Response to treatment in a prospective cohort of patients with large ulcerated lesions suspected to be Buruli Ulcer (Mycobacterium ulcerans disease)

BACKGROUND: The World Health Organization (WHO) advises treatment of Mycobacterium ulcerans disease, also called "Buruli ulcer" (BU), with a combination of the antibiotics rifampicin and streptomycin (R+S), whether followed by surgery or not. In endemic areas, a clinical case definition is recommended. We evaluated the effectiveness of this strategy in a series of patients with large ulcers of > or =10 cm in longest diameter in a rural health zone of the Democratic Republic of Congo (DRC). METHODS: A cohort of 92 patients with large ulcerated lesions suspected to be BU was enrolled between October 2006 and September 2007 and treated according to WHO recommendations. The following microbiologic data were obtained: Ziehl-Neelsen (ZN) stained smear, culture and PCR. Histopathology was performed on a sub-sample. Directly observed treatment with R+S was administered daily for 12 weeks and surgery was performed after 4 weeks. Patients were followed up for two years after treatment. FINDINGS: Out of 92 treated patients, 61 tested positive for M. ulcerans by PCR. PCR negative patients had better clinical improvement than PCR positive patients after 4 weeks of antibiotics (54.8% versus 14.8%). For PCR positive patients, the outcome after 4 weeks of antibiotic treatment was related to the ZN positivity at the start. Deterioration of the ulcers was observed in 87.8% (36/41) of the ZN positive and in 12.2% (5/41) of the ZN negative patients. Deterioration due to paradoxical reaction seemed unlikely. After surgery and an additional 8 weeks of antibiotics, 98.4% of PCR positive patients and 83.3% of PCR negative patients were considered cured. The overall recurrence rate was very low (1.1%). INTERPRETATION: Positive predictive value of the WHO clinical case definition was low. Low relapse rate confirms the efficacy of antibiotics. However, the need for and the best time for surgery for large Buruli ulcers requires clarification. We recommend confirmation by ZN stain at the rural health centers, since surgical intervention without delay may be necessary on the ZN positive cases to avoid progression of the disease. PCR negative patients were most likely not BU cases. Correct diagnosis and specific management of these non-BU ulcers cases are urgently needed.This study was supported by the Directorate-General for Development and Cooperation (DGDC), Brussels, Belgium, the European Commission (International Science and Technology Cooperation Development Program) (project no. INCO-CT-2005-051476-BURULICO), and by a grant from the Health Services of Fundacao Calouste Gulbenkian. K.K. was supported by a grant from DGDC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Burden of <i>Mycobacterium ulcerans</i> Disease (Buruli Ulcer) and the Underreporting Ratio in the Territory of Songololo, Democratic Republic of Congo

<div><p>Background</p><p>Cutaneous infection by <i>Mycobacterium ulcerans</i>, also known as Buruli ulcer (BU), represents the third most common mycobacterial disease in the world after tuberculosis and leprosy. Data on the burden of BU disease in the Democratic Republic of Congo are scanty. This study aimed to estimate the prevalence rate and the distribution of BU in the Songololo Territory, and to assess the coverage of the existing hospital-based reporting system.</p><p>Methods</p><p>We conducted a cross-sectional survey (July–August 2008) using the door-to-door method simultaneously in the two rural health zones (RHZ) of the Songololo Territory (RHZ of Kimpese and Nsona-Mpangu), each containing twenty health areas. Cases were defined clinically as active BU and inactive BU in accordance with WHO-case definitions.</p><p>Results</p><p>We detected 775 BU patients (259 active and 516 inactive) in a total population of 237,418 inhabitants. The overall prevalence of BU in Songololo Territory was 3.3/1000 inhabitants, varying from 0 to 27.5/1000 between health areas. Of the 259 patients with active BU, 18 (7%) had been reported in the hospital-based reporting system at Kimpese in the 6–8 months prior to the survey.</p><p>Conclusion</p><p>The survey demonstrated a huge variation of prevalence between health areas in Songololo Territory and gross underreporting of BU cases in the hospital-based reporting system. Data obtained may contribute to better targeted and improved BU control interventions, and serve as a baseline for future assessments of the control program.</p></div

Prevalence of Buruli ulcer in the Territory of Songololo, July–August 2008.

<p>BU: Buruli ulcer.</p

Distribution of active BU cases in the Songololo Territory, July–August 2008.

<p>Distribution of active BU cases in the Songololo Territory, July–August 2008.</p

Location of the survey zone.

<p>A. Map of Africa showing the location of the Democratic Republic of Congo. B. Map of the Democratic Republic of Congo showing the location of the province of Bas-Congo. C. Map of the Province of Bas-Congo showing the location of the two health zones surveyed in 2008.</p

Prevalence of Buruli ulcer disease in Africa.

<p>BU: Buruli ulcer.</p

Clinico-epidemiological features of active BU cases in the Territory of Songololo, July–August 2008.

*<p>X² test unless otherwise specified.</p><p>†Two-sided Fisher exact test (An expected cell value was less than 5).</p><p>‡n = 182 because of 5 missing data.</p><p>Ωn = 73 because of one case with disseminated lesions.</p

Distribution of total number of BU cases (active and inactive) in the Songololo Territory, July–August 2008.

<p>Distribution of total number of BU cases (active and inactive) in the Songololo Territory, July–August 2008.</p