Skin neglected tropical diseases in Cameroon : the need for integrated control and elimination

Among the updated WHO list of 20 Neglected Tropical Diseases, about six manifests on the skin and are now known as Skin-NTDs. NTDs have not received equal attention from the international community compared to HIV/AIDS, malaria and tuberculosis although their burdens in terms of disability adjusted life years (DALYs) are comparable. Following advocacy for over a decade and half, NTDs are now being prioritized on the global health agenda, and the WHO has set a 2020 roadmap for accelerating work to overcome the global impact of NTDs. For this PhD thesis, we aimed at determining the current burden of major skin-NTDs in Cameroon and make recommendations for proper control strategies. The basis was surveillance data from 2000 to 2014 for leprosy and Buruli ulcer available at the National Control Programme office, community-based surveys and a literature review. We confirmed that Cameroon attained elimination of leprosy as a public health problem in 2000. Between 2000 and 2014, the leprosy prevalence and the detection dropped significantly, with the steepest reductions occurring between 2000 and 2005, followed by a stagnation from 2006 to 2014. We also showed a persistent but moderate transmission of leprosy, with an increasing trend between 2007 and 2014. Ten health districts had not achieved leprosy elimination, and eighteen were high leprosy-burdened according to the Leprosy Burden Score at the end of 2014. The increasing trend in leprosy transmission and the persistence of high-burdened districts were attributed to reduction in key leprosy control activities secondary to waning of resource allocation by the government and support partners. Some 3700 Buruli ulcer (BU) cases, with an annual average of 264 cases were treated from 2001 to 2014 in Cameroon. Control activities began in two endemic foci of Ayos and Akonolinga in the centre region and were later expanded to Ngoantet-Mbalmayo in the centre, Bankim in the Adamawa and Mbonge in the southwest regions following a national survey in 2004. Analysis of data from treatment centres created at these foci, further revealed presence of BU in 64 health districts mainly from the southern part of the country. BU case-detection increased between 2001 and 2005, and then declined progressively until 2014 and beyond. Analysis of key BU control indicators showed deterioration from 2010 to 2014 and beyond. We also highlighted the importance of differential diagnosis in a context of co-endemicity of mycobacterial diseases, through a case-report of cutaneous tuberculosis misdiagnosed for BU. BU activities in Cameroon were supported by two partners, who from 2010, reduce their support significantly to complete withdrawal of one of them in 2014. Currently there is little funding from the government budget, which is insignificant compared to the expressed needs. We also confirmed the resurgence of yaws in Cameroon through a survey among the pygmy population in the east region, and building on this, we have determined the status of yaws in 53 of 189 health districts and confirmed 37 of them as endemic for yaws. Research conducted within the framework of this thesis, has increased our understanding of skin-NTDs, the efforts made in their control, and the challenges faced by the control activities in Cameroon. Based on these, we have recommended an integrated surveillance and control strategy of skin-NTDs to the National Control Programme. To the scientific community we recommend, accelerated research and development activities for point-of-care diagnostic tests, shorter treatment courses, and vaccines for reinforcement of prevention of these NTDs

The burden of leprosy in Cameroon: fifteen years into the post-elimination era

Cameroon achieved the elimination target of leprosy in 2000, and has maintained this status ever since. However, a number of health districts in the country continue to report significant numbers of leprosy cases. The aim of this study was to assess the burden of leprosy in Cameroon from 2000 to 2014.; We obtained and analysed using the new leprosy burden concept of analysis, leprosy surveillance data collected between 2000 and 2014 from the National Leprosy Control Programme.; Cameroon achieved leprosy elimination in 2000, registering a prevalence rate of 0.94/10,000 population. The prevalence rate dropped further to reach 0.20/10,000 population (78% reduction) in 2014. Similarly, the new case detection rate dropped from 4.88/100,000 population in 2000 to 1.46/100,000 population (85.3% reduction) in 2014. All 10 regions of the country achieved leprosy elimination between 2000 and 2014; however, 10 health districts were still to do so by 2014. The number of high-leprosy-burden regions decreased from 8 in 2000 to 1 in 2014. Seven and two regions were respectively medium and low-burdened at the end of 2014. At the health districts level, 18 remained at the high-leprosy-burdened level in 2014.; The leprosy prevalence and detection rates as well as the overall leprosy burden in Cameroon have dropped significantly between 2000 and 2014. However, a good number of health districts remain high-leprosy-burdened. The National Leprosy Control Programme should focus efforts on these health districts in the next coming years in order to further reduce the burden of leprosy in the country

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

Mapping suitability for Buruli ulcer at fine spatial scales across Africa: A modelling study.

Buruli ulcer (BU) is a disabling and stigmatising neglected tropical disease (NTD). Its distribution and burden are unknown because of underdiagnosis and underreporting. It is caused by Mycobacterium ulcerans, an environmental pathogen whose environmental niche and transmission routes are not fully understood. The main control strategy is active surveillance to promote early treatment and thus limit morbidity, but these activities are mostly restricted to well-known endemic areas. A better understanding of environmental suitability for the bacterium and disease could inform targeted surveillance, and advance understanding of the ecology and burden of BU. We used previously compiled point-level datasets of BU and M. ulcerans occurrence, evidence for BU occurrence within national and sub-national areas, and a suite of relevant environmental covariates in a distribution modelling framework. We fitted relationships between BU and M. ulcerans occurrence and environmental predictors by applying regression and machine learning based algorithms, combined in an ensemble model to characterise the optimal ecological niche for the disease and bacterium across Africa at a resolution of 5km x 5km. Proximity to waterbodies was the strongest predictor of suitability for BU, followed potential evapotranspiration. The strongest predictors of suitability for M. ulcerans were deforestation and potential evapotranspiration. We identified patchy foci of suitability throughout West and Central Africa, including areas with no previous evidence of the disease. Predicted suitability for M. ulcerans was wider but overlapping with that of BU. The estimated population living in areas predicted suitable for the bacterium and disease was 46.1 million. These maps could be used to inform burden estimations and case searches which would generate a more complete understanding of the spatial distribution of BU in Africa, and may guide control programmes to identify cases beyond the well-known endemic areas

Prevalence and risk factors associated with Haemophilus ducreyi cutaneous ulcers in Cameroon

Epidemics of yaws-like cutaneous ulcers are regularly documented in children in the tropics. They occur mainly in poor and remote communities without access to health facilities. The integration of molecular tools into yaws control efforts has made it possible to describe Haemophilus ducreyi (HD) as a major cause of cutaneous ulcers. The objective of this study was to determine the prevalence of HD as cause of cutaneous ulcers, investigate its presence in asymptomatic individuals and identify associated risk factors. A cross-sectional study was conducted in yaws endemic districts of Cameroon. Participants included people presenting yaws-like ulcers and asymptomatic individuals. Swab samples were collected from each participant and tested for HD and Treponema pallidum (TP) using an established qPCR method. Additionally, demographic, habitat, proximity, and hygiene characteristics were collected using a structured questionnaire. A total of 443 individuals participated in the study, including 271 ulcer cases and 172 asymptomatic contacts. The prevalence of HD in ulcers was 30.3% (Confidence Interval (CI) 95% [24.8-35.7]) and the prevalence of asymptomatic HD carriage was 8.6% (CI95% [4.5-12.9]). TP was also detected in our sample among ulcer cases but in lower proportion (5.2% CI95% [2.5-7.8]) compared to HD. The adjusted logistic regression model showed that women were as much at risk of having HD cutaneous ulcer as men regardless of age. Physical proximity to a confirmed ulcer case was the major factor identified favouring HD transmission. HD ulcers were more likely to be present on Bantu individuals compared to Baka as well as HD colonization. These findings highlight HD as the most common cause of cutaneous ulcers in yaws-endemic communities in Cameroon. The exact implications of detecting HD on intact skin are not yet clear. Further studies are needed to understand the significance of this carriage in the spread dynamics of the disease

Evaluating the yaws diagnostic gap: A survey to determine the capacity of and barriers to improving diagnostics in all yaws-endemic countries

BACKGROUND: Yaws, caused by Treponema pallidum subsp. pertenue, is a skin neglected tropical disease. It is targeted for eradication by 2030, primarily using mass drug administration (MDA) with azithromycin. Traditionally, diagnosis of yaws has relied on clinical examination and serological testing. However, these approaches have poor diagnostic performance. To achieve eradication, more accurate diagnostics are required to determine whether MDA should be initiated or continued as well as for post-elimination surveillance. Molecular tools will be crucial for detecting antimicrobial resistant cases, which have the potential to derail eradication efforts. In order to determine the feasibility of introducing novel, more accurate, diagnostics for yaws surveillance purposes, it is necessary to understand current in-country diagnostic capacity. This study therefore aimed to understand the current capacity of, and challenges to, improving diagnostics for yaws in all yaws-endemic countries worldwide. METHODOLOGY/ PRINCIPLE FINDINGS: An online survey was sent to all 15 yaws-endemic countries in July 2021. The survey asked about past prevalence estimates, the availability of different diagnostic tools, and perceived barriers to enhancing capacity. Fourteen countries responded to the survey, four of which did not have a current National Policy for yaws eradication in place. Over 95% of reported that yaws cases from the past five years had not been confirmed with serological or molecular tools, largely due to the limited supply of rapid serological tests. Only four countries reported having operational laboratories for molecular yaws diagnosis, with only one of these having a validated assay to detect azithromycin resistance. CONCLUSIONS AND SIGNIFICANCE: This study highlights the diagnostic capacity constraints across all respondent countries. Countries are in need of access to a sustainable supply of serological tests, and development of molecular testing facilities. Sufficient sustainable funding should be made available to ensure that appropriate diagnostic tools are available and utilised

LAMP4yaws: Treponema pallidum, Haemophilus ducreyi loop mediated isothermal amplification - protocol for a cross-sectional, observational, diagnostic accuracy study.

INTRODUCTION: Yaws, caused by the bacterium Treponema pallidum subsp. pertenue, is a neglected tropical disease targeted for eradication by 2030. Improved diagnostics will be essential to meet this goal. Diagnosis of yaws has relied heavily on clinical and serological tools. However, the presence of coendemic cutaneous skin ulcer diseases, such as lesions caused by Haemophilus ducreyi (HD), means these techniques do not provide a reliable diagnosis. Thus, new diagnostic tools are needed. Molecular tools such as PCR are ideal, but often expensive as they require trained technicians and laboratory facilities, which are often not available to national yaws programmes. METHODS AND ANALYSIS: The LAMP4yaws project is a cross-sectional, observational, diagnostic accuracy study of a combined Treponema pallidum (TP) and HD loop mediated isothermal amplification (TPHD-LAMP) test performed under real world conditions in three endemic countries in West Africa. Individuals with serologically confirmed yaws will be recruited in Cameroon, Côte d'Ivoire and Ghana. Each participant will provide paired swabs, one of which will be sent to the respective national reference laboratory for yaws quantitative PCR and the other will be tested for both TP and HD using the TPHD-LAMP test at local district laboratories. Sensitivity and specificity of the TPHD-LAMP test will be calculated against the reference standard qPCR. We will also assess the acceptability, feasibility and cost-effectiveness of the test. We anticipate that results from this study will support the adoption of the TPHD-LAMP test for use in global yaws eradication efforts. ETHICS AND DISSEMINATION: We have received ethical approval from all relevant institutional and national ethical committees. All participants, or their parents or guardians, must provide written informed consent prior to study enrolment. Study results will be published in an open access journal and disseminated with partners and the World Health Organization. TRIAL REGISTRATION NUMBER: NCT04753788

Buruli ulcer in Cameroon: the development and impact of the National Control Programme

BACKGROUND: Cameroon is endemic for Buruli ulcer (BU) and organised institutional BU control began in 2002. The objective was to describe the evolution, achievements and challenges of the national BU control programme (NBUCP) and to make suggestions for scaling up the programme. METHODS: We analysed collated data on BU from 2001 to 2014 and reviewed activity reports NBUCP in Cameroon. Case-detection rates and key BU control indicators were calculated and plotted on a time scale to determine trends in performance. A linear regression analysis of BU detection rate from 2005-2014 was done. The regression coefficient was tested statistically for the significance in variation of BU detection rate. PRINCIPAL FINDINGS: In 14 years of BU control, 3700 cases were notified. The BU detection rate dropped significantly from 3.89 to 1.45 per 100 000 inhabitants. The number of BU endemic health districts rose from two to 64. Five BU diagnostic and treatment centres are functional and two more are planned for 2015. The health system has been strengthened and BU research and education has gained more interest in Cameroon. CONCLUSION/SIGNIFICANCE: Although institutional BU control Cameroon only began 30 years after the first cases were reported in 1969, a number of milestones have been attained. These would serve as stepping stones for charting the way forward and improving upon control activities in the country if the major challenge of resource allocation is dealt with