The Benefits of a Combination of Surgery and Chemotherapy in the Management of Buruli Ulcer Patients Authors & Institutions

The benefits of a combination of surgery and chemotherapy in the management of Buruli ulcer patients Authors & Institutions:

1. Pius Agbenorku 2. Joseph Akpaloo

Plastic & Burns Surgery Unit Department of Surgery Komfo Anokye Teaching Hospital School of Medical Sciences College of Health Sciences Kwame Nkrumah University of Science &Technology Kumasi, Ghana 3. Margaret Agbenorku 4. Emma Gotah

Health Education Unit Global Evangelical Mission Hospital Apromase-Ashanti Ghana

5. Paul Saunderson 6. Linda Lehman

American Leprosy Missions 1 ALM Way Greenville SC 29601 USA Presenter: Dr Pius Agbenorku

WHO Annual Meeting on Buruli ulcer Geneva, March 15 – 17, 2006 BACKGROUND INFORMATION

Buruli ulcer • Is a tropical swampy climate disease, caused by Mycobacterium ulcerans • Is one of the commonest diseases associated with most typical villages such as those in the Bomfa sub-district of Ejisu-Juaben District in the Ashanti Region of Ghana • These villages are inhabited mainly by the “poor of the poor – the poorest of the poor” who are mainly subsistence farmers Fig. 1. 0: Map Showing Kumasi, Bomfa, Ejisu and Konongo

Ejisu Bomfa Konongo Background contd.

• The population of the Bomfa sub-district is 21,924 • Children form about 16.5% of the total population • Bomfa village is about 36 km from Ejisu, its district capital town Background contd.

•There are three (3) health facilities in the Bomfa sub-district namely: – Bomfa Health Centre at Bomfa village –Agyenkwa Clinic at Nobewam – Huttel Health Centre at Buamadumase Problem Statement

The problems: • the rate at which the people are infected • the mode of treatment they are given • their conditions at hospitals if they ever get there • the recurrence of the disease in some patients Problem statement contd.

• Are there any socio-economic factors influencing the treatment and cure of the Buruli ulcer patient? • Can antibiotic treatment alone or surgery alone or their combination enhance the cure rate? • Can the additional application of various methods of prevention of disability (POD) help to make life better for these patients? Problem statement contd.

• These questions are what this study tries to find answers for • Though one cannot claim the final authority in finding absolute solutions to these problems the findings from this study – might become a more or less part solution to the Buruli ulcer menace – could be applied to similar conditions – in the Ashanti Region of Ghana – other parts of Ghana beyond Ghana METHODOLOGY

• The adoption of the Bomfa sub-district in the Ejisu-Juaben District was the first step for a definite population • By the permission and advice from the Ejisu-Juaben District Health Administration a team was set in place METHODOLOGY contd.

• Training for 12 health centre staffs • Training for 16 community volunteers • Training for 10 school teachers METHODOLOGY contd.

• Health education - in the communities - house to house - schools - market places - durbars - any special meetings - anywhere/anytime Methodology contd.

• All this were made possible with the help of motivated community volunteers who were engaged in the active case detection “Patients’ In-take and Engagement Form’’ was filled for the patients at the beginning of the medical intervention Protocol for Treatment

I. Antibiotics Treatment: • WHO guidelines were strictly adhered to • The antibiotics used: – Rifampicin tablets given 10mg/kg of body mass – Streptomycin injection given deep intramuscularly daily in the dosage of 15mg/kg body mass Protocol for Treatment contd.

• The medications were generally given 4 weeks before surgery • After surgery the medications continued for the next 4 weeks • Some continued for 4 more weeks making a total of 12 weeks • Most often the medications were given on out-patient basis with monitoring from the local health centre staff or hospital team Protocol for Treatment contd.

II. Surgery • Surgery is done as soon as the patient is fit for anaesthesia • usually after the first course of the antibiotics (4 weeks) • Excision is done first a week later grafting - split-thickness skin graft • Generally cases that needed contracture release were done after the wounds had been treated Protocol for Treatment contd.

• Normally patients stayed further on admission 2- 3 weeks after the final surgery • Further dressings and drug therapy were continued on out-patient basis • Patients were reviewed fortnightly initially • Later, monthly either – in the hospital – at the community health centre OR – at home by the local staff or hospital team. Protocol for Treatment contd.

III. Prevention of Disability (POD) • Currently the treatment of BU is not complete without the element of POD • It has therefore become an integral part of the treatment process just as antibiotics and surgery • Several exercises have been developed for patients depending on the location of their lesion ¾ to regain the proper functioning of the affected part all patients both young and old went through a process of disability prevention which started from the very first day of treatment Protocol for Treatment contd.

POD • continued in the operating theatre • splinting, proper positioning and bandaging • thorough wound care procedures even after discharge from hospital • till the patient totally regained the use of the affected part • drastically reduced to over 90% the number of contractures that had to be released • thereby reducing the period of hospitalization RESULTS

• “Patients’ In-take and Engagement Form” was filled for these 65

62 were AFBs positive by ZN stain or confirmed by histopathology or by clinical assessment

The following findings from the 62 forms are therefore a good representation of all patients Table 2: DEDUCTIVE AGE LIMITS OF PATIENTS FROM TABLE 1 IN RELATION TO THEIR ECONOMIC STRENGTH

AGE LIMITS No. OF PATIENTS 0 – 14 26 Children 15 – 29 17 Working force 30 – 44 5 Working force 45 – 59 1 Working force 60 – 75+ 13 The aged TOTAL 62 Table 2: DEDUCTIVE AGE LIMITS OF PATIENTS FROM TABLE 1 IN RELATION TO THEIR ECONOMIC STRENGTH contd.

• Table 2, which is a deduction from Table 1, groups the patients into three categories: –I -children majority of whom are pupils; – II - working force and – III - the aged. Table 2: DEDUCTIVE AGE LIMITS OF PATIENTS FROM TABLE 1 IN RELATION TO THEIR ECONOMIC STRENGTH contd.

• This categorization helps in looking at the socio- economic status of patients – their ability to pay for services rendered them – as well as their ability to look after themselves • This categorization represents 26:23:13 ratio of the disease among children, the working force and the aged respectively Fig. 2.0: AGE RANGE OF BU PATIENTS

Fig.1.0:AGE DISTRIBUTION OF PATIENTS

14 0 – 4 5 – 9 12 10 – 14 15 – 19 10 20 – 24 25 – 29 30 – 34 No. OF PATIENTS 8 35 – 39 40 – 44 6 45 – 49 50 – 54 55 – 59 4 60 – 64 65 – 69 70 – 74 2 75 – 79+

0 1 AGE RANGE Fig.3.0: ECONOMIC STATUS OF PATIENTS

Fig.3.0: ECONOMIC STATUS OF PATIENTS

30 26

23 25

13 No. OF PATIENTS 15 Series1

0 Children Working Force The Aged ECONOMIC STATUS Fig.4.0: MARITAL STATUS OF PATIENTS

Fig.4.0: MARITAL STATUS OF PATIENTS

26 25

17 15 Series1 PATIENTS No. OF

10 10 9

0 Single Married Divorced Widower/Widow MARITAL CATEGORY Table 4: BU PATIENTS’MEDICAL HISTORY

SERIAL SOBU DOHT(W/M/Y) SOL(CM/L) TOT DOH NO. (Days) 1 Late ulcer 3 – 6m 10 -20 AB + (EX + SG) 25 2 “ 6 – 10w 6 – 10 AB + (EX + SG) 11 3 Nodule 3 – 5w 1 – 2 AB + (EX) 2 4 Late ulcer 1y+ 10 – 20 AB + (EX + SG) 55 5 “ 7 – 12m 10 – 20 “ 89 6 “ 3 – 6m 10 – 20 “ 45 7 “ 7 – 12m 10 – 20 “ 17 8 “ 7 – 12m >20 “ 49 9 Nodule 0 -2w 1 – 2 AB + (EX) 2 10 Plaque 3 – 5w 3 – 5 “ 14 Table 4: BU PATIENTS’MEDICAL HISTORY contd.

SERIAL SOBU DOHT(W/M/Y) SOL(CM/L) TOT DOH NO. (Days) 11 Late ulcer 1y+ >20 AB + (EX + SG + 41 RC) 12 Late ulcer 1y+ 10 – 20 AB + (EX + SG) 33 13 Late ulcer 3 -5m 10 – 20 “ 28 14 Nodule 0 – 2w 1 – 2 AB + (EX) 2 15 Nodule 6 – 10w 1 – 2 “ 2 16 Late ulcer 7 – 12m 6 -10 AB + (EX + SG) 42 17 “ 3 – 6m 10 -20 “ 36 18 “ 1y+ >20 “ 48 19 “ 1y+ 10 -20 “ 72 20 Late ulcer 6 – 10w 6 – 10 AB + (EX + SG) 34 Table 4: BU PATIENTS’MEDICAL HISTORY contd.

SERIAL SOBU DOHT(W/M/Y) SOL(CM/L) TOT DOH No. (Days) 21 Nodule 0 – 2 w 1 – 2 AB + (EX) 2

22 Late ulcer 7 – 12 m 10 – 20 AB + (EX + SG) 48 23 “ 3 – 6 m >20 “ 36 24 “ 3 – 6 m 6 – 10 AB + (EX + SG) 41 25 “ 7 – 12 m 10 – 20 AB + (EX + SG + RC) 60 26 “ 1y+ 10 – 20 AB + (EX + SG) 29 27 “ 1y+ 6 – 10 “ 44 28 “ 3 – 6 m 10 – 20 “ 30 29 “ 6 – 10 w >20 AB + (EX + SG + RC) 90 30 “ 7 – 12 m 6 – 10 AB + (EX + SG) 90 Table 4: BU PATIENTS’MEDICAL HISTORY contd.

SERIAL SOBU DOHT(W/M/Y) SOL(CM/L) TOT DOH NO. (Days) 31 Nodule 3 – 5w 1 – 2 AB + (EX) 2 32 Late ulcer 3 – 6m 10 -20 AB + (EX + SG) 44 33 “ 6 – 10w 6 – 10 AB + (EX + SG) 39 34 Late ulcer 1y+ 10 – 20 AB + (EX + SG) 60 35 “ 7 – 12m 10 – 20 “ 70 36 “ 3 – 6m 10 – 20 “ 40 37 “ 7 – 12m 10 – 20 “ 30 38 “ 7 – 12m >20 “ 42 39 Late ulcer 1y+ >20 AB + (EX + SG + RC) 39 40 Late ulcer 1y+ 10 – 20 AB + (EX + SG) 31 Table 4: BU PATIENTS’MEDICAL HISTORY contd.

SERIAL SOBU DOHT(W/M/Y) SOL(CM/L) TOT DOH No. (Days) 41 Late ulcer 3 -5m 10 – 20 “ 38 42 “ 1y+ 10 -20 “ 52 43 Late ulcer 6 – 10w 6 – 10 AB + (EX + SG) 34 44 Late ulcer 6 – 10w 6 – 10 AB + (EX + SG) 36 45 Late ulcer 3 – 6m 10 – 20 AB + (EX + SG) 30 46 “ 7 – 12m 10 – 20 “ 20 47 “ 7 – 12m >20 “ 42 48 Late ulcer 1y+ >20 AB + (EX + SG + RC) 49 49 “ 3 – 6m 10 – 20 “ 20 Table 4: BU PATIENTS’MEDICAL HISTORY contd.

SERIAL SOBU DOHT(W/M/Y) SOL(CM/L) TOT DOH No. (days) 50 Late ulcer 3 -5m 10 – 20 “ 38 51 “ 1y+ 10 -20 “ 62 52 Late ulcer 6 – 10w 6 – 10 AB + (EX + SG) 44 53 Late ulcer 6 – 10w 6 – 10 AB + (EX + SG) 36 54 Late ulcer 3 -5m 10 – 20 “ 28 55 “ 1y+ 10 -20 “ 39 56 Late ulcer 6 – 10w 6 – 10 AB + (EX + SG) 34 57 “ 1y+ 6 – 10 “ 44 58 “ 3 – 6m 10 – 20 “ 30 59 “ 6 – 10w >20 AB + (EX + SG + RC) 90 60 “ 7 – 12m 6 – 10 AB + (EX + SG) 79 61 Late ulcer 1y+ >20 AB + (EX + SG + RC) 57 62 Late ulcer 1y+ 10 – 20 AB + (EX + SG) 51 Table 4: BU PATIENTS’MEDICAL HISTORY contd.

Legend: • DOHT – Duration Of Home Treatment • SOL (CM/L) – Size Of Lesion in Centimeter by Length • TOT - Type Of Treatment • DOH - Duration Of Hospitalization • (W/M/Y) – Week/Month/Year • SOBU – Stage Of the Buruli Ulcer • AB + (EX) – Antibiotics and Excision • AB + (EX + SG) – Antibiotics, Excision and Skin Grafting • AB + (EX + SG + RC) – Antibiotics, Excision, Skin Grafting and Contracture Release Table 4: BU PATIENTS’MEDICAL HISTORY contd.

• Table 4 includes the diagnoses of the 62 patients • Each was treated with antibiotics and surgery which involved excision, skin grafting, contracture release for 7 patients later • 55 (88.7%) of the Buruli ulcer patients from Bomfa had their cases being late ulcers • There were: – 6 patients (i.e. 9.7%) with nodules – 1 plaque (1.6%) which all were excised Type of Treatment

• From Table 4: • All the patients had antibiotics – Streptomycin and Rifampicin - (AB) • All the nodules were excised – Nodulectomies and also had antibiotics - AB + (EX) • There was only 1 plaque which also had antibiotics and excision – AB + (EX) • All the ulcers had antibiotics, were excised and were skin-grafted - AB + (EX + SG) • Seven (7) of the ulcers had in addition their contractures released - AB + (EX + SG + RC) Type of Treatment contd.

• Multiple surgeries were done on 55 patients • Single surgeries for the nodules (6) and the plaque (1)- i.e.7 patients had single surgeries • Excisions - 55 • STSG – 55 • Contracture Release = 7 • Total number of surgeries done = 6+1+55+55+7 = 124 on the sixty-two (62) patients

None of these 62 patients needed amputation Table 5: LOCATION OF BURULI ULCER ON PATIENTS

Location of Lesion No. of Patients Head + Neck Region 1 Upper limbs 11 Trunk of body 4 Lower limbs 45 Perineum 1 TOTAL 62 Fig. 5.0: Location of BU lesions on patients

Fig. 5.0:LOCATION OF BU LESION OF PATIENTS

45 45

25 No. of Patients

20 No. OF PATIENTS OF No.

15 11 10

5 4 1 1 0 Head + Neck Upper limbs Trunk of body Lower limbs Perineum Region LESION LOCATION Fig. 5.0: Location of BU lesions on patients contd.

• Forty-five (45) out of the sixty-two (62) patients had their lesions on their lower limbs representing 72.6% of the total number of patients treated • Fifty-six (56) out of the sixty-two (62) patients had their lesions on the lower and upper limbs combined representing 90.3% of the total number of patients treated • One (1) patient had his lesion on the head and neck region representing 1.6% of the total number of patients in the series Duration of Hospital Admission

• Table 4.0 shows that the number of days spent at the hospital depended on the stage and size of the ulceration which was greatly affected by the duration of home treatment as well • Median = 23 days • Mode = 90 days • Mean = Summation fx/62 = 39.8 days Case Presentations

Fig. 6.0

Fig. 7.0 Case Presentations contd.

Fig. 8.0 Fig. 9.0 Case Presentations contd.

Fig. 10.0 Fig. 11.0 Case Presentations contd.

Fig. 12.0

Fig. 13.0 Case Presentations contd.

Fig. 14a Fig. 14b Case Presentations contd.

Fig. 15.0 Fig. 17.0 Case Presentations contd.

Fig. 19.0

Fig. 18.0 Case Presentations contd.

Fig. 21.0

Fig. 20.0 CONCLUSION

• In the attempt to identify the factors enhancing the control of Buruli ulcer in an endemic area with reference to the Bomfa Pilot Project, the paper has been able to establish the following: • The application of Buruli chemotherapy has resulted in “minimal” surgery as against the traditional extensive tissue excision in the pre-chemotherapeutic era. CONCLUSION contd.

• The recommended dosage of Rifampicin and Streptomycin was strictly adhered to • The “dual” mode of treatment (surgery + chemotherapy) reduced hospital admission period which directly reduced the cost of treatment • Surgery and chemotherapy combined play a major role in the control of Buruli ulcer RECOMMENDATIONS

• All the 62 patients in the series need regular and long term follow-ups so as to look for any signs of recurrences • The combination of chemotherapy and surgery is recommended to Buruli ulcer management centres ACKNOWLEDGEMENT

• We are grateful to the nursing staff of the Global Evangelical Mission Hospital, Apromase-Ashanti for the accurate documentation of patients’ data • The financial support from the American Leprosy Missions was appreciated for the implementation of the Bomfa Pilot Project which formed the basis of this paper • We appreciated the advice and support - from Ejisu-Juaben District Health Administration - from Ashanti Regional Health Administration ACKNOWLEDGEMENT contd.

We appreciated the co-operation of • the nurses at the community health centres • the community volunteers • the patients’ care-takers • the patients who were the subjects of this study