Oral Treatment for Mycobacterium ulcerans Infection: Results From a Pilot Study in Benin

Mycobacterium ulcerans infection is responsible for severe skin lesions in sub-Saharan Africa. We enrolled 30 Beninese patients with Buruli ulcers in a pilot study to evaluate efficacy of an oral chemotherapy using rifampicin plus clarithromycin during an 8-week period. The treatment was well tolerated, and all patients were healed by 12 months after initiation of therapy without relaps

Buruli Ulcer Surveillance, Benin, 2003–2005

We reviewed Buruli ulcer (BU) surveillance in Benin, using the World Health Organization BU02 form. We report results of reliable routine data collected on 2,598 new and recurrent cases from 2003 through 2005

Clinical epidemiology of laboratory-confirmed Buruli ulcer in Benin: a cohort study

Background Buruli ulcer, caused by Mycobacterium ulcerans, was identifi ed as a neglected emerging infectious disease by WHO in 1998. Although Buruli ulcer is the third most common mycobacterial disease worldwide, understanding of the disease is incomplete. We analysed a large cohort of laboratory-confi rmed cases of Buruli ulcer from Pobè, Benin, to provide a comprehensive description of the clinical presentation of the disease, its variation with age and sex, and its eff ect on the occurrence of permanent functional sequelae. Methods Between Jan 1, 2005, and Dec 31, 2011, we prospectively collected clinical and laboratory data from all patients with Buruli ulcer diagnosed at the Centre de Dépistage et de Traitement de l’Ulcère de Buruli in Pobè, Benin. We followed up patients to assess the frequency of permanent functional sequelae. All analyses were done on cases that were laboratory confi rmed. Findings 1227 cases of laboratory-confi rmed Buruli ulcer were included in the analysis. Typically, patients with Buruli ulcer were children (median age at diagnosis 12 years) presenting with a unique (1172 [96%]) large (≥15 cm, 444 [36%]) ulcerative (805 [66%]) lesion of the lower limb (733 [60%]). Atypical clinical presentation of Buruli ulcer included Buruli ulcer osteomyelitis with no identifi able present or past Buruli ulcer skin lesions, which was recorded in at least 14 patients. The sex ratio of Buruli ulcer widely varied with age, with male patients accounting for 57% (n=427) of patients aged 15 years and younger, but only 33% (n=158) of those older than 15 years (odds ratio [OR] 2·59, 95% CI 2·04–3·30). Clinical presentation of Buruli ulcer was signifi cantly dependent on age and sex. 54 (9%) male patients had Buruli ulcer osteomyelitis, whereas only 28 (4%) of female patients did (OR 2·21, 95% CI 1·39–3·59). 1 year after treatment, 229 (22% of 1043 with follow-up information) patients presented with permanent functional sequelae. Presentation with oedema, osteomyelitis, or large (≥15 cm in diameter), or multifocal lesions was signifi cantly associated with occurrence of permanent functional sequelae (OR 7·64, 95% CI 5·29–11·31) and operationally defi nes severe Buruli ulcer. Interpretation Our fi ndings have important clinical implications for daily practice, including enhanced surveillance for early detection of osteomyelitis in boys; systematic search for M ulcerans in osteomyelitis cases of non-specifi c aspect in areas endemic for Buruli ulcer; and specifi c disability prevention for patients presenting with osteomyelitis, oedema, or multifocal or large lesions. Our fi ndings also suggest a crucial underestimation of the burden of Buruli ulcer in Africa and raise key questions about the contribution of environmental and physiopathological factors to the recorded heterogeneity of the clinical presentation of Buruli ulcer

Contribution of the community health volunteers in the control of buruli ulcer in Bénin

Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans. Usually BU begins as a painless nodule, plaque or edema, ultimately developing into an ulcer. The high number of patients presenting with ulcers in an advanced stage is striking. Such late presentation will complicate treatment and have long-term disabilities as a consequence. The disease is mainly endemic in West Africa. The primary strategy for control of this disease is early detection using community village volunteers.In this retrospective, observational study, information regarding Buruli ulcer patients that reported to one of the four BU centers in Bénin between January 2008 and December 2010 was collected using the WHO/BU01 forms. Information used from these forms included general characteristics of the patient, the results of diagnostic tests, the presence of functional limitations at start of treatment, lesion size, patient delay and the referral system. The role of the different referral systems on the stage of disease at presentation in the hospital was analyzed by a logistic regression analysis. About a quarter of the patients (26.5%) were referred to the hospital by the community health volunteers. In our data set, patients referred to the hospital by community health volunteers appeared to be in an earlier stage of disease than patients referred by other methods, but after adjustment by the regression analysis for the health center, this effect could no longer be seen. The Polymerase Chain Reaction (PCR) for IS2404 positivity rate among patients referred by the community health volunteers was not systematically lower than in patients referred by other systems.This study clarifies the role played by community health volunteers in Bénin, and shows that they play an important role in the control of BU

Protection against Mycobacterium ulcerans Lesion Development by Exposure to Aquatic Insect Saliva

BACKGROUND: Buruli ulcer is a severe human skin disease caused by Mycobacterium ulcerans. This disease is primarily diagnosed in West Africa with increasing incidence. Antimycobacterial drug therapy is relatively effective during the preulcerative stage of the disease, but surgical excision of lesions with skin grafting is often the ultimate treatment. The mode of transmission of this Mycobacterium species remains a matter of debate, and relevant interventions to prevent this disease lack (i) the proper understanding of the M. ulcerans life history traits in its natural aquatic ecosystem and (ii) immune signatures that could be correlates of protection. We previously set up a laboratory ecosystem with predatory aquatic insects of the family Naucoridae and laboratory mice and showed that (i) M. ulcerans-carrying aquatic insects can transmit the mycobacterium through bites and (ii) that their salivary glands are the only tissues hosting replicative M. ulcerans. Further investigation in natural settings revealed that 5%–10% of these aquatic insects captured in endemic areas have M. ulcerans–loaded salivary glands. In search of novel epidemiological features we noticed that individuals working close to aquatic environments inhabited by insect predators were less prone to developing Buruli ulcers than their relatives. Thus we set out to investigate whether those individuals might display any immune signatures of exposure to M. ulcerans-free insect predator bites, and whether those could correlate with protection. METHODS AND FINDINGS: We took a two-pronged approach in this study, first investigating whether the insect bites are protective in a mouse model, and subsequently looking for possibly protective immune signatures in humans. We found that, in contrast to control BALB/c mice, BALB/c mice exposed to Naucoris aquatic insect bites or sensitized to Naucoris salivary gland homogenates (SGHs) displayed no lesion at the site of inoculation of M. ulcerans coated with Naucoris SGH components. Then using human serum samples collected in a Buruli ulcer–endemic area (in the Republic of Benin, West Africa), we assayed sera collected from either ulcer-free individuals or patients with Buruli ulcers for the titre of IgGs that bind to insect predator SGH, focusing on those molecules otherwise shown to be retained by M. ulcerans colonies. IgG titres were lower in the Buruli ulcer patient group than in the ulcer-free group. CONCLUSIONS: These data will help structure future investigations in Buruli ulcer–endemic areas, providing a rationale for research into human immune signatures of exposure to predatory aquatic insects, with special attention to those insect saliva molecules that bind to M. ulcerans

Serological Evaluation of Mycobacterium ulcerans Antigens Identified by Comparative Genomics

A specific and sensitive serodiagnostic test for Mycobacterium ulcerans infection would greatly assist the diagnosis of Buruli ulcer and would also facilitate seroepidemiological surveys. By comparative genomics, we identified 45 potential M. ulcerans specific proteins, of which we were able to express and purify 33 in E. coli. Sera from 30 confirmed Buruli ulcer patients, 24 healthy controls from the same endemic region and 30 healthy controls from a non-endemic region in Benin were screened for antibody responses to these specific proteins by ELISA. Serum IgG responses of Buruli ulcer patients were highly variable, however, seven proteins (MUP045, MUP057, MUL_0513, Hsp65, and the polyketide synthase domains ER, AT propionate, and KR A) showed a significant difference between patient and non-endemic control antibody responses. However, when sera from the healthy control subjects living in the same Buruli ulcer endemic area as the patients were examined, none of the proteins were able to discriminate between these two groups. Nevertheless, six of the seven proteins showed an ability to distinguish people living in an endemic area from those in a non-endemic area with an average sensitivity of 69% and specificity of 88%, suggesting exposure to M. ulcerans. Further validation of these six proteins is now underway to assess their suitability for use in Buruli ulcer seroepidemiological studies. Such studies are urgently needed to assist efforts to uncover environmental reservoirs and understand transmission pathways of the M. ulcerans

A case of guilt by association: Water bug bite incriminated in M. ulcerans infection

Buruli ulcer is a cutaneous mycobacterial disease caused by Mycobacterium ulcerans, whose incidence is increasing steadily, especially in West Africa. This study reports a first documented case of M. ulcerans infection which can be attributed to a water bug bite at the site of the primary lesion

Defining and targeting high-risk populations in Buruli ulcer–Authors' reply

International audienceWe thank Jordi Landier and colleagues for their comments about our recent Article in The Lancet Global Health. 1 In their work, Landier and coworkers generalise some of our observations on Buruli ulcer in Benin to those for Cameroon, the country that has the fifth highest prevalence of Buruli ulcer worldwide. Briefly, they make use of age and sex distribution from the Cameroon national census to show that patients aged 5–14 years were twice as likely to be affected by Buruli ulcer as older individuals; and that boys were over-represented in individuals younger than 15 years, women were over-represented in patients aged 15–50 years, and that men and women were equally represented in patients older than 50 years. They advocate the use of national census references to produce incidence rates and incidence rate ratios (IRRs), which they believe to be the proper way to draw valid conclusions.</p

Draft Genome Sequence of Mycobacterium ulcerans S4018 Isolated from a Patient with an Active Buruli Ulcer in Benin, Africa

International audienceCurrently, there are only two publicly available genomes of Mycobacte-rium ulcerans—the causative agent of the neglected, but devastating, tropical disease Buruli ulcer. Here, we report the draft genome sequence of isolate S4018, recovered from an active cutaneous lesion of a patient with Buruli ulcer in Benin, Africa

Establishment of Quantitative PCR (qPCR) and Culture Laboratory Facilities in a Field Hospital in Benin: 1-Year Results

International audienceNo simple diagnostic tool is available to confirm Mycobacterium ulcerans infection, which is an emerging disease reported in many rural areas of Africa. Here, we report the 1-year results of a hospital laboratory that was created in an area of endemicity of Benin to facilitate the diagnosis of M. ulcerans infection.</p