Buruli Ulcer Cases Research Articles

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

Buruli ulcer, caused by Mycobacterium ulcerans, was identified 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-confirmed 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 effect on the occurrence of permanent functional sequelae. 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 confirmed. 1227 cases of laboratory-confirmed 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 identifiable 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 significantly 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 significantly associated with occurrence of permanent functional sequelae (OR 7·64, 95% CI 5·29-11·31) and operationally defines severe Buruli ulcer. Our findings 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-specific aspect in areas endemic for Buruli ulcer; and specific disability prevention for patients presenting with osteomyelitis, oedema, or multifocal or large lesions. Our findings 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. Agence Nationale de la Recherche (ANR), Fondation Raoul Follereau, Fondation pour la Recherche Médicale (FRM), and Institut des Maladies Génétiques (IMAGINE).

Buruli Ulcer Disease in Republic of the Congo

Buruli Ulcer Disease in Republic of the Congo

Late onset of the serological response against the 18 kDa small heat shock protein of Mycobacterium ulcerans in children.

A previous survey for clinical cases of Buruli ulcer (BU) in the Mapé Basin of Cameroon suggested that, compared to older age groups, very young children may be less exposed to Mycobacterium ulcerans. Here we determined serum IgG titres against the 18 kDa small heat shock protein (shsp) of M. ulcerans in 875 individuals living in the BU endemic river basins of the Mapé in Cameroon and the Densu in Ghana. While none of the sera collected from children below the age of four contained significant amounts of 18 kDa shsp specific antibodies, the majority of sera had high IgG titres against the Plasmodium falciparum merozoite surface protein 1 (MSP-1). These data suggest that exposure to M. ulcerans increases at an age which coincides with the children moving further away from their homes and having more intense environmental contact, including exposure to water bodies at the periphery of their villages.

Management of Mycobacterium ulcerans disease (buruli ulcer) in the Territory of Songololo, Democratic Republic of Congo: Outcomes, challenges and prospects

Background: Buruli ulcer is caused by infection with Mycobacterium ulcerans, an organism which belongs to the family of bacteria that causes tuberculosis and leprosy. Without treatment, the infection leads to destruction of skin and soft tissue with large ulcers usually on limbs, resulting to long-term functional disability. The General Reference Hospital of the “Institut Médical Evangélique” of Kimpese, located in the Territory of Songololo, known to be one of the main Buruli ulcer (BU) foci in the Democratic Republic of Congo, launched in 2004 a specialized BU program, offering in-patient treatment free-of-charge and supplementary aid. Although the number of BU cases admitted in the hospital was rising, a survey conducted in July-August 2008, in the Territory of Songololo, showed that only one in thirteen active BU cases was notified at the hospital at Kimpese in the 8 months prior to the survey. Methods & Materials: We conducted a prospective observational study from 2009 through 2012 to assess the impact of decentralization and integration of BU control activities at the primary level of the health system in Songololo. Results: The preliminary impact evaluation of the decentralization showed: (i) strong increase in case detection (3.6 times more cases detected), four years (2004-2007) before the Songololo survey conducted in 2008, 183 new cases have been reported, while 655 were detected after (2009-2012); (ii) the preponderance of category I lesions the last four years; (iii) around 50% of reported cases were confirmed by at least one laboratory test; (iv) three-quarters of reported cases have been treated in peripheral health centres; (v) increase in number of health areas reporting cases: On average, 15 out of 40 health areas before and 28 out of 40 after. Conclusion: Decentralization and integration of BU control activities seem to be key ways of improvement of access to diagnosis and care at the most peripheral level of the health system. Partnership with health zones are of utmost importance for the implementation of a simple, functional, and efficient surveillance system in a resource-limited context, exportable in other BU endemic regions of the country. Meanwhile, sustaining the project's impact remains a big challenge in the region.

Buruli Ulcer Caused byMycobacterium ulceransSubspshinshuense

Buruli ulcer, a severe skin infectious disease caused by Mycobacterium ulcerans, is prevalent in tropical and subtropical areas. Recently, cases of Buruli ulcer have been increasing in Japan. All cases have been sporadic, and to date the pathogenic organism has not been detected in materials from the environment. Three members of the same family were seen with large indurated plaques on their face and extremities in the winter of 2010. Skin biopsy specimens of their lesions showed extensive necrosis of deep dermis and subcutaneous fat. Acid-fast bacilli were detected in each biopsy specimen by Ziehl-Neelsen stain, and bacteriological analysis of cultured microorganisms revealed the strains to be M ulcerans subsp shinshuense. The patients were treated with a combination of antibiotics and surgical debridement. Insertion sequence 2404 was detected from a crayfish captured in a stagnant water channel in the backyard of the family's house. We report a rare instance of familial occurrence of Buruli ulcer in Japan. Detection of insertion sequence 2404 from a crayfish suggests that the pathogenic organism may reside in an aquatic environment in Japan, as in other endemic areas. To prevent this serious infectious disease, further investigation is needed to clarify the transmission pathway.

Genotyping Tools for Mycobacterium ulcerans-Drawbacks and Future Prospects.

Mycobacterium ulcerans infection (Buruli ulcer) is a neglected but treatable skin disease endemic in over 30 countries. M. ulcerans is an environmental mycobacteria with an elusive mode of transmission to humans. Ecological and Molecular epidemiological studies to identify reservoirs and transmission vectors are important for source tracking infections especially during outbreaks and elucidating transmission routes. Research efforts have therefore focused on genotyping strains of the mycobacteria from clinical and environmental samples. This review discusses genotyping tools for differentiating M. ulcerans strains from other environmental and Mycolactone Producing Mycobacteria (MPMs). We highlight tools that have been adapted from related fields and propose ways these could be enhanced to resolve intra-species variation for epidemiological, transmission, evolutionary studies, and detection of emerging drug resistant strains. In the wake of increasing cases of Buruli ulcer, cumulative efforts including improvement in diagnostic methods and fine-tuning of genotyping tools are crucial to complement public health efforts in reducing infections.

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

BackgroundCutaneous infection by Mycobacterium ulcerans, 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.MethodsWe 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.ResultsWe 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.ConclusionThe 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.

Household cost of out-patient treatment of Buruli ulcer in Ghana: a case study of Obom in Ga South Municipality

BackgroundThe economic burden of diseases has become increasingly relevant to policy makers as healthcare expenditure keep rising in the face of limited and competing resources. Buruli ulcer (BU), a neglected but treatable tropical disease caused by Mycobacterium ulcerans, the only known environmental mycobacterium is capable of causing long term disability when left untreated. However, most BU studies have tended to focused on its bacteriology, epidemiology, entomology and other social determinants to the neglect of its economic evaluation. This paper reports estimated the household economic costs of BU and describe the intangible cost suffered by BU patients in an endemic area.MethodsRetrospective one year cost data was used. A total of 63 confirmed BU cases were randomly sampled for the study. Economic cost and cost burden of BU were estimated. Sensitivity analysis was conducted to test the robustness of the cost estimates. Intangible cost measured stigmatization, pain, functional limitation and social isolation of children.ResultsThe annual total household economic cost was US$35,915.98, of which about 65% was cost incurred by children with a mean cost of US$521.04. The mean annual household cost was US$570.09. The direct cost was 96% of the total cost. Non-medical cost accounts for about 97% of the direct cost with a mean cost of US$529.27. The mean medical cost was US$18.94. The main cost drivers of the household costs were transportation (78%) and food (12%). Caregivers and adult patients lost a total of 535 productive days seeking care, which gives an indirect cost valued at US$1,378.67 with a mean of US$21.88. A total of 365 school days (about 1 year) were lost by 19 BU patients (mean, 19.2 days). Functional loss and pain were low, and stigma rated moderate. Most children suffering from BU (84%) were socially isolated.ConclusionHousehold cost burden of out-patient BU ulcer treatment was high. Household cost of BU is therefore essential in the design of its intervention. BU afflicted children experience social isolation.

Mycobacterium ulcerans disease (Buruli ulcer) in Gabon: 2005-2011

The first cases of Buruli ulcer (BU) in Gabon were described in the 1960s. Between 2005 and 2011, 301 clinically suspected cases of BU were found in all nine provinces of Gabon, and their lesions sampled for microbiological confirmation. Polymerase chain reaction (PCR) found 120 (39.9%) of these lesions positive and 181 (60.1%) negative for Mycobacterium ulcerans. The confirmed cases came mainly from the province of Moyen-Ogooué, particularly from localities along the Ogooué River (n=117; 52.5% of the samples in this province were PCR-positive). The detection rates per 100,000 inhabitants in this province ranged from 94.7 cases in 2005 to 28 in 2007, after an absence of active case-finding in 2006. The final three PCR-positive cases were found in the province of Estuaire. The characteristics of the confirmed BU patients (that is, PCR-positive) were identical to those described in other African countries: most patients were younger than 15 years old, and most lesions were found on both the upper and lower limbs. The group of suspected cases (PCR-negative) differed from the PCR-positive group for patient age (most patients were aged 15 to 49 years), lesion location (more frequently on the lower limbs), and ulceration (more frequent in the suspected cases). Some PCR-negative patients probably had other diseases; this underlines the importance of the differential diagnosis of BU. The cure rate of PCR(-)confirmed cases in our study was 88%; treatment was the antibiotic combination recommended by the World Health Organization (WHO). Our study demonstrates that BU is endemic in Gabon and is a public health problem there. Patients consult late with often extensive lesions. Awareness campaigns should be pursued to ensure earlier treatment of patients. The influence of HIV on BU in Gabon also deserves particular attention.

Geographic Distribution, Age Pattern and Sites of Lesions in a Cohort of Buruli Ulcer Patients from the Mapé Basin of Cameroon

Buruli ulcer (BU), a neglected tropical disease of the skin, caused by Mycobacterium ulcerans, occurs most frequently in children in West Africa. Risk factors for BU include proximity to slow flowing water, poor wound care and not wearing protective clothing. Man-made alterations of the environment have been suggested to lead to increased BU incidence. M. ulcerans DNA has been detected in the environment, water bugs and recently also in mosquitoes. Despite these findings, the mode of transmission of BU remains poorly understood and both transmission by insects or direct inoculation from contaminated environment have been suggested. Here, we investigated the BU epidemiology in the Mapé basin of Cameroon where the damming of the Mapé River since 1988 is believed to have increased the incidence of BU. Through a house-by-house survey in spring 2010, which also examined the local population for leprosy and yaws, and continued surveillance thereafter, we identified, till June 2012, altogether 88 RT-PCR positive cases of BU. We found that the age adjusted cumulative incidence of BU was highest in young teenagers and in individuals above the age of 50 and that very young children (<5) were underrepresented among cases. BU lesions clustered around the ankles and at the back of the elbows. This pattern neither matches any of the published mosquito biting site patterns, nor the published distribution of small skin injuries in children, where lesions on the knees are much more frequent. The option of multiple modes of transmission should thus be considered. Analyzing the geographic distribution of cases in the Mapé Dam area revealed a closer association with the Mbam River than with the artificial lake.

Rapid Assessment Survey of The Prevalence of Buruli Ulcer in The Health District of South Maniema, Maniema Province, The Democratic Republic of The Congo

Background: Buruli ulcer (BU) is endemic in more than 30 countries worldwide. Africa is the most affected continent with 16 confirmed endemic countries and 7 suspected or potential endemic countries. In the Democratic Republic of the Congo, a survey in 2004 showed the presence of suspected cases of BU in five of the country’s 11 provinces. The current survey was carried out in 2010 to confirm the endemicity of BU is the southern part of the Maniema Province and to provide support for case management and control measures if necessary. Method: The method of the survey was based on the protocol of rapid prevalence assessment survey (RPAS), proposed by the Buruli ulcer control Program of the World Health Organization (WHO) Regional Office for Africa to confirm BU endemic in countries. It included: awareness campaign and sensitization of health workers and communities in suspected endemic areas, followed by clinical screening of patients with suspected BU lesions and sampling of suspicious lesions by swab or fine needle aspiration (FNA) for laboratory confirmation of diagnosis, mainly by PCR. WHO-recommended treatment is proposed for cases which clinical features were in favor of the diagnosis of Buruli ulcer. Results: The survey in the Southern part of Maniema province targeted six of the nine health zones of Kasongo district. The three other health zones in the district were not be visited for accessibility and security reasons. A total of 66 suspected cases of Buruli ulcer were found at the Hospital of Kindu and in the six visited health zones. The lab tests with Ziehl-Nielsen (ZN) technique have confirmed 9 cases of BU. PCR tests confirmed eight cases of BU, including three who were not positive to the ZN tests. This makes a total of 12 BU patients confirmed by ZN and/or PCR and gives a proportion of laboratory confirmation of 18%. Discussions: Based on the results of this survey all health zones in South Maniema were classified as Buruli ulcer endemic areas, because of the same geo-climatic features that characterize all of them. These findings are similar to those of previous studies in the same province. The low confirmation rate of BU suspected cases by laboratory tests (18%) could be explained by the fact that many of the suspicious lesions which were sampled were very old wounds and had been evolving for several years. The WHO Regional Office for Africa has developed a plan of surveys, using the same rapid assessment protocol to confirm the endemicity of Buruli ulcer in other suspected endemic provinces of the DRC and in other member states of WHO African Region.

Buruli Ulcer and Mycolactone-Producing Mycobacteria

Buruli ulcer (BU) is an emerging human disease caused by Mycobacterium ulcerans, which mainly affects the extremities. It is most endemic in sub-Saharan Africa; however, it has been reported worldwide, including in some non-tropical areas. "M. ulcerans subsp. shinshuense" is proposed as a subspecies of M. ulcerans, which have been reported from Japan and China. A total of 35 BU cases have been reported as of November 2012. Although M. ulcerans is categorized as nontuberculous mycobacteria, it has some unique characteristics that could only be observed in this bacterium. It possesses a giant virulent plasmid, composed of 174-kbp nucleotides, coding polyketide synthase to produce macrolide toxin called mycolactone. The discovery of such a linkage of plasmid and its pathogenesis has not been reported in other human disease-causing mycobacteria.

Climate and landscape factors associated with Buruli ulcer incidence in Victoria, Australia.

BackgroundBuruli ulcer (BU), caused by Mycobacterium ulcerans (M. ulcerans), is a necrotizing skin disease found in more than 30 countries worldwide. BU incidence is highest in West Africa; however, cases have substantially increased in coastal regions of southern Australia over the past 30 years. Although the mode of transmission remains uncertain, the spatial pattern of BU emergence in recent years seems to suggest that there is an environmental niche for M. ulcerans and BU prevalence.Methodology/Principal FindingsNetwork analysis was applied to BU cases in Victoria, Australia, from 1981–2008. Results revealed a non-random spatio-temporal pattern at the regional scale as well as a stable and efficient BU disease network, indicating that deterministic factors influence the occurrence of this disease. Monthly BU incidence reported by locality was analyzed with landscape and climate data using a multilevel Poisson regression approach. The results suggest the highest BU risk areas occur at low elevations with forested land cover, similar to previous studies of BU risk in West Africa. Additionally, climate conditions as far as 1.5 years in advance appear to impact disease incidence. Warmer and wetter conditions 18–19 months prior to case emergence, followed by a dry period approximately 5 months prior to case emergence seem to favor the occurrence of BU.Conclusions/SignificanceThe BU network structure in Victoria, Australia, suggests external environmental factors favor M. ulcerans transmission and, therefore, BU incidence. A unique combination of environmental conditions, including land cover type, temperature and a wet-dry sequence, may produce habitat characteristics that support M. ulcerans transmission and BU prevalence. These findings imply that future BU research efforts on transmission mechanisms should focus on potential vectors/reservoirs found in those environmental niches. Further, this study is the first to quantitatively estimate environmental lag times associated with BU outbreaks, providing insights for future transmission investigations.

Buruli Ulcer in Gabon, 2001–2010

To the Editor: Worldwide, Buruli ulcer is the third most common mycobacterial infection, following only tuberculosis and leprosy (1,2). It has been identified in 30 countries, including 12 African countries (1–3). For Gabon, the first report of a case consistent with Buruli ulcer was published in 1961 (4). The patient was a European woman who sought care at a hospital in Lambarene for a painless upper arm nodule, which evolved into a plaque and then an extensive ulcer. The only other Buruli ulcer reports available for Gabon are a case report from 1968 and a case-series report from 1986 (5,6). We report data for Buruli ulcer in this sub-Saharan African country for 2001–2010, including prevalence within a hospital population and clinical presentation of the cases. These data can be used to assess long-term developments in the number of cases of Buruli ulcer in this region. In Gabon, the major focus of Buruli ulcer is the area around Lambarene (population ≈25,000), the capital of Moyen Ogooue Province (population ≈35,000). It is located near the equator in the central African rainforest. Lambarene lies near the confluence of 2 major rivers, Ogooue and Ngounie, and is the starting point for one of the largest river deltas in Africa. Numerous lakes are present throughout the region. The Albert Schweitzer Hospital in Lambarene serves the entire province. At this hospital, Buruli ulcer is diagnosed on the basis of clinical presentation. In addition, tissue samples are sent to the Prince Leopold Institute of Tropical Medicine in Belgium for PCR analysis. All cases are treated surgically, and since 2006, patients have received rifampin and streptomycin as well. Since 2007, patient information has been recorded on a BU-02 form, designed by the World Health Organization to register and report cases of Buruli ulcer (1). We reviewed cases of Buruli ulcer at the Albert Schweitzer Hospital. We checked the hospital registry and patient records from 2001 through 2010 to identify probable cases of Buruli ulcer on the basis of clinical appearance and response to treatment. We also gathered information from BU-02 forms from 2007 through 2010. During 2001–2010, the number of patients admitted to surgical wards because of suspected Buruli ulcer ranged from 5 to 40 per year (average 25 patients/year) (Figure). Despite moderate variability from year to year, the number of cases over the years increased (χ2 for trend, p = 0.003), which could be associated with increased awareness of the disease. The variability was not caused by changes in the number of patients hospitalized. Figure Number (line) and prevalence (in parentheses) of Buruli ulcer cases, Gabon, 2001–2010. During 2007–2010, detailed clinical information from BU-02 forms was available for 77 patients. PCR results were available for 57 patients and confirmed the diagnosis for 39. Patient ages ranged from 2 to 72 years; 40 (52%) patients were 5 cm. The lesions were located on the lower arm for 41 (53%) patients, upper arm for 28 (36%) patients, chest and/or back for 7 (9%) patients, and perineal region for 1 (1%) patient. Depending on the type of lesion, the length of hospitalization ranged from 1 to 352 days (median 31 days). The longest hospitalization was almost 1 year; the patient was a child who had severe lesions and lived in conditions in which adequate wound care and follow-up after hospital discharge were unlikely. In Gabon, the available data on Buruli ulcer come mainly from surgical wards in areas where prevalence is high. A national survey of hospital registration data in 2005 detected 3 cases in Ngounie Province in southern Gabon and 5 cases in Woleu-Ntem Province in northern Gabon. All cases are thought to have been acquired locally, thus establishing the existence of 2 previously unknown foci (U. Ateba Ngoa et al., unpub. data). Buruli ulcer has a strong economic effect on the community and health facilities. For example, in 2010, management of the disease at the Albert Schweitzer Hospital cost an estimated 554–1,660 euros per person, not including drug costs (7). In 2009, African countries where Buruli ulcer is endemic, including Gabon, signed the Cotonou Declaration (8). According to this declaration, these countries have committed themselves to fight Buruli ulcer by several measures, including assessing the magnitude of the disease and conducting surveillance.

Buruli-Ulcer Induced Disability in Ghana: A Study at Apromase in the Ashanti Region

Objectives. To describe trends and category of disabilities caused by Buruli ulcer disease. Design. This retrospective study was set up to quantify information on the disability trends caused by Buruli ulcer (BU) using data on patients attending BU and chronic ulcer clinics from 2004 to 2009, at Global Evangelical Mission Hospital, Apromase. Methods. Data was retrieved from the WHO BU1 form, case registry book, surgical theatre register, and BU patients' records book of the hospital. Disability was measured as the incapability of patients to perform one or more daily activities due to his/her state of BU disease before treatment. Results. A total of 336 positive BU cases comprising 181 males (53.9%) were recorded of which 113 (33.6%) cases of disabilities were identified. A mean age of 52.5 (±1.32) years was recorded. For the trend of disabilities, the year 2009 recorded the highest (N = 34, 31.0%). The lesions were mostly located at the lower limbs (N = 65, 57.5%) region of the patients. Lesions with diameter >15 cm were the major (59.3%) category of lesions. Conclusion. Trend of disability reveals proportional increase over the years from 2004 to 2009. Contracture at the knee and ankle joints was the commonest disability recorded.

Detection of Mycobacterium ulcerans by the Loop Mediated Isothermal Amplification Method

BackgroundBuruli ulcer (BU) caused by Mycobacterium ulcerans (M. ulcerans) has emerged as an important public health problem in several rural communities in sub-Saharan Africa. Early diagnosis and prompt treatment are important in preventing disfiguring complications associated with late stages of the disease progression. Presently there is no simple and rapid test that is appropriate for early diagnosis and use in the low-resource settings where M. ulcerans is most prevalent.MethodologyWe compared conventional and pocket warmer loop mediated isothermal amplification (LAMP) methods (using a heat block and a pocket warmer respectively as heat source for amplification reaction) for the detection of M. ulcerans in clinical specimens. The effect of purified and crude DNA preparations on the detection rate of the LAMP assays were also investigated and compared with that of IS2404 PCR, a reference assay for the detection of M. ulcerans. Thirty clinical specimens from suspected BU cases were examined by LAMP and IS2404 PCR.Principal FindingsThe lower detection limit of both LAMP methods at 60°C was 300 copies of IS2404 and 30 copies of IS2404 for the conventional LAMP at 65°C. When purified DNA extracts were used, both the conventional LAMP and IS2404 PCR concordantly detected 21 positive cases, while the pocket warmer LAMP detected 19 cases. Nine of 30 samples were positive by both the LAMP assays as well as IS2404 PCR when crude extracts of clinical specimens were used.Conclusion/SignificanceThe LAMP method can be used as a simple and rapid test for the detection of M. ulcerans in clinical specimens. However, obtaining purified DNA, as well as generating isothermal conditions, remains a major challenge for the use of the LAMP method under field conditions. With further improvement in DNA extraction and amplification conditions, the pwLAMP could be used as a point of care diagnostic test for BU

Detection of Mycobacterium ulcerans in the Environment Predicts Prevalence of Buruli Ulcer in Benin

Background Mycobacterium ulcerans is the causative agent of Buruli ulcer (BU). In West Africa there is an association between BU and residence in low-lying rural villages where aquatic sources are plentiful. Infection occurs through unknown environmental exposure; human-to-human infection is rare. Molecular evidence for M. ulcerans in environmental samples is well documented, but the association of M. ulcerans in the environment with Buruli ulcer has not been studied in West Africa in an area with accurate case data.Methodology/Principal FindingEnvironmental samples were collected from twenty-five villages in three communes of Benin. Sites sampled included 12 BU endemic villages within the Ouheme and Couffo River drainages and 13 villages near the Mono River and along the coast or ridge where BU has never been identified. Triplicate water filtrand samples from major water sources and samples from three dominant aquatic plant species were collected. Detection of M. ulcerans was based on quantitative polymerase chain reaction. Results show a significant association between M. ulcerans in environmental samples and Buruli ulcer cases in a village (p = 0.0001). A “dose response” was observed in that increasing numbers of M. ulceran- positive environmental samples were associated with increasing prevalence of BU cases (R2 = 0.586).Conclusions/SignificanceThis study provides the first spatial data on the overlap of M. ulcerans in the environment and BU cases in Benin where case data are based on active surveillance. The study also provides the first evidence on M. ulcerans in well-defined non-endemic sites. Most environmental pathogens are more broadly distributed in the environment than in human populations. The congruence of M. ulcerans in the environment and human infection raises the possibility that humans play a role in the ecology of M. ulcerans. Methods developed could be useful for identifying new areas where humans may be at high risk for BU.

Sero-Epidemiology as a Tool to Screen Populations for Exposure to Mycobacterium ulcerans

BackgroundPrevious analyses of sera from a limited number of Ghanaian Buruli ulcer (BU) patients, their household contacts, individuals living in BU non-endemic regions as well as European controls have indicated that antibody responses to the M. ulcerans 18 kDa small heat shock protein (shsp) reflect exposure to this pathogen. Here, we have investigated to what extent inhabitants of regions in Ghana regarded as non-endemic for BU develop anti-18 kDa shsp antibody titers.Methodology/Principal FindingsFor this purpose we determined anti-18 kDa shsp IgG titers in sera collected from healthy inhabitants of the BU endemic Densu River Valley and the Volta Region, which was so far regarded as BU non-endemic. Significantly more sera from the Densu River Valley contained anti-18 kDa shsp IgG (32% versus 12%, respectively). However, some sera from the Volta Region also showed high titers. When interviewing these sero-responders, it was revealed that the person with the highest titer had a chronic wound, which was clinically diagnosed and laboratory reconfirmed as active BU. After identification of this BU index case, further BU cases were clinically diagnosed by the Volta Region local health authorities and laboratory reconfirmed. Interestingly, there was neither a difference in sero-prevalence nor in IS2404 PCR positivity of environmental samples between BU endemic and non-endemic communities located in the Densu River Valley.ConclusionsThese data indicate that the intensity of exposure to M. ulcerans in endemic and non-endemic communities along the Densu River is comparable and that currently unknown host and/or pathogen factors may determine how frequently exposure is leading to clinical disease. While even high serum titers of anti-18 kDa shsp IgG do not indicate active disease, sero-epidemiological studies can be used to identify new BU endemic areas.

A disseminated case of Buruli ulcer at Macenta in the forest region of Guinea in West Africa

The author report a confirmed case of Buruli ulcer at Macenta in the forest region of Guinea in West Africa. An 8 years old girl came to the general hospital of Macenta located in the forest region of Guinea at 800km south-west of Conakry. Her story reveals that she used to swim in the local river of Man region in Ivory Coast. There is no notion of trauma or insect bite. The disease started 2 years ago by a nodule of the skin in her right leg which had ulcerated; she received various traditional treatments.

Effect of a Control Project on Clinical Profiles and Outcomes in Buruli Ulcer: A Before/After Study in Bas-Congo, Democratic Republic of Congo

BackgroundBuruli ulcer (BU) is a necrotizing bacterial infection of skin, subcutaneous tissue and bone caused by Mycobacterium ulcerans. Although the functional impairment caused by BU results in severe suffering and in socio-economic problems, the disease remains largely neglected in Africa. The province of Bas-Congo in Democratic Republic of Congo contains one of the most important BU foci of the country, i.e. the Songololo Territory in the District of Cataractes. This study aims to assess the impact of a BU control project launched in 2004 in the Songololo Territory.MethodsWe used a comparative non-randomized study design, comparing clinical profiles and outcomes of the group of patients admitted at the General Reference Hospital (GRH) of the “Institut Médical Evangélique” (IME) of Kimpese 3 years before the start of the project (2002–2004) with those admitted during the 3 years after the start of the project (2005–2007).ResultsThe BU control project was associated with a strong increase in the number of admitted BU cases at the GRH of IME/Kimpese and a fundamental change in the profile of those patients; more female patients presented with BU, the proportion of relapse cases amongst all admissions reduced, the proportion of early lesions and simple ulcerative forms increased, more patients healed without complications and the case fatality rate decreased substantially. The median duration since the onset of first symptoms however remained high, as well as the proportion of patients with osteomyelitis or limitations of joint movement, suggesting that the diagnostic delay remains substantial.ConclusionImplementing a specialized program for BU may be effective in improving clinical profiles and outcomes in BU. Despite these encouraging results, our study highlights the need of considering new strategies to better improve BU control in a low resources setting.