatial scales: landscape, habitat and community. Using this multi-scale, multidisciplinary approach, we will attempt to generate predictive models to enhance the scientific understanding of this disease in nature and how the mycobacterium is transmitted in the aquatic environment.
31 THE COMPLETE GENOME SEQUENCE OF MYCOBACTERIUM ULCERANS STRAIN AGY99
Dr Tim Stinear
The project to determine the genome sequence of a west African epidemic strain of Mycobacterium ulcerans is now complete.
This project was conducted at the Institut Pasteur, Paris, and funded by the Génopole Program of the Institut Pasteur, the Association Française Raoul Follereau, WHO and the National Health and Medical Research Council of Australia.
A genome is the complete DNA sequence of an organism. In simple terms, DNA is a coded set of inherited instructions made up of four repeating sugar units. These four repeating units link together in an organism-specific sequence (the so-called DNA sequence) and they contain all the information necessary for an organism to live and replicate. Within the DNA sequence are discrete segments called genes. A specific gene holds the blueprint for a specific proteinm, and by determining the location of all the genes in a DNA sequence it becomes possible to predict the proteins that the organism will produce.
Bacterial genomes usually contain a single, circular DNA sequence of around 5 000 000 sugar units. Higher order organisms such as humans have genomes 1000 times larger than bacteria and the simplest life forms, viruses, have genomes 1000 times smaller than bacteria. Importantly, related organisms have a related sequence of the four DNA sugars. To determine the complete genome sequence of a bacterium means to determine the specific order of the 5 000 000 units of the four DNA sugars.
Knowing the complete DNA sequence for a pathogenic bacterium such as M. ulcerans provides key insights into its make-up and how it causes disease; it provides the fundamental resource that scientists use to develop such things as new diagnostic tests, high discrimination tools for molecular epidemiology, improved antibiotics and vaccines.
For M. ulcerans strain Agy99, we have established that its genome comprises a main circular chromosome of 5 631 606 units (or base pairs) and a smaller circular element (called a plasmid) of 174 155 base pairs. The plasmid was a key finding of the project as this element harbours the genes required for the production of the M. ulcerans toxin, mycolactone (1). Mycolactone is a key virulence factor for M. ulcerans.
Analysis of the genome has revealed other insights into this pathogen. It has revealed a genome rich in insertion sequence elements (ISEs). ISEs are short “parasitic” DNA sequences that perform no essential cell function but encode a gene that permits the sequence to copy itself. Approximately 7% of the DNA sequence is made up of ISEs. The genome also contains a very high proportion of pseudogenes. These are non-functional gene sequences caused by DNA mutations. There were 5026 individual genes identified, 692 (14%) of which were predicted to be pseudogenes. Such a high level of gene inactivation helps explain some of the characteristics of M. ulcerans, such as its slow growth rate. Other features of the genome include two new mycobacterial viruses, known as prophage, embedded within the genome sequence. In some bacteria, prophage harbour virulence genes, such as those responsible for toxin synthesis. The impact of the M. ulcerans prophage on the bacterium and their role in disease is as yet unknown.
Computer-based analysis of the genome and its comparison with other mycobacterial genomes has revealed at least 20 predicted gene sequences that may produce antigens that are specific for M. ulcerans. These sequences are currently being studied in more detail with the aim of testing their applicability for the development of a serodiagnostic test for Buruli ulcer.
32 The structure of the M. ulcerans genome is reminiscent of M. leprae – i.e. a genome in decay –and this is entirely consistent with the hypothesis that M. ulcerans is a pathogen that has evolved to occupy a specific environmental niche, such as the salivary glands of certain aquatic insects.
The publication of the complete genome sequence is anticipated for 2005 and will provide a solid platform for accelerating and improving the research effort into this enigmatic pathogen.
Reference
1. Stinear TP et al. Giant plasmid-encoded polyketide synthases produce the macrolide toxin of Mycobacterium ulcerans. Proceedings of the National Academy of Sciences of the United States of America, 2004, 101:1345–1349.
33 REPORT ON BURULI ULCER CONTROL ACTIVITIES FOR THE YEAR 2004 AND OUTLOOK FOR 2005 IN BENIN
Dr Christian Johnson
Summary of programme objectives
General objective
To iimprrovee Buruli ullcceer cconttrroll iin Beniin.
Specific objectives
To iincreeaasse tthe rrate offeeaarrly--ssttaage ccaasse--ffinding to 50%
To rrrreatt aallll ttrraceed accttiivee casses offBurrulli ulcer..
To rreeduce tthe diissabilitiiees ccaussed by thee diisseaasse tto 5%..
To proviidee pssychosociall ssupportt tto aafffectteed indiviiduaallss,, famiilliieess aand communiittiiess.
To promottee sccieenttiiffiicc reessearcch on Burulii ullceerr.
To provide health education to communities where the condition is endemic.
To conduct advocacy work and resource mobilization.
Objective 1. To increase the rate of early-stage case-finding to 50%.
Every department in which the condition is endemic now has a working Buruli Ulcer Detection and Treatment Centre (CDTUB).
Results
Screening activities
Areas covered:
– Atlantique-Littoral: Zê, Sô-Ava
– Zou-Collines: Zagananado, Ouinhi, Zogbodomè
– Mono-Couffo: Lalo, Toviklin
– Ouémé-Plateau
Detection rates:
34 – Non-ulcerated forms traced: 27%
– Mixed forms: 14.84%
– Mixed and non-ulcerated forms: 42%
– Handicap on admission: 22%
The challenge for 2005 – improve the results of screening and referral in the areas covered.
Activities:
● Maintain regular and ongoing supervision of the community links in each health area;
● Intensify meetings with the most active links so as to win their loyalty;
● Provide better surveillance coverage in different health areas.
Objective 2. To treat all traced active cases of Buruli ulcer
Referral of cases traced
No. of cases traced: 925
No. of cases treated by the CDTUB: 822 (88.86 %)
Biological confirmation (laboratory tests)
Table 1: Breakdown of cases by CDTUB
CDTUB Number Proportion Allada 133 16% Lalo 126 15% Pobè 165 20% Zinvié 68 8% Zagnanado 330 40% TOTAL 822 100%
35 Table 2: Breakdown of cases by provenance
Department Number Proportion Atlantique 172 20.92% Couffo 107 13.02% Littoral 18 2.19% Mono 12 1.46% Nigeria/Togo 5 0.60% Ouémé 252 30.66% Plateau 43 5.23% Zou 201 24.45% Not stated 12 1.46% Total 822 100%
Figure 1, 2, 3: Distribution of new and recurrent cases by gender.
36 Figure 4: Clinical forms
Figure 5: Localization of lesions
37 What are the challenges?
Provide effective treatment of 100% of cases traced
Reduce the relapse rate (carry out a study to establish their rate)
Improve the quality of treatment at the CDTUB:
– Access to care:
- geographical: antibiotherapy at local level
- financial: PNLUB (National Buruli Ulcer Control Programme) and partners
- cultural: awareness raising
– Workers’ skills levels:
- training (tutorials)
- standardization of treatment procedures (pain control protocol, dressings, etc.)
Risk avoidance: adherence to asepsis procedures
Efficacy: relapses and sequelae on completion of treatment
Efficiency: reduction of hospital stays for direct and indirect costs
Humaneness of approach: play areas, sociocultural facilities, psychological support groups
How?
Arrange once-weekly active screening for traced cases refusing hospitalization
Request assistance from local elected officials and village chiefs to raise awareness among patients refusing hospitalization.
Conduct awareness raising sessions in villages (the disease: the microbe and its toxin, surgical treatment, relapses and the need for check-ups, treatment procedures, etc.).
Objective 3: Reduce the disabilities caused by the disease to below 5%.
Enter under the PIRP (i.e. prevention of disabilities and physical rehabilitation) component of PNLUB implementation:
Problems arising
Rate of sequelae still high
Need for a strategy to prevent sequelae during hospital stays
Need for a strategy to correct sequelae occurring after scarring
Need to rehabilitate those with handicaps stemming from Buruli ulcer, etc.
38 Actions undertaken
The logical framework has been put in place
A feasibility study in the different centres has been carried out with ANESVAD, among other groups
Recruitment of a physiotherapist for the CDTUB at Allada
What are the challenges?
To reduce the rate of sequelae after healing from 8% to 2%
Develop a pain control protocol for the CDTUB
Turn passive (posture) and if possible active physiotherapy into ongoing activities, at a patient’s bedside (help from nursing assistants)
Provide supervision of rehabilitation work
Make the patient’s rehabilitation activities comprehensive and systematic and ensure they last for the entire hospital stay (from admission to complete scarring)
Monitor work of physiotherapists.
Objective 4: Provide psychosocial support for affected individuals, families and communities
● Social support for the destitute
● Mental health care for patients and those affected
● Feeding in the hospital environment
● Schooling for children, etc.
Objective 5: Promote scientific research on Buruli ulcer
Vacutex study
Antibiotherapy study
Oxygenotherapy study
Design of the surveillance system
Treatment procedures
Biological components of patient surveillance
Cost study
Epidemiology and environmental risk factors
Mapping
39 Prevalence survey in northern Benin.
Objective 6: Provide health education to communities where the condition is endemic
On what subject?
For what target?
By what channel?
Using what medium?
– communication plan
In 2004,
Local awareness raising (ANESVAD, FFL)
– general public (Zê, Zogbodomey, Zagnanado, Ouinhi)
– targeted groups (Parents’ and teachers’ associations: Allada, Toffo)
– mass pubic via local radios (Atlantique and Zou)
– production of image boxes (ANESVAD)
Training programmes (ANESVAD)
– health workers (Zou, Collines, Ouémé, Plateau)
– teachers (Zou)
Objective 7: Conduct advocacy work and resource mobilization
Partnership strengthening meeting:
– Aide et Action Association, 8th FED, CNRP, BN
Drafting an action plan for 2004–2008
Advocacy work with the partners of PNLUB
ANESVAD funding for screening, tooling-up and awareness raising activities, etc.
40 In brief
The sum of all the foregoing actions produces the following curve for Buruli ulcer cases in Benin
New Buruli ulcer cases in Benin (1989-2004)
900 800 700 s
e 600 s a c
f 500 o
r 400 e b
m 300 u
N 200 100 0
9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 98 99 99 99 99 99 99 99 99 99 99 00 00 00 00 00 1 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 Year
Acknowledgements
WHO
ANESVAD
AFRF
FFL
ARFB
MSF
Government of Benin
Matuoka Fund
Rotary Club Milan
Aide et Action Association
Staff of the various CDTUBs
Staff of the PNLUB
Various directorates of public health (DDSP) in the different geographical departments
All the other sections of the Ministry of Public Health that lent us their assistance
41 THE BURULI ULCER SITUATION IN BURKINA FASO
Dr Christophe Kafando
Background
Until 2003, 30 cases had been reported in the country. However, these figures fail to reflect the true situation because of the following factors:
Common borders with countries in which the disease is endemic;
A large flow of populations across these borders;
The mainly agricultural and livestock raising nature of the population’s activities;
Existence of many agricultural development projects;
Ignorance of the disease among the population and health workers.
Activities during 2004
Detection
A total of two cases were detected at the dermatology service of Yo university teaching hospital.
Training
A total of 8 surgeons and 60 nurses from health districts located on the border with countries in which the disease is endemic were trained to diagnose the disease.
One physician was given training in mapping in March 2004.
One physician took part in the international training workshop on Buruli ulcer held at Yaoundé in July 2004.
Information, education and communication
Advocacy to encourage the adoption of a national Buruli ulcer control programme;
As a result, control of the disease has now become a priority in Burkina Faso.
Institutional capacity-building, thanks to the procurement of teaching material.
42 Difficulties/constraints
A cutback in the size of the team (from 4 to 1) has led to an overload of work, which has made it unable to undertake all the activities at the right moment.
Activities in 2005
Rebuilding the team.
Supervising the health workers trained in 2004.
Drawing up and introducing a national Buruli ulcer control programme.
43 THE BURULI ULCER CONTROL SITUATION IN CAMEROON
Dr Charles Nsom Mba
Introduction
The disease, which has long been familiar to the indigenous populations and is experienced as a curse, has been identified by the health system. During the past four years, approximately 200 new cases have been diagnosed each year. The Cameroonian health system is beginning better to recognize the disease in patients. This has led to an improvement in the national response, with the assistance of partners such as WHO, ALES and Médecins Sans Frontières, who work in the field with our teams providing their support to Government efforts to control the disease.
Activities carried out at the national level
Adoption of the operational plan at the national coordination meeting at the beginning of the year. Participation in the WHO Advisory Group meeting in March 2004 in Geneva. Organization of a workshop to develop and adopt the technical facilities for each health-care level. Support for the environmental study in collaboration with the Swiss Tropical Institute. Logistic support to Ayos health district (four-wheel drive vehicle). Organization, at Yaoundé, of the International Workshop on Buruli ulcer case management. Organization of the workshop to adapt the guide to case management.
Activities carried out at the operational level
Provision of medical and surgical case management. Training in physiotherapy for staff from the health areas. Organization of information campaigns on the disease for the populations. Participation in the national prevalence survey. Organization of and participation in the field visits (Ayos and Akonolinga) by participants in the Yaoundé International Workshop on Buruli ulcer case management.
Statistical data
Total number of cases notified: 932 New cases: 914 – 209 (Ayos and Akonolinga) – 705 (remainder of the country, following the national prevalence survey) Recurrent cases: 18 Forms: – oedema: 93 (10.04%) – nodules: 73 (6.55%) – ulcers: 700 (75.10%) – plaques: 75 (8.29%)
44 Outlook for 2005
Extension of activities into new disease foci: centre, south, east
Provision of case management Staff training Development of infrastructure Information campaigns Advocacy on behalf of funding Operational research activities
Conclusion
The disease is indeed present in Cameroon and is growing in importance. It is an authentic public health problem that is becoming more familiar to the populations and to medical staff. The Government and its partners are willing to continue with control efforts, with international support and collaboration.
Our thanks are due to the World Health Organization, Aide aux Lépreux Emmauüs–Suisse, Médecins Sans Frontières–Suisse and to the Cameroon Pasteur Centre for their unfailing support for efforts to control Buruli ulcer in Cameroon.
45 THE BURULI ULCER SITUATION IN THE REPUBLIC OF THE CONGO
Dr Damas Obvala
Introduction
In 1970, the first cases of Buruli ulcer in the Congo were detected in the village of Loaka, in Kakamoeka district, hence the name Loaka sore;
In 2001, diagnosis of Buruli ulcer was confirmed thanks to a joint MoH/WHO survey;
The disease is endemic in 3 out of 11 departments;
July 2003, adoption of a strategic control plan;
August 2003, training for a pool of physicians/surgeons with the assistance of Professor Henri Assé;
January 2004, creation of a national control programme, attached to the existing leprosy control programme;
July 2004, resumption of BU activities;
Number of patients detected to date: 235;
Lack of suitable case-management facilities.
Activities carried out in 2004
January 2004, creation of the National Buruli Ulcer Control Programme, attached to the existing Leprosy Control Programme.
Organization of the programme
Initial supervisory missions (situation inventory) in departments where the disease is endemic: Kouilou, Niari and Bouenza, in September and November 2004;
Combined mission to provide information, case detection, patient recruitment and follow-up of cases having undergone surgery in Kouilou department, November 2004;
Supervision of community intermediaries in Kouilou department;
Training for 50 schoolteachers in departments in which the disease is endemic;
Training for 50 community intermediaries in Niari and Bouenza departments;
Provision of surgical treatment for Buruli ulcer at the A. Sicé hospital in Pointe-Noire and the base hospitals in Nkayi and Dolisie.
46 Distribution of cases per department, clinical form, age and sex Nodule Ulcer Plaque Oedema Child Adult Male Female Total Kouilou 18 160 7 3 75 107 90 92 182 Niari 1 28 – – 15 14 17 12 29 Bouenza 1 23 – – 11 13 13 11 24 TOTAL 20 211 7 3 101 134 120 115 235
Surgery: 44 cases underwent operations, 22 at the A. SICE hospital in Pointe-Noire, 15 at the hospital in Nkayi and 7 at the hospital in Dolisie.
ObservationsPrevalence of Buruli ulcer is highest in Kakamoeka district, Kouilou department, followed by Niari and Bouenza.
The above results reflect the activities carried out in 2003 and 2004.
The number of cases is probably higher in the departments in which the disease is known to be endemic.
It is planned to carry out a national prevalence survey in 2005.
Provision of surgical treatment is ineffective; the facilities in which surgery is provided and their equipment need to be improved.
Difficulties
Most health centres (Makabana and Mouindi-Kakamoeka) are in a poor state of repair;
Vehicles for activities in the field are in short supply;
There is a lack of information, education, communication material to provide communities with more information;
Shortage of medical and surgical equipment;
Difficulties in providing proper surgical case management for patients (cost of hospital stay, consumables etc).
47 Suggestions
Rehabilitate and equip the health centres in Makabana, Mouindi and Kakamoeka, to enable them to provide proper case management.
Provide the National Buruli Ulcer Control Programme with a four-wheel drive vehicle for supervision and follow-up of activities in the three departments.
Provide the teams in the departments with information material for outreach activities, to improve communication with the populations.
Provide affordable financial resources to enable programmed activities to be carried out.
ConclusionThere is no doubt that Buruli ulcer is present in the Congo and that it constitutes an authentic public health problem.
Since July 2004, activities have been effectively revived and resumed.
The bases for proper case management are being laid down.
The implementation of activities is still subject to major constraints.
Our sincere thanks are due to the Global Buruli Ulcer Initiative and to other partners for having funded the activities undertaken this year. We take this opportunity also to call for the support of other development partners to enable us to rehabilitate and equip our health facilities in order to provide better treatment for our patients.
48 BURULI ULCER CONTROL IN CÔTE D’IVOIRE
Dr Moussa Diabaté
Presentation of Côte d’Ivoire
Geographical information
Côte d’Ivoire covers an area of 322 465 km² and is bounded to the east by Ghana, to the west by Guinea and Liberia, to the north by Burkina Faso and Mali and to the south by the Atlantic Ocean.
The country is generously watered by four major rivers, which are, from east to west:
the Comoé
the Bandama, on which there are two hydroelectric dams, at Taabo and Kossou
the Sassandra, on which there is a hydroelectric dam at Buyo
the Cavally, which flows along the border with Liberia.
These rivers and their tributaries, together with the reservoirs behind the dams, lagoons and other areas of stagnant water, are used for agriculture and livestock-raising. The farms attract people, and with them, the risk of outbreaks and spread of water-borne diseases.
Demographic data
Côte d’Ivoire has an estimated population of 16 million, with an average population density of 46 inhabitants per km².
The main demographic features are:
Rural population: 69% Urban population: 31% Population aged under 15 years: 45% Average annual growth rate: 3.8%
Social and economic data
Economic situation
The economy relies essentially on agriculture.
Agriculture is heavily turned towards export crops such as cocoa, coffee, cotton, rubber and bananas, etc.
49 Health data
Health indicators
Crude birth rate: 45‰
Crude death rate: 12‰
Infant mortality rate: 88‰
Infant-child mortality rate: 165‰
Maternal mortality rate: 840 per 100 000 newborn child.
Life expectancy at birth: 56 years
Health coverage
Doctor/patient ratio: 9/400
Nurse/patient ratio: 2/570
Population per rural clinic: 10 000
Coverage in rural areas: 68%
Buruli ulcer: scale and the situation
Epidemiological situation
According to a national survey conducted at the end of 1997, the disease exists on a considerable scale; annual incidence has increased since 1991 and the aggregate number of cases is 10 382. Cases have been notified in 56 out of 58 departments visited. At the end of 2004, the aggregate number of cases was approximately 18 000.
The war has been responsible for large-scale population movements and a number of treatment centres being moved. In addition, essential activities to prevent Buruli ulcer have been disturbed; an evaluation of activities is therefore called for.
Control activities in 2004
The 2004 Buruli ulcer plan of action had the following objectives:
To increase detection of nonulcerative forms of Buruli ulcer.
To provide clinical case management for Buruli ulcer patients.
To enhance the programme’s management/coordination.
Activities carried out
Control activities
50 Surgical missions to private denominational centres (a project funded by ANESVAD, which has been operating since 2003). A total of 51 surgical operations carried out: 32 at Kongouanou clinic and 19 at the Saint Michel Centre in Zoukougbeu.
Capacity-building activities
Training for health workers (project funded by the Medical Assistance Program (MAP International) and American Leprosy Missions (ALM)) at Taabo (Tiassalé health district); 1 physician, 10 nurses and 24 community health workers have been trained.
A training manual on rehabilitation and prevention of disabilities is being prepared by Mr Fabricio Bonifacio.
Research project on green clay (hydrated aluminium silicate): clinical and therapeutic trial
Buruli ulcer is the subject of several theses.
Fitting out health facilities in Taabo subprefecture: 8 kits, each containing 3 sets of instruments for minor surgery were distributed to Taabo health facility.
Participation in the HealthMapper workshop on Buruli ulcer held on 10–12 March 2004 at WHO headquarters in Geneva. On completion of the training, it was possible to use the software to map Buruli ulcer.
Participation in the international workshop on Buruli ulcer case management at Yaoundé (Cameroon). The major recommendations made at this meeting, which took place on 19–23 July 2004 at Yaoundé were:
– preparation of a manual on case management of disabilities and physical rehabilitation; – organization, by countries, of training workshops on case management.
External audit of the ANESVAD Foundation’s projects. At the request of the ANESVAD Foundation, the Price Waterhouse Cooper auditing firm conducted an external audit of the projects funded by the foundation. The audit covered projects carried out in 2002–2004. The firm has not yet submitted its findings.
Constraints:
– The main constraint is the political and military crisis besetting Côte d'Ivoire since September 2002. – Moreover, as a result of the audit requested by the ANESVAD Foundation, all the projects submitted to it by DC PNUM have been suspended, reducing coverage to 65.7%.
Actions to be carried out in 2005, expected outcomes and needs
Case detection and awareness-raising activities
Active case detection by a team of specialists in the field
Training community health workers in case detection, case management at the peripheral level and community education.
National Mycobacterial Ulcer Control Day
51 Case management activities
Integration, into pilot health facilities, of treatment for Buruli ulcer patients (staff training, equipment)
Adoption of a national treatment protocol
Requests to partners for the rehabilitation and social reinsertion of cured patients
Encouraging research
Encouraging and providing support for theses on mycobacterial ulcers in the medical and pharmaceutical training and research establishments (UFR);
Forming partnerships with national and international research institutions.
Enhancing the Programme's management/coordination
Ensuring the management organization chart is both functional and operational.
Regular supervision and evaluation of activities in the field.
Strengthening links with partners.
Participation in the different national and international meetings on Buruli ulcer.
Expected outcomes
Buruli ulcer is familiar to everyone (the community, partners, political authorities)
Case notification has improved during the year
ABuruli ulcer treatment protocol has been implemented nationally
At least three decentralized Buruli ulcer case management centres are operational
At least two research projects on Buruli ulcer are under way
Management and coordination of the programme have been enhanced.
Needs
Needs are so manifold that we are in the process of identifying priorities per project. An evaluation of the project by partners is required. The Government of Côte d’Ivoire will lend assistance, but partners will be heavily relied on in order to pool our efforts.
Conclusion
Decentralization of control efforts by building up the human and material capacity of peripheral public health facilities and the inclusion of Buruli ulcer in their minimum package of activities is still the major challenge that has to be taken up in order to ensure affective and efficient control of this scourge in Côte d’Ivoire.
52 EPIDEMIOLOGICAL SITUATION IN THE DEMOCRATIC REPUBLIC OF THE CONGO
Dr Jackie Singa Nyota
The first case to be documented, by Van Oye and Ballion, dates back to 1950 and occurred in Kwilu district.
Since that date and until 31 November 2004, some 1000 cases had been confirmed out of a total of more than 3000 suspect cases (sources: publications, oral communications, reports by health services, etc.) We should mention that between 1989 and November 2004, more than 180 confirmed cases were notified in Bas-Congo province.
The data collected show only the tip of the iceberg. Buruli ulcer is under-notified in the Democratic Republic of the Congo for the following reasons:
the shortcomings of the health system,
the lack of training
the absence of a surveillance system.
Main activities carried out in 2004 (with the support of WHO)
The national survey of Buruli ulcer prevalence, the preliminary findings of which showed that the disease is hyper-endemic in five regions: Bas-Congo, Bandundu, Equateur, Maniema and the urban province of Kinshasa.
The organization, in September 2004, of the national workshop to draw up and adopt the policy and strategy document, the highlight of which is the integration of Buruli ulcer control activities into existing primary health care by relying, at the intermediate level, on the leprosy and tuberculosis coordination offices (hence the new name CPLT-UB).
The introduction of a surveillance plan and of active case detection in Bas-Congo province in November 2004.
The drafting of technical documents on case management (medical, surgical and rehabilitation) and on case confirmation in the Democratic Republic of the Congo, in December 2004.
Development of the training project for Buruli ulcer focal points in the different health areas of Bas-Congo and Bandundu provinces and the urban province of Kinshasa.
The drafting of the 2005–2008 development plan for the PNLUB.
Difficulties encountered
Failure to build up the human and material resources at the intermediate (provincial coordinating offices) and peripheral (health area focal points) levels, as a result of which: a. There is a need for material and financial support to build up human and material capacity.
53 b. At the peripheral level, there is a need further to reinforce the health areas by designating community intermediaries in areas in which the disease is highly endemic.
Conclusions and recommendations
In order to reduce the prevalence of Buruli ulcer in the Democratic Republic of the Congo and to prevent the disabilities for which it is responsible, adequate financial and material resources are needed in order to: determine the actual level of prevalence;
provide case management for patients;
confirm cases; train medical staff;
inform the population;
introduce a surveillance plan.
Activities planned for 2005
1. Reproduction and dissemination of the policy and strategy document.
2. Building up the capacity of at least four medical facilities to provide case management (at Kinshasa, Bas-Congo and Bandundu).
3. Training for focal points in health areas in three provinces (Bas-Congo, Bandundu and Kinshasa urban province). 4. Organization of the annual meeting on Buruli ulcer in conjunction with the leprosy and tuberculosis programmes (September 2005) with the following main themes:
– briefing on the policy and strategy document; – training for leprosy, tuberculosis and Buruli ulcer coordinating officers to enable them to act as training officers at the provincial level; – determination of prospects for the future by discussing the 2005–2008 development plan. 5. Introduction of the surveillance system:
– information aids – case management – case confirmation – informing the community through community intermediaries.
54 THE BURULI ULCER SITUATION IN GABON
Dr Louis Bayonne Manou
Buruli ulcer is an endemic disease throughout the subregion and has severe social and economic consequences.
This explains the need for a cooperation programme between the Ministry of Health and WHO for the purpose of:
determining the prevalence of the disease and reducing morbidity;
establishing a national Buruli ulcer control programme;
introducing a system of surveillance and setting up facilities to provide case management of patients.
Survey protocol
Organization of the survey
A preparatory or pre-survey phase took place in May 2004. The survey proper was carried out in October 2004.
Samples
Samples were taken from 43 patients, with two samples being systematically taken from each of them:
One sample was sent to the laboratory at Libreville medical faculty for histopathological examination and Ziehl-Neelsen stain.
One sample was sent to the laboratory of Professor F. Portaels in Brussels for culture and PCR.
Results
Number of samples: 43
Number of results from the laboratory: 35
Positive results: 20 (57%)
Age range: 2–79 years (average age = 48.5 years)
Sex: 11 men; 9 women
Profession: schoolchildren, labourers, peasants
Types of lesion
Nonulcerative forms
Nodules: 1
55 Papules: 1
Plaques: none
Ulcerative forms
Ulcers: 18
Site
Lower limb: 16
Upper limb: 3
Buttocks: 1
The diagnosis was confirmed by at least two of the following four examinations.
Histopathology: 16
Ziehl-Neelsen stain: 12
PCR (+): 10
Culture?
Outlook for 2005
Capacity building
May 2005. Organization of an awareness-raising and training workshop for health officials
July 2005. Training of at least two health workers per health department from the interior of the country in Buruli ulcer case detection and treatment.
Awareness-raising
31 December 2005
Design and dissemination of information, education and communication aids.
Organization of information and awareness meetings among the population.
Design and broadcasting of radio and television announcements.
Conclusions
Buruli ulcer is still not familiar to Gabon’s population and health officials. This makes it necessary:
To raise awareness among and inform the population and organize workshops for health officials.
In the light of the preliminary findings, to make it clear that Buruli ulcer is present in the country.
56 To set up facilities to provide case management for patients and to strengthen the surveillance system.
To set up a national Buruli ulcer control programme.
57 REPORT ON BURULI ULCER CONTROL ACTIVITIES IN GHANA IN 2004
Dr Edwin Ampadu
Introduction
In 2004, the main activities in Ghana focused on surveillance, capacity development, strengthening of health facilities and advocacy. This report covers the main achievements in these areas.
Surveillance and early detection
Of the 60 targeted endemic districts, 31 regularly report data to the programme. A total of 1157 cases were recorded from the 31 districts in 7 out of the 10 regions. Ulcerative lesions constituted 66.2% of the total cases, the disability rate was 12% and the recurrence rate was 12.4%. Only 3.9% of the cases were confirmed by laboratory methods. To improve early detection at the community level, 230 volunteers were trained in the Upper Denkyira, Ashanti Akim North, Ahafo Ano North and Amansie West districts.
Capacity development
The main focus of capacity development was to implement a multidisciplinary one-week practical training of health workers to improve knowledge and skills in diagnosing and treating Buruli ulcer. The training covers clinical and differential diagnosis, laboratory diagnosis (with emphasis on collection and transport of specimens to the laboratory), anaesthesia, surgical treatment (with emphasis on excision and skin grafting) and prevention of disabilities. Four training sessions were held during the year; 13 doctors and 32 nurses from 11 hospitals were trained; 75 patients were treated during these training sessions. The Sasakawa Memorial Health Foundation in Japan also sponsored one doctor for a 6-month training course in advance plastic surgery. Thanks to the donation of surgical instruments from ANESVAD, all the hospitals where the trainees came from have benefited from this donation.
Surgical review meeting
In June 2004, a mid-year review meeting of the training carried out was held at the KCCR to review progress, identify problems and collectively find solutions to improve future trainings. About 40 participants, including the national facilitators and the health workers who participated in the training sessions, attended the meeting. The recommendations included a refresher training every 9 months, rotation of training sites to improve the capacity of host hospitals and the need to incorporate physiotherapy in the management of cases.
58 Plans for 2005
Improving surveillance and early detection.
Capacity development (training of health and village health workers, and schoolteachers).
Strengthening of facilities – improvement of the infrastructure and provision of equipment.
Implementation of antibiotic treatment.
Advocacy, social and resource mobilization efforts.
59 OVERVIEW OF BURULI ULCER CONTROL IN GUINEA IN 2004
Dr Adama Marie Bangoura
Epidemiological situation
Case detection and data analysis
The real scale of the epidemic nationwide is unknown. The aggregate number of cases for the period 1995–2004 was 635 patients. In 2004, 146 new cases were detected.
Table 1: Geographical distribution of cases
Prefecture Number of cases % N'zérékoré 33 22.60 Lola 15 10.27 Macenta 42 28.77 Yomou 23 15.75 Beyla 12 8.22 Kérouané 10 6.85 Guéckedou 08 5.48 Kissidougou 03 2.05 Total 146 100
A total of 95% of Buruli ulcer patients live in the Guinea forestière region (the only one in which there has been an evaluation); all six prefectures, including the refugee camps, are affected. This year, Kissidougou prefecture has also been included.
Figure 1: Distribution of Buruli ulcer patients by age, Guinea, 2004
12% 21%
67%
0-15 16-45 46 and over
The16–45 year age group is apparently the most affected; 20% of patients are aged under 15 years.
60 Figure 2: Distribution of Buruli ulcer patients by clinical form, Guinea, 2004
3% 9%
88%
Ulcerative Preulcerative Osteomyelitis
The high proportion of ulcerative forms testifies to the tardiness of case detection.
Figure 3: Distribution by sex of Buruli patients, Guinea, 2004
women men
47%
53%
There is a higher number of women patients.
Figure 4: Distribution of Buruli ulcer patients by location of lesion, Guinea, 2004
lower limb upper limb other
7% 3%
90%
61 Activities
Strengthening the system of surveillance
In 2003, tools for collecting data were developed and introduced. An evaluation of this activity in 2004 (in terms of results) showed that most health workers find the data collection tools easy to use, although some difficulties were experienced in completing the forms.
In order to improve case confirmation, the National Buruli Ulcer Control Programme (PNLUB) drew up a guide to taking and sending samples.
In June and October 2004, supervision of control activities was carried out by the central level, together with two joint missions by AGUIRAF in the Forestière region.
Improving the skills of human resources
National level. Training in surgical case management for health workers (7 training workshops).
International level. Participation in international training workshops on Buruli ulcer in the African Region in Ghana, training in the use of data and mapping for public health purposes at WHO, Geneva, and in surgical case management of Buruli ulcer in Cameroon
Case management
Table 2: Outcome of treatment of Buruli ulcer cases, 2004
Outcome Number of cases % Cured 88 60.27 Receiving treatment 37 25.34 Lost to follow-up 09 6.16 Referred 11 7.53 Deceased 01 0.68 Total 146 100
Surgery was the only treatment provided.
Laboratory confirmation of cases
Out of a total of 93 samples on which Ziehl-Neelsen staining was carried out, 31 were positive. In 2004, an improvement in the percentage of cases confirmed was noted.
Evaluation
With funding provided by FFL, in conjunction with AGUIRAF and with the technical assistance of the FFL medical adviser, PNLUB carried out an evaluation of the level of endemicity of Buruli ulcer in Boffa, Boké and Kindia in Basse Guinée.
62 Purpose
To explore the prefectures of Boffa, Boké and Kindia in order to identify suspected Buruli ulcer cases.
Expected outcomes
Confirmation that the disease is endemic in those prefectures
Provision of data to enable FFL to take a decision regarding additional funding above that is planned for Guinée Forestière and to enable other donors to focus their actions.
Methodology
Visits to the political, administrative and health authorities; Explanation of the disease to local communities using the media (rural radio stations in Boké and Kindia, Kamsar community radio and the Guinean radio and TV service); training for a pool of investigators, distribution of documents on Buruli ulcer, consultation of patients and taking of samples from suspected cases, treatment for patients (dressing and drugs).
Results
Patient consultations: 482 (Kindia = 192, Boké = 161, Boffa = 129)
Ulcerations of any etiology = 287; skin diseases = 170; others = 48
Samples taken: 51. Provision of treatment and information: dressings and distribution of antibiotics, pain killers and consumables.
Building up institutional and management capacity
Logistic support: one four-wheel-drive all-terrain vehicle (WHO)
Feasibility study for the building of the PNLUB coordinating office
Community mobilization/resources
Production of TV programmes and broadcasting of educational messages on Buruli ulcer by rural radio and television stations.
Provision of 80 skin graft holders for the N’Zérékoré regional hospital and CMPA (Nippon Foundation) and receipt de 30 CD-ROM and cartoon booklets (a gift from WHO).
Printing and distribution by PNLUB in schools and health facilities of posters and leaflets on Buruli ulcer.
Problems
Surveillance
Ignorance about the nationwide scale of the disease
Inadequacy of case-detection and confirmation activities
Case management
Insufficient staff trained in case management
63 Treatment is inaccessible and unaffordable
Existing facilities are inadequate and there are no Buruli ulcer treatment and detection centres (CTDUB)
Surgical and laboratory equipment is outdated or non-existent
There are insufficient drugs and consumables.
Goal
The goal set by the national health development plan (PNDS) is to reduce prevalence of Buruli ulcer by 25% in Guinea by 2015.
Overall objective of the plan of action 2005
To reduce morbidity and mortality from Buruli ulcer by 5% in Guinea in 2005.
Specific objectives:
To marshal resources for the implementation of the POA.
To increase the proportion of early forms detected from 7% to 12% by the end of 2005.
To provide case management for at least 50% of the patients detected in 2005.
To improve the skills of health workers and the facilities and equipment required to run the programme and to provide case management for patients.
To provide rehabilitation for at least 2% of patients with disabilities by the end of 2005.
Prospects for 2005
Line of action no. 1: Building up facilities and equipment
Construction of a CDTUB at NZérékoré and of the headquarters of the national coordinating office.
Improving the surgical and laboratory equipment of existing treatment centres.
Line of action no. 2: Improving the quality of services and care
Introduction of treatment with topical antibiotics as an adjunct to surgery.
Provision of supplies of drugs, laboratory reagents and consumables.
Provision of food for hospitalized patients.
Line of action no. 3: Development of human resources
Continuation of training for staff in diagnosis and surgical case management of Buruli ulcer.
64 Line of action no. 4: Consolidation of the programme's achievements and strengthening the system of surveillance
Supervision of control activities.
Organization of early detection and community information campaigns.
Organization of the meeting to coordinate the strengthening of partnership for Buruli ulcer control.
Production of a documentary on Buruli ulcer.
Line of action no. 5: Stimulating research in order to:
Evaluate the level of endemicity of the disease in at least two natural regions (Basse and Haute Guinée).
Introduction of a database on treatment of Buruli ulcer using traditional medicine in Guinea.
KAP survey in Basse Guinée and Guinée Forestière.
Table 3: Itemized consolidated budget
Item of expenditure BND WHO Others Total (nat. dev. budget) Infrastructure 10 588 – 200 000 210 588 Equipment 21 228 – 158 724 166 952 Study and research 12 000 12 000 34 000 58 000 Training – 40 000 223 260 263 260 Management and operations 60 800 10 000 25 000 98 800 Drugs and consumables 10 000 10 000 120 000 140 000 Food aid 15 000 – – 15 000 Health promotion – 11 000 18 100 29 100 Advocacy 7 000 20 000 37 000 3 000 Supervision 5 000 24 000 32 000 10 000 Total 106 616 823 084 1 050 700 96 000
Conclusion
Buruli ulcer remains a little-known disease for most health workers and the public at large in Guinea. In spite of the economic crisis buffeting Guinea, significant progress has been registered.
The Ministry of Health remains mobilized in order as rapidly as possible to control this disease with the assistance of all its development partners. Implementation in 2005 of the activities described above should result in improved control of the disease in our country.
65 Acknowledgements
Our thanks are due to all our development partners for their support, and in particular to WHO, AGUIRAF, ANESVAD, Nippon Foundation, FFL, IMT in Antwerp, PNLUB and RCI.
66 MYCOBACTERIUM ULCERANS IN PAPUA NEW GUINEA IN 2004
Sr Joseph OBE FRCS, Specialist Surgeon Wewak General Hospital, Easat Sepik Province, Papua New Guinea
Epidemiology
Sepik
Females Males Total Adults 6 2 8 Children 6 5 11 Total 12 7 19
Sites of lesions
Limbs: 12 (upper 6, lower 6)
Back: 2
Chest: 1
Not known: 4
A detailed analysis is not available, but more than half were oedematous type.
Sandaun
Vanimo Females Males Subtotal 2 Adults - 1 1 Children 1 4 5 Subtotal 1 1 5 6 Raihu Females Males Subtotal2 Adults – – – Children 4 2 6 Subtotal 2 4 2 6 Total 5 7 12
Total: 1 adult, 11 children
Sites of lesions
67 Limbs: 6 (upper 1, lower 5)
Shoulder: 3
Back: 3
Abdomen: 1
Type analysis not available.
Communications breakdown meant no figures could be obtained from Oro, Port Moresby and Western provinces.
Activities in 2004
March: Presented Annual Report to Annual Geneva Buruli Ulcer Meeting
April: Presentation- Update on MBU Treatment, Wewak General Hospital Clinical meeting
April: Civil unrest – arranged visit to Oro cancelled.
24 June: Translation of Comic into Tok Pisin- translation authorized.
Attended International Training Workshop On Management of Buruli ulcer 19-23 July: Cameroon
September: Presentation at Annual National Surgical symposium; modification of undergraduate medicine PBL learning module on BU
November:Presentation on BU to the hospital physiotherapy department for the trainees.
Ongoing teaching of medical personnel
Diagnosis of MBU
Investigations of MBU
Treatment: new drug regimen, technique of skin grafting, management of contractures.
Groups and individuals taught. - 1 residents RMO, 2 registrars, 2 visiting fellows, 17 medical students, 12 trainee physiotherapists
Annus horribilis
At the beginning of the year:
Health Department funding failure – all casual staff laid off, phones and faxes cut off, electricity cut off, water cut off, vehicles off the road, no fuel, no spare parts, untrained ward clerk, records system foundering.
Health facilities department failure – no boiler, no autoclaves, no X-ray machine.
Health department supplies failure – no laboratory reagents, so no AFB smears, drugs supply intermittent and unreliable, no money to dispatch histopathology specimens.
68 Staff shortages, no money for training.
Critically placed hospital – Angoram-non functional 10 years!!
Later:
Provincial government grant – extra surgeon and registrar, limited materials supplied.
December – new Director of Medical Services appointed surgeon, taking part of the load.
Records system in-service conducted by Health Department.
Local financial support.
New Provincial Health Advisor appointed.
Action plans for 2005
Meeting with Callan Services team re personnel distribution in affected areas – January.
Retrieve Tok Pisin comic translation – achieved 7 February.
Get Tok Pisin comic to printers – achieved 7 Feb 7.
Get Tok Pisin from printers – achieved 18 February; first 1500 copies.
Meeting with newly appointed Provincial Health Advisor re Angoram Health Centre, and all MBU village Aid Posts – achieved 18 February.
Meeting with Save the Children fund manager re village comic distribution – 20 February.
Meeting with university campus dean to establish MBU module in teacher’s training course for all teachers who will serve the area – April.
Meeting with Catholic Health Secretary re distribution of comic to aid posts – April.
Meeting with Catholic Education Secretary re distribution of comics in schools – April.
Meeting with Callan services to arrange in-service for all their village-based rehabilitation officers – April.
Organize team visit to Angoram – fixed for 7 April.
Surgeon, anaesthetist, theatre nurse, biomedical engineer, Callan Services rehabilitation physiotherapist, local district health manager. Tok Save to all hospital staff on diagnosis, treatment and management of all MBU cases, distribution of Buruli ulcer forms. Start a local register.
Visit Angoram schools to distribute comic – 7 April.
Meeting with district education officer re ongoing distribution in schools – 7 April.
Meeting with Divine Word University and Help Resources visual aid departments to collate a body of teaching material – April.
Orthopaedic operations on any cases with fixed contractures, paralysis, tendon transfers, etc. – team arriving 23 April. All junior staff and new surgeons seconded for learning that week.
69 Work on the teaching package – July/August.
Second orthopaedic visit – 1–14 July.
Run workshop for village-based rehabilitation officers on MBU – July/August.
Visits to other centres for in-service to all health staff on MBU; provision of comics for schools in affected areas, and Buruli ulcer reporting forms provided – July/August/September. Raihu Vanimo and Bewani in Sandaun province, and Popondetta Hospital in Oro province.
Patrol to affected Sepik area aid posts and schools – August 2005. Provide comics, teaching materials, run in-service for health staff.
Follow-up visit (November 2005).
Audit the year’s programme. Prepare a programme for 2006 to fill the deficits – December.
Expected results
Resuscitation of Angoram as an active health centre.
All Angoram staff familiar with MBU appearance and management, including immediate referral to area rehabilitation officer.
Appropriate referral of cases established.
Referred cases now presenting earlier with lesser disability.
All area bush rehabilitation officers educated and know how to diagnose MBU, start correction of deformities and refer.
Forms distributed and returned for all cases seen in 2005.
All known cases adequately treated including village rehabilitation.
Ongoing schools programme established to be taught twice a year, with materials on site.
Ongoing village health educator programme established to be taught twice a year.
Local doctors in Vanimo, Raihu, and Popondetta fully aware of MBU protocols, following them, and able to do adequate excision and grafting, and deal with joint contractures.
University teacher training course module available and in use.
All disabilities related to MBU dealt with by the visiting teams.
70 SUMMARY OF BURULI ULCER PLANNED ACTIVITIES IN SOUTH SUDAN
Dr Abdullahi Ahmed
The main aim of the Buruli ulcer control programme is to expand the interventions for control of Buruli ulcer in south Sudan. This is to be done through rehabilitation of health facilities and laboratories for early detection and management of patients, training of health workers to manage patients effectively, training village volunteers to carry out public awareness campaign and case-findings in the villages.
Goal
The main goal of this proposal is to scale up the Buruli ulcer intervention activities in south Sudan in order to control the disease.
Objectives
In order to achieve the stated goal above, the following objectives have to be met:
Promote early detection and management of cases.
Standardize case management both surgical and medical.
Ensure that cases of Buruli ulcer are confirmed by laboratory means.
Strengthen the institutions through provision of essential equipment, drugs and dressing materials.
Creating Buruli ulcer awareness in the community by training health workers, school teachers and village volunteers.
Standardize recording and reporting systems for Buruli ulcer cases.
Activities
In order to achieve these objectives, the Buruli ulcer control programme intends to carry out the following activities in 2005.
Objective 1: Promote early detection and management of cases
Train one surgeon from Nimule hospital for management of cases. This surgeon will be trained in Ghana in surgical and medical management of cases.
Organize one workshop in Nimule for 6 core surgical staff to help the surgeon in surgical management of cases. These will include the 2 theatre attendants, laboratory technicians, 2 surgical ward nurses and 1 clinical officer
Organize one training workshop for 21 health workers drawn from Nimule hospital and from other health units and centers in Magwi County. These health workers will be trained in
71 recognition of Buruli ulcer, managing simple cases and referral of cases to the hospital. They will also be involved in Buruli ulcer awareness creation
Objective 2: Standardize case management, both surgical and medical
Develop standardized surgical and medical management protocols in line with WHO recommended regimens. These will have to be developed in Nairobi in consultation with WHO experts.
Distribution of these protocols to all hospitals, health centers and units managing Buruli ulcer in south Sudan.
Objective 3: Ensuring that cases of Buruli ulcer are confirmed by laboratory means
Organize one 3-day refresher training workshop for the laboratory technicians. This will take place in Yambio.
Objective 4: Strengthen the institutions through provision of essential equipment, drugs and dressing materials
Renovation of the surgical theatre of Tambura Hospital for emergency major operations and routine minor operations. The major operations in this hospital shall be done by the Yambio surgeon when he is called upon to do so on patients who cannot be referred to Yambio hospital.
Provision of 8 major surgical kits to the hospitals for surgical operations; 3 major kits each will be given to Nimule and Yambio hospitals where surgeons will be carrying out operations routinely; 1 major kit each will be supplied to Tambura Hospital for emergency operations.
Provision of 22 minor surgical kits to 2 hospitals of Tambura and Nzara and 9 health centres.
Provision of Buruli ulcer drugs, including rifampicin and streptomycin, to all treatment centres and hospitals.
Supply of dressing materials to all health centres and units.
Objective 5: Creating Buruli ulcer awareness in the community
Organize two 3-day training workshops for 44 health workers, school teachers and village volunteers; 22 participants will attend each workshop in Yambio and Nimule. Their role will be to create awareness, register Buruli ulcer patients, case-finding and follow-up.
Objective 6: Standardize recording and reporting systems for Buruli ulcer cases
Print and distribute BU 01 and 02 standardized recording and reporting forms. These forms will be distributed to all health facilities managing Buruli ulcer for proper recording and reporting of cases.
Objective 7: Ensure efficiency and effectiveness of the programme
Organize efficient and effective supervision of the programme.
72 PREVALENCE OF BURULI ULCER DISEASE IN ADJUMANI DISTRICT, UGANDA, IN 2004
Dr Henry Wabinga
Introduction
Buruli ulcer disease is predominant in tropical areas with hot humid climates that are associated with swampy flood-prone landscapes. Adjumani district in north-west Uganda (Fig.1) has this favourable climate and wetlands suitable for the disease and was known as an endemic area in the 1960s–1970s. However, recently, cases of buruli ulcer have not been reported in this region, which has prompted a sensitization workshop to be organized for health workers concerning management of the disease. In January 2004, a sensitization workshop was carried out for health managers of various health units throughout the district, with the aim of improving the knowledge on management of the disease and also dissemination of standard guidelines to manage this disease.
It was assumed that an improvement in the knowledge of Buruli ulcer by health workers would result in increasing numbers of cases of the disease being diagnosed in these health units. The aim of this presentation is to show the impact of this sensitization workshop on the case reporting of Buruli ulcer in Adjumani District.
Methodology
Adjumani district is administratively divided into six subcounties with each subcounty having at least one government health unit capable of diagnosing Buruli ulcer. There are also many health units run by nongovernmental organizations (NGOs).
In June 2004 (6 months after the sensitization workshop), attempts were made to review all records of health centres level III and above (i.e. health units capable of diagnosing Buruli ulcer disease) in the district.
The coordinator of Buruli ulcer activities in Uganda Wabinga, accompanied by a clinical officer, visited 5 out of 6 subcounties in the district. The sixth subcounty (Dzaipi) could not be reached because of insecurity.
In each health unit, impatient and outpatient registers were retrieved and reviewed and, wherever necessary, clinical notes were also retrieved. Patients with a diagnosis of Buruli ulcer disease had the demographic and clinical data analysed.
Results
A total of 10 health units had their records reviewed. Adjumani Hospital, which is a referral hospital, had 3 cases diagnosed as Buruli ulcer, all of whom were patients in the hospital at the time of the survey. The diagnosis was confirmed on PCR in 2 cases. However in the records unit, the record clerks were not classifying the disease as an entity but rather collectively as skin wounds.
In Ofua health centres, the records reviewed 3 cases.
73 In Alere health centre, 1 case was recorded. In these two health centers the diagnosis was clinical and ZN stain confirmed. The sociodemographic and clinical data of the 7 cases are presented in Table 1.
Table 1: Age, sex and site of lesion in 7 cases in whom buruli ulcer disease was diagnosed in Adjumani
Age and sex Site and clinical form Health unit 8 M Ulcer lower limb Alere 48 F Ulcer lower limb Ofua 19 M Ulcer lower limb Ofua 30 F Ulcer lower limb Ofua 8 M Ulcer anterior abdomen wall Adjumani 12 M Ulcer anterior abdominal wall Adjumani 8 F Ulcer anterior abdominal wall Adjumani
Conclusions
Burulu ulcer disease appears to be still a public problem in Adjumani district, and probably the insecurity may not allow patients to present in health units. There are other health units the study group could not assess as a result of insecurity. It is also strongly believed that buruli ulcer disease in Adjumani district is only managed by traditional health workers and therefore patients do not seek western medicine. It is recommended to carry out community diagnosis of the disease to determine its actual prevalence.
74 HOW TO EVALUATE THE EFFICACY OF HYPERBARIC OXYGEN THERAPY (HOT) IN MYCOBACTERIUM ULCERANS DISEASE: THE HOT PROJECT IN THE CDTUB OF ALLADA, BENIN
Giorgio Leigheb,1 Fabrizio Leigheb, Roch Christian Johnson,2 Ghislain Emmanuel Sopoh,3 Ange Dossou,3
1University of Eastern Piedmont “A.Avogadro” 2National Buruli Ulcer Control Programme, Benin 3CDTUB of Allada, Benin
The hyperbaric chamber for the hyperbaric oxygen therapy (HOT) project sponsored by Rotary International, Milan Aquileia Club is in function at the CDTUB of Allada in Benin and is hosted in a new building structure built thanks to the help of the Follereau Foundation of Luxemburg.
Now it is time to start with a pilot study to evaluate the efficacy of HOT in the different stages of Mycobacterium ulcerans disease. We suggested a scientific protocol where the patients selected in four (plus one) different groups (in relation to the extension and stage of the disease) are submitted to a double-blind protocol. In fact, for each group of patients commonly treated with antibiotics therapy plus surgery a randomization is performed obtaining a subgroup of half of the patients to be submitted also to HOT. In this way it is possible to observe, after a standard time (2–6 months), whether a statistically significant improvement of the clinical/histological status is obtained in the subgroup of HOT-treated subjects.
We will present in detail the modality screening of the patients, how to choose the patients for each group and how to perform HOT.We will expose the problems connected to the practical management of this fascinating research, hoping in this way to improve the recovery of the disease and even to cure many young people affected by Buruli ulcer disease. Our effort with this pilot study represents a very important goal: the demonstration of the efficacy of HOT on a good number of cases could suggest the right way to be followed in the future to beat this terrible disease.
75 TELEPATHOLOGY: SUPPORT FOR THE HOT (HYPERBARIC OXYGEN THERAPY) PROJECT IN THE ALLADA HOSPITAL OF BENIN
Dr Claudio Clemente, Casa di Cura S. Pio X, Milan, Italy
Buruli ulcer may simulate, clinically and histopathologically, different non-neoplastic (i.e. pyoderma gangrenosun, cutaneous ulcerative tuberculosis, etc.) and neoplastic skin lesions (necrotizing squamous cell carcinoma, ulcerated melanoma, cutaneous lymphoma or sarcoma). In the trial to evaluate the efficacy of HOT in patients with Buruli ulcer, activated by the Rotary Club of Milan Aquileia, the selection of cases is particularly important. No false-positive patient may be included in the trial. Selection must be obtained by:
accurate clinical evaluation (clinical diagnosis supported by photographic documentation)
histopathological diagnosis by biopsy material, confirmed by histochemical stain (Ziehl-Neelsen).
We think that telemedicine/telepathology may be useful when used as a support to select and to accept cases into the HOT trial for Buruli ulcer. All the patients are documented by digital clinical images; the surgical specimens (excisions or biopsies) are treated locally by the pathology service of Cotonou, and the histopathological slides are examined by the local pathologist (Dr Ballè). Digital images (virtual slides) are also produced and sent, together to clinical images, to Milan (Dr Clemente, Servizio di Anatomia Patologica e Citopatologia, Casa di Cura S. Pio X, Milano, Italy) and Novara (Professor Leigheb, Clinica Dermatologica Università degli Studi del Piemonte Orientale “A. Avogadro” Dipartimento di Scienze mediche Facoltà di Medicina, Azienda Ospedaliera “Maggiore della Carità”) by Internet.
The local equipment, installed in August 2004 in Allada Hospital, and recently verified by the collaboration of Dr Fabrizio Leigheb and Eng Roberto Rosti, consists of:
a digital camera (Nikon Coolpix 3100) for clinical documentation; clinical pictures are performed before, during and after HOT;
an Internet connection;
a digital imaging Nikon Coolscope. This is a microscope/computer that includes all the functions necessary for observation, image capture and network communications features. Using Nikon Coolscope it is possible to transform a histopathological slide on glass into a digital slide or digital picture to see remotely by Internet.
All the diagnostic procedures are performed according to WHO guidelines (Portaels F, Johnson P, Meyers WM. Buruli ulcer: diagnosis of Mycobacterium ulcerans disease. Geneva, World Health Organization, 2001).
The next step is to carry out pathology services and produce locally the histopathological slides of all specimens of biopsied patients and to install a satellite connection so that a wide band can be used to transmit the digital slides from Milan. This support is important not only to have a real time clinical and histopathological diagnosis but also for educational proposals of a continuous learning for the local medical doctors.
The same microscope and connection will be used by the local pathologist for other different cases for second opinions. The goal of this project is not to substitute the local pathologist but to support his work by these new technologies. The Allada pathology service might became a reference point also for other hospitals in this African area and a good example to reproduce in other countries.
76 VACUTEX™: A CAPILLARY DRESSING TO IMPROVE THE TREATMENT OF BURULI ULCER PATIENTS
Mrs Angela Doran
VACUTEX is a rapid capillary action dressing manufactured by Protex HealthCare (UK) Ltd. Its patented technology is centred on a three-layer construction, in which one of the two outer polyester layers draw exudates/interstitial fluids from the wound surface and transports them into the central cotton/polyester layer and then subsequently upward into the third upper layer of the dressing. Therefore, VACUTEXis able to debride and deslough the wound, and as a result create the ideal environment for wound healing to take place.
Wounds by their very nature are complex. Therefore, taking into account the additional factor of certain wounds being difficult to treat because of their location, a highly versatile and conformable dressing is required for maximum effectiveness.
This point is particularly relevant to the treatment of Buruli ulcer in that both difficult to treat areas and extensive wound sites are common, requiring time-consuming practice and extensive surgery to excise and then treat further. Often, varying degrees of spacticity and even consequential amputation may be the result.
Use of VACUTEXas the dressing of choice to assist with debriding and desloughing of Buruli ulcers prior to surgery, and afterwards to enhance the healing environment, may result in much improved healing times; plus additional beneficial outcomes, such as improved quality of life, i.e. more spontaneous recovery and shorter hospital stays and, as a consequence, significant financial benefits.
In conjunction with the Centre de Depistage et de Traitement de l’ulcere de Buruli “le Luxembourg” d’Allada and WHO, Protex HealthCare (UK) Ltd. is sponsoring a comparative trial of VACUTEX dressings versus standard protocol dressings in the treatment of Buruli and other difficult-to-heal ulcers, with the aim of achieving improved patient outcomes, and also cost benefits to health-care providers.
This presentation will encompass the primary features and benefits of VACUTEXand detail some of the initial responses to treatment in the form of case studies presented by the medical team from Allada.
77 THE ROLE OF SURGICAL MISSIONS IN THE MANAGEMENT OF BURULI ULCER IN CÔTE D'IVOIRE
Professor H. Assé, Institute for Reconstructive Surgery, Abidjan, Côte d'Ivoire
By surgical mission, we mean entrusting a team with the task of performing surgical activities for the benefit of a population that has difficulty attending regular surgical services.
Background
No one remembers exactly when surgical missions began in Côte d’Ivoire.
However, at the national level it was in 1992 that the first local surgical team was formed in order to carry out surgery on a monthly basis at a rural leprosy hospital some 400 km from our service.
In 2001, this strategy was transferred to three peripheral centres providing case management for Buruli ulcer.
the Demi Emile Centre (Zouan-hounien)
the St Michel clinic (Zoukougbeu)
the Kongouanou rural dispensary
These centres, which have an operating theatre and sterilization unit provided by ANESVAD, have no trained staff capable of carrying out day-to-day surgery.
So far, it is only thanks to the surgical missions that it has been possible to keep them operational.
Rationale for the surgical missions
Under normal circumstances, in order to organize surgery, the following three fundamental requirements have to be met:
an operating theatre
a surgical team
patients
A surgical mission is justified by the absence of one of these three elements.
Objectives of the surgical missions
The surgical mission has a three-fold objective:
To provide surgical case management at the local level.
To train local staff to provide proper case management of Buruli ulcer.
78 To ensure the sustainability of surgical activities by training a local team.
Organization of surgical missions
A surgical mission is divided into three major phases:
Preparation of the mission
Organization of activities in the field during the mission
Post-operational follow-up
In order to improve their quality, it is essential to evaluate these missions.
Results of the surgical missions in Côte d’Ivoire
Between 2001 and 2004, surgical missions made it possible to carry out 932 surgical operations in the three peripheral centres located in endemic areas, thereby providing local case management.
All the staff at the centres have been trained to provide proper case management of Buruli ulcer.
The average length of stay for ulcerative forms has been shortened to 50 days, thereby improving the patient turnover rate and achieving rapid reinsertion into society.
However, unfortunately most patients consult at the ulcerative stage.
Besides, surgical skills are not effectively being transmitted because the centres currently have no staff capable of acquiring such skills.
79 CLINICAL ASPECTS AND THERAPEUTIC APPROACH TO BURULI ULCER SEQUELAE
Professor H. Assé, Dr P. Meredith
Most Buruli ulcer control programmes neglect management of sequelae. This makes it difficult to ensure the social and professional rehabilitation of patients, most of whom are young.
Proper case management of Buruli ulcer sequelae calls for a sound understanding of the mechanism underlying their onset, which is dominated by fibrosis and tissue contracture.
Anatomical structures involved
Development of sequelae involves the skin, muscles, tendons, joints and bones.
Conditions determining the onset of sequelae
Several factors contribute to the onset of sequelae. The most important of them are:
Oedema, ulceration, superinfection, the site of the lesion, immobilization, pain, time taken by scarring, unsuitable treatment and absence of physiotherapy.
Classification of sequelae
Buruli ulcer sequelae may be classified into five major groups:
sequelae affecting the skin
sequelae affecting the muscles and tendons
sequelae affecting the joints
sequelae affecting the bones
deformities
Clinical features
Buruli ulcer sequelae affect young patients. They are essentially the consequence of nodular and oedematous forms. The lesions are generally located on the upper limbs. There are several clinical pictures:
Face and neck: sequelae essentially involve the skin and involve contracture of the loose edges and natural openings.
80 Thorax: sequelae affecting the skin involve contractures and disfiguring plaques of scar tissue.
Limbs: the four types of sequelae are found on the limbs and are responsible for severe disabilities.
A number of clinical pictures are worth our attention:
constriction of the thorax and brachia
closure of the thorax and brachia
limited mobility of the elbow
dorsal contracture of the hand
lateral contracture of the hand
stiffness of the knee on extension
limited mobility of the knee
talipes equinus
amputations
Treatment
Treatment has a three-fold purpose:
To prevent the onset of sequelae.
To correct scarring.
To restore function.
Treatment is thus both preventive and curative.
Methods:
restorative surgery
functional rehabilitation
orthosis
Treatment calls for sound coordination of methods and team work.
Treatment calls for authentic commitment by Buruli ulcer control programmes and for a training policy for plastic surgeons.
81 THE ROLE OF VOLUNTEER SURGEONS IN BURULI ULCER CONTROL
Dr Rémy Zilliox
The tsunami that unleashed itself on South-East Asia has also affected humanitarian activities, highlighting the numerous shortfalls of the charity-driven process. The magnitude of the disaster, having diverted the attention of the entire world towards that continent, has also served to mask other equally serious disasters in other regions that are completely out of the media spotlight. The funds collected or pledged for this disaster face an uncertain future while there are other more pressing health emergencies elsewhere.
The outpouring of uncoordinated goodwill (and not-so-good will) has led to an inextricable situation where kind-heartedness, lack of preparation, incompetence, poor emergency management, proselytism, political competition, lack of respect for local traditions and customs, exaction of leaders and uneven distribution of donations have all been thrown into the same pot in the name of humanitarianism.
This term in itself is inappropriate and obsolete because it emphasizes suffering and is a source of annoyance to some. So what should it be replaced by? Technical cooperation? Targeted aid? Partnership in the area of health?
In the small world of Buruli ulcer control, we find the following:
At the local level:
First and foremost, the patient suffering from the disease; and
A health system that does what it can to care for the patient but which is dependent on the State, which imposes political, social and economic restrictions.
At the external level:
First and foremost WHO, whose authority is undisputed and which acts in an advisory and supportive capacity at the global level;
More or less organized charitable associations with relatively significant financial resources and professional paid staff.
In addition, a plethora of goodwill represented as well as can be expected in small agencies or associations as sanctioned by the 1901 French law.
These men and women, who are aware of the Buruli ulcer situation, want to become involved for a number of reasons that are not always clear, such as kind-heartedness, altruism, need for a change of scenery, need to move on after a setback or purely out of scientific interest.
As far as medical and paramedical personnel are concerned, the mere fact of choosing a profession in medicine involving science and technology is already a sign of altruism.
82 What can we offer volunteers and what can we do with them?
Volunteers should not get in the way, or be a burden or a source of problems.
They should be useful, efficient and produce results. This implies that they must be trained in their technical duties and trained to deal with their new environment (cf. Interplast training).
This type of volunteerism, which can be put to good use, must be completely apolitical and religiously neutral and also respect local structures, usages and customs.
At the same time, volunteers must also be able, as far as possible, to find whatever it is they were seeking, hence the need for them to be well informed beforehand to avoid any false hopes or disappointment (no administrative or financial constraints).
A disillusioned volunteer will leave and never come back.
There is a limited number of stakeholders involved in Buruli ulcer control and this makes anything possible; the question is how?
We propose the following three-pronged approach:
Training and information
Buruli ulcer is not inevitable. Pathogenesis, prevention and treatment have become increasingly well known and should be disseminated.
Organization and budgeting
Stakeholders, material and financial resources should be organized optimally as they are few and far between. While it is true that the crisis in South-East Asia gave rise to a spectacular display of what appears to be generosity on an international scale, it is equally true that over the past decade or so, charitable associations have been running on considerably tighter budgets and making do with fewer material resources. Everything must be done to optimize financial and human resources.
Ecumenism
All the stakeholders involved in Buruli ulcer control must be united in concerted action and in a spirit of wholehearted ecumenism. Coordination of all the resources needed to undertake work in this field must override the interests of States, agencies, nongovernmental organizations and charitable associations. Volunteers must be integrated within action as a whole. There is no point in dispersing efforts.
What are the expectations and hopes of the various stakeholders?
First of all, the patient hopes to be treated and cured with a minimum of sequelae and in the best of conditions (no disorders induced by treatment).
Local health facilities, health-care providers and physicians expect tangible assistance in dealing with large numbers of patients with which they are unable to cope: they need medical supplies (dressings, surgical instruments, etc.), technical advice, training and information, and financial resources.
83 Volunteers, despite their sometimes limited means, do however possess surgical “expertise” that they are willing to offer to others.
How can we manage these myriad expectations and contingencies while at the same time remaining efficient and cost-effective and putting the interest of the patient first? Who should be responsible for coordination?
At the workshop held in Yaoundé in July 2004, it was proposed that Buruli ulcer should be dealt with by a “surgical strike” from a WHO task force to assist affected countries. This proposal was made on the understanding that the countries concerned would have to participate in financing activities conducted locally.
84 BASIC PLASTIC SURGERY SKILLS FOR DISTRICT/COMMUNITY DOCTORS TO MANAGE BURULI ULCER PATIENTS IN GHANA
P. Agbenorku, P. Saunderson, M. Agbenorku, R. Adator, L. Tuuli, E. Brobbey
Since 1994, the Buruli ulcer patients that were treated at the Plastic and Burns Surgery Unit of the Komfo Anokye Teaching Hospital and the Evangelical Presbyterian Church of Ghana Medical Centre at Krapa- Ejisu (now called Global Evangelical Mission Hospital, Apromase-Ashanti) both in the Ashanti Region, were overwhelming not only in their numbers but especially in their severity and complications. This was because these patients reported very late for treatment. There was therefore the need to adopt a system whereby these patients could be seen earlier and preferably in their own local or nearby health institutions. One way to let this happen was to bring training facilities in the management of Buruli ulcer patients to various district/community health-care providers. A training workshop in basic plastic surgery skills was thus designed for the Buruli ulcer endemic districts in the Ashanti Region.
From November 2001 to October 2004, 7 such training workshops were held in 5 hospitals in 5 different districts in the region, with participation from 26 hospitals/health centres drawn from 8 districts in the Ashanti Region.
A total of 128 health personnel comprising 34 doctors, 32 medical assistants, 25 anaesthetists, 84 nurses, 47 others (disease control officers, administrator, health educationists, etc.) were trained during the 7 workshops.
These trainees were to form the core of the so-called Buruli ulcer management teams (BUMTs), which are now active in 6 of the institutions that participated in the programme.
85 WHO ESSENTIAL SURGICAL CARE TRAINING TOOLS LINKED TO BURULI ULCER
Dr Meena Nathan Cherian
At primary health-care facilities, there is either lack of or inadequately trained health personnel in the essential surgical procedures and linked equipment. Most often, specialist doctors (surgeons and anaesthesiologists) are not available to perform essential surgical interventions to reduce death and disability from road injuries, falls, burns, infections, domestic violence and pregnancy-related complications.
WHO/EHT (Essential Health Technologies) developed a reference manual Surgical care at the district hospital, which addresses the basic surgical and anaesthesia procedures linked to the management of Buruli ulcer, such as:
Operating room (prerequisites, scrubbing, gowning, skin prep, draping, sterilization, infection prevention and universal precautions)
Basic principles of wound care
Tissue handling, haemostasis, sutures, cellulitis, abscess
Skin grafting techniques, haemorrhage
Preoperative assessment (anaemia, medical conditions)
Anaesthesia (intravenous access, fluids, ketamine, general and spinal anaesthesia, toxicity, postoperative care)
Postoperative care, pain relief
Cardiopulmonary resuscitation
Oxygen, essential equipment use, maintenance
Quality of care (evaluation, record-keeping, patient consent, referral, team management, bedside teaching)
WHO/EHT also developed an Integrated management package on emergency and essential surgical care (IMEESC) e-learning tool, meeting the needs of Buruli ulcer training programmes. This tool targets policy-makers and health-care providers to provide guidance on WHO recommendations for minimum standards on emergency and essential surgical care in trauma, obstetrics and anaesthesia at first-referral level health-care facilities. The IMEESC tool is being introduced in countries through WHO training workshops, in collaboration with ministries of health, and partners for use in the development of policy, training curricula, emergency equipment lists, needs assessment, and as teaching tools (video, self - earning, PowerPoint slides), best practice protocols for safety of clinical procedures, HIV prevention and in disaster situations.
The Emergency and Essential Surgical Care Project in the Clinical Procedures Unit is a horizontal programme and collaborates with other programmes such as Buruli ulcer, HIV, emergency, and maternal and child health.
86 TRAINING MODULES ON THE MANAGEMENT OF BURULI ULCER CONTROL PROGRAMME AT THE HEALTH DISTRICT LEVEL
Dr Alexandre Tiendrebeogo
Justification
Since the launch of the Global Buruli Ulcer Initiative in 1998, WHO has prepared and disseminated several materials for advocacy with national authorities, awareness and sensitization of communities and training of health staff. Produced training materials cover diagnostics, case management and rehabilitation of affected patients. However, Buruli ulcer control activities remain in a vertical structure in most of the endemic countries of the WHO African Region. Suspected cases are often referred to specific services (reference centres) for laboratory confirmation of diagnosis and for case management, which was mainly surgical until recently.
Confirmation of the effectiveness of combined antibiotic treatment, and the association of rifampicin and aminosid, opens the way to medical treatment of Buruli ulcer cases, mainly of early forms that are non- ulcerative lesions or small-sized ulcers. Control activities can therefore be integrated in peripheral health services, and the district health team must play a key role in organizing and managing Buruli ulcer control programmes in areas endemic for the disease.
For this purpose, the WHO Regional Office for Africa developed training modules on Buruli ulcer control programme management at district level. These modules are to complement other training materials, already available for health staff. They can be used to hold training workshops of district health teams or for self-learning by Buruli ulcer control programme managers at intermediate or central levels.
Objectives of the training modules
General objective
To contribute to organizing control of Buruli ulcer in countries of the WHO African Region.
Specific objectives
To complement available training material on Buruli ulcer, mainly for medical officers at intermediate and district levels.
To skill district health team members in organizing and managing a Buruli ulcer control programme.
To facilitate the implementation of control activities at district level in endemic countries.
To facilitate the integration of control activities in peripheral-level health services of endemic countries.
87 Contents of the training modules
The training modules comprise a set of 11 booklets separated in two files. These are:
The facilitator file, including a booklet with the following five chapters:
General organization of the training workshop
Role of the facilitators’ team
Preparation of the workshop
Holding the workshop
Answer sheets of the module exercises
The participant file, including the following 10 booklets:
Module 1: Introduction to the training modules
Module 2: Assessing the burden of Buruli ulcer in a health district
Module 3: Detection of Mycobacterium ulcerans disease cases
Module 4: Management of Mycobacterium ulcerans disease cases
Module 5: Primary prevention and tertiary prevention (rehabilitation) of Buruli ulcer cases
Module 6: Monitoring and evaluation of Buruli ulcer control activities
Module 7: Health staff supervision for Buruli ulcer control
Answer booklet to the module exercises
Glossary booklet for terms and definitions used in Buruli ulcer control
Evaluation booklet (pre and post tests of the workshop)
How to use the modules
The training modules will be produced in the two languages in use in the endemic countries of the WHO African Region (English and French). Two workshops on training-of-trainers will be held: one for English-speaking countries and the second for French-speaking ones. Following these workshops, national trainers will implement a plan of training of health district medical officers and team members in each country. After being trained, district health teams will be able to set up a diagnostic and management network of Buruli ulcer cases, train and supervise peripheral-level heath-centre staff, monitor and evaluate control activities within their districts, using the WHO-recommended Buruli ulcer forms.
88 Conclusion
These training modules will facilitate:
Introducing Buruli ulcer control activities as a public health problem in endemic districts
Integrating Buruli ulcer control activities in general health services at district and peripheral levels in endemic countries.
After implementing the training-of-trainers, training of district health team members and peripheral-level health-care staff, Buruli ulcer control activities will be fully integrated into primary health care of endemic districts.
89 INTERACTIVE WEB-BASED LEARNING COURSES ON MYCOBACTERIUM ULCERANS INFECTION
Dr Sunil Deepak
Mycobacterium ulcerans infection, also known as Buruli ulcer, is a reemerging disease that has been known to the medical community for a long time and that has caused severe outbreaks in a number of countries over the past decade. The launch of the WHO Global Buruli Ulcer initiative (GBUI) in 1998 has promoted the bringing together of clinicians, experts and research scientists to pool our knowledge of management of this disease, including diagnosis, differential diagnosis, treatment, prevention of disabilities and rehabilitation.
At the same time, there are still many gaps in our knowledge about M. ulcerans infection, some of which are being investigated and studied so that the existing knowledge is periodically updated.
Several teaching and learning materials on M. ulcerans infection have already been produced, especially through WHO, while some others are under preparation.
The Medical Support Department of the Italian nongovernmental organization, Amici di Raoul Follereau (AIFO), in collaboration with WHO/GBUI, proposes to produce some interactive web-based self-learning materials on M. ulcerans infection to supplement the existing teaching and learning materials, with following objectives: 1. To allow any recent gains in knowledge about the disease and its management to be reflected in the web-based self-learning materials that can be easily modified and updated regularly.
2. To reach health-care providers and researchers in more countries where M. ulcerans infection may be unrecognized or under-diagnosed.
3. To promote better learning about the disease through an interactive approach. Some examples of interactive self-learning materials on M. ulcerans are presented, which can be made available through the Internet (through the WHO AIFO web sites) and though CD-roms. Feedback from the field about the materials would be important to improve their quality and usefulness. The materials, initially prepared in English, can be translated into other languages for wider use.
90 TRAINING OF DOCTORS FROM ENDEMIC COUNTRIES IN BASIC PLASTIC SURGERY TO MANAGE BURULI ULCER
Professor Henri Assé
Rationale
Buruli ulcer is a disabling disease that is endemic in rural areas, mainly in poor countries. Treatment of the disease, which relies essentially upon surgery, makes use of plastic surgery skills. In Africa, where the disease is a public health problem, the possibilities for treatment are limited because of the lack of trained people. The few referral centres that exist are unable to provide either early surgical treatment or case management on the spot; these are the only effective strategies for controlling the disease. In order to make good these shortcomings, it is vital to develop the skills of medical staff by providing them with training in basic plastic surgery. This proposed training will also improve the management of other disabling diseases endemic in the same areas as Buruli ulcer.
Organization of training
Selection of candidates
Applications for candidates to be submitted by countries (ministry of health and Buruli ulcer control programme). Applications to be examined by WHO. Candidates must meet the following requirements: a qualification in medicine (physician or surgeon); at least one year’s experience managing Buruli ulcer; a signed commitment to serve for at least five years in Buruli ulcer control.
Training centres
Two training facilities need to be identified in Africa; one of them in French-speaking Africa (possibly Côte d’Ivoire) and the other in English-speaking Africa (possibly Ghana). These centres will provide the greater part of the training.
European training facility
After theoretical and practical training in Africa in Côte d’Ivoire and Ghana, a course will be held in Europe at a service collaborating with the project. Dr Patrick Meredith of Switzerland, a Swiss plastic surgeon with interest in Buruli ulcer and the development of plastic surgery in Africa and a member of the European Association of Plastic Surgeons, has been charged with selecting the hospitals in Europe.
Duration of training
Although this has yet to be determined, I propose a 12-month training course comprising 9 months’ theoretical and practical training in Africa and a 3-month traineeship in a service in Europe.
The rationale for 9 months’ training in Africa is that the trainees will themselves operate upon and monitor a number of patients in actual field conditions. Training in Europe should be in spring when most operations are carried out; in summer, services are often suspended because of holidays.
Outstanding issues
These include the course content, funding and certification.
91 THE ROLE OF TRAINING IN THE PREVENTIONOF DISABILITIES FROM BURULI ULCER
Ms Valérie Simonet
WHO has defined health as a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.
The severe consequences of Buruli ulcer, despite the possibilities offered by surgery, for peoples’ participation in everyday activities such as education, social relations, personal hygiene, work, economic activity etc. have brought WHO to address the question of preventing disabilities caused by the disease.
Accordingly, in 2004, rehabilitation was recognized as one of the three essential elements of Buruli ulcer case management, alongside surgery and treatment with antibiotics.
In Cameroon, at Ayos district hospital in Centre province, Aide aux Lépreux Emmaüs Suisse is providing support for a training project to prevent disabilities from Buruli ulcer. Provision of the two main modules (between June and November 2004) made it possible to offer a number of solutions and paths related to the main features of the training, its specificities, objectives and the requirements in order to attain them.
Some aspects of re-education and rehabilitation relating to Buruli ulcer are quite conventional and are common to numerous illnesses: joint mobilization, stretching, building-up muscles, provision of prostheses, etc. In contrast, treatment of skin involvement is poorly known, with the exception of treatment of major burns victims in specialized services. Nevertheless, it is the first-line treatment for the prevention of disabilities from Buruli ulcer, which affects essentially the skin. Early use of these treatment techniques (skin mobilization, positioning, compressions, apparatus) should, to a large extent, make it possible to avert disabling mobility deficits, which it will often be possible to treat later only by surgery.
Spectacular success was occasionally achieved after this training course. However, the most important and radical change lies not in what you can see but rather in what you cannot see. The true hallmark of successful case management is the absence of disability, which is defined as “discordance between the activity and status of the individual and the expectations of his or her social environment”.
92 PREVENTION OF DISABILITY IN PEOPLE WITH BURULI ULCER: THE DEVELOPMENT OF A MANUAL FOR FIELD USE
Linda F. Lehman, Paul Saunderson
Purpose of presentation
This presentation will demonstrate the process and challenges of developing the Buruli ulcer prevention of disability (POD) manual for field use. Observation of existing Buruli ulcer rehabilitation training manuals from several west African programmes focused on rehabilitation efforts appropriate for referral centres where resources and a highly specialized staff are available. This POD manual was developed to identify and address problems earlier within Buruli ulcer management programmes preventing complications and disability at the field level. The manual is most helpful if it is used in conjunction with a participatory method of training to develop knowledge and skills. Periodic supervision with on-the-job training will be the key to ensuring that POD activities are developed and appropriately implemented.
The manual targets three groups. The first group is health workers who require guidelines for implementing POD to help them do their job better and avoid common mistakes. The second group is people providing supervision and training of others. The last group is programme managers who will ensure that POD is an essential component of correct management of Buruli ulcer.
The manual objects are to facilitate health workers and managers to:
understand the importance of early POD action;
identify and document the person’s problems;
determine interventions based on identified problems;
provide the needed interventions to prevent or minimize disability;
teach the person affected by Buruli ulcer and the family how to do self-care;
monitor the response to the intervention and modify as needed;
refer to other specialized services.
This manual was the outcome of reviewing existing documents, observation of patient treatment and listening to patient, family and health-worker needs and requests in several west African countries from 2002 to 2004. The outline of the essentials interventions included in the manual was developed with health workers in an Ashanti region POD training in 2003. These essential interventions are needed before and after surgery and are summarized as follows:
Health education and self-care training
Wound management
Oedema control
Scar management
“Anti-deformity” positioning and splinting
93 Management of pain
Exercise and activity to prevent or improve soft tissue and joint contractures
Adaptations in activities of daily living to empower and enable participation and independence
Observations
The implementation and integration of essential POD interventions early within the disease control programme can minimize complications and disability. Success will be determined by the health-care workers’ and managers’ ability to influence partners, negotiate and advocate policies, teach others to provide adequate interventions using locally available materials and develop local technology as needed.
Conclusions
The active participation in local, regional, national and international Buruli ulcer health activities are essential for ensuring that both basic and complex POD interventions are integrated and implemented within disease programmes. The disease requires a holistic approach, training and supervision, educational and training materials and collaboration between government and nongovernmental organizations. Important needs and limited resources encourage partnerships, innovation and a commitment to development.
94 PRESENTATION OF A HANDBOOK ILLUSTRATED BY PHOTOGRAPHS ON BURULI ULCER PREVENTION AND REHABILITATION TECHNIQUES
Mr Fabrizio Bonifacio
An easy-to-use illustrated photo-manual written in plain language.
Overview of chapters
Buruli ulcer
Summary of bodily functions/parts affected by Buruli ulcer
Circulation
Skin
Peripheral nerve
Muscle
Bone
Joint
Introduction to physiotherapy in Buruli ulcer treatment
Assessment of joints
Assessment of upper limb joints
Assessment of lower limb joints
Prevention of muscle contracture
Moving about
Use of props to assist patients in getting about
Bandaging
Massage
Orthosis
Basic physiotherapy equipment
Buruli ulcer treatment
Upper limbs
Lower limbs
95 Examples of chapters
The more important chapters are illustrated with photos to provide ample explanation.
Example 1: Joint assessment
– assessment of upper limb joints
– assessment of lower limb joints
Example 2: Prevention of muscle contracture
Example 3: Moving about
Example 4: Bandaging
Example 5: Massage
Example 6: Orthosis
Example 7: Basic physiotherapy equipment
Presentation of the chapter on rehabilitation methods
Parts of the body
Presentation record
Preventive therapy
Post-scarring therapy
Conclusion and acknowledgement
96 WILLINGNESS-TO-PAY FOR A HYPOTHETICAL DRUG FOR TREATING BURULI ULCER, GHANA, 2003
Mumma GA,1 Whitney EAS,1,2 Dadzie F,1 Owusu-Edusei K,1 Asiedu K,3 Addo BO,4 Adomako J,4 Etuaful S,4 Ampadu E,4 Klutse E,4 Appah B,4 and Ashford DA1
1Centers for Disease Control and Prevention; 2Emory University; 3WHO; 4Ministry of Health of Ghana
Introduction
Recent reports suggest that combination antibiotics without or with reduced surgery may be an effective treatment for Buruli ulcer. However, there are no studies assessing the economic health benefits of a drug treatment for the disease. The benefit to an individual of a service or intervention is that individual’s maximum willingness-to-pay (WTP) for it. We estimated the average household WTP for a hypothetical drug having a 95% efficacy of treating all stages of Buruli ulcer in three rural, endemic districts of Ghana: Atwima, Amansie West and Upper Denkyira.
Methods
In October 2003, we interviewed the heads of households affected by Buruli ulcer in Atwina, Amansie West and Upper Denkyira districts about their WTP for a hypothetical drug having a 95% efficacy of treating all stages of the disease. A household was defined as a basic social and economic unit where the residents ate from the same pot. An affected household was one in which a household member had been reported to have Buruli ulcer from 1998 to 2003. Respondents were asked questions about their WTP for the drug, and about their household’s socioeconomic status, education, and Buruli ulcer disease characteristics. We examined the average change in household WTP for the hypothetical drug by using a linear multivariate model. Independent variables included the districts, levels of education of the heads of household and Buruli ulcer patients, number of people residing in a household, number of household members with the disease, the patient’s age, sex, stage, location and duration of Buruli ulcer, and a wealth index that we constructed from an asset list provided by households. We converted all calculations from Cedis to 2003 United States dollars (US$).
Results
We enrolled and interviewed 390 heads of households in which 468 Buruli ulcer patients resided; 39 were excluded from the analysis because of incomplete survey responses. The 351 heads of households who were included in the analysis were willing to pay an average of US$ 157.80 (95% CI: US$ 152.00–163.70) for the hypothetical drug. Heads of households in Atwina and Upper Denkyira districts, but not those in Amansie West district, were willing to pay significantly more than the average for the hypothetical drug, US$ 203.70 (p<0.01) and US$ 225.50 (p<0.0001), respectively. Heads of households with a primary or middle school education, but not those without any formal education, were willing to pay significantly more than the average for the hypothetical drug, US$ 192.00 (p<0.03) and US$ 185.10 (p<0.05), respectively. Heads of households for households having a socioeconomic status below the median wealth index were willing to pay significantly less than the average for the drug, US$ 183.00 (p<0.05).
Conclusion
The average WTP for a household affected by Buruli ulcer for a hypothetical 95% effective drug was US$ 157.80, and varied by socioeconomic status, education and district. These WTP results can facilitate cost-benefit and cost-effectiveness analyses of hypothetical drug treatment strategies for Buruli ulcer.
97 A FRAMEWORK FOR MEASURING QUALITY OF LIFE IN BURULI ULCER PATIENTS
Frank N. F. Dadzie
Introduction
The WHO definition of health as “a state of complete physical, mental and social well-being not merely the absence of disease…”1 implies that the measurement of health, and health outcomes of interventions, must include not only an indication of changes in the frequency and severity of diseases but also an assessment of the state of well-being associated with health states. This goal can be achieved by measuring the improvement or deterioration in the quality of life (QOL) associated with the relevant health states. The QOL measurement captures “an individual’s perception of their position in life in the context of culture and value systems in which they live, and in relation to their goals, expectations, standards and concerns”. It is a broad ranging concept affected in a complex way by the person’s physical health, psychological state, personal beliefs, social relationships and their relationship to salient features of their environment.
Generally, there are satisfactory ways of measuring the frequency and severity of a disease, the outcome(s) of its intervention and the degree of disability it engenders, but there are no generally accepted instruments for measuring well-being in terms of QOL changes. The challenge to social scientists is how to develop instruments for measuring the change in QOL that can be adapted to different diseases under variant conditions, and to generate results that are comparable across different cultural settings.
Quality of life implications of Buruli ulcer
Buruli ulcer typically results in extensive scarring, permanent disability or, in very rare cases, death. In recent times, several studies have published prevalence rates of the disease in most of the endemic countries and communities (e.g. Portaels, 1995; Marston et al., 1995; Asiedu and Etuaful, 1998; van der Werf, 1999; Amofa et al., 2002; Ellen et al., 2003). Other studies continue to investigate the epidemiological and economic burden (e.g. Dadzie, 2001; Mumma et al., 2002, 2003, 2004; Drummond, 2004), while still others endeavor to establish the efficacy of drugs in combatting the disease. While these efforts are laudable, especially in the context of a disease whose mode of transmission is unknown, no efforts are presently expended on capturing the QOL implications of the disease. This paper discusses the need for measuring QOL changes associated with the various health states of Buruli ulcer, and the framework by which QOL may be measured.
The need to measure the QOL of Buruli ulcer patients derives from the debilitating outcomes that its patients continue to endure in the various health states of the disease. While it rarely kills its patients, Buruli ulcer confers various forms of disability and functional limitations on its patients. Thus, the lives of the patients are affected in complex ways that can be captured as a multi-dimensional index that could be used to measure and monitor the effect of the disease on patients’ well-being. Such a measure of well- being would have the following other uses:
serve as a basis for selecting interventions provide a framework for monitoring QOL changes for a given population at risk for Buruli ulcer; identify inequalities in the QOL of patients in different health states of the disease; the result would be used for cost utility analyses.
98 The framework
The health outcomes of any disease may be classified into: a) health-related outcomes, and, b) non-health- related outcomes. For Buruli ulcer, the health-related outcomes include scarring, functional limitations, disability and, in very rare cases, death. The non-health-related outcomes are the psychological state of the patient, personal and cultural issues associated with the disease, its effects on social relationships, its cognitive effects as well as other intangible effects. Each of these outcomes needs to be captured in the measurement process in order to observe the true changes in the multidimensional measure of well-being. In a comprehensive review covering 30 years, Hansluwka (1985) assessed that the challenge remained to develop appropriate measures that are comparable, yet reflect the multidimensional nature of health.
Table 1 features a list of 13 instruments resulting from waves of development of standardized instruments to measure various aspects of health as defined by WHO. The first set of instruments (1–5) was developed to measure the most severe health states among age groups and individuals living in long-term care institutions. The second set (6–9) was developed with clinical and general populations in mind, and combined self-assessment of descriptions of different dimensions of health and of performance in different activities and roles. This effort was spearheaded by WHO. The third wave (10–13) of instruments was developed and used in primary health settings. Disease-specific measures are more often used in clinical trials or with individuals receiving specialized treatment. Nearly all instruments are intended to provide data that would be useful for monitoring health status within clinical, research or evaluation settings.
Table 1: Quality of life (QOL) instruments
No. Instrument Source 1 Quality of Well-Being Scale Fanshel and Bush, 1970 2 McMaster Health Index Chambers et al., 1976 3 Sickness Impact Profile Bergner et al., 1976 4 Nottingham Health Profile Hunt et al., 1981 5 Health Utilities Index Mark 3 Feeny et al., 1995 6 EuroQol Quality of Life Scale Krabbe et al., 1999 7 Short-Form 36 Health Survey Ware et al., 1993
8 WHO QOL-Bref WHO QOL Group, 1998 9 WHO DAS-II WHO, 1999 10 QOL Index Spitzer et al., 1981 11 Functional Status Jette et al., 1986
12 COOP Charts for Primary Health Practice Nelson et al., 1987 13 Duke Health Profile Packerson et al., 1990
The need for a unique quality of life measure
The need for cross-cultural comparison of the data generated through surveys compels researchers to improvise on a multidimensional index for health. Two of the most popular indices are the quality- adjusted life year (QALY) and the disease-adjusted life year (DALY). QALY refers to a year of life in a
99 health state adjusted by the utility (quality of life) associated with the health state (Drummond, Stoddart, and Torrance, 1987), whereas DALY represents the present value of future years of lifetime lost through premature mortality, and the present value of future lifetime adjusted for the average severity …C C of any mental or physical disability caused by a disease or injury (Fox-Rushby and Hanson, 2001). Once the survey results of a disease-based questionnaire are reduced to an index , monitoring the changes in QOL becomes routine.
There are distinguishing features for DALY and QALY. While DALY is a disease-specific index, it is not based on self-assessed utility associated with the relevant health state. Rather, it depends on experts’ (mostly physicians) assessment of utility. On the other hand, QALY uses self-assessed utility associated with a health state, but it is not disease specific. Thus, none of these popular indices seem appropriate for Buruli ulcer. The index for Buruli ulcer-related quality of life (1) needs to be disease specific and (2) requires patients’ self-assessed utility for each health state of the disease. Therefore, Buruli ulcer requires a unique QOL index that incorporates these two features. In particular, the challenge lies in the methods for eliciting utilities.
There are two ways of eliciting patient utilities: direct elicitation and indirect elicitation. By direct elicitation, individuals are asked to compare their current health states relative to other health states, or to death. In indirect elicitation, there are three steps to accomplish: a. For population sample, measure utilities of different combinations of attributes; b. Ask individuals to classify health states by attributes; c. Apply utility weights from population-based samples to health-state classifications The problem with the indirect elicitation is that this method is based on populations whose preferences may not map directly onto the Buruli ulcer populations This paper therefore recommends the use of the direct elicitation method for deriving patient preferences. This paper proposes that a team of experts be assembled to agree on a generic QOL measure for Buruli ulcer, and the core areas of inquiry that would form the basis for survey instruments that would be designed, tested and modified if necessary for eventual application in all endemic communities.
References
1. Amofa GK et al. (2002). The burden and epidemiological characteristics of Buruli ulcer in Ghana: results of a national case search. Emerging Infectious Diseases, 8(2):167–170.
2. Asiedu K, Etuaful SKN (1998). Socioconomic implications of Buruli ulcer in Ghana: a three-year review. American Journal of Tropical Medicine and Hygiene, 59(6):1015–1022.
3. Bergner M et al. (1976). The sickness impact profile: conceptual formulation and methodology for the development of health status measure. International Journal of Health Services, 6(3):393– 415.
4. Chambers LW et al. (1976). Development and application of an index of social function. Health Services Research, 11(4):430–441.
5. Dadzie FNF (2001). Economic situation analysis of Buruli ulcer in Ghana [unpublished mimeoC
preparedC for WHO-GBUI].
6. DrummondC C, James RG, Butler [insert initial(s)] (2004). Mycobactrium ulcerans treatment costs in Australia. Emerging Infectious Diseases, 10(6):1038–43
7. Ellen DE et al. Assessment of functional limitations caused by Mycobacterium ulcerans infection: towards a Buruli ulcer functional limitation score. Tropical Medicine and International Health, 8(1):90–96.
100 8. Fanshel S, Bush JW (1970). A health status index and its application to health services outcomes. Operations Research, 18(6):1021–1065.
9. Feeny D et al. (1995). Multi-attribute health status classification systems: Health Utility Index. PharmacoEconomics, 7(6):490–502.
10. Hunt SM et al. (1981). The Nottingham Health profile: subjective health status and medical consultations. Social Science and Medicine, 15(3 pt.1):221–229.
11. Jette AM et al. (1986). The functional staus questionnaire reliability and validity when used in primary care. Journal of General Internal Medicine, 1(3):143–149.
12. Krabbe PF et al. (1999). The effect of adding a cognitive dimension to the EuroQol multi attribute health status classification system. Journal of Clincal Epidemiology, 52(4):293–301.
13. Marston BJ et al. (1995). Emergence of Buruli ulcer disease in Daloa Region of Côte d’Ivoire. American Journal of Tropical Medicine, 52(3):219–224.
14. Mumma et al. (2002; 2003; 2004) The costs to households per case of Buruli ulcer in the Ashanti and central regions of Ghana [unpublished report prepared for WHO; presented and the 5th, 6th and 7th Buruli Ulcer Advosry Group Meetings in Geneva.
101 STRENGTHENING BURULI ULCER SURVEILLANCE: EVALUATING THE EFFICACY OF EDUCATIONAL MATERIALS
Dr Clare Dykewicz
Significant under-reporting and late detection of Buruli ulcer persists in countries endemic for the disease. In 2003, the Ministry of Health of Ghana (MOH) noted that 72% of reported Buruli ulcer cases had late (ulcerative) disease. In 2004, the MOH identified under-recognition of early cases of the disease as a significant barrier to achieving good surveillance, and requested assistance from the United States Centers for Disease Control and Prevention (CDC) assistance in improving Buruli ulcer education as a means of strengthening Buruli ulcer surveillance.
A preliminary investigation conducted in January 2005 revealed that distribution of the WHO comic book on Buruli ulcer to schoolchildren is the main means of educating the general population in Ghana about the disease. However, the educational efficacy of the comic book is unknown. CDC proposes to assess the current knowledge, attitudes, practices and beliefs about Buruli ulcer in endemic villages in Ghana in which the comic book has been distributed.
We plan to use the results of this assessment to develop an improved educational programme that is adapted for an audience of Ghanaian schoolchildren, implement it in an intervention area and assess its efficacy in improving knowledge, attitude, practices and beliefs regarding Buruli ulcer.
Once an educational programme adapted to Ghana is shown to be effective by field testing, it can be implemented throughout Ghana. We hypothesize that widespread use of an efficacious educational programme will result in a decreasing percentage of reported Buruli cases that are in the late (ulcerative) form, leading to decreased morbidity and disability from the disease.
102 STANDARDIZED RECORDING AND REPORTING SYSTEM USING THE BU 02 FORM AND HEALTHMAPPER
Dr Ghislain Sopoh
The development of a surveillance system requires a reliable strategy for data collection, compilation of collected data and data analysis in order that information useful for decision-making can then be extracted.
The forms used for data collection must be simple and easy for staff to use. To this end, WHO has designed a form (BU 02) intended to be used to record data at both health facility and community level.
The data collected on the BU 02 form can be compiled at the nearest specialist treatment centre, where an initial analysis of the data can also be carried out. Using data from the BU 02 form, it is possible to calculate most indicators necessary for the epidemiological surveillance of Buruli ulcer.
For two years, the form has been used in Benin to record and report over 1500 cases. Registers with detachable sheets were created for this purpose. These registers are made available to Buruli ulcer detection and treatment centres, as well as to case detection teams. A report is sent to the relevant institution each quarter by simply detaching the top two sheets. The stub is kept at the data collection point. The data is centralized at the CDTUB (Buruli ulcer detection and treatment centre) in Allada, which regularly calculates the indicators and is responsible for mapping the data. Thus this database makes information on the following indicators available to every level of the health pyramid at any given time:
Number of recorded cases over a given period
Proportion of different forms of the disease
Proportion of laboratory-confirmed cases
Ratio of number of nodules to number of ulcers
Proportion of disabilities
Proportion of post-treatment sequelae
Relapse rate
ExamplesC are given on the tables attached as annexes. C
Equally, case distribution over the period is mapped so that the level of endemicity in each district can be tracked (see examples of maps).
Time permitting, we will describe the principles for recording and analysing data (tables, graphs and maps) using the electronic version of the BU 02 form.
103 MYCOBACTERIUM ULCERANS TOXIC MACROLIDE, MYCOLACTONE MODULATES THE HOST IMMUNE RESPONSE AND CELLULAR LOCATION OF M. ULCERANS IN VITRO AND IN VIVO.
Sarojini Adusumilli,1 Armand Mve-Obiang,2 Tim Sparer,1 Wayne Meyers,3 John Hayman,4 P.L.C. Small1
1Microbiology Department, University of Tennessee, Knoxville, TN, USA 2Mycobacterial Immunology, Pasteur Institute of Brussels, Brussels, Belgium 3Division of Microbiology, Armed Forces Institute of Pathology, Washington, DC, USA 4Department of Anatomy and Cell Biology, Monash University, Melbourne, Australia
Mycobacterium ulcerans produces an extracellular infection (Buruli ulcer) characterized by immunosuppression. This unusual mycobacterial pathology is attributed to an immunomodulatory macrolide toxin, mycolactone. M. marinum, a related mycobacterial pathogen, which causes an intracellular granulomatous disease. We have explored the role of mycolactone in the virulence of M. ulcerans using genetically defined mycolactone-negative mutants. Two types of mycolactone-negative mutants were used in these studies: 1) strains that had a deleted portion of the mycolactone gene cluster, and 2) mutants containing transposon insertions in mycolactone biosynthesis genes.
Using a guinea-pig model, we show that WT M. ulcerans produces an extracellular infection, whereas mycolactone-negative mutants produce an intracellular inflammatory infection similar to that of M. marinum. Chemical complementation of both classes of M. ulcerans mutants with mycolactone restores WT M. ulcerans pathology, showing that the phenotypes associated with mutant strains are caused solely by the loss of mycolactone genes. We have also studied mycolactone cellular effects in vitro using both murine macrophages and human neutrophils. In vitro mycolactone mutants are phagocytosed more efficiently than WT M. ulcerans. However, mycolactone-negative mutants are capable of growth within macrophages in vitro and are able to persist for in vivo for 6 weeks without causing disease. Mycolactone is toxic for human neutrophils, as it is for macrophages. Neither WT M. ulcerans nor mycolactone negative strains are strong neutrophil attractants.
Studies also demonstrate host specificity for M. ulcerans disease. Whereas M. ulcerans produces an extracellular minimally inflammatory infection in guinea-pigs, M. marinum produces an intracellular inflammatory infection. In mice, both M. marinum and M. ulcerans produce intracellular infections, suggesting that there are crucial differences in the recognition of M. ulcerans and mycolactone by mice and guinea-pigs.
Finally, we have explored the cellular effects of mycolactone using a wide range of concentrations. These studies show that mycolactone causes both apoptosis and necrosis. However, necrosis is only associated with concentrations of mycolactone above 1 ug.
104 HIGH RATES OF APOPTOSIS IN MYCOBACTERIUM ULCERANS CULTURE POSITIVE LESIONS OF BURULI ULCER
Dr Douglas Walsh
Background
Buruli ulcer, a disease caused by Mycobacterium ulcerans, causes ulcerative skin disease likely generated by a toxin that mediates apoptosis.
Methods
We analysed paraffin-embedded sections of surgically excised Buruli ulcer lesions (2 ulcers and 1 oedematous plaque) and adjacent non-lesional skin samples (n = 9) for apoptosis by an indirect immunofluorescent terminal deoxynucleotide-transferase mediated dUTP-digoxigenin nick-end labelling (TUNEL) assay. All samples were stained for acid-fast bacilli (AFB) and cultured for mycobacteria, and most were analysed with an M. ulcerans-specific diagnostic polymerase chain reaction (PCR).
Results
TUNEL(+) bodies were numerous in both ulcers and the plaque, and sparse or absent in adjacent non- lesional skin. AFB tissue stains and cultures for M. ulcerans were positive only in the 3 lesions. The PCR for M. ulcerans was positive in all 3 lesions and in 4 of 6 non-lesional tissue samples; 3 contained sparse TUNEL(+) bodies.
Interpretation
An abundance of TUNEL(+) bodies in the 3 AFB stain (+), culture (+) and PCR (+) Buruli ulcer lesional samples, but not in nearby AFB stain (–), culture (–) and PCR (+) non-lesional skin samples, strengthen the evidence that apoptosis is an important tissue destruction mechanism closely associated with viable M. ulcerans.
105 LOCAL AND SYSTEMIC IMMUNE RESPONSE TO M. ULCERANS INFECTION AND CORRELATIONS WITH HISTOPATHOLOGY
Phillips R, Horsfield C, Mangan J, Laing K, Butcher P, Nyamekye B, Awuah P, Nyarko KM, Osei- Sarpong F, Etuaful S, Kolk A, Lucas S, Wansbrough-Jones M
Introduction
In the early stages of Buruli ulcer, nodules show extensive subcutaneous necrosis and abundant clumps of extracellular acid fast bacilli (AFB) but, in long-standing lesions there is a mixture of acute and chronic inflammation with granulomas and the number of AFB is greatly reduced, suggesting cell mediated immunity plays a role in healing. In one study, 30% of lesions healed spontaneously, suggesting an adequate immune response can eliminate infection. It has been reported that Buruli ulcer patients are unable to mount an adequate TH1 response, so we have investigated the cytokine response of whole blood from patients infected with M. ulcerans (Mu) with disease at different stages and used real-time polymerase chain reaction (PCR) to quantify tissue cytokines. Tissue responses were correlated with semi-quantitative histopathology.
Methods
Patients with Mu disease were recruited from 3 districts in Ghana. Using a whole-blood assay IFN-and IL-10 responses to Mu sonicate, Mu culture filtrate (Ag423, Ag425) and M. tuberculosis sonicate were measured in 44 subjects with active Mu disease (16 nodules, 28 ulcers), 29 healed Buruli ulcer patients, 27 household contacts, 30 non-endemic area controls, 30 untreated tuberculosis patients and 29 tuberculosis patients (HIV negative) during treatment. Expression of cytokine mRNAs was quantified by real-time PCR in tissue from 46 Buruli ulcer patients and 11 with other conditions.
Results
Significant interferon (IFN) production in response to whole-blood stimulation with Mu sonicate was detected in patients with ulcers (632.5 ± 125.7 pg/ml; mean +/– SE), which was higher than that in patients with nodules (243.2 ± 79.11; p = 0.0108 Mann Whitney) but similar to subjects with healed Buruli ulcer (522.7 ± 97; p = 0.1872). The mean IFNresponse in household contacts of Buruli ulcer patients was 133.9 ± 31, which was not significantly different from that in 30 healthy control subjects from a non-endemic area (78.3 ± 9). Results in 30 patients with untreated, smear-positive pulmonary tuberculosis and 29 tuberculosis patients on treatment for more than 2 weeks were 110.2 ± 22 and 226.7 ± 76 respectively, showing that Buruli ulcer patients responded better to Mu antigens than tuberculosis patients. Similar results were found using M. tuberculosis sonicate as antigen but treated tuberculosis patients had higher responses. In contrast, IL-10 results were higher in patients with active Mu disease (831 ± 123 pg/ml) than in those with healed lesions (396 ± 45 pg/ml), but the pattern of response was similar to that seen in tuberculosis. Two culture filtrate antigens of Mu gave similar results and neither appeared to be highly specific.
106 In tissue samples, there was higher expression of Th1 cytokine mRNAs including IFNcompared with Th2 cytokines, and expression levels were similar between nodules and ulcers. There was significantly higher expression of IL-8 and other pro-inflammatory cytokines in 46 tissue samples with neutrophilia than in 12 without acute inflammation; patients administered antibiotics appeared to mount a profound IL-8 response. A total of 10 tissue samples containing granulomas showed high mRNA expression for IFN-, IL-1, IL-12p35, IL-12p40, IL-15 and TNF-compared with 19 tissues without granulomas.
Conclusions
In the early stages of M. ulcerans disease there was a mixed TH1 and TH2 cytokine response, but the TH1 response emerged as the dominant type. Acute inflammation with high IL-8 expression followed antibiotic therapy, suggesting that it heralded the onset of healing and granuloma formation when there was high IFN, IL-1, IL-12p35, IL-12p40, IL-15 and TNF-expression.
107 SUSCEPTIBILITY TO DEVELOP BURULI ULCER IS ASSOCIATED WITH NATURAL RESISTANCE-ASSOCIATED MACROPHAGE PROTEIN 1 POLYMORPHISMS
Y. Stienstra, T.S. van der Werf *, E. Oosterom, I.M. Nolte, W.T.A. van der Graaf, S. Etuaful, P. Raghunathan, E. Whitney-Spotts, E.O. Ampadu, K. Asamoa, E.Y. Klutse, G.J. te Meerman, J.W. Tappero, D.A. Ashford, G. van der Steege.
University Medical Center Groningen, the Netherlands; National Program for Buruli ulcer, Accra, and St Martin’s Catholic Hospital, Agroyesum, and Dunkwa Government Hospital, Dunkwa on Offin, Ghana; and Meningitis & Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta GA, USA.
Development of Buruli ulcer after exposure to M. ulcerans might be determined by genetic host factors. To test this hypothesis, we took finger-prick blood dried on filter papers (FTA) from consenting study subjects in Ghana. We enrolled 182 Buruli ulcer patients (102 with positive laboratory confirmation) and 193 matched healthy controls, and studied three polymorphisms in the NRAMP1 gene: 3’ UTR, D543N and INT4. All three polymorphisms tested were in Hardy-Weinberg equilibrium. D543N was significantly associated with Buruli ulcer: the odds ratio of the GA genotype versus the GG genotype was 2.50 (95% CI: 1.26–4.96). Combination of G+-GA–ins/ins had an odds ratio 2.56 (95% CI:1.14–5.71) in Buruli ulcer patients.
In conclusion, a genetic polymorphism in the NRAMP1 gene plays a role in susceptibility to developing Buruli ulcer, with an estimated attributable risk of 12.8%. Other genetic and environmental risk factors should, however, also be considered.
* presenting author
108 NERVE DAMAGE BY BACTERIA CAUSING BURULI ULCER – ULTRASTRUCTURE OF MOUSE INOCULATED WITH MYCOBACTERIUM ULCERANS
Masamichi Goto1, Hajime Saito2, Kazue Nakanaga3, Norihisa Ishii3, Suguru Yonezawa1
1Kagoshima University 2Hiroshima Environment and Health Association 3National Institute of Infectious Diseases Leprosy Research Center
Buruli ulcer is an intractable skin disease caused by Mycobacterium ulcerans. It is observed in tropical area such as Africa and Australia. Large, necrotizing, relatively painless, deep skin ulcers are formed mainly in the extremities. Because of chronic course and occasional complication of severe deformities, socioeconomic handicap is a great problem.
A recent study demonstrated that phenolic glycolipid-I (PGL-I), a M. leprae-specific membranous antigen responsible for Schwann cell invasion, is present in Buruli ulcer. Thus, we hypothesized that not only M. leprae but also M. ulcerans may invade peripheral nerves.
Materials and methods
Bacterial suspension of M. ulcerans colony 97-107 cultured at 32 °C in 7H9 culture medium (CFU = 1.3X106/ml, 25ml) was inoculated into the bilateral footpads of female BALB/c mice. Local swelling and redness were observed at day 33 after the inoculation, and sequential histopathological examination was then performed.
Perfusion fixation by 10% formalin was done, and hind limbs were histopathologically examined by HE, acid-fast staining and immunohistochemistry using anti-PGL-I antibody. In selected cases, perfusion fixation by 2% glutaraldehyde was also done, and hind limbs embedded in Epon, cut into 1mm were examined. Where nerve damage was observed, electron microscopic examination was performed.
Results
Day 33 after the inoculation of M. ulcerans. Dermal erosion and extensive oedema of subcutaneous tissue were associated with infiltration of small numbers of neutrophils and monocyte. Granuloma formation was absent. Small clusters of long acid-fast bacilli (AFB) were noted, mainly in the stroma and in the cytoplasm of monocytes (Figure 1). Peripheral nerves were well preserved even in the oedematous lesion.
Day 55 after the inoculation of M. ulcerans. Remarkable deep skin ulcer and extensive subcutaneous oedema were observed. Large numbers of acid-fast bacilli formed clusters in the oedematous stroma. Many nerve bundles were well preserved, but some showed vacuolar change of Schwann cells (Figure 2), and others were invaded by numerous AFB with massive nerve damage. Ultrastructurally, the AFB were mainly in the endoneurium, and Schwann cells were spare (Figure 3). PGL-I immunohistochemistry was negative.
109 Discussion
Among the mycobacterial species, only M. leprae is known to show neurotropism and causes nerve damage. In the previous studies, mild degenerative change with thickening of Schwann cell basal lamina and vacuolar change of axons were reported {Mwanatambwe, 2000}, but direct nerve invasion by the AFB has not been found. Our study first demonstrated that nerve bundles are damaged by numerous M. ulcerans. This finding raises a new possibility of the pathogenesis of the “painlessness” of Buruli ulcer.
*
Figure 1* Figure 2 Figure 3
Day 33. Macrophage contains Day 55. Vacuolar change of Nerve damage with endoneurial numerous bacilli Schwann cells (*) invasion of bacilli
110 VACCINE OPTIMALIZATION BY EXPERIMENTAL MOUSE MODEL FOR MYCOBACTERIUM ULCERANS FOOTPADS INFECTION
Dr Audrey Tanghe
As of now, there is no specific vaccine against Mycobacterium ulcerans, but evidence in the literature has suggested a cross-reactive protective role of the M. bovis BCG vaccine used against tuberculosis. To achieve an early diagnosis, to find the mechanism of transmission and to focus on a vaccine are priorities to control the disease. Many studies have shown that DNA vaccination is a good way for a new vaccination protocol. Previous studies have shown that prior vaccination with plasmidique DNA vaccine, encoding either antigen 85A (Ag85A-DNA) or antigen 85B (Ag85B-DNA), offers good protection in C57BL/6 (B6) mice infected with M. tuberculosis H37Rv. This antigen 85 complex is a 30–32 kDa family of three proteins (Ag85A, Ag 85B and Ag85C), which all possess a mycolyl transferase enzyme activity, important for the biogenesis of the mycobacterial envelop. In view of these results, and because little is known about the antigens implicated in M. ulcerans protection, our laboratory has focused its work on antigen 85A.
In 2001, we identified and sequenced the Ag 85A component from M. ulcerans strain 5150. A cross- reactive protection was demonstrated. Indeed, prior vaccination with either BCG or plasmid Ag85A-DNA from BCG was able to reduce significantly the bacterial load in the footpads of mice infected with M. ulcerans, strain 5150, B6. Unfortunately, the protection observed after vaccination with Ag85A-DNA from BCG was below the one given by BCG vaccine alone. So we decided to analyse a) the protective efficacy of a DNA vaccine encoding the species-specific Ag85A protein from M. ulcerans, b) the prime/boost strategy combining DNA followed by the protein injection and c) double BCG vaccine. In spite of a good sequence identity between the two Ag85A homologs in M. bovis BCG and in M. ulcerans, results suggest that the vaccination with the DNA encoding the specific M. ulcerans Ag 85A has the same protective effect as the Ag85A-DNA from BCG.
After cloning and purification of the specific protein 85A from M. ulcerans,, we used a vaccination protocol combining DNA and protein boost, in B6 mice. Immunological response studies have shown production of Th1 cytokines (IL-2 and IFN-) increased by the boost with the protein compared with the DNAp vaccine alone. An infection with 105 AFB of 04-855 M. ulcerans strain was done, 12 weeks after the last immunization, in the footpads of the mice. The protective effect was measured by the delay for the appearance of footpad swelling and with an “oditest” measure apparatus. Unfortunately, the boost with the protein does not give better protection in comparison with the BCG vaccine. In humans, BCG seems to give a short-term protection against the development of Buruli ulcer and a more sustained immunoprophylactic effect for the most severe form of the disease, the osteomyelitis.
A booster vaccination with BCG can offer additional protection against leprosy than with a single BCG injection. Therefore, we decided to investigate protection in mice injected twice intravenously with M. bovis BCG. The experiments were carried out on B6, BalbC and BalbB10 mice. Infection with 105 AFB of M. ulcerans strain 04-855 took place 10.5 and 14 months after the first injection of BCG. According to our preliminary first data, it is clear that a double or single injection with BCG does not give complete protection and that double BCG injection does not increase the protective effect of the single injection. Nevertheless, a new, similar experiment will be done on young mice with a reduced time between BCG injections and M. ulcerans infection in mouse footpads. The study of the sensibility of different haplotype mouse strains to M. ulcerans strain 04-855 footpad infection is in progress and will allow a better understanding of the immunological implication of H-2 molecules and to define a more susceptible mouse strain for further development of vaccine candidates against M. ulcerans.
111 CONSTRUCTION OF MYCOLACTONE-NEGATIVE MUTANTS OF MYCOBACTERIUM ULCERANS MAY CONTRIBUTE TO THE DEVELOPMENT OF VACCINE CANDIDATES AGAINST BURULI ULCER
Armand Mve-Obiang,1 Brian Ranger,2 Kris Huygen,1 Pamela Small2
1Pasteur Institute of Brussels 2University of Knoxville, TN, USA
Mycobacterium ulcerans causing Buruli ulcer is a mycobacterium whose pathogenicity is related to the production of a polyketide toxin called mycolactone (ML). The genes involved in the synthesis of this toxin are localized on a 174 kb plasmid (1). So far, there is no effective vaccine against Buruli ulcer, and little is known on the immune mechanisms involved in protection (2). As for all other mycobacterial infections, generation of potent CD4+ and CD8+ mediated responses against protein antigens is thought to be essential, although it is not excluded that neutralization of the toxin by antibodies may also be important. Using transposon mutagenesis, we have produced a number of ML-negative mutants, inactivated in genes involved in the toxin biosynthesis. Southern-blot and sequencing were performed to prove that each mutant was the result of one transposon insertion. Mass spectrometry and thin-layer chromatography allowed physical demonstration of the loss of ML production, and in vitro cytotoxicity tests on L929 cells were carried out and confirmed the absence of ML activity. Intradermal injection in guinea-pig skin of the ML-negative mutants did not cause the typical Buruli ulcer necrosis, and, in contrast to M- producing, wild type M. ulcerans (which is extracellular in this model), the ML-negative mutants were found inside the host macrophages. Experiments are in progress to evaluate in mouse footpad model (3) the immunogenicity and the protective efficacy of ML-negative mutants and DNA vaccines encoding for a number of genes involved in ML biosynthesis.
References
1. Stinear TP et al. (2004). Giant plasmid-encoded polyketide synthases produce the macrolide toxin of Mycobacterium ulcerans. Proceedings of the National Academy of Sciences of the United States of America, 101:1345–1349.
2. HuygenH K. H (2003). Prospects for vaccine development against Buruli disease. Expert Review of Vaccines, 2:561–569.
3. Tanghe A et al. (2001). Protective efficacy of a DNA vaccine encoding antigen 85A from Mycobacterium bovis BCG against Buruli ulcer. Infection and Immunity, 69:5403–5411.
112 NEW LABORATORY TOOLS FOR STUDYING MYCOBACTERIUM ULCERANS INFECTION
Gerd Pluschke, Jean-Pierre Dangy, Diana Diaz, Simona Rondini, Dorothy Yeboah-Manu
Swiss Tropical Institute, Basel, Switzerland*
Our goal is to develop new immunological and molecular biological tools that facilitate research on the immunology, pathogenesis and transmission of Buruli ulcer.
A quantitative real-time PCR method for the detection of Mycobacterium ulcerans DNA (Rondini et al., 2003) has been used to analyse the development of satellite infection foci in Buruli ulcer lesions.
Results obtained with a microarray-based system for the analysis of genomic DNA have shown that insertional/deletional diversity is common in M. ulcerans. This may facilitate development of a fingerprinting method for micro-epidemiological field studies.
Primary isolation of M. ulcerans from surgical specimens has been optimized (Yeboah-Manu et al., 2004). Under optimal conditions, cultivation turned out to be as sensitive as other laboratory methods for reconfirmation of clinical diagnosis.
Monoclonal antibodies specific for immunodominant protein antigens, capsular components and the mycolactone toxin of M. ulcerans are being generated and characterized. One of the immunodominant proteins identified may be a suitable target structure for an immunological test detecting infection and/or exposure to M. ulcerans.
References
1. Rondini S et al. (2003). Development and application of a real-time polymerase chain reaction assay for the quantification of Mycobacterium ulcerans DNA. Journal of Clinical Microbiology, 41, 4231– 4237
2. YeboahH -Manu D H (2004). Evaluation of decontamination methods and growth media for primary isolation of Mycobacterium ulcerans from surgical specimens. Journal of Clinical Microbiology, 42:5875–5876.
*In collaboration with: Thomas Bodmer (University of Bern), Ernestina Mensah-Quainoo (Ghana Health Service, Ga West District, Amasaman), David Ofori-Adjei (Noguchi Memorial Institute for Medical Research, Legon), Françoise Portaels (Institute of Tropical Medicin, Antwerp), Pamela Small (University of Tennessee) and Timothy Stinear (Monash University, Melbourne).
113 SENSITIVITY OF PCR FOR IS2404 INSERTION SEQUENCE OF MYCOBACTERIUM ULCERANS IN DIAGNOSIS OF BURULI ULCER FROM PUNCH BIOPSIES
Phillips R, Horsfield C, Kuijper S, Lartey A, Tetteh I, Etuaful S, Nyamekye B, Awuah P, Nyarko K.M, Osei-Sarpong F, Lucas S, Kolk A.H.J, Wansbrough-Jones M.
Punch biopsies from M. ulcerans disease lesions have been used to compare the sensitivity and specificity of direct smear, culture, polymerase chain reaction (PCR) and histopathology in making the diagnosis of Mycobacterium ulcerans disease in a field setting. PCR for the insertion element IS2404 was modified to include uracil-N-glycosylase and dUTP instead of dTTP to reduce the risk of cross-contamination. The gold standard for confirmation of clinically diagnosed Buruli ulcer was a definite histological diagnosis, or positive culture for M. ulcerans, or a smear positive for acid-fast bacilli (AFB) together with a possible histological diagnosis. For 70 clinically diagnosed cases of M. ulcerans disease, the modified PCR was 98–100% sensitive and gave a rapid result. The sensitivities of microscopy, culture and histology were 43%, 50% and 83% respectively. A 4mm punch biopsy was preferred to a 6 mm punch biopsy since it was less likely to bleed and to need stitching. Given adequate technical expertise and controls, the PCR was viable in this teaching hospital setting in Ghana and, in routine practice, we would recommend Ziehl- Neelson staining of biopsies to detect AFB, followed by PCR in AFB-negative cases only, in order to minimize costs. Histology and culture remain important as quality control tests, particularly in studies of treatment efficacy.
114 GENOTYPING MYCOBACTERIUM ULCERANS, MYCOBACTERIUM MARINUM AND RELATED SPECIES USING MYCOBACTERIAL INTERSPERSED REPETITIVE UNITS
P. Stragier,1 A. Ablordey,1 P. Suykerbuyk,1 W.M. Meyers,2 F. Portaels1
1Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerpen, Belgium 2Armed Forces Institute of Pathology, Washington DC, USA
A novel category of variable tandem repeats (VNTR) called mycobacterial interspersed repetitive units (MIRUs) has been identified for Mycobacterium ulcerans (n = 51) and M. marinum (n = 55) (1).
A total of 15 possible MIRU loci were localized in the genome of M. marinum and were used for genotyping M. ulcerans, M. marinum, M. liflandii (n = 4), 1 M. shottsii (ATCC 700981), and 1 M. marinum-like organism considered a possible “missing link” between M. marinum and M. ulcerans. Some 6 MIRU loci were found polymorphic, and locus-specific PCR at these loci differentiated 9 M. ulcerans genotypes, 13 M. marinum genotypes and unique genotypes for each of the following species: M. shottsii,“M. liflandii” and the “missing link”. Both earlier and recent isolates of M. ulcerans from 6 African countries as well as old and recent isolates belong to the same genotype, emphasizing the great spatio-temporal homogeneity among African isolates. Unlike M. ulcerans, the genotypes of the 13 M. marinum isolates did not clearly predict their geographical origin. However, using MIRU-VNTR typing, all M. ulcerans and M. marinum isolates of American origin and the original American M. liflandii and M. shottsii were closely related, suggesting a common American ancestor for these pathogenic species on the American continents.
MIRU-VNTR typing can be directly applied on Ziehl-Neelsen positive clinical samples. For example, by this method we differentiated an isolate from Sudan from the other African M. ulcerans. Remarkably, in Papua New Guinea, a relatively small geographical area compared with Africa, three genotypes were found. Initial findings suggest that one of these genotypes resembles M. ulcerans from Cameroon; however, this requires confirmation.
MIRU typing is a rapid and effective method for determining the origin of isolates and rapid identification of genotypes of M. ulcerans, M. marinum and related species. Moreover, MIRU typing should have significant potential for the discrimination of relapse from reinfection in M. ulcerans disease.
Reference
1. Stragier P et al. (2005). Genotyping Mycobacterium ulcerans and Mycobacterium marinum by using mycobacterial interspersed repetitive units. Journal of Bacteriology, 187(5):1639–1647.
115 STUDY OF THE M. ULCERANS PROTEOME
L. Marsollier1, P. Taffelmeyers1, A. Naman1, P. Lenormand1, J.C Roussselle1, J. P. Saint André2,P. Legras2, J. Aubry3, T. Stinear4, P. Small5, B. carbonnelle2, S. T. Cole1, G. Reysset1
1 Institut Pasteur, Paris 2 Faculté de Médecine, Angers 3 Faculté de Pharmacie, Nantes 4 Monash University, Melbourne 5 University of Tennessee, Knoxville
Using genomic and post-genomic techniques, an exhaustive proteome study is under way in order to study the relationship between the bacillus and its host, the water bug. The study will make it possible to identify and compare bacterial proteins produced in vitro and in vivo (by the water bug).
Apart from answering fundamental questions, the information gathered through this research into the proteome will subsequently be used to develop diagnostic, vaccine and preventive tools.
116 IDENTIFICATION OF MYCOBACTERIUM ULCERANS IN THE ENVIRONMENT BY PCR: LIMITATIONS OF IS2404 AS PROOF FOR M. ULCERANS IN THE ENVIRONMENT, AND DEVELOPMENT OF A MYCOLACTONE-SPECIFIC PROBE
Heather Williamson, Brian Ranger, Tim Stinear, and P.L.C. Small
Several lines of evidence suggest that reliance on IS2404 as a probe for Mycobacterium ulcerans in Africa may not be definitive: 1) IS2404 has been detected in several M. marinum isolates as well as in the frog pathogen, M. liflandii; 2) PCR positivity does not correlate with the ability to culture organisms (personal communication, Francoise Portales, Laurent Marsollier). Although this could be because organisms are in a non-culturable state in the environment, Laurent Marsollier has shown that M. ulcercans can be readily cultured from laboratory-infected insects; 3) AFB (acid-fast bacilli) staining of PCR-positive environmental samples reveals few or no AFBs; 4) the yield of IS2404-positive samples in the environment is extremely high and spans many species, suggesting lack of specificity; 5) bands produced from environmental samples are faint, leading to the suggestion that few organisms are present; and yet in M.ulcerans hundreds of copies of the IS element are found; 6) we have recently obtained IS2404-PCR positive environmental samples from Michigan and Tennessee, suggesting that this insertion sequence may be widely distributed in nature.
In preliminary studies with environmental isolates collected in Ghana, we obtained a high proportion of IS2404 samples – sometimes as high as 75%. Following consultation with investigators from the United States Centers for Disease Control and Prevention (CDC), we began to include insects collected locally (Michigan and Tennessee) in these studies as negative controls and found several confirmed positives. Because we suspected that many of these samples were not truly positive for M. ulcerans, we considered whether the use of a mycolactone probe might be more specific. The polyketide synthases for the mycolactone core are encoded by mlsA. Within mlsA lies the ER region, which is present in three copies. Although the copy number of the plasmid has not been determined, it is likely to be present in 1–3 copies meaning that each M. ulcerans bacteria will possess 3–9 copies of the ER. In a true environmental reservoir where bacterial replication occurs, it would be reasonable to expect to find at least 10 organisms present, which would translate into 30–90 copies of the ER. This should be detectable by PCR.
When we used a DNA probe for the ER (5’- gagatcggtcccgacgtctac-3’ and 5’-ggcttgactcatgtcacgtaagg-3’) against a group of environmental samples, our positivity rate fell to 2%. Although this probe is not likely to be 100% specific for M. ulcerans because other environmental bacteria may contain the mycolactone plasmid, a probe to the ER is likely to be more specific for M. ulcerans than IS2404. It is of some interest that in Australia, the rate of IS2404-positive strains is much lower than that in Africa, suggesting that IS2404 may have greater M. ulcerans specificity in Australia.
Although it is likely that some of the IS2404-positive samples from the environment really do contain M. ulcerans, results from our studies suggest that the presence of IS2404 in environmental samples should no longer be considered presumptive evidence for the presence of M. ulcerans without further validation.
117 BURULI ULCER CONTROL INTEGRATION MODEL FOR PUBLIC HEALTH ESTABLISHMENTS: PILOT PROJECT TO IMPROVE AWARENESS OF AND TREAT BURULI ULCER PATIENTS IN TAABO, CÔTE D’IVOIRE
Dr Julien Ake Ake, Aubin Koffi Yao
The problem
In Côte d'Ivoire, a national survey conducted in 1997 helped reveal an incidence of some 15 000 cases of Buruli ulcer, spread through 56 of the country’s 58 districts. Each year, about 2500 new cases are reported.
In the country as a whole, there are approximately 1700 health establishments in operation and a widespread network of community health workers, all coordinated in some 80 health districts. However, only six health establishments provide proper treatment of patients.
It will be noted that such cases very often consist of ulcerations or complicated cases, with lower reporting of pre-ulcerative forms. The epidemiological picture of the disease nationwide is also poorly known.
If the condition is to be more effectively combated and its harmful consequences alleviated, access to care must be improved and awareness and monitoring activities extended. To do so, the Buruli ulcer control programme must be centralized by incorporating it in the general health effort.
After developing the relevant intervention tools, MAP International for west and central Africa and ALM, in collaboration with the National Mycobacterial Ulcers Control Programme (PNUM), decided to undertake a pilot project for integrating the Buruli ulcer control programme with the general public health system.
Project title: Pilot project for promoting awareness of and treating Buruli ulcer patients in Taabo
Project area: Taabo Sub-prefecture, Tiassalé Health District.
Project duration: 30 months: from July 2004 to December 2006.
Overall objective: To test a model for integrating the Buruli ulcer control programme into the public health structures of Côte d’Ivoire.
Specific objectives
To identify, train and equip a local coordinator with the tools for supervising activities. To strengthen the ability of 20 nurses, 25 community health workers, 2 surgeons and 2 physiotherapy assistants to improve knowledge, conduct early tracing, prevent disability and carry out epidemiological surveillance.
118 To equip 4 rural health centres, 1 rural dispensary and 1 private infirmary with nodulectomy kits, public awareness tools and reporting registers. To provide the Taabo General Hospital (reference hospital) with excision-grafting and nodulectomy kits, public awareness tools and a reporting register. To provide pharmaceutical drugs and medical consumables to all patient treatment facilities, with the support of the PNUM. To strengthen the abilities of 10 Christian volunteers to provide schooling and psycho-spiritual support to hospitalized patients. To establish a partnership with a specialized agency for providing training, physical rehabilitation and socioeconomic reintegration for cured patients who suffer incapacitating sequelae.
Interest arising from the project
It reduces the cost of treating patients and providing support for their families and the health system:
– less uprooting from patients’ ordinary places of residence
– fewer ulcerated forms and complications
– shorter hospital stays
– better use made of existing skills and capacities: local health facilities and equipment, health professionals and community health workers.
Treatment of patients in their home settings, thereby avoiding homesickness and other problems relating to being cut off from families.
Lasting assistance
– incorporation of the project in the health district
– availability of local skills and capacities to ensure that assistance will be longer lasting
– involvement of the beneficiary community
Better mapping of the disease
Treatment of Buruli ulcer becomes a day-to-day activity and part of the core activities of health services.
Preliminary results
Statistics relating to screening activities and treatment of Buruli ulcer cases from November 2004 to January 2005.
119 Clinical form
Table 1: Breakdown by clinical form
Clinical form Total Percentage Pre-ulcerative form 21 24 Ulcerated form 54 63 Mixed form 10 12 With complications* 1 1 Total 86 100
*affecting bone.
Table 2.Trends in pre-ulcerative and ulcerated forms
60
50
40 s e s
a Ulcerative c
30 f
o Nonulcerative
% 20
10
0 Nov Dec Jan Year
120 We see more cases detected at the pre-ulcerative stage and fewer ulcerated cases.
Conclusion
The preliminary results are so encouraging that we are in a hurry to reach the end of the pilot project and move into the extension phase.
121 ANNEX 1: Resolution WHA57.1 – Surveillance and control of Mycobacterium ulcerans disease (Buruli ulcer)
The Fifty-seventh World Health Assembly,
Having considered the report on surveillance and control of Mycobacterium ulcerans disease 1 (Buruli ulcer);
Deeply concerned about the spread of Buruli ulcer, especially among children, and its health and socioeconomic impact in poor rural communities;
Aware that early detection and treatment minimize the adverse consequences of the disease;
Noting with satisfaction the progress made by the Global Buruli Ulcer Initiative since its inception in 1998, in coordinating control and research activities among partners;
Concerned that several factors, including late detection of cases and lack of effective tools for diagnosis, treatment and prevention, impede further progress;
Mindful that achievement of two of the United Nations Millennium Development Goals, namely, to eradicate extreme poverty and hunger and to achieve universal primary education, may be hampered by the negative impact of neglected diseases of the poor, including Buruli ulcer,
1. URGES Member States in which Buruli ulcer is or threatens to become endemic:
(1) to assess the burden of Buruli ulcer and, where necessary, establish a control programme; (2) to accelerate efforts to detect and treat cases at an early stage; (3) where feasible, to build up effective collaboration with other relevant disease-control activities; (4) within the context of health-system development, to establish and sustain partnerships at country level for control of Buruli ulcer; (5) to ensure that sufficient national resources are available to meet control needs, including access to treatment and rehabilitation services; (6) to provide training to general doctors to improve surgical skills; (7) to provide training to all health workers in the prevention of disability;
2. ENCOURAGES all Member States:
(1) to participate in the Global Buruli Ulcer Initiative; (2) to intensify research to develop tools to diagnose, treat and prevent the disease, as well as to integrate Buruli ulcer into the national disease surveillance system; (3) to intensify community participation in the recognition of disease symptoms;
3. CALLS UPON the international community, organizations and bodies of the United Nations system, donors, nongovernmental organizations, foundations and research institutions:
(1) to cooperate directly with countries in which the disease is endemic in order to strengthen control and research activities;
122 (2) to develop partnerships and to foster collaboration with organizations and programmes involved in health-system development in order to ensure that effective interventions can reach all those in need; (3) to provide support to the Global Buruli Ulcer Initiative;
4. REQUESTS the Director-General:
(1) to continue to provide technical support to the Global Buruli Ulcer Initiative, in order particularly to advance understanding of the disease burden and to improve early access to diagnosis and treatment by general strengthening of health infrastructures; (2) to foster technical cooperation among countries as a means of strengthening surveillance, control and rehabilitation services; (3) to promote research on better diagnostic, treatment and preventive tools through the coordination and support by the Special Programme for Research and Training in Tropical Diseases.
21 May 2004 A57/VR/7
123 ANNEX 2: LIST OF PARTICIPANTS
Dr George Abram, International Anti-Leprosy Organization, P.O. Box 851, Takoradi, Ghana – Tel: +233 31 24855, Fax: +233 31 31580 – E-mail: [email protected]
Dr Phyllis Addo, Noguchi Memorial Institute for Medical Research, P.O. Box LG 581, Legon, Accra, Ghana – Tel: +233 244 586 937/233 21 513 208/501178-80, Fax: +233 21 502182 – E-mail: [email protected]
Dr Ambroise Adeye, Centre de dépistage et de traitement de l'ulcère de Buruli « Raoul et Madeleine Follereau » Pobé, B.P. 191 Pobé, Benin – Tel: +229 25 05 08 – E-mail: [email protected]
Mr Joseph Adomako, Amansie West District Health Administration, c/o Regional Health Administration, P.O. Box 1908, Kumasi, Ghana – E-mail: [email protected]
Prof. Ohene Adjei, Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana – Tel: 233 1 60511, Fax: +233 51 62017 – E-mail: [email protected]
Dr Pius Agbernorku, Reconctructive Plastic Surgery & Burns Unit, Department of Surgery, School of Medical Sciences, UST Komfo, Anokye Teaching Hospital, Kumasi, Ghana – Tel: +233 51 60429, Fax: 233 51 60137 –E-mail: [email protected]
Mr Antonio de Almeida, 85, rue des Parcs, 2000 Neuchâtel, Suisse – Tel: +41 32 721 36 91 – E-mail: [email protected]
Dr Edwin Ampadu, National Buruli Ulcer Control Programme, Disease Control Unit (Korle-Bu), Ministry of Health, P. O. Box KB 493, Accra, Ghana – Tel: +233 21 686337, Fax: +233 21 686336 – E-mail: [email protected]
Prof. Henri Assé, UFR des sciences médicales d'Abidjan-cocody, 22 BP 688, Abidjan 22, Côte d'Ivoire – Tel: + 22522 43 60 44 – E-mail: [email protected]
Dr Eric Aombe Bafende, IME/Hôpital de Kimpese, PO Box 68, Kimpese, Bas-Congo, Democratic Republic of the Congo – Tel: +243 81 502 74 69 – E-mail: [email protected]
Dr Adama Marie Bangoura, Programme national de lutte contre l’Ulcère de Buruli, Ministère de la Santé publique, B.P. 585, Conakry, Guinée – Tel: 224 40 70 07 – E-mail: [email protected]
Dr Louis Bayonne Manou, Centre Hospitalier de Libreville, B.P 3205, Libreville, Gabon – Tel: 241 72 1 20/241 06 24 98 35 – E-mail: [email protected]
Dr Eric Benbow, Department of Entomology, 243 Natural Science Bldg., Michigan State University, East Lansing, MI 48824, United States of America – el: +1 517 355 8309, Fax: 1 517 353 4354 – E-mail [email protected]
Ms Elisa de Biurrun Bakedano, C/Sinesio Delgado nº4, Pabellón 13, Centro Nacional de Medicina Tropical, Instituto de Salud Carlos III, 28029 Madrid, Spain/Espagne – Tel: +91 822 29 40, Fax: +91 387 77 56 – E-mail: [email protected]
Dr Daniel Boakye, Noguchi Memorial Institute for Medical Research, P.O. Box LG 581, Legon, Accra, Ghana – Tel: +233 21 500 374/501178-80, Fax: 233 21 502182 – E-mail: [email protected]
124 Ms Roelien Boerma, Department of Internal Medicine, Groningen University Medical Centre, PO Box 30001, 9700 RB, Groningen, The Netherlands – E-mail: [email protected]
Mr Fabrizio Bonifacio, Via Cavour 9, 39100 Bolzano, Italie – E-mail: [email protected]
Dr Gisela Bretzel, Department of Infectious Diseases & Tropical Medicine, Ludwig-Maximilians- University Munich, Leopoldstrasse 5, D-80802 Munich, Germany –Tel: +49 89 2180 3618; Fax: 49 9 61 12 – E-mail: [email protected]
Mr Thierry Brunet de Courssou, La Tuilerie, 85120 La Tardière, France – E-mail: [email protected]
Dr Annick Chauty, Centre de dépistage et de traitement de l'ulcère de Buruli « Raoul et Madeleine Follereau » Pobé, B.P. 191 Pobé, Bénin/Benin – Tel: +229 25 05 08 – E-mail: [email protected]
Dr Philippe Chemaly, 16, rue Gabriel Péri, 94220 Charenton le Pont, France – E-mail: [email protected]
Dr Emile China, Association Raoul Follereau du Benin, 08BP.121 TP, Cotonou, Benin – Tel: 229 30 3 50, Fax: +229 30 95 74 – E-mail: [email protected]
Dr Claudio Clemente, Anatomia Patologica e Citopatologia, Casa di Cura S. Pio X, Via F. Nava 31, Milano, 20159 Milano, Italy – Tel: +39 02 6951 6440, Fax: +39 02 6951 6449 – E-mail: [email protected]
Prof. Stewart Cole, Institut Pasteur, Unité génétique moléculaire bactérienne, 28, rue due Docteur Roux, 75724 Paris Cedex 15, France –
Dr Eric Comte, Médecins Sans Frontières–Switzerland, Medical Department, 78 rue de Lausanne, 1211 Genève 21, Switzerland – Tel. +41 22 849 89 41 – E-mail: [email protected]
Dr Pierre Couppié, Service de Dermatologie, Centre Hospitalier Général de Cayenne, Rue des Flamboyants, BP 6006, 97306 Cayenne Cedex, French Guiana – Tel: +594 594 39 53 25/5359, Fax: +594 594 39 5283 – E-mail: [email protected]
Mr Frank Dadzie, Department of Economics, Clark Atlanta University, 233 James P Brawley Dr., SW, Atlanta, GA 30314, United States of America – Tel: +1 770 925 0551, Fax: +1 404 880 6276 – E-mail: [email protected]
Dr Sunil Deepak, Medical Support Department, AIFO - Via Borselli 4-6, 40135 Bologna, Italy – Tel: +39 051 43 34 02/ 39 051 61 45 437, Fax: +39 051 43 40 46 – E-mail: [email protected]
Dr Moussa Diabaté, Programme national de lutte contre les ulcères à Mycobactéries, 22 BP 1701, Abidjan 22, Côte d'Ivoire – Tel/Fax: +225 20 22 43 47 (Standard: +225 20 22 00 10 – Cell: +225 07 23 4616/05271359) – E-mail: [email protected]
Mrs Angela Doran, Pro-Tex Capillary Dressings Limited, 319 Asmec Centre, Eagle House, The Ring, Bracknell, Berkshire, RG12 1HB, United Kingdom – Tel: +44 118 974 0440, Fax: +44 118 979 8554 – E- mail: [email protected]
Mr Chris Doyle, American Leprosy Missions, 1 ALM Way, Greenville SC 29601, United States of America – E-mail: [email protected]
Dr Clare Dykewicz, Meningitis and Special Pathogens Branch, DBMD/NCID, Centers for Disease Control and Prevention, 1600 Clifton Rd., NE Mail stop C09, Atlanta, GA 30333, United States of America – Tel: +1 404 639 4138, Fax: +1 404 639 0070 – E-mail: [email protected]
Dr Samuel Etuaful, St. Martin’s Catholic Hospital, Agroyesum, P.O. Box K.S. 8298, Kumasi, Ghana – Tel: +233 27 555445/24 3 510116, Fax:33 21 32 603 – E-mail: [email protected]
125 Dr Sara Eyangoh, Laboratoire Des Mycobactéries, Centre Pasteur du Cameroun, BP 1274 Yaoundé, Cameroon – Tel: +237 2 23 18 03, Fax: +237 2 23 15 64 – E-mail: [email protected]; [email protected]
Prof. Bernhard Fleischer, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, 20359 Hamburg, Germany – Tel: +49 40 4 28 18 401, Fax: +49 40 4 28 18 400 – E-mail: fleischer@bni- hamburg.de
Mr Kazuyuki Fukunishi, 8-216 Yoshida Kaguraoka-cho, Sakyo-ku, Kyoto 606-8311, Japan – E-mail: easternroad [email protected]
Dr Antonio Galoforo, vicolo San Giuseppe, 10, c.a.p. 25123, Brescia, Italy
Alain Gaulier, Centre Hospitalier d'Argenteuil, 69 rue Proudhon, 95107 Argenteuil cedex, France – Tel: +331 34 23 17 59 (ou 18 63) – E-mail: [email protected]
Mrs Christine Gilbert, La Tuilerie, 85120 La Tardière, France
Dr José Ramón Gómez Echevarría, Director Médico Sanatorio de Fontilles, 03791 Vall de Laguar, Fontilles, Alicante, Spain – Tel: +96 558 33 50 – E-mail: [email protected]
Prof. Masamichi Goto, Department of Human Pathology, Field of Oncology Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan – Tel: +81 99 275 5270, Fax: +81 99 265 7235 – E-mail: [email protected]
Prof. Jacques Grosset, Center for Tuberculosis Research, Johns Hopkins University School of Medicine, 424 N. Bond Street, Baltimore, MD 21231-1001, United States of America – Tel. +1 410 955 3507, Fax: + 1 410 614 8173 – E-mail: [email protected]
Dr Augustin Guédénon, Association Française Raoul Follereau, 31 rue de Dantzig BP 79, 75722 Paris Cedex 15, France – Tel: +331 53 68 98 98, Fax: +331 485 6 22 22 – E-mail: [email protected]
Dr Richard Hehl, Aide aux Lépreux Emmaüs-Suisse, Case postale 5252, 3001 Berne, Switzerland – Tel: +41 31 311 77 97, Fax: +41 31 318 08 41 – E-mail: [email protected]
Mr Jacques Herdener, Service d'Entraide Médicale, Missionnaire SEMM, Rue J.J 2 Sellon, 1202 Genève, Switzerland
Ms Ainhoa Ibarguren, Anesvad, Teófilo Guiard 2, 48001 Bilbao, Spain – Tel: +34 94 441 80 08, Fax: 34 94 441 07 39 – E-mail: [email protected]
Dr Herwig Jansen, Internal Medicine, 30 Witte Bremlaan, 2360 Oud-Turnhout, Belgium/Belgique – Tel: 32 475 42 29 20, Fax: +32 14 45 00 86 – E-mail: [email protected]
Dr Baohong Ji, Association Française Raoul Follereau, 31 rue de Dantzig BP 79, 75722 Paris Cedex 15, France – Tel: +331 53 68 98 98, Fax: +331 485 6 22 22 – E-mail: [email protected]
Dr Christian Johnson, Programme National de Lutte contre l’Ulcère de Buruli, Ministère de la Santé Publique, 06 BP 2572, Cotonou, Benin – Tel: +229 33 1827, Fax: +229 33 7057 – E-mail: [email protected]
Dr Paul Johnson, Infectious Diseases Department, Austin Health, Heidelberg 3084, Melbourne, Australia – Tel: +613 9496 6678, Fax: +613 9496 6677 – E-mail: [email protected]
Sister Joseph, Wewak General Hospital, Private Bag, Wewak, East Sepin Province, Papua New Guinea – Tel: +675 856 2166/1219, Fax: +675 856 27670 – E-mail:[email protected]
Dr Christophe Kafando, 07 BP 5325, Ouagadougou 07, Burkina Faso – Tel: +223 30 87 90
126 Prof. Alphonse Kouamé Kadio, Centre d'entomologie médicale et vétérinaire (CEMV), Université de Bouaké, Abidjan, Côte d'Ivoire – Tel: +225 07 71 24 58, +225 22 41 43 51, Fax: +225 22 42 47 78 – E-mail: [email protected]
Prof. Jean-Marie Kanga, Centre de Dermatologie, CHU de Treichville, 18 BP 2890, Abidjan 18, Côte d'Ivoire – Tel: +225 21 24 28 62, Fax: +225 21 24 15 55 – E-mail: [email protected]
Mr David Karashima, International Program Department, The Nippon Foundation, 1-2-2 Akasaka, Minato-ku, Tokyo 107-8404, Japan – Tel. +81 3 6229 5181, Fax: +81 3 6229 5180 – E-mail: [email protected]
Dr Yves Kean, ONG PCE-CI, 08 BP 88, Cidex 02, Abidjan 08, Côte d’Ivoire – Tel/Fax: +225 22 48 91 84
Dr Anatole Kibadi Kapay, Programme National de Lutte contre l’ulcère de Buruli, c/o Monsieur le Représentant de l’OMS, Kinshasa, Boîte postale 1899, Kinshasa I, Democratic Republic of the Congo – Tel: +243 89 73 293 – E-mail: [email protected]
Mr Ryan Kimbirauskas, Department of Entomology, 243 Natural Science Bldg., Michigan State University, East Lansing, MI 48824, United States of America – Tel: +1 517 355 8309, Fax: +1 517 353 4354 – E-mail: [email protected]
Prof. Henry-Valère Kiniffo, Association Raoul Follereau du Benin, 08BP.121 TP, Cotonou, Benin – Tel: +229 30 13 50, Fax: +229 30 95 74 – E-mail: [email protected]
Mrs Odile Kiniffo, c/o Association Raoul Follereau du Benin, 08BP.121 TP, Cotonou, Benin – Tel: +229 30 13 50, Fax: +229 30 95 74 – E-mail: [email protected]
Mr Aubin Koffi Yao, MAP Côte d'Ivoire, 01 B.P. 1658, Abidjan 01, Côte d'Ivoire – Tel: +225 22 471- 383/471-382, Fax: +225 22 47 38 08 – E-mail: [email protected]
Mr Robert Kohll, Fondation Luxembourgeoise Raoul Follereau, 151, avenue du 10 Septembre, 2551 Luxembourg, Luxembourg – Tel: +352 44 66 06 1, Fax: 352 45 96 53 – E-mail: [email protected]
Mr Samuel Kouassi Kouakou, ONG PCE-CI, 08 BP 88, Cidex 02, Abidjan 08, Côte d'Ivoire – Tel/Fax: +225 22 48 91 84 – E-mail: [email protected]
Dr Kanga Kouamé, Centre de Dermatologie du CHU de Treichville Abidjan, 08 BP 88, Cidex 02, Abidjan 08, Côte d'Ivoire – E-mail: [email protected]
Dr Ferdinand Lali, Faculty of Science, Department of Biochemistry, Makerere University, PO Box 7062, Kampala, Uganda – +256-78-380999 (Direct Mobile), +256-41-530555/6 (Dept. Secretary) – E-mail: [email protected]
Ms Muriel Laterali, Ecluse 72, 2000 Neuchâtel, Switzerland – Tel: +41 32 721 20 67 – E-mail: [email protected]
Ms Linda F. Lehman, American Leprosy Missions, Dom Prudencio Gomes 675 Apt 202, CEP 30535- 580 Belo Horizonte, Minas Gerais, Brasil –Tel: +55 31 3375 8057 (Cell: +55 31 9637-5576), Fax: +1 720 293 2512 – E-mail: [email protected]
Mr Fabrizio Leigheb, Novara, Italy
Prof. Giorgio Leigheb, University of Eastern Piedmont "A. Avogadro"- Dermatologic Clinic of Novara, Ospedale Maggiore della Carità, Corso Mazzini 18, 28100 Novara, Italy – Tel: +39 0321 3733269, Fax: +39 0321 3733586 – E-mail: [email protected]
Dr Yatta Lori Luggor, Yambio Hospital, Southern Sudan, P.O. Box 1488 Eldoret, Kenya –Tel: +254 0722333072 – E-mail: [email protected]
127 Ms Verónica Malda, ANESVAD, Henao 29, 48009 Bilbao, Spain – Tel: 34 94 441 80 08, Fax: 34 94 441 07 39 – E-mail: [email protected]
Mr Curt Malloy, Infectious Disease Research Institute, 1124 Columbia Street, Suite 600, Seattle, Washington 98104, United States of America – Tel: +1 206 381 0883, Fax: + 1 206 381 3678 – E-mail: [email protected]
Dr Nina Marano, Centers for Disease Control and Prevention, National Center for Infectious Diseases, Meningitis and Special Pathogens Branch, Division of Bacterial and Mycotic Diseases, 1600 Clifton Rd, N.E. (MS C09), Atlanta, GA 30333, United States of America/Etats-Unis d'Amérique – Tel: +1 404 639 3831, Fax: +1 404 639 3039 – E-mail: [email protected]
Père Marco, Frères Capucins, 06 BP 2546, Abidjan 06, Côte d’Ivoire – Tel: +225 22 50 27 30 – E-mail: [email protected]
Dr Laurent Marsollier, Institut Pasteur, 28, rue du Docteur Roux, 75724 Paris, France – Tel: +331 40 61 37 19, Fax: +331 40 61 35 83 – E-mail: [email protected]
Dr Herbert Matzinger, Seitweg 24, 3400 Klosterneuburg, Austria – E-mail: [email protected]
Dr Patrick Meredith, Fondation Meredith, pour le développement de la chirurgie reconstructive et réparatrice en Afrique de l’Ouest, La Bassire, 1267 Vich, Switzerland – Tel: +41 22 362 2766, Fax: +41 22 362 3447 – E-mail: [email protected]
Mrs Valérie Meredith, Fondation Meredith, La Bassire, 1267 Vich, Switzerland – Tel: +41 22 3644640 – E-mail: [email protected]
Prof. Richard W. Merritt, Department of Entomology, 243 Natural Science Bldg., Michigan State University, East Lansing, MI 48824, United States of America/Etats-Unis d'Amérique – Tel: +1 517 355 8309, Fax: +1 517 353 4354 – E-mail: [email protected]
Mr Abanda Meva'a, Médecins Sans Frontières, Quartier Mballa2, Yaoundé, BP 12069, Cameroun – Tel./Fax: +237 220 90 29
Dr Wayne M. Meyers, Department of Environmental and Infectious Disease Sciences, Armed Forces Institute of Pathology, Washington DC 20306-6000, United States of America – Tel: +1 202 782 1873, Fax +1 202 782 7161 – E-mail: [email protected]
Mr Andrew Morpeth, Pro-Tex Capillary Dressings Limited, 319 Asmec Centre, Eagle House, The Ring, Bracknell, Berkshire, RG12 1HB, United Kingdom – Tel: +44 118 974 0440, Fax: +44 118 979 8554 – E- mail: [email protected]
Mr Peter Morrow, Pro-Tex Capillary Dressings Limited, 319 Asmec Centre, Eagle House, The Ring, Bracknell, Berkshire, RG12 1HB, United Kingdom – Tel: +44 118 974 0440, Fax: +44 118 979 8554 – E- mail: [email protected]
Ms Annelies Mulder, Department of Internal Medicine, Groningen University Medical Centre, PO Box 30001 9700 RB, Groningen, The Netherlands – E-mail: [email protected]
Prof. Claude P. Muller, Laboratoire national de santé du Luxembourg, P.O. Box 1102, L - 1011 Luxembourg – Tel: +352 49 06 04, Fax: +352 49 06 86 – E-mail: [email protected]
Mr Roland Müller, Aide aux Lépreux Emmaüs-Suisse, Case postale 5252, 3001 Berne, Switzerland – Tel: +41 31 311 77 97, Fax: 41 31 318 0841 – E-mail: [email protected]
Dr Gerald Mumma, Mailbox # E-90, PEFP/CDD/OWCD, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, United States of America – Tel: +1 404 498 6296, Fax: +1 404 498 6145 – E-mail: [email protected]
128 Dr Armand Mve-Obiang, Immunologie mycobactérienne, Institut Pasteur de Bruxelles, Rue Engeland 642, 1180-Bruxelles, Belgium – Tel: +32 02 373 3365, Fax: +32 02 373 3367 – E-mail: [email protected]
Dr François Ngos, Médecins Sans Frontières, Quartier Mballa2, Yaoundé, BP 12069, Cameroun – Tel./Fax: +237 220 90 29 – E-mail: [email protected]
Ms Willemien A. Nienhuis, Parcours 4, 9285 SC Buitenpost, The Netherlands – Tel: +31 511542324/+31 646157449 – E-mail: [email protected]
Dr Joerg Nitschke, Kaulbachstr 28, 22607 Hamburg, Germany/Allemagne – Tel.: +49 40 89709958 (Mobile: +49 0171 4735837), Fax: +49 40 89709959 – E-mail: [email protected]
Dr Akpedze Nomenyo, Programme national de Lutte contre l'ulcère de Buruli, Ministère de la Santé, Direction des soins de santé primaires, Service des maladies transmissibles, Lomé, Togo – Tel: 228 251 59 59 (mobile:228 914 41 90) – E-mail: [email protected]
Dr Charles Nsom Mba, Programme national de Lutte contre Ulcère de Buruli, Direction de la Lutte contre la Maladie, Ministère de la Santé Publique, Cameroun – Tel: +237 223 93 48, Fax: +237 222 44 19 – E-mail: [email protected]
Dr Kofi Mensah Nyarko, Tepa District Hospital, P.O.Box 80, Tepa Ashanti, Ghana – Tel: +233 244 698209 – E-mail: [email protected]
Dr Michelle Obono,E-mail: [email protected]
Dr Damas Obvala, Programme national de lutte contre l’ulcère de Buruli, Ministère de la Santé, c/o Monsieur le Représentant de l’OMS, Boîte postale 2465, Brazzaville, Congo – Tel: +242 20 21 64, Fax: +242 94 17 26 – E-mail: [email protected]
Mr Jaiyesimi Oludotun Olusegun, Eye Foundation Hospital, 27B, Isaac John Street, G.R.A., Ikeja, Lagos, Nigeria – Tel: +234 1 4938141 (Mobile: +234 1 8028596641) – Fax: +234 1 4971015 – E-mail: [email protected]
Dr Elena Pagano, Médecins Sans Frontières, Quartier Mballa2, Yaoundé, BP 12069, Cameroun – Tel./Fax: +237 220 90 29 – E-mail: [email protected] ; [email protected]
Dr Claudio Paparo, via Ospedale, 4, c.a.p. 20010, Inveruno (Mi) Italy/Italia – Tel. +39 2 97289084, Fax +39 2 97289147 – E-mail: [email protected]
Dr Richard Phillips, Division of Infectious Disease, St George’s Hospital Medical School, Cranmer Terrace, London SW17 0RE – United Kingdom – Tel: 44 208 725 5827, Fax: 44 208 725 3487 – E-mail: [email protected]
Dr Brigitte Pittet-Cuenod, Service de Chirurgie plastique et reconstructrice, Université de Genève – Tel: +41223727997 – E-mail: [email protected]
Prof. Gerd Pluschke, Department of Molecular Immunology, Swiss Tropical Institute, 4002 Basel, Switzerland – Tel: + 41 61 284 8235, Fax: +41 61 271 8654 – E-mail: [email protected]
Dr Franco Poggio, Rotary International, Rotary Club Milano Aquileia, Distretto 2040, Piazza Velasca, 5, 20122 Milano, Italy – Tel: +39 02 80 40 16, Fax: +39 02 72 022 844 – E-mail: [email protected]
Dr Gian Battista Priuli, Hôpital St Jean de Dieu, B. P. 7 Tanguieta, Bénin – Tel: +229 83 0011 (Satellite: +871 76 24 68 340), Fax: +229 83 0010 (Satellite: +871 76 24 68341) – E-mail: [email protected]
Dr Enrico Pupulin, 648, Rue De Maupassant, 01220 Divonne les Bains, France – E mail: [email protected]
129 Mr Jehan-Michel Rondot, Association Française Raoul Follereau, 31 rue de Dantzig BP 79, 75722 Paris Cedex 15, France – Tel: +331 53 68 98 98, Fax: +331 485 6 22 22 – E-mail: direction-aide@raoul- follereau.org
Mr Roberto Rosti, Via Roma 114 - 20096 Pioltello (Milano), Italy – E-mail: [email protected]
Dr Paul Saunderson, American Leprosy Missions, 1 ALM Way, Greenville SC 29601, United States of America – Tel: +1 864 241-1750, Fax: +1 864 271-7062 – E-mail: [email protected]
Prof. Yuki Shimomura, Kobe International University, 9-1-6 Koyocho-naka, Higashinada-ku, Kobe 658-0032, Japan – Tel: +81 78 845 3410, Fax: +81 72 664 6149 – E-mail: [email protected]
Ms Vera Siegmund, Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Strasse 74, 20359 Hamburg, Germany – Tel: +49 40 4 28 18 467, Fax: +49 40 4 28 18 400 – E-mail: siegmund@bni- hamburg.de
Ms Valérie Simonet, Aide aux Lépreux Emmaüs-Suisse, Case Postale 5252, 3001 Berne, Suisse/Switzerland – Tel: +41 31 311 77 97, Fax: +41 31 318 08 41 – E-mail: [email protected]
Dr Jackie Singa Nyota, Programme national de lutte contre l’ulcère de Buruli, c/o Monsieur le Représentant de l’OMS, Kinshasa, Boîte postale 1899, Kinshasa I, Democratic Republic of the Congo – Tel: +43 880 26 61 – E-mail: [email protected]
Dr Vinciane Sizaire, Médecins Sans Frontières, 67-74 Saffron Hill, London EC1N 8QX, United Kingdom – Tel: +44 20 7404 6600 – E-mail: [email protected]
Prof. Pamela L. Small, Department of Microbiology, 409 Walters Life Sciences, University of Tennessee, Knoxville, TN 37996-0845, United States of America – Tel: 865 74 4042, Fax: +865 974 4007 – E-mail: [email protected]/[email protected]
Dr Jérôme Son, Programme national de lutte contre les ulcères à mycobactéries, Programme national de lutte contre les ulcères à Mycobactéries, 22 BP 1701, Abidjan 22, Côte d'Ivoire – Tel: +225 20 22 00 10, Fax: +225 20 22 43 47 – E mail: [email protected]
Dr Ghislain Sopoh, Centre de Dépistage et de Traitement de l'ulcère de Buruli d'Allada, 01 BP 875, Cotonou, Bénin/Benin - Tel: +229 37 13 75 (Cell: +229 90 33 79), Fax: +229 37 13 76 – E-mail: [email protected]
Prof. Sambou Soumaré, Chirurgie «A», Hôpital du Point G, B.P. 333, Bamako, Mali – Tel: +223 223 37 11 – E-mail: [email protected]
Mr René Stäheli, Aide aux Lépreux Emmaüs-Suisse, Case postale 5252, 3001 Berne, Switzerland – Tel: +41 31 311 77 97, Fax: 41 31 318 0841 – E-mail: [email protected]
Dr Tim Stinear, Department of Microbiology, Monash University, Wellington Rd Clayton, VIC 3800, Australia – Tel: +61 3 99054809, Fax: +61 3 99054811 – E-mail: [email protected]
Mr Patrick Suykerbuyck, c/o Department of Microbiology, Institute of Tropical Medicine, Nationalestraat 155, 2000, Antwerp, Belgium – E-mail: [email protected]
Dr Audrey Tanghe, Immunologie mycobactérienne, Institut Pasteur de Bruxelles, Rue Engeland 642, 1180 Bruxelles, Belgium – Tel: +32 2 373 33 65 – E-mail: [email protected]
Dr Alphonse Um Boock, Aide aux Lépreux Emmaüs-Suisse, Regional Office for Africa, BP 5807, Yaoundé, Cameroon – Tel: +237 222 2378, Fax: +237 222 0563 – E-mail: [email protected]
Dr Tjip van der Werf, Department of Internal Medicine, Groningen University Medical Centre, PO Box 30001 9700 RB, Groningen, The Netherlands – Tel: +31 50 3611501 (pager 55255), Fax: +31 50 3613216 – E-mail: [email protected]
130 Prof. Henry Wabinga, Department of Pathology, Faculty of Medicine, Makerere University, Kampala, Uganda – Tel: +256 41 53 17 30 / 077 64 99 13, Fax: +256 41 53 04 12 – E-mail: [email protected]
Dr Maurice Waldburger, Clinique de rhumatologie, Service de médecine physique et rééducation, Hôpital cantonal, 1708 Fribourg, Switzerland – Tel.: +41 26 426 73 90 – E-mail: [email protected]
Dr S. Douglas Walsh, Department of Clinical Investigation, Eisenhower Army Medical Center, Ft. Gordon, Georgia 30905, United States of America – Tel: +1 706 787 3944 (Dermatology), +1 706 787 4273 (Dept of Clinical Investigation), Cell: +1 706 830 2485, Fax: +1 706 787 1354 – E-mail: [email protected]
Dr Mark Wansbrough-Jones, Division of Infectious Disease, St George’s Hospital Medical School, Cranmer Terrace, London SW17 0RE, United Kingdom – Tel: +44 208 725 5827, Fax: +44 208 725 3487 – E-mail: [email protected]
Ms Heather Williamson, Department of Microbiology, 409 Walters Life Sciences, University of Tennessee, Knoxville, TN 37996-0845, United States of America – Tel: +865 974 4042, Fax: +865 974 4007 – E-mail: [email protected]
Mr Atsushi Yagi, Flat 2, 3 Bridge Street, Aberystwyth, SY23 1PY, United Kingdom – Tel: +44 7980 89 7166 – E-mail: [email protected]
Dr Jérémie Koffi Yao, Centre de Dermatologie, CHU de Treichville, 18 BP 2890, Abidjan 18, Côte d'Ivoire – Tel: +225 21 24 28 62, Fax: +225 21 24 15 55 – E-mail: [email protected]
Dr Remy Zilliox, Interplast-France, 1, Rue Laborde, 69500 Bron, France – Tel: +33 78 75 21 62 – E-mail: [email protected]
WHO/OMS
Dr Abdullahi Ahmed, WHO South Sudan Office, P.O. Box 63565, UN Avenue, Gigiri, Nairobi, Kenya – Tel: +254 20 622 382/622843, Fax: +254 20 623 640 – E-mail: [email protected]
Dr Anarfi Asamoa-Baah, Communicable Diseases, World Health Organization, 20, avenue Appia, 1211 Genève 27, Switzerland – Tel: +41 22 791 2214, Fax: +41 22 791 4752 – E-mail: [email protected]
Dr Kingsley Asiedu, Global Buruli Ulcer Initiative, Communicable Diseases Control, Prevention & Eradication, 20, avenue Appia, 1211 Genève 27, Switzerland – Tel: +41 22 791 2803/2498, Fax: +41 22 791 4777 – E-mail: [email protected]
Dr Meena Nathan Cherian, Clinical Procedures, Department Essential Health Technologies, Health Technology and Pharmaceuticals, World Health Organisation 20, avenue Appia CH 1211,Geneva 27, Switzerland – Tel: +41 22 791 4011, Fax: +41 22 791 1385 – E-mail: [email protected]
Dr Hiroyoshi Endo, Communicable Diseases Control, Prevention & Eradication, 20, avenue Appia, 1211 Genève 27, Switerland – Tel: +41 22 791 2853, Fax: +41 22 791 4777 – E-mail: [email protected]
Mr Chapal Khashnabis, Disability and Rehabilitation, Non Communicable Diseases, World Health Organization 20, avenue Appia CH 1211,Geneva 27, Switzerland – Tel: +41 22 791 2977, Fax: +41 22 791 4874 – E-mail: [email protected]
Dr Federico Montero, Disability and Rehabilitation, Non Communicable Diseases,
131 World Health Organization 20, avenue Appia CH 1211,Geneva 27, Switzerland – Tel: +41 22 791 2977 Fax: +41 22 791 4874 – E-mail: [email protected]
Dr Luc Noël, Clinical Procedures, Department Essential Health Technologies, Health Technology and Pharmaceuticals, World Health Organisation 20, avenue Appia CH 1211,Geneva 27, Switzerland – Tel:+41 22 791 3681, Fax: +41 22 791 1385 – E-mail: [email protected]
Ms Claire Préaud, HealthMap, GIS, Communicable Disease Surveillance and Response, Communicable Diseases Control, Prevention & Eradication, 20, avenue Appia, 1211 Genève 27, Switerland – Tel: +41 22 791 1620,– E-mail: [email protected]
Dr Ireneaus Sindani, WHO South Sudan Office, P.O. Box 63565, UN Avenue, Gigiri, Nairobi, Kenya – Tel: +254 20 622 382/622843, Fax: +254 20 623 640 – E-mail: [email protected]
Dr Alexandre Tiendrebeogo, WHO Regional Office for Africa, Harare, Zimbabwe – E-mail: [email protected]
Dr Nevio Zagaria, Strategy Development & Monitoring for Eradication & Elimination (CEE), Communicable Diseases Control, Prevention & Eradication, 20, avenue Appia, 1211 Genève 27, Switzerland – Tel: +41 22 791 12534/14743, Fax: +41 22 791 4777 – E-mail: [email protected]
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