Human African trypanosomiasis in the Democratic Republic of the Congo: disease distribution and risk.

BACKGROUND: For the past three decades, the Democratic Republic of the Congo (DRC) has been the country reporting the highest number of cases of human African trypanosomiasis (HAT). In 2012, DRC continued to bear the heaviest burden of gambiense HAT, accounting for 84 % of all cases reported at the continental level (i.e., 5,968/7,106). This paper reviews the status of sleeping sickness in DRC between 2000 and 2012, with a focus on spatio-temporal patterns. Epidemiological trends at the national and provincial level are presented. RESULTS: The number of HAT cases reported yearly from DRC decreased by 65 % from 2000 to 2012, i.e., from 16,951 to 5,968. At the provincial level a more complex picture emerges. Whilst HAT control in the Equateur province has had a spectacular impact on the number of cases (97 % reduction), the disease has proved more difficult to tackle in other provinces, most notably in Bandundu and Kasai, where, despite substantial progress, HAT remains entrenched. HAT prevalence presents its highest values in the northern part of the Province Orientale, where a number of constraints hinder surveillance and control. Significant coordinated efforts by the National Sleeping Sickness Control Programme and the World Health Organization in data collection, reporting, management and mapping, culminating in the Atlas of HAT, have enabled HAT distribution and risk in DRC to be known with more accuracy than ever before. Over 18,000 locations of epidemiological interest have been geo-referenced (average accuracy ≈ 1.7 km), corresponding to 93.6 % of reported cases (period 2000-2012). The population at risk of contracting sleeping sickness has been calculated for two five-year periods (2003-2007 and 2008-2012), resulting in estimates of 33 and 37 million people respectively. CONCLUSIONS: The progressive decrease in HAT cases reported since 2000 in DRC is likely to reflect a real decline in disease incidence. If this result is to be sustained, and if further progress is to be made towards the goal of HAT elimination, the ongoing integration of HAT control and surveillance into the health system is to be closely monitored and evaluated, and active case-finding activities are to be maintained, especially in those areas where the risk of infection remains high and where resurgence could occur.

Mapping the capacities of fixed health facilities to cover people at risk of gambiense human African trypanosomiasis.

BACKGROUND: The emphasis placed on the activities of mobile teams in the detection of gambiense human African trypanosomiasis (HAT) can at times obscure the major role played by fixed health facilities in HAT control and surveillance. The lack of consistent and detailed data on the coverage of passive case-finding and treatment further constrains our ability to appreciate the full contribution of the health system to the control of HAT. METHODS: A survey was made of all fixed health facilities that are active in the control and surveillance of gambiense HAT. Information on their diagnostic and treatment capabilities was collected, reviewed and harmonized. Health facilities were geo-referenced. Time-cost distance analysis was conducted to estimate physical accessibility and the potential coverage of the population at-risk of gambiense HAT. RESULTS: Information provided by the National Sleeping Sickness Control Programmes revealed the existence of 632 fixed health facilities that are active in the control and surveillance of gambiense HAT in endemic countries having reported cases or having conducted active screening activities during the period 2000-2012. Different types of diagnosis (clinical, serological, parasitological and disease staging) are available from 622 facilities. Treatment with pentamidine for first-stage disease is provided by 495 health facilities, while for second-stage disease various types of treatment are available in 206 health facilities only. Over 80% of the population at-risk for gambiense HAT lives within 5-hour travel of a fixed health facility offering diagnosis and treatment for the disease. CONCLUSIONS: Fixed health facilities have played a crucial role in the diagnosis, treatment and coverage of at-risk-population for gambiense HAT. As the number of reported cases continues to dwindle, their role will become increasingly important for the prospects of disease elimination. Future updates of the database here presented will regularly provide evidence to inform and monitor a rational deployment of control and surveillance efforts. Support to the development and, if successful, the implementation of new control tools (e.g. new diagnostics and new drugs) is crucial, both for strengthening and expanding the existing network of fixed health facilities by improving access to diagnosis and treatment and for securing a sustainable control and surveillance of gambiense HAT.

Risk for human African trypanosomiasis, Central Africa, 2000-2009.

Comprehensive georeference records for human African trypanosomiasis in Cameroon, Central African Republic, Chad, Congo, Equatorial Guinea, and Gabon were combined with human population layers to estimate a kernel-smoothed relative risk function. Five risk categories were mapped, and ≈3.5 million persons were estimated to be at risk for this disease.

Practices in research, surveillance and control of neglected tropical diseases by One Health approaches: A survey targeting scientists from French-speaking countries.

One health (OH) approaches have increasingly been used in the last decade in the fight against zoonotic neglected tropical diseases (NTDs). However, descriptions of such collaborations between the human, animal and environmental health sectors are still limited for French-speaking tropical countries. The objective of the current survey was to explore the diversity of OH experiences applied to research, surveillance and control of NTDs by scientists from French-speaking countries, and discuss their constraints and benefits. Six zoonotic NTDs were targeted: echinococcoses, trypanosomiases, leishmaniases, rabies, Taenia solium cysticercosis and leptospiroses. Invitations to fill in an online questionnaire were sent to members of francophone networks on NTDs and other tropical diseases. Results from the questionnaire were discussed during an international workshop in October 2019. The vast majority (98%) of the 171 respondents considered OH approaches relevant although only 64% had implemented them. Among respondents with OH experience, 58% had encountered difficulties mainly related to a lack of knowledge, interest and support for OH approaches by funding agencies, policy-makers, communities and researchers. Silos between disciplines and health sectors were still strong at both scientific and operational levels. Benefits were reported by 94% of respondents with OH experience, including increased intellectual stimulation, stronger collaborations, higher impact and cost-efficiency of interventions. Recommendations for OH uptake included advocacy, capacity-building, dedicated funding, and higher communities' involvement. Improved research coordination by NTD networks, production of combined human-animal health NTD impact indicators, and transversal research projects on diagnostic and reservoirs were also considered essential.

Validation of a rapid immunochromatographic assay for diagnosis of Trypanosoma cruzi infection among Latin-American Migrants in Geneva, Switzerland.

Chagas' disease is a global public health problem due to the recent exchange of population between Latin America and other regions, including Europe. The recent development of rapid diagnostic tests (RDTs) for Trypanosoma cruzi infection may improve patient access to diagnosis and care worldwide. We evaluated the diagnostic accuracy of the Chagas Stat-Pak RDT in a cohort of undocumented Latin-American migrants living in Geneva, Switzerland. Study participants were enrolled in a primary health care center. The Chagas Stat-Pak test was performed independently on blood and serum samples. A combination of two commercialized enzyme-linked immunosorbent assay (ELISA)-based serological tests was used for comparison (reference standard). A total of 999 adults (median age, 36 years) were included in the study; the majority were women (83%) and originally from Bolivia (47%) or Brazil (25%). A total of 125 participants (12.5%) were diagnosed with T. cruzi infection; with the exception of three individuals, all individuals diagnosed with T. cruzi were originally from Bolivia. The sensitivity and specificity of the Chagas Stat-Pak test on blood samples were 95.2% (95% confidence interval [95% CI], 89.2% to 97.9%) and 99.9% (95% CI, 99.3% to 100%), respectively. When the test was performed on serum samples, the sensitivity was 96% (95% CI, 91% to 98.3%), and the specificity was 99.8% (95% CI, 99.2% to 99.9%). The concordance of test results for blood and serum samples was 99.7%. Both negative and positive predictive values were above 98%. The Chagas Stat-Pak is an accurate diagnostic test for T. cruzi infection among Latin-American migrants living in Europe. The mild deficit in sensitivity should be interpreted in light of its ease of use and capacity to provide immediate results, which allow more people at risk to have access to diagnosis and care both in countries where Chagas' disease is endemic and in countries where this disease is not endemic.

The Atlas of human African trypanosomiasis: a contribution to global mapping of neglected tropical diseases.

BACKGROUND: Following World Health Assembly resolutions 50.36 in 1997 and 56.7 in 2003, the World Health Organization (WHO) committed itself to supporting human African trypanosomiasis (HAT)-endemic countries in their efforts to remove the disease as a public health problem. Mapping the distribution of HAT in time and space has a pivotal role to play if this objective is to be met. For this reason WHO launched the HAT Atlas initiative, jointly implemented with the Food and Agriculture Organization of the United Nations, in the framework of the Programme Against African Trypanosomosis. RESULTS: The distribution of HAT is presented for 23 out of 25 sub-Saharan countries having reported on the status of sleeping sickness in the period 2000-2009. For the two remaining countries, i.e. Angola and the Democratic Republic of the Congo, data processing is ongoing. Reports by National Sleeping Sickness Control Programmes (NSSCPs), Non-Governmental Organizations (NGOs) and Research Institutes were collated and the relevant epidemiological data were entered in a database, thus incorporating (i) the results of active screening of over 2.2 million people, and (ii) cases detected in health care facilities engaged in passive surveillance. A total of over 42 000 cases of HAT and 6 000 different localities were included in the database. Various sources of geographic coordinates were used to locate the villages of epidemiological interest. The resulting average mapping accuracy is estimated at 900 m. CONCLUSIONS: Full involvement of NSSCPs, NGOs and Research Institutes in building the Atlas of HAT contributes to the efficiency of the mapping process and it assures both the quality of the collated information and the accuracy of the outputs. Although efforts are still needed to reduce the number of undetected and unreported cases, the comprehensive, village-level mapping of HAT control activities over a ten-year period ensures a detailed and reliable representation of the known geographic distribution of the disease. Not only does the Atlas serve research and advocacy, but, more importantly, it provides crucial evidence and a valuable tool for making informed decisions to plan and monitor the control of sleeping sickness.

Human Trypanosoma evansi infection linked to a lack of apolipoprotein L-I.

Humans have innate immunity against Trypanosoma brucei brucei that is known to involve apolipoprotein L-I (APOL1). Recently, a case of T. evansi infection in a human was identified in India. We investigated whether the APOL1 pathway was involved in this occurrence. The serum of the infected patient was found to have no trypanolytic activity, and the finding was linked to the lack of APOL1, which was due to frameshift mutations in both APOL1 alleles. Trypanolytic activity was restored by the addition of recombinant APOL1. The lack of APOL1 explained the patient's infection with T. evansi.

The future of Chagas disease control.

In the past 15 years, there have been major advances in the control of Chagas disease in most of the countries endemic for this infection. Attention now turns to the future continuity of surveillance and control interventions - especially in regions where control has been so successful that the epidemiological significance of Chagas disease is in steep decline. The effort and expenditure of the recent past cannot continue indefinitely, but a degree of surveillance and selective intervention will be required because of the risk of new infestations and infections resulting from adventitious silvatic vectors accidentally entering houses. In this review, we summarize the progress of multinational control initiatives against Chagas disease. In addition, we suggest that the most sustainable approach to future surveillance involves both the primary healthcare system and university-based teams, with progressively greater attention given to case detection and treatment. Such an idea is not new, but we believe that it merits extensive discussion because of the different ways that research and health interventions are financed and because of the need to establish clearer reporting links between the research communities and the national health authorities.

Short report: Human trypanosomiasis caused by Trypanosoma evansi in a village in India: preliminary serologic survey of the local population.

After discovery of the first recorded case of human infection with Trypanosoma evansi, serologic screening of 1,806 persons from the village of origin of the patient in India was performed using the card agglutination test for trypanosomiasis and T. evansi. A total of 410 (22.7%) people were positive by whole blood, but only 81 were confirmed positive by serum. However, no trypanosomes were detected in the blood of 60 people who were positive at a high serum dilution. The results probably indicate frequent exposure of the human population to T. evansi in the study area, which suggests frequent vector transmission of parasites to humans. Although T. evansi is not infective for humans, a follow-up of seropositive persons is required to observe the evolution of human infection with this parasite.

Human trypanosomiasis caused by Trypanosoma evansi in India: the first case report.

We report an Indian farmer who had fluctuating trypanosome parasitemia associated with febrile episodes for five months. Morphologic examination of the parasites indicated the presence of large numbers of trypanosomes belonging to the species Trypanosoma evansi, which is normally a causative agent of animal trypanosomiasis known as surra. Basic clinical and biologic examinations are described, using several assays, including parasitologic, serologic, and molecular biologic tests, all of which confirmed the infecting species as T. evansi. Analysis of cerebrospinal fluid indicated no invasion of the central nervous system (CNS) by trypanosomes. Suramin, a drug used exclusively for treatment of early-stage human African trypanosomiasis with no CNS involvement, effected apparent cure in the patient. This is the first case reported of human infection due to Trypanosoma evansi, which was probably caused by transmission of blood from an infected animal.

Monitoring the Progress towards the Elimination of Gambiense Human African Trypanosomiasis.

BACKGROUND: Over the last few years, momentum has gathered around the feasibility and opportunity of eliminating gambiense human African trypanosomiasis (g-HAT). Under the leadership of the World Health Organization (WHO), a large coalition of stakeholders is now committed to achieving this goal. A roadmap has been laid out, and indicators and milestones have been defined to monitor the progress of the elimination of g-HAT as a public health problem by 2020. Subsequently, a more ambitious objective was set for 2030: to stop disease transmission. This paper provides a situational update to 2012 for a number of indicators of elimination: number of cases annually reported, geographic distribution of the disease and areas and populations at different levels of risk. RESULTS: Comparing the 5-year periods 2003-2007 and 2008-2012, the area at high or very high risk of g-HAT shrank by 60%, while the area at moderate risk decreased by 22%. These are the areas where g-HAT is still to be considered a public health problem (i.e. > 1 HAT reported case per 10,000 people per annum). This contraction of at-risk areas corresponds to a reduction of 57% for the population at high or very high risk (from 4.1 to 1.8 million), and 20% for moderate risk (from 14.0 to 11.3 million). DISCUSSION: Improved data completeness and accuracy of the Atlas of HAT enhanced our capacity to monitor the progress towards the elimination of g-HAT. The trends in the selected indicators suggest that, in recent years, progress has been steady and in line with the elimination goal laid out in the WHO roadmap on neglected tropical diseases.

Resistance to normal human serum reveals Trypanosoma lewisi as an underestimated human pathogen.

Human-infectious trypanosomes such as Trypanosoma cruzi, T. brucei rhodesiense, and T. b. gambiense can be discriminated from those only infecting animals by their resistance to normal human serum (NHS). These parasites are naturally resistant to trypanolysis induced by the human-specific pore-forming serum protein apolipoprotein L1 (ApoL-1). T. lewisi, a worldwide distributed parasite, has been considered as rat-specific and non-pathogenic to the natural hosts. Here we provide evidence that 19 tested T. lewisi isolates from Thailand and China share resistance to NHS. Further investigation on one selected isolate CPO02 showed that it could resist at least 90% NHS or 30 µg/ml recombinant human ApoL-1 (rhApoL-1) in vitro, in contrast to T. b. brucei which could not survive in 0.0001% NHS and 0.1 µg/ml rhApoL-1. In vivo tests in rats also demonstrated that this parasite is fully resistant to lysis by NHS. Together with recent reports of atypical human infection by T. lewisi, these data allow the conclusion that T. lewisi is potentially an underestimated and thus a neglected human pathogen.

Treatment of human African trypanosomiasis--present situation and needs for research and development.

Human African trypanosomiasis re-emerged in the 1980s. However, little progress has been made in the treatment of this disease over the past decades. The first-line treatment for second-stage cases is melarsoprol, a toxic drug in use since 1949. High therapeutic failure rates have been reported recently in several foci. The alternative, eflornithine, is better tolerated but difficult to administer. A third drug, nifurtimox, is a cheap, orally administered drug not yet fully validated for use in human African trypanosomiasis. No new drugs for second-stage cases are expected in the near future. Because of resistance to and limited number of current treatments, there may soon be no effective drugs available to treat trypanosomiasis patients, especially second-stage cases. Additional research and development efforts must be made for the development of new compounds, including: testing combinations of current trypanocidal drugs, completing the clinical development of nifurtimox and registering it for trypanosomiasis, completing the clinical development of an oral form of eflornithine, pursuing the development of DB 289 and its derivatives, and advancing the pre-clinical development of megazol, eventually engaging firmly in its clinical development. Partners from the public and private sector are already engaged in joint initiatives to maintain the production of current drugs. This network should go further and be responsible for assigning selected teams to urgently needed research projects with funds provided by industry and governments. At the same time, on a long term basis, ambitious research programmes for new compounds must be supported to ensure the sustainable development of new drugs.

Eradication of yaws: historical efforts and achieving WHO's 2020 target.

BACKGROUND: Yaws, one of the 17 neglected tropical diseases (NTDs), is targeted for eradication by 2020 in resolution WHA66.12 of the World Health Assembly (2013) and the WHO roadmap on NTDs (2012). The disease frequently affects children who live in poor socioeconomic conditions. Between 1952 and 1964, WHO and the United Nations Children's Fund (UNICEF) led a global eradication campaign using injectable benzathine penicillin. Recent developments using a single dose of oral azithromycin have renewed optimism that eradication can be achieved through a comprehensive large-scale treatment strategy. We review historical efforts to eradicate yaws and argue that this goal is now technically feasible using new tools and with the favorable environment for control of NTDs. We also summarize the work of WHO's Department of Control of Neglected Tropical Diseases in leading the renewed eradication initiative and call on the international community to support efforts to achieve the 2020 eradication goal. The critical factor remains access to azithromycin. Excluding medicines, the financial cost of yaws eradication could be as little as US$ 100 million. CONCLUSIONS: The development of new tools has renewed interest in eradication of yaws; with modest support, the WHO eradication target of 2020 can be achieved.

Where the road ends, yaws begins? The cost-effectiveness of eradication versus more roads.

INTRODUCTION: A disabling and disfiguring disease that "begins where the road ends", yaws is targeted by WHO for eradication by the year 2020. The global campaign is not yet financed. To evaluate yaws eradication within the context of the post-2015 development agenda, we perform a somewhat allegorical cost-effectiveness analysis of eradication, comparing it to a counterfactual in which we simply wait for more roads (the end of poverty). METHODS: We use evidence from four yaws eradication pilot sites and other mass treatment campaigns to set benchmarks for the cost of eradication in 12 known endemic countries. We construct a compartmental model of long-term health effects to 2050. Conservatively, we attribute zero cost to the counterfactual and allow for gradual exit of the susceptible (at risk) population by road (poverty reduction). We report mean, 5th and 95th centile estimates to reflect uncertainty about costs and effects. RESULTS: Our benchmark for the economic cost of yaws eradication is uncertain but not high -US$ 362 (75-1073) million in 12 countries. Eradication would cost US$ 26 (4.2-78) for each year of life lived without disability or disfigurement due to yaws, or US$ 324 (47-936) per disability-adjusted life year (DALY). Excluding drugs, existing staff and assets, the financial cost benchmark is US$ 213 (74-522) million. The real cost of waiting for more roads (poverty reduction) would be 13 (7.3-20) million years of life affected by early-stage yaws and 2.3 (1.1-4.2) million years of life affected by late-stage yaws. DISCUSSION: Endemic countries need financing to begin implementing and adapting global strategy to local conditions. Donations of drugs and diagnostics could reduce cost to the public sector and catalyze financing. Resources may be harnessed from the extractive industries. Yaws eradication should be seen as complementary to universal health coverage and shared prosperity on the post-2015 development agenda.

Epidemiology of human African trypanosomiasis.

Human African trypanosomiasis (HAT), or sleeping sickness, is caused by Trypanosoma brucei gambiense, which is a chronic form of the disease present in western and central Africa, and by Trypanosoma brucei rhodesiense, which is an acute disease located in eastern and southern Africa. The rhodesiense form is a zoonosis, with the occasional infection of humans, but in the gambiense form, the human being is regarded as the main reservoir that plays a key role in the transmission cycle of the disease. The gambiense form currently assumes that 98% of the cases are declared; the Democratic Republic of the Congo is the most affected country, with more than 75% of the gambiense cases declared. The epidemiology of the disease is mediated by the interaction of the parasite (trypanosome) with the vectors (tsetse flies), as well as with the human and animal hosts within a particular environment. Related to these interactions, the disease is confined in spatially limited areas called "foci", which are located in Sub-Saharan Africa, mainly in remote rural areas. The risk of contracting HAT is, therefore, determined by the possibility of contact of a human being with an infected tsetse fly. Epidemics of HAT were described at the beginning of the 20th century; intensive activities have been set up to confront the disease, and it was under control in the 1960s, with fewer than 5,000 cases reported in the whole continent. The disease resurged at the end of the 1990s, but renewed efforts from endemic countries, cooperation agencies, and nongovernmental organizations led by the World Health Organization succeeded to raise awareness and resources, while reinforcing national programs, reversing the trend of the cases reported, and bringing the disease under control again. In this context, sustainable elimination of the gambiense HAT, defined as the interruption of the transmission of the disease, was considered as a feasible target for 2030. Since rhodesiense HAT is a zoonosis, where the animal reservoir plays a key role, the interruption of the disease's transmission is not deemed feasible.