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Received: 8 April 2021ꢀ ꢀRevised: 1 June 2021ꢀ ꢀAccepted: 10 June 2021

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DOI: 10.1111/myc.13339

R E V I E W A R T I C L E

Serious fungal diseases in Democratic Republic of Congo – Incidence and prevalence estimates

Guyguy K. Kamwiziku1 ꢀ| Jean-Claude C. Makangara1 ꢀ| Emma Orefuwa2ꢀ| David W. Denning2,3

1Department of Microbiology, Kinshasa

Abstract

University Hospital, University of Kinshasa, Kinshasa, Democratic Republic

A literature review was conducted to assess the burden of serious fungal infections

of Congo

in the Democratic Republic of the Congo (DRC) (population 95,326,000). English and French publications were listed and analysed using PubMed/Medline, Google Scholar

and the African Journals database. Publication dates spanning 1943–2020 were in-

cluded in the scope of the review. From the analysis of published articles, we estimate a total of about 5,177,000 people (5.4%) suffer from serious fungal infections in the DRC annually. The incidence of cryptococcal meningitis, Pneumocystis jirovecii pneumonia in adults and invasive aspergillosis in AIDS patients was estimated at 6168, 2800 and 380 cases per year. Oral and oesophageal candidiasis represent 50,470 and 28,800 HIV-infected patients respectively. Chronic pulmonary aspergillosis posttuberculosis incidence and prevalence was estimated to be 54,700. Fungal asthma (allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization) probably has a prevalence of 88,800 and 117,200. The estimated prevalence of recurrent vulvovaginal candidiasis and tinea capitis is 1,202,640 and 3,551,900 respectively.Further work is required to provide additional studies on opportunistic infections for improving diagnosis and the implementation of a national surveillance programme of fungal disease in the DRC.

2Global Action Fund for Fungal Infections, Geneva, Switzerland

3Manchester Fungal Infection Group, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK

Correspondence

Guyguy K. Kamwiziku, Department of Microbiology, Kinshasa University Hospital, University of Kinshasa, Congo. Email: [email protected]

K E Y W O R D S

aspergillosis, candidiasis, cryptococcosis, fungal infection, HIV/AIDS, Pneumocystis, tinea capitis, Tuberculosis

1ꢀ |ꢀ INTRODUCTION

tertiary care provision responsibility. The provincial level provides technical supervision, monitoring and translation of directives and
With a surface area of 2,345,000 km², DRC is the second largest country in Africa after Algeria. It has a population of around 95,326,000 inhabitants of which more than 60% live in rural areas.1,2 The DRC shares 9,165 kilometres of border with 9 countries (Figure 1).3 The country is currently ranks 176 out of 189 countries on the Human Development Index. In 2019, GDP per capita $545, a 2.13% decline from 2018.4 With regards to health system architecture, the Ministry of Public Health is structured in the form of a 3-level pyramid. The national level has normative, regulatory and offers secondary reference health care. The operational level includes 516 Health Zones (HZ) with 393 General Reference Hospitals and 8,504 planned Health Areas (HA) of which 8,266 have a Health Centre. The function of this level is to implement the primary health care strategy. At this level, there are 2004 health centres for the detection and treatment of tuberculosis (CSDT) and 4,587 sites for the detection and treatment of HIV (SDT). In 2019, the DRC integrated 1752 existing CSDTs into the management of HIV-TB co-infection. A HZ is a geographically limited space covering a theoretical

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Mycoses. 2021;00:1–11.

wileyonlinelibrary.com/journal/myc

© 2021 Wiley-VCH GmbH. ꢀ ꢀ1
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KAMWIZIKU et Al.

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population of 100,000 to 150,000 inhabitants with a general reference hospital (GRH). The health system also integrates private for-profit and not-for-profit sector health facilities (health services of non-governmental organisations and faith-based organisations). The majority of GRHs lack intensive care, laboratory services (with parasitology, biochemistry, bacteriology and haematology services) and imaging X-ray, ultrasound, electrocardiogram, non stress test, Optical coherent tomography, etc). In the same way, the three University Clinics are under-equipped to serve as tertiary reference facilities. The DRC has 29 pharmaceutical industry companies, and wholesale supply and distribution is provided by 150 authorised establishments.5,6 There is an imbalance in the organisation of training courses and in the equitable distribution of health workers between rural and urban areas and between health structures. Health staff are concentrated in the capital Kinshasa and in the urban centres of the provinces. Health workforce indicators are low, using the benchmark ratio of 1 doctor per 10,000 inhabitants, only three out of ten provinces have staff numbers that meet or exceed international standards.3 Communicable diseases with epidemic potential are an ongoing issue in the DRC.3,4 The Director General for Disease Control has placed certain infectious diseases under epidemiological surveillance, including acute flaccid paralysis, cholera, leprosy, neonatal tetanus, plague, viral haemorrhagic fever, yellow fever, monkey-pox, measles, avian flu, bloody and simple diarrhoea, meningitis, malaria, typhus, pertussis, typhoid fever, acute respiratory infections, sexually transmitted infections, several neglected tropical diseases (NTDs), AIDS and tuberculosis (TB). Despite their known association with co-infections such as HIV and TB, fungal diseases are a glaring omission from the priority list of infectious diseases being surveilled. DRC is in a phase of epidemiological transition, characterised by an

FI G U R E 1ꢀMap of the Democratic

Republic of Congo with the neighbouring countries

FI G U R E 2ꢀlocalisation of main

institutions publishing articles in Democratic Republic of Congo

KAMWIZIKU et Al.

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increase in the incidence of non-communicable diseases such as cancer and diabetes which heighten the need to address fungal infections as a public health issue of growing significance. information from multiple sources, all described in Table 2. The assumptions used to compute annual incidence or prevalence are also shown.
There is no surveillance programme for fungal diseases in the
DRC.6 Given the poor availability and accessibility of diagnostics in the DRC, fungal infections unfortunately remain grossly underestimated. Despite the paucity of data, some studies have been conducted in DRC which allow for baseline modelling to be carried out. The aim of this literature review is to take stock of the current incidence and prevalence of fungal infections in DRC.

3ꢀ |ꢀ RESULTS 3.1ꢀ |ꢀ Country's profile

In the DRC, endemic diseases have a high mortality: malaria is the leading cause of death with a prevalence of 23%. HIV/AIDS and TB are also common. The DRC is among 30 countries with the highest burden of TB ranking 11th in the world and 3rd in Africa. It is also one of 13 countries facing the dual challenge of HIV-TB co-infection and drug resistance at the same time.3,14 Although HIV prevalence is declining in the DRC, at 0.8%, its epidemiology is complex. It is higher among women in some provinces and four times higher in urban areas. Apart from HIV and TB co-infection, which are well supported and documented, the prevalence and incidence of other opportunistic infections is not known due to the lack of any diagnostic capability in most health facilities.

2ꢀ |ꢀ MATERIALS AND METHODS

This literature review was based on articles about fungal infections using the Google Scholar and PubMed/Medline search engines, African newspapers, health reports, epidemiological journals in DRC and WHO reports (Figure 2). The articles searched were mostly in English. The keywords searched were: fungal infection, opportunistic disease, HIV/AIDS, tuberculosis, chronic pulmonary, cryptococcosis, histoplasma, all associated with DRC. The oldest article retrieved was from 1943 and the most recent was from 2020. There are few studies on fungal diseases in the DRC and many of them are more than a decade old so we extended our searches to studies in border countries that have already estimated the burden of some fungal infections. We first considered Central African Countries and then, other sub-Saharan African countries. The countries chosen were those that are close to the four major universities in the DRC that use published articles. Where no article was found from the DRC or neighbouring countries, we used data from other countries within Africa and if this was not available, then data from other countries outside the African region. The socio-demographic data were taken from the National Health Development Plan 2016-2020 reports and the 2017 reports of the National Statistics Institute (Table 1). The HIV prevalence and deaths were taken from the 2019 UNAIDS report. To evaluate the incidence of children and adults at risk of developing the OIs, we have assessed different factors impacting on OI incidence in the literature.7 Considering that people living with HIV infection (PLWHIV) who are not on ART generally develop profound immunodeficiency over 7 years for adults and 5 years for children and that the rate failure of ART is 11%, we estimated the population of PLWHIV at risk.8 TB rates were taken from the WHO Global report 2019, and we derived the pulmonary TB survivors. Asthma prevalence in adults living in Kinshasa was assumed to apply to the

3.2ꢀ |ꢀ Review of serious fungal infections

The scarcity of articles on fungal infections has prompted us to use prevalence or incidence from other countries to estimate the burden in the DRC. The summary shown in Table 2 and 3 is derived from the various populations at risk and the rate per 100,000 inhabitants. Each year in DRCongo approximately 5,079,278 people are affected by fungal diseases, 5.32% of the whole population.

3.2.1ꢀ |ꢀ Fungal skin infections: Tinea capitis and

neglected tropical diseases

In children, tinea capitis is the most common superficial fungal infection. Our estimation is 3,551,862 children have tinea capitis, a rate of 3,726 per 100,000. An old study (1959) gave a disparate prevalence of tinea capitis by region, the lowest prevalence was 2.9% in the middle part of the DRC and the high was 20% in the East part.42,43 No recent study is published, but it is a common problem. Neglected tropical skin fungal diseases have not been reported recently. An old study from the Belgian Congo (currently DRC) found 9 cases of my-

cetoma in 1954.44 A strain of Catenulostroma chromoblastomycosum

is deposited with the information that it is from a case of chromoblastomycosis from Zaire (currently DRC).45 Sporothrix schenckii is a ubiquitous fungus, causing mostly non-life-threatening localised infections of the skin and subcutaneous tissues - only one case is reported from DRC in an HIV patient.46 No data was found for basidi-

obolomycosis, chromoblastomycosis, rhinoporidioisis or Conidiobolus or

Emergomyces infections. They are probably rare. whole country.9 Chronic obstructive pulmonary disease (COPD)

10

  • prevalence was taken from the Cameroon
  • and it was assumed

that 10.5% were admitted to hospital each year, as in Algeria.11 Lung

12

cancer was taken from Global cancer observatory (Globocan) and acute myeloid leukaemia from the WHO expert committee.13 No stem cell or organ transplantation procedures are done in the DRC. We used the various populations and denominators and estimated prevalence or incidence of different fungal diseases using

4ꢀ ꢀꢀꢁ

KAMWIZIKU et Al.

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TA B L E 1ꢀThe basic demographics of

the country

  • Data
  • Number
  • Reference
  • Comments

2

  • Population
  • 95 326 400

520 000 233 520 3 551 860 380
2019

15 16
2

  • HIV infection
  • Prevalence 2019

Annual incidence 2019 With 2019 population Annual incidence
Pulmonary tuberculosis Asthma numbers in adults Acute myeloid leukaemia

17

Abbreviation: HIV, Human Immunodeficiency Virus.

TA B L E 2ꢀAssumptions underlying the assessment of serious fungal diseases burden

  • Fungal disease
  • Underlying condition
  • Assumptions made
  • References

18

  • Cryptococcal meningitis
  • HIV/AIDS

HIV/AIDS
12.2% of AIDS patients

19

Pneumocystis pneumonia

10% PCP as newly diagnosed HIV/AIDS adults over 2 years

20,21 22-26

Disseminated histoplasmosis Invasive aspergillosis

  • HIV/AIDS
  • 1.5% of advanced HIV disease

  • HIV/AIDS; COPD; Leukaemia; lung cancer
  • 10% of AML patients develop IA. Rate

in non-AML same as in AML. 1.3% of admitted COPD patients, 2.6% of lung cancer patients and 4 per 1000 HIV/ AIDS patients develop IA

27-29

  • Chronic pulmonary aspergillosis (CPA)
  • Tuberculosis, COPD
  • 22% of TB survivors with cavities, 2% of

those without cavities and assumed pulmonary TB is the underlying diagnosis in 80% of all CPA cases

30 31

Allergic Broncho pulmonary aspergillosis Asthma
(ABPA)
2.5% of adult asthmatics

32

Severe asthma with fungal sensitisation
(SAFS)

  • Severe asthma
  • 33% of worst 10% of adult asthmatics.

33

  • Candidaemia
  • 5/100,000 (mean of 2-11/100,000) with

30% in ICU (critical care and postsurgical patients) and 70% in cancer and other immunocompromised patients

34

Candida peritonitis

  • Pancreatitis, major abdominal surgery
  • 1 patient with hospital-acquired (almost

all post-operative) Candida peritonitis for every 2 patients with candidaemia, in ICU

35,36 37,38

  • Oral candidiasis
  • HIV/AIDS

HIV/AIDS
90% of untreated HIV patients

  • Oesophageal candidiasis
  • 20% of patients not on ARVs and 0.5% of

those on ARVs

39 40

Recurrent candida vaginitis (≥4x/year)

6% of adult women

  • Mucormycosis
  • Affects 2 per million of the population

based on data from Europe

41

  • Tinea capitis
  • 7.38% of school-age children

Abbreviations: AML, Acute myeloid leukaemia; ARV, antiretroviral; COPD, Chronic obstructive pulmonary disease; HIV/AIDS, Human Immunodeficiency Virus/ Acquired ImmunoDeficiency Syndrome; IA, invasive aspergillosis; ICU, Intensive Care Unit; PCP, Pneumocystis pneumonia; TB, Tuberculosis.

Other data from Cameroon found 34.8% of women had vaginal can-

3.2.2ꢀ |ꢀ Candida diseases

didiasis, suggesting this problem is more frequent than in Europe and the USA, and likely to be underestimated by our estimate.47 Although blood culture is fairly widespread in DRC, there are no data on the frequency of candidaemia. Using a low average country incidence, of 5/100 000,48 we estimate ~4,770 patients annually. In France, the ratio of candidaemia to intra-abdominal candidiasis
No data on recurrent vulvovaginal candidiasis (rVVC), candidaemia and Candida peritonitis were found. The prevalence of rVVC is thought to be 2523/100 000, using a 6% proportion of women aged between 15 and 54, or to affect about 1.2 million women.39

KAMWIZIKU et Al.

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TA B L E 3ꢀEstimate of serious fungal infections in Republic Democratic of Congo

No underlying disease
Critical

  • care
  • Serious Fungal

Infection
Respiratory Cancer disease
Total

  • Burden
  • Estimate
  • HIV/AIDS
  • +immunocompromised +surgery Rate/100,000

Cryptococcal meningitis

  • I
  • –

––

  • 6168
  • –
  • –

––
–––
6.5 2.9 0.6
6168

  • Pneumocystis
  • I

I
2800 595
––
2800 595 pneumonia adult
Pneumocystis pneumonia children

  • Pneumocystis
  • I

I
––
3016 380

  • –
  • –
  • –

–
3.2 3.2
3016 3063 pneumonia total

  • Invasive
  • 2560
  • 123

aspergillosis

CPA post TB CPA post TB CPA – all

  • I
  • –

––––––––

  • –
  • 11,580
  • –

––––
–––––
12.1 38.3 57.4 93.2 123 5.0
11,580 36,500 54,700 88,800 117,200 4770
PPPPI

  • –
  • 36,500

  • –
  • 54,700

  • ABPA
  • –
  • 88,800

  • SAFS
  • –
  • 117,200

Candidaemia Candida peritonitis Oral candidiasis

  • –
  • –

–––

  • 3340
  • 1430

  • 715
  • I
  • –
  • –

––

  • 0.8
  • 715

  • I
  • 50,470

28,800
––
52.9 30.2
50,470

  • 28,800
  • Oesophageal

candidiasis
I
Recurrent Candida vaginitis (>4x/ year)

  • 1,202,640
  • –
  • –
  • –
  • –
  • 2523
  • 1,202,640

Mucormycosis Histoplasmosis Fungal keratitis Tinea capitis

  • I
  • –
  • –
  • –
  • 190
  • –

–––

  • 0.2
  • 190

  • I
  • –
  • –
  • 840
  • –

––

  • 0.9
  • 840

  • I
  • 12,680

3,551,900 4,767,220

  • –
  • –
  • 13.3

3726
12,680 3,551,900 5,177,427

  • P
  • –
  • –

  • Total burden
  • 92,229
  • 312 180
  • 3653
  • 2145

Abbreviations: ABPA, Allergic bronchopulmonary aspergillosis; CPA, Chronic pulmonary aspergillosis; I, incidence; P, prevalence; SAFS, Severe asthma with fungal sensitisation; TB, tuberculosis.

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  • Monograph on Dimorphic Fungi

    Monograph on Dimorphic Fungi A guide for classification, isolation and identification of dimorphic fungi, diseases caused by them, diagnosis and treatment By Mohamed Refai and Heidy Abo El-Yazid Department of Microbiology, Faculty of Veterinary Medicine, Cairo University 2014 1 Preface When I see the analytics made by academia.edu for the visitors to my publication has reached 244 in 46 countries in one month only, this encouraged me to continue writing documents for the benefit of scientists and students in the 5 continents. In the last year I uploaded 3 monographs, namely 1. Monograph on yeasts, Refai, M, Abou-Elyazeed, H. and El-Hariri, M. 2. Monograph on dermatophytes, Refai, M, Abou-Elyazeed, H. and El-Hariri, M. 3. Monograph on mycotoxigenic fungi and mycotoxins, Refai, M. and Hassan, A. Today I am uploading the the 4th documents in the series of monographs Monograph on dimorphic fungi, Refai, M. and Abou-Elyazeed, H. Prof. Dr. Mohamed Refai, 2.3.2014 Country 30 day views Egypt 51 2 Country 30 day views Ethiopia 22 the United States 21 Saudi Arabia 19 Iraq 19 Sudan 14 Uganda 12 India 11 Nigeria 9 Kuwait 8 the Islamic Republic of Iran 7 Brazil 7 Germany 6 Uruguay 4 the United Republic of Tanzania 4 ? 4 Libya 4 Jordan 4 Pakistan 3 the United Kingdom 3 Algeria 3 the United Arab Emirates 3 South Africa 2 Turkey 2 3 Country 30 day views the Philippines 2 the Netherlands 2 Sri Lanka 2 Lebanon 2 Trinidad and Tobago 1 Thailand 1 Sweden 1 Poland 1 Peru 1 Malaysia 1 Myanmar 1 Morocco 1 Lithuania 1 Jamaica 1 Italy 1 Hong Kong 1 Finland 1 China 1 Canada 1 Botswana 1 Belgium 1 Australia 1 Argentina 4 1.
  • Septic Arthritis Due to Histoplasma Capsulatum in a Leukaemic Patient

    Septic Arthritis Due to Histoplasma Capsulatum in a Leukaemic Patient

    Ann Rheum Dis: first published as 10.1136/ard.44.2.128 on 1 February 1985. Downloaded from Annals of the Rheumatic Diseases, 1985, 44, 128-129 Case report Septic arthritis due to Histoplasma capsulatum in a leukaemic patient PAULA G JONES,' KENNETH ROLSTON,' AND ROY L HOPFER2 From the Section of 'Infectious Diseases, Department of Internal Medicine and 2Department of Laboratory Medicine, the University of Texas M.D. Anderson Hospital and Tumor Institute at Houston, 6723 Bertner Avenue, Houston, Texas 77030, USA SUMMARY A case of septic, histoplasmal monoarthritis of the knee in a leukaemic patient is described. Ketoconazole therapy failed to eliminate the infection, but after histoplasmosis was diagnosed prolonged therapy with amphotericin B was curative. Key words: fungi, histoplasmosis, leukaemia, myeloproliferative disorders, antifungal agents. copyright. A 29-year-old man with acute myelogenous ramycin, and trimethoprim-sulphamethoxazole, the leukaemia refractory to chemotherapy was admitted patient was given amphotericin B empirically, re- to the hospital with fever, diarrhoea, and neut- sulting in prompt defervescence. A total dose of 180 ropenia on 23 September 1983. On physical ex- mg of pamphotericin B was given over five days. amination the patient's temperature was 38-5°C. His Broad-spectrum antibiotics were given for 22 days pulse was 120/min, blood pressure, 150/60 mmHg, because of the possibility of bacterial infection. http://ard.bmj.com/ and respiratory rate 18/min. He had severe mucosi- Chest roentgenograms during this period showed an tis of the oropharynx. There were no other signifi- infiltrate in the lower left lung. The patient was cant physical findings.
  • Diagnosis of Histoplasmosis

    Diagnosis of Histoplasmosis

    Brazilian Journal of Microbiology (2006) 37:1-13 ISSN 1517-8382 DIAGNOSIS OF HISTOPLASMOSIS Allan Jefferson Guimarães1,2; Joshua D. Nosanchuk2; Rosely Maria Zancopé-Oliveira1* 1Serviço de Micologia, Departamento de Micro-Imuno-Parasitologia, Instituto de Pesquisa Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil; 2Department of Medicine (Division of Infectious Diseases) & Microbiology and Imunology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York Submitted: January 31, 2006; Approved: February 13, 2006 ABSTRACT Endemic mycoses can be challenging to diagnose and accurate interpretation of laboratory data is important to ensure the most appropriate treatment for the patients. Although the definitive diagnosis of histoplasmosis (HP), one of the most frequent endemic mycoses in the world, is achieved by direct diagnosis performed by micro and/or macroscopic observation of Histoplasma capsulatum (H. capsulatum), serologic evidence of this fungal infection is important since the isolation of the etiologic agents is time-consuming and insensitive. A variety of immunoassays have been used to detect specific antibodies to H. capsulatum. The most applied technique for antibody detection is immunodiffusion with sensitivity between 70 to 100 % and specificity of 100%, depending on the clinical form. The complement fixation (CF) test, a methodology extensively used on the past, is less specific (60 to 90%). Detecting fungal antigens by immunoassays is valuable in immunocompromised individuals where such assays achieve positive predictive values of 96-98%. Most current tests in diagnostic laboratories still utilize unpurified antigenic complexes from either whole fungal cells or their culture filtrates. Emphasis has shifted, however, to clinical immunoassays using highly purified and well-characterized antigens including recombinant antigens.
  • Traveler Information

    Traveler Information

    Traveler Information QUICK LINKS Fungal Disease—TRAVELER INFORMATION • Introduction • Geographic Distribution • Risk Factors • Symptoms • Prevention • Need for Medical Assistance Traveler Information FUNGAL DISEASE INTRODUCTION Fungi are found in soil and on vegetation, as well as on many indoor surfaces and human skin. More than 1.5 million different species of fungi exist, but only several hundred are known to cause human infection. In healthy persons, fungal disease is generally asymptomatic or self-limited. However, infection can lead to significant disease, particularly in persons who are immune compromised. In travelers, important fungal infections to be aware of include coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis. These fungal diseases are acquired by the respiratory route and often affect the respiratory system. Infections occur after inhalation of spores found in dust, soil, bird/bat guano, or decaying vegetation following excavation, construction, landscaping, earthquakes, dirt bike riding, spelunking, and other activities. GEOGRAPHIC DISTRIBUTION Coccidioidomycosis, also known as valley fever, is a fungal infection caused by fungi that grow in the soil, mainly in the southwestern United States, parts of Mexico, and Central and South America. Coccidioidomycosis is a growing health concern and a common cause of pneumonia in endemic areas. At least 30-60% of people who live in an endemic region are exposed to the fungus at some point during their lives. In most people the infection will resolve spontaneously, but for those who develop severe infections or chronic pneumonia, medical treatment is necessary. Exposures of concern include arid regions and places where excavation is occurring. Histoplasmosis is an infection caused by a fungus that grows as a mold in soil and as yeast in animal and human hosts.
  • Luciano Polonelli

    Luciano Polonelli

    Luciano Polonelli Department of Biomedical, Biotechnological and Translational Sciences, Unit of Microbiology and Virology, University of Parma, Parma, Italy Tel.: +39 0521 903429; Fax: +39 0521 993620; e-mail: [email protected] History of Medical Mycology File 2 (1895-1950) 1895 Giuseppe Marconi (1862-1940), born in Naples, Italy, Professor of Veterinary Pathology and Clinic in the Royal University of Pisa, Italy, isolated and cultivated for the first time Cryptococcus farciminosum, the agent of epizootic lymphangitis, in the form of sterile mycelium (1895). Piero Redaelli and Raffaele Ciferri transferred (1934) C. farciminosum to the genus Histoplasma, as H. farciminosum (Rivolta and Micellone 1883, Redaelli and Ciferri 1934), mainly because of its dimorphic nature that made it similar to the tissue form of H. capsulatum var. capsulatum Darling 1906. Robert J. Weeks, Arvind A. Padhye and Libero Ajello, at the Division of Mycotic Diseases, Center for Infectious Diseases, Centers for Disease Control (C.D.C.) Atlanta, Georgia, U.S.A. (1985), observed that this fungus generated macro- and microconidia resembling those of the capsulatum and duboisii varieties of H. capsulatum when incubated at room temperature, thus reducing the fungus to a varietal status as H. capsulatum var. farciminosum (Rivolta, 1873) Weeks, Padhye & Ajello, 1985. Raffaele Ciferri (1960) reduced Histoplasma duboisii (Vanbreuseghem, 1992) to varietal status as H. capsulatum var. duboisii (Vanbreuseghem, 1992), Ciferri, 1960 [Ajello, 1998; Marcone, 1895; Redaelli and Ciferri, 1934; Weeks et al., 1985]. 1 1896 The American surgeon Emmet Rixford (1865-1938), born in Bedford, Canada, first graduated in engineering and then Doctor in Medicine (1891), and Thomas C.
  • WO 2013/038197 Al 21 March 2013 (21.03.2013) P O P C T

    WO 2013/038197 Al 21 March 2013 (21.03.2013) P O P C T

    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2013/038197 Al 21 March 2013 (21.03.2013) P O P C T (51) International Patent Classification: Geir [NO/NO]; Bj0rndalen 81, N-7072 Heimdal (NO). A01N 43/16 (2006.01) A01N 43/653 (2006.01) MYRVOLD, Rolf [NO/NO]; 0vre Gjellum vei 28, N- A61K 31/734 (2006.01) A01P 3/00 (2006.01) 1389 Heggedal (NO). A01N 43/90 (2006.01) (74) Agent: DEHNS; St Bride's House, 10 Salisbury Square, (21) International Application Number: London EC4Y 8JD (GB). PCT/GB20 12/052274 (81) Designated States (unless otherwise indicated, for every (22) International Filing Date kind of national protection available): AE, AG, AL, AM, 14 September 2012 (14.09.2012) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (25) English Filing Language: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (26) Publication Language: English HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, (30) Priority Data: ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, 1116010.8 15 September 201 1 (15.09.201 1) GB NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, (71) Applicant (for all designated States except US): AL- RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, GIPHARMA AS [NO/NO]; Industriveien 33, N-1337 TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, Sandvika (NO).