[Evolution and impact of the One Health approach in Switzerland and worldwide]. / Évolution et impact de l'approche une seule santé (One Health) en Suisse et dans le monde.

Integrated approaches to health such as One Health are needed to tackle complex problems that cannot be solved by a single discipline or country, such as climate change, biodiversity loss or antimicrobial resistance. The Swiss Tropical and Public Health Institute (Swiss TPH), one of the international pioneers in One Health with its African partners, the Institute of Global Health at the University of Geneva, which has also adopted One Health, and other activities in Berne and Zurich, make Switzerland a hub for One Health research and development worldwide. This article summarizes the development of the One Health approach in Switzerland, and uses examples to demonstrate its added value.

Les approches intégrées de la santé comme One Health « une seule santé ¼ sont nécessaires pour aborder les problèmes complexes ne pouvant être résolus par une seule discipline, un seul pays comme le changement climatique, la perte de biodiversité ou la résistance aux antimicrobiens. L'Institut tropical et de santé publique suisse (Swiss TPH), l'un des pionniers internationaux en One Health avec ses partenaires en Afrique, l'Institut de santé globale de l'Université de Genève, qui a aussi adopté One Health, et d'autres activités à Berne et Zurich, font de la Suisse une plaque tournante de recherche et développement sur l'approche One Health dans le monde. Cet article résume l'évolution de cette approche en Suisse et montre à travers d'exemples sa valeur ajoutée.

Clinical features and management of a severe paradoxical reaction associated with combined treatment of Buruli ulcer and HIV co-infection.

BACKGROUND: In West and Central Africa Buruli ulcer (BU) and HIV co-infection is increasingly recognised and management of these two diseases combined is an emerging challenge for which there is little published information. In this case we present a severe paradoxical reaction occurring after commencing antibiotic treatment for BU combined with antiretroviral therapy for HIV, and describe its clinical features and management. This includes to our knowledge the first reported use of prednisolone in Africa to manage a severe paradoxical reaction related to BU treatment. CASE PRESENTATION: A 30 year old immunosuppressed HIV positive man from Cameroon developed a severe paradoxical reaction 24 days after commencing antibiotic treatment for BU and 14 days after commencing antiretroviral therapy for HIV. Oral prednisolone was successfully used to settle the reaction and prevent further tissue loss. The antiretroviral regimen was continued unchanged and the BU antibiotic treatment not prolonged beyond the recommended duration of 8 weeks. A second small local paradoxical lesion developed 8 months after starting antibiotics and settled with conservative treatment only. Complete healing of lesions occurred and there was no disease recurrence 12 months after commencement of treatment. CONCLUSIONS: Clinicians should be aware that severe paradoxical reactions can occur during the treatment of BU/HIV co-infected patients. Prednisolone was effectively and safely used to settle the reaction and minimize the secondary tissue damage.

Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria: two open-label, randomized trials in Nimba County, Liberia.

BACKGROUND: Safety surveillance of widely used artemisinin-based combination therapy (ACT) is essential, but tolerability data in the over five years age group are largely anecdotal. METHODS: Two open-label, randomized trials were conducted in Nimba County, Liberia: i) the main tolerability trial with 1,000 Plasmodium falciparum malaria patients aged over five years (Study-T), and, ii) an efficacy trial with a secondary objective of collecting tolerability data among 300 children age six to 59 months (Study-E). In both studies patients were randomized to fixed-dose artesunate-amodiaquine (ASAQ Winthrop®) or artemether-lumefantrine (AL, Coartem®), respectively. Clinical- and laboratory-adverse events (AEs) were recorded until day 28. RESULTS: Study-T: most patients experienced at least one AE. Severe AEs were few, primarily asymptomatic blood system disorders or increased liver enzyme values. No treatment or study discontinuation occurred. Mild or moderate fatigue (39.8% vs 16.3%, p < 0.001), vomiting (7.1% vs 1.6%, p < 0.001), nausea (3.2% vs 1.0%, p = 0.01), and anaemia (14.9% vs 9.8%, p = 0.01) were more frequently recorded in the ASAQ versus AL arm. Study-E: mild or moderate AEs were common, including anaemia, fatigue, vomiting or diarrhoea. The few severe events were asymptomatic blood system disorders and four clinical events (pneumonia, malaria, vomiting and stomatitis). CONCLUSION: Both ASAQ and AL were well tolerated in patients of all age groups. No unexpected AEs occurred. Certain mild or moderate AEs were more frequent in the ASAQ arm. Standardised safety surveillance should continue for all forms of ACT. TRIAL REGISTRATION: The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN40020296, ISRCTN51688713, (http://www.controlled-trials.com).

Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial.

BACKGROUND: Prospective efficacy monitoring of anti-malarial treatments is imperative for timely detection of resistance development. The in vivo efficacy of artesunate-amodiaquine (ASAQ) fixed-dose combination (FDC) was compared to that of artemether-lumefantrine (AL) among children aged six to 59 months in Nimba County, Liberia, where Plasmodium falciparum malaria is endemic and efficacy data are scarce. METHODS: An open-label, randomized controlled non-inferiority trial compared the genotyping adjusted day 42 cure rates of ASAQ FDC (ASAQ Winthrop®) to AL (Coartem®) in 300 children aged six to 59 months with uncomplicated falciparum malaria. Inclusion was between December 2008 and May 2009. Randomization (1:1) was to a three-day observed oral regimen (ASAQ: once a day; AL: twice a day, given with fatty food). Day 7 desethylamodiaquine and lumefantrine blood-concentrations were also measured. RESULTS: The day 42 genotyping-adjusted cure rate estimates were 97.3% [95% CI: 91.6-99.1] for ASAQ and 94.2% [88.1-97.2] for AL (Kaplan-Meier survival estimates). The difference in day 42 cure rates was -3.1% [upper limit 95% CI: 1.2%]. These results were confirmed by observed proportion of patients cured at day 42 on the per-protocol population. Parasite clearance was 100% (ASAQ) and 99.3% (AL) on day 3. The probability to remain free of re-infection was 0.55 [95% CI: 0.46-0.63] (ASAQ) and 0.66 [0.57-0.73] (AL) (p = 0.017). CONCLUSIONS: Both ASAQ and AL were highly efficacious and ASAQ was non-inferior to AL. The proportion of patients with re-infection was high in both arms in this highly endemic setting. In 2010, ASAQ FDC was adopted as the first-line national treatment in Liberia. Continuous efficacy monitoring is recommended. TRIAL REGISTRATION: The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN51688713, ISRCTN40020296.

Dealing with snakebite in rural Cameroon: A qualitative investigation among victims and traditional healers.

BACKGROUND: Snakebite is a neglected tropical disease (NTD) affecting rural and remote populations globally, who are additionally burdened by poverty and the lack of effective healthcare systems. Delayed healthcare and use of traditional treatments are very frequent. The purpose of our study was to explore perceptions of snakes, impact of snakebite, and knowledge and opinions of different snakebite treatments with the aim of identifying opportunities for improving snakebite management. METHODS: This is a qualitative descriptive study based on semi-structured interviews with 21 snakebite victims and 4 traditional healers in 4 villages of Akonolinga health district, Center Region, Cameroon. Analysis focused on describing participants' perceptions of snakes, the impact of snakebite on the victims' lives, and their opinions of different treatment options. RESULTS: Respondents were fearful of snakes and knowledgeable about envenoming symptoms and treatments. The experience of snakebite led to increased vigilance and avoidance behaviours, which sometimes resulted in financial loss for the victims. A range of traditional treatments were described, including tourniquets, black-stone application and medicinal plant decoctions. However, opinions were ambivalent regarding their efficacy, depending especially on previous personal experiences. Still, traditional treatments were said to be more available and cheaper than hospital care, and in particular, than antivenom. Nevertheless, most victims preferred hospital treatment if the financial and transportation barriers were lifted. Both snakebite victims and traditional healers were of the opinion that collaboration between health services and traditional healers could help to improve snakebite management and outcomes. CONCLUSION: Our study shows that snakebite victims are in favour of using antivenom for the treatment of snakebite and would welcome better access to it. However, its current unavailability and high cost pushes them to turn to traditional treatments. On the other hand, traditional healers are in favour of collaborating with health facilities. These results are very encouraging for the improvement of snakebite management in Cameroon along the lines of the WHO Snakebite Envenoming Strategy for Prevention and Control: ensuring access to safe and effective treatment, and increasing partnership and coordination between communities, traditional healers, and conventional caregivers.

SARS-CoV-2 antibody seroprevalence and associated risk factors in an urban district in Cameroon.

The extent of SARS-CoV-2 circulation in many African countries remains unclear, underlining the need for antibody sero-surveys to assess the cumulative attack rate. Here, we present the results of a cross-sectional sero-survey of a random sample of residents of a health district in Yaounde, Cameroon, conducted from October 14 to November 26, 2020. Among the 971 participants, the test-adjusted seroprevalence of anti-SARS-CoV-2 IgG antibodies was 29·2% (95% CI 24·3-34·1). This is about 322 times greater than the 0.09% nationwide attack rate implied by COVID-19 case counts at the time. Men, obese individuals and those living in large households were significantly more likely to be seropositive, and the majority (64·2% [58·7-69·4]) of seropositive individuals reported no symptoms. Despite the high seroprevalence, most of the population had not been infected with SARS-CoV-2, highlighting the importance of continued measures to control viral spread and quick vaccine deployment to protect the vulnerable.

Novel transdisciplinary methodology for cross-sectional analysis of snakebite epidemiology at national scale.

BACKGROUND: Worldwide, it is estimated that snakes bite 4.5-5.4 million people annually, 2.7 million of which are envenomed, and 81,000-138,000 die. The World Health Organization reported these estimates and recognized the scarcity of large-scale, community-based, epidemiological data. In this context, we developed the "Snake-Byte" project that aims at (i) quantifying and mapping the impact of snakebite on human and animal health, and on livelihoods, (ii) developing predictive models for medical, ecological and economic indicators, and (iii) analyzing geographic accessibility to healthcare. This paper exclusively describes the methodology we developed to collect large-scale primary data on snakebite in humans and animals in two hyper-endemic countries, Cameroon and Nepal. METHODOLOGY/PRINCIPAL FINDINGS: We compared available methods on snakebite epidemiology and on multi-cluster survey development. Then, in line with those findings, we developed an original study methodology based on a multi-cluster random survey, enhanced by geospatial, One Health, and health economics components. Using a minimum hypothesized snakebite national incidence of 100/100,000/year and optimizing design effect, confidence level, and non-response margin, we calculated a sample of 61,000 people per country. This represented 11,700 households in Cameroon and 13,800 in Nepal. The random selection with probability proportional to size generated 250 clusters from all Cameroonian regions and all Nepalese Terai districts. Our household selection methodology combined spatial randomization and selection via high-resolution satellite images. After ethical approval in Switerland (CCER), Nepal (BPKIHS), and Cameroon (CNERSH), and informed written consent, our e-questionnaires included geolocated baseline demographic and socio-economic characteristics, snakebite clinical features and outcomes, healthcare expenditure, animal ownership, animal outcomes, snake identification, and service accessibility. CONCLUSIONS/SIGNIFICANCE: This novel transdisciplinary survey methodology was subsequently used to collect countrywide snakebite envenoming data in Nepal and Cameroon. District-level incidence data should help health authorities to channel antivenom and healthcare allocation. This methodology, or parts thereof, could be easily adapted to other countries and to other Neglected Tropical Diseases.

Geneva Health Forum: The Forum of Innovative Practices in Global Health.

In the past years, Global Health has interfaced with important challenges related to several dynamic changes. Technological progress, the digital revolution and the emergence of new actors in the field of health, increase the possibility of finding solutions to these unprecedented challenges. Starting from these assumptions, the idea of providing an adequate platform for good management of the health system has flowed into the creation of a meeting place that would allow a wide exchange of information, ideas sharing and proposals for new collaborations: the Geneva Health Forum (GHF). The GHF is a global health conference that aims to promote critical reflections and constructive debates on contemporary global health issues, thus influencing and informing policy formulation with experience from the field. The profile and impact of the Geneva Health Forum has grown year on year, establishing itself as a unique forum, ranging from more traditional sessions to innovative events.

Snakebite epidemiology and health-seeking behavior in Akonolinga health district, Cameroon: Cross-sectional study.

BACKGROUND: Snakebite envenoming causes 81,000-138,000 annual human deaths and pain, terror, or disability in 4.5-5.4 million victims. Accurate community-based epidemiological data is scarce. Our objective was to assess snakebite incidence, mortality, and health-seeking behavior, in an affected health district of Cameroon. METHODS: We conducted a cross-sectional multicluster household survey in Akonolinga health district, Centre Region, Cameroon, from October to December 2016. Using probability-proportional-to-size, 20 villages were randomly selected, then, all inhabited households were systematically selected. Annual incidence and adjusted odds-ratio for predictors were estimated. FINDINGS: Among the 9,924 participants, 66 suffered a snakebite during the past year: the resulting incidence is 665 (95%CI: 519-841) per 100,000 inhabitants per year. Victims were aged 5-75y (median: 34y), 53% were male and 57% farmer-cultivators. Two children died (case-fatality rate: 3%); 39 (59%) presented severity signs, including 2 (3%) neurotoxic syndromes, 20 (30%) systemic digestive syndromes, and 17 (26%) severe cytotoxic syndromes. Non-severe cases included 20 (30%) mild cytotoxic syndromes and 7 (11%) dry bites. Only two victims (3%) received antivenom. 59 (89%) used family traditional practices, 25 (38%) traditional healers, and 31 (47%) consulted health facilities. Median delays to these three care-options were 5, 45, and 60 minutes, respectively. Traditional treatments included incisions (n = 57; 86%), tourniquets (n = 51; 77%) and black-stones (n = 44; 67%). The two last procedures were also used in health facilities (n = 18). Consulting traditional healers was associated with severity (adjusted-OR: 19.6 (2.5-156), p = 0.005) and complications (aOR: 17.3, 2.4-123, p = 0.004). Long-term disabilities were subjective psychological trauma (n = 47; 71%), finger amputation (n = 1; 2%), ankylosis (n = 1; 2%) and chronic pain (n = 1; 2%). CONCLUSIONS: We observed alarming levels of snakebite incidence, mortality, antivenom scarcity, and use of traditional medicine. It could represent several thousands of victims at national level. We suggested conducting a country-wide study, and improving antivenom supply, first-aid training, for traditional healers and health professionals.

Evaluation of three parasite lactate dehydrogenase-based rapid diagnostic tests for the diagnosis of falciparum and vivax malaria.

BACKGROUND: In areas where non-falciparum malaria is common rapid diagnostic tests (RDTs) capable of distinguishing malaria species reliably are needed. Such tests are often based on the detection of parasite lactate dehydrogenase (pLDH). METHODS: In Dawei, southern Myanmar, three pLDH based RDTs (CareStart Malaria pLDH (Pan), CareStart Malaria pLDH (Pan, Pf) and OptiMAL-IT)were evaluated in patients presenting with clinically suspected malaria. Each RDT was read independently by two readers. A subset of patients with microscopically confirmed malaria had their RDTs repeated on days 2, 7 and then weekly until negative. At the end of the study, samples of study batches were sent for heat stability testing. RESULTS: Between August and November 2007, 1004 patients aged between 1 and 93 years were enrolled in the study. Slide microscopy (the reference standard) diagnosed 213 Plasmodium vivax (Pv) monoinfections, 98 Plasmodium falciparum (Pf) mono-infections and no malaria in 650 cases. The sensitivities (sens) and specificities (spec), of the RDTs for the detection of malaria were- CareStart Malaria pLDH (Pan) test: sens 89.1% [CI95 84.2-92.6], spec 97.6% [CI95 96.5-98.4]. OptiMal-IT: Pf+/- other species detection: sens 95.2% [CI95 87.5-98.2], spec 94.7% [CI95 93.3-95.8]; non-Pf detection alone: sens 89.6% [CI95 83.6-93.6], spec 96.5% [CI95 94.8-97.7]. CareStart Malaria pLDH (Pan, Pf): Pf+/- other species: sens 93.5% [CI95 85.4-97.3], spec 97.4% [95.9-98.3]; non-Pf: sens 78.5% [CI95 71.1-84.4], spec 97.8% [CI95 96.3-98.7]. Inter-observer agreement was excellent for all tests (kappa > 0.9). The median time for the RDTs to become negative was two days for the CareStart Malaria tests and seven days for OptiMAL-IT. Tests were heat stable up to 90 days except for OptiMAL-IT (Pf specific pLDH stable to day 20 at 35 degrees C). CONCLUSION: None of the pLDH-based RDTs evaluated was able to detect non-falciparum malaria with high sensitivity, particularly at low parasitaemias. OptiMAL-IT performed best overall and would perform best in an area of high malaria prevalence among screened fever cases. However, heat stability was unacceptable and the number of steps to perform this test is a significant drawback in the field. A reliable, heat-stable, highly sensitive RDT, capable of diagnosing all Plasmodium species has yet to be identified.

Knowledge, attitude and practices of snakebite management amongst health workers in Cameroon: Need for continuous training and capacity building.

BACKGROUND: Snakebite has only recently been recognized as a neglected tropical disease by the WHO. Knowledge regarding snakebites and its care is poor both at the population level, and at the health care staff level. The goal of this study was to describe the level of knowledge and clinical practice regarding snakebite among health care staff from Cameroon. METHODS: A two-day training dedicated to snakebite and its care was organized in 2015 in Yaoundé, capital city of Cameroon. A total of 98 health care staff from all over Cameroon attended the training. Prior to and after the training, an evaluation quantified the attendees' level of knowledge. Pre- and post-training evaluations were compared to assess knowledge improvement. RESULTS: Overall, prior to the training knowledge regarding snakebite and care was poor, and wrong beliefs that "pierre noire" or tourniquet were useful in case of snakebite were common. Knowledge was statistically improved after the training. CONCLUSION: Trainings dedicated to all type of health care staff towards snakebite to improve care are needed, this training must take into consideration the context and the targeted population.

Mycobacterium ulcerans infection: control, diagnosis, and treatment.

The skin disease Buruli ulcer, caused by Mycobacterium ulcerans, is the third most common mycobacterial disease after tuberculosis and leprosy and mainly affects remote rural African communities. Although the disease is known to be linked to contaminated water, the mode of transmission is not yet understood, which makes it difficult to propose control interventions. The disease is usually detected in its later stages, when it has caused substantial damage and disability. Surgery remains the treatment of choice. Although easy and effective in the early stages of the disease, treatment requires extended excisions and long hospitalisation for the advanced forms of the disease. Currently, no antibiotic treatment has proven effective for all forms of M ulcerans infection and research into a new vaccine is urgently needed. While the scientific community works on developing non-invasive and rapid diagnostic tools, the governments of endemic countries should implement active case finding and health education strategies in their affected communities to detect the disease in its early stages. We review the diagnosis, treatment, and control of Buruli ulcer and list priorities for research and development.

The "Buruli Score": Development of a Multivariable Prediction Model for Diagnosis of Mycobacterium ulcerans Infection in Individuals with Ulcerative Skin Lesions, Akonolinga, Cameroon.

BACKGROUND: Access to laboratory diagnosis can be a challenge for individuals suspected of Buruli Ulcer (BU). Our objective was to develop a clinical score to assist clinicians working in resource-limited settings for BU diagnosis. METHODODOLOGY/PRINCIPAL FINDINGS: Between 2011 and 2013, individuals presenting at Akonolinga District Hospital, Cameroon, were enrolled consecutively. Clinical data were collected prospectively. Based on a latent class model using laboratory test results (ZN, PCR, culture), patients were categorized into high, or low BU likelihood. Variables associated with a high BU likelihood in a multivariate logistic model were included in the Buruli score. Score cut-offs were chosen based on calculated predictive values. Of 325 patients with an ulcerative lesion, 51 (15.7%) had a high BU likelihood. The variables identified for the Buruli score were: characteristic smell (+3 points), yellow color (+2), female gender (+2), undermining (+1), green color (+1), lesion hyposensitivity (+1), pain at rest (-1), size >5cm (-1), locoregional adenopathy (-2), age above 20 up to 40 years (-3), or above 40 (-5). This score had AUC of 0.86 (95%CI 0.82-0.89), indicating good discrimination between infected and non-infected individuals. The cut-off to reasonably exclude BU was set at scores <0 (NPV 96.5%; 95%CI 93.0-98.6). The treatment threshold was set at a cut-off ≥4 (PPV 69.0%; 95%CI 49.2-84.7). Patients with intermediate BU probability needed to be tested by PCR. CONCLUSIONS/SIGNIFICANCE: We developed a decisional algorithm based on a clinical score assessing BU probability. The Buruli score still requires further validation before it can be recommended for wide use.

Differential Diagnosis of Skin Ulcers in a Mycobacterium ulcerans Endemic Area: Data from a Prospective Study in Cameroon.

BACKGROUND: Clinical diagnosis of Buruli ulcer (BU) due to Mycobacterium ulcerans can be challenging. We aimed to specify the differential diagnosis of skin lesions in a BU endemic area. METHOD: We conducted a prospective diagnostic study in Akonolinga, Cameroon. Patients presenting with a skin ulcer suspect of BU were included. M. ulcerans was detected using swabs for Ziehl-Neelsen staining, PCR and culture. Skin punch biopsies were taken and reviewed by two histopathologists. Photographs of the lesions were taken and independently reviewed by two dermatologists. Final diagnosis was based on consensus, combining the results of laboratory tests and expert opinion. RESULTS/ DISCUSSION: Between October 2011 and December 2013, 327 patients with ulcerative lesions were included. Median age was 37 years (0 to 87), 65% were males, and 19% HIV-positive. BU was considered the final diagnosis for 27% of the lesions, 85% of which had at least one positive laboratory test. Differential diagnoses were vascular lesions (22%), bacterial infections (21%), post-traumatic (8%), fistulated osteomyelitis (6%), neoplasia (5%), inflammatory lesions (3%), hemopathies and other systemic diseases (2%) and others (2%). The proportion of BU was similar between HIV-positive and HIV-negative patients (27.0% vs. 26.5%; p = 0.940). Half of children below 15 years of age were diagnosed with BU, compared to 26.8% and 13.9% among individuals 15 to 44 years of age and above, respectively (chi2 p<0.001). Children had more superficial bacterial infections (24.3%) and osteomyelitis (11.4%). CONCLUSION: We described differential diagnosis of skin lesions in a BU endemic area, stratifying results by age and HIV-status.

The urgent need for clinical, diagnostic, and operational research for management of Buruli ulcer in Africa.

Despite great advances in the diagnosis and treatment of Buruli ulcer, it is one of the least studied major neglected tropical diseases. In Africa, major constraints in the management of Buruli ulcer relate to diagnosis and treatment, and accessibility, feasibility, and delivery of services. In this Personal View, we outline key areas for clinical, diagnostic, and operational research on this disease in Africa and propose a research agenda that aims to advance the management of Buruli ulcer in Africa. A model of care is needed to increase early case detection, to diagnose the disease accurately, to simplify and improve treatment, to reduce side-effects of treatment, to deal with populations with HIV and tuberculosis appropriately, to decentralise care, and to scale up coverage in populations at risk. This approach will require commitment and support to strategically implement research by national Buruli ulcer programmes and international technical and donor organisations, combined with adaptations in programme design and advocacy. A critical next step is to build consensus for a research agenda with WHO and relevant groups experienced in Buruli ulcer care or related diseases, and we call on on them to help to turn this agenda into reality.

Impact of human immunodeficiency virus on the severity of buruli ulcer disease: results of a retrospective study in cameroon.

BACKGROUND: Buruli ulcer is the third most common mycobacterial disease after tuberculosis and leprosy and is particularly frequent in rural West and Central Africa. However, the impact of HIV infection on BU severity and prevalence remains unclear. METHODS: This was a retrospective study of data collected at the Akonolinga District Hospital, Cameroon, from January 1, 2002 to March 27, 2013. Human immunodeficiency virus prevalence among BU patients was compared with regional HIV prevalence. Baseline characteristics of BU patients were compared between HIV-negative and HIV-positive patients and according to CD4 cell count strata in the latter group. Buruli ulcer time-to-healing was assessed in different CD4 count strata, and factors associated with BU main lesion size at baseline were identified. RESULTS: Human immunodeficiency virus prevalence among BU patients was significantly higher than the regional estimated prevalence in each group (children, 4.00% vs 0.68% [P < .001]; men, 17.0% vs 4.7% [P < .001]; women, 36.0% vs 8.0% [P < .001]). Individuals who were HIV positive had a more severe form of BU, with an increased severity in those with a higher level of immunosuppression. Low CD4 cell count was significantly associated with a larger main lesion size (ß-coefficient, -0.50; P = .015; 95% confidence interval [CI], -0.91-0.10). Buruli ulcer time-to-healing was more than double in patients with a CD4 cell count below 500 cell/mm(3) (hazard ratio, 2.39; P = .001; 95% CI, 1.44-3.98). CONCLUSION: Patients who are HIV positive are at higher risk for BU. Human immunodeficiency virus-induced immunosuppression seems to have an impact on BU clinical presentation and disease evolution.

Prevalence of Buruli ulcer in Akonolinga health district, Cameroon: results of a cross sectional survey.

BACKGROUND: Buruli ulcer (BU) is a chronic, indolent necrotizing disease of the skin and underlying tissues caused by Mycobacterium ulcerans, which may result in functional incapacity. In 2002, Médecins Sans Frontières (MSF) opened a BU programme in Akonolinga Hospital, Cameroon, offering antibiotic treatment, surgery and general medical care. Six hundred patients have been treated in the project to date. However, due to the nature of the disease and its stigmatization, determining the exact prevalence and burden of disease is difficult and current estimates may not reflect the magnitude of the problem. The objectives of this survey were to estimate the prevalence of BU in the health district of Akonolinga, describe the geographic extension of the highly endemic area within the health district, and determine the programme coverage and its geographical distribution. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional population survey using centric systematic area sampling (CSAS). A 15x15 km grid (quadrats of 225 km(2)) was overlaid on a map of Akonolinga district with its position chosen to maximize the area covered by the survey. Quadrats were selected if more than 50% of the quadrat was inside of the health district. The chiefdom located closest to the centre of each quadrat was selected and Buruli cases were identified using an active case finding strategy (the sensitivity of the strategy was estimated by capture-recapture). WHO-case definitions were used for nodules, plaque, ulcer, oedema and sequelae. Out of a total population of 103,000 inhabitants, 26,679 were surveyed within the twenty quadrats. Sensitivity of the case finding strategy was estimated to be 84% (95%CI 54-97%). The overall prevalence was 0.47% (n = 105) for all cases including sequelae and 0.25% (n = 56) for active stages of the disease. Five quadrats had a high prevalence of >0.6% to 0.9%, 5 a prevalence >0.3% to 0.6% and 10 quadrats <0.3%. The quadrats with the high prevalence were situated along the rivers Nyong and Mfoumou. Overall coverage of the project was 18% (12-27%) for all cases and 16% (9-18%) for active cases, but was limited to the quadrats neighbouring Akonolinga Hospital. CONCLUSIONS/SIGNIFICANCE: Prevalence was highest in the area neighbouring the Nyong River. Coverage was limited to the area close to the hospital and efforts have to be made to increase access to care in the high prevalence areas. Use of the CSAS method was particularly useful for project planning and to identify priority areas of intervention. An added benefit of the method is that the survey procedure incorporated an awareness campaign, providing information about the disease and treatment to the population.