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.

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.

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.

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.

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.

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.

Atypical human infections by animal trypanosomes.

The two classical forms of human trypanosomoses are sleeping sickness due to Trypanosoma brucei gambiense or T. brucei rhodesiense, and Chagas disease due to T. cruzi. However, a number of atypical human infections caused by other T. species (or sub-species) have been reported, namely due to T. brucei brucei, T. vivax, T. congolense, T. evansi, T. lewisi, and T. lewisi-like. These cases are reviewed here. Some infections were transient in nature, while others required treatments that were successful in most cases, although two cases were fatal. A recent case of infection due to T. evansi was related to a lack of apolipoprotein L-I, but T. lewisi infections were not related to immunosuppression or specific human genetic profiles. Out of 19 patients, eight were confirmed between 1974 and 2010, thanks to improved molecular techniques. However, the number of cases of atypical human trypanosomoses might be underestimated. Thus, improvement, evaluation of new diagnostic tests, and field investigations are required for detection and confirmation of these atypical cases.

Neurological aspects of neglected tropical diseases: an unrecognized burden.

Neglected tropical diseases are a group of mostly infectious diseases that thrive among poor populations in tropical countries. A significant proportion of the conditions affecting the neurological system in such countries can be attributed to neglected tropical diseases of helminth, protozoan, bacterial, or viral origin. The neurological burden of neglected tropical diseases has not been thoroughly investigated yet, but is expected to be significant; its full appreciation, estimation, and recognition present significant challenges, as shown by the case of the "silent epidemic" of epilepsy. While tropical infections involving the nervous system are today largely preventable or treatable, as vaccines or chemotherapeutic agents are available to kill or neutralize the responsible agents, associated morbidity - when established - cannot be cured. In resource-poor settings it is likely that many infections will not be treated and will therefore progress into their advanced and severe stages, thus being increasingly associated with irreversible morbidity; this is also the case for neurological morbidity, which often entails permanent disability. Public health should aim at reducing the burden of tropical neurological diseases through interventions addressing the infection, the associated morbidity, and the disability deriving from it.

Estimating and mapping the population at risk of sleeping sickness.

BACKGROUND: Human African trypanosomiasis (HAT), also known as sleeping sickness, persists as a public health problem in several sub-Saharan countries. Evidence-based, spatially explicit estimates of population at risk are needed to inform planning and implementation of field interventions, monitor disease trends, raise awareness and support advocacy. Comprehensive, geo-referenced epidemiological records from HAT-affected countries were combined with human population layers to map five categories of risk, ranging from "very high" to "very low," and to estimate the corresponding at-risk population. RESULTS: Approximately 70 million people distributed over a surface of 1.55 million km(2) are estimated to be at different levels of risk of contracting HAT. Trypanosoma brucei gambiense accounts for 82.2% of the population at risk, the remaining 17.8% being at risk of infection from T. b. rhodesiense. Twenty-one million people live in areas classified as moderate to very high risk, where more than 1 HAT case per 10,000 inhabitants per annum is reported. DISCUSSION: Updated estimates of the population at risk of sleeping sickness were made, based on quantitative information on the reported cases and the geographic distribution of human population. Due to substantial methodological differences, it is not possible to make direct comparisons with previous figures for at-risk population. By contrast, it will be possible to explore trends in the future. The presented maps of different HAT risk levels will help to develop site-specific strategies for control and surveillance, and to monitor progress achieved by ongoing efforts aimed at the elimination of sleeping sickness.

Leishmaniasis worldwide and global estimates of its incidence.

As part of a World Health Organization-led effort to update the empirical evidence base for the leishmaniases, national experts provided leishmaniasis case data for the last 5 years and information regarding treatment and control in their respective countries and a comprehensive literature review was conducted covering publications on leishmaniasis in 98 countries and three territories (see 'Leishmaniasis Country Profiles Text S1, S2, S3, S4, S5, S6, S7, S8, S9, S10, S11, S12, S13, S14, S15, S16, S17, S18, S19, S20, S21, S22, S23, S24, S25, S26, S27, S28, S29, S30, S31, S32, S33, S34, S35, S36, S37, S38, S39, S40, S41, S42, S43, S44, S45, S46, S47, S48, S49, S50, S51, S52, S53, S54, S55, S56, S57, S58, S59, S60, S61, S62, S63, S64, S65, S66, S67, S68, S69, S70, S71, S72, S73, S74, S75, S76, S77, S78, S79, S80, S81, S82, S83, S84, S85, S86, S87, S88, S89, S90, S91, S92, S93, S94, S95, S96, S97, S98, S99, S100, S101'). Additional information was collated during meetings conducted at WHO regional level between 2007 and 2011. Two questionnaires regarding epidemiology and drug access were completed by experts and national program managers. Visceral and cutaneous leishmaniasis incidence ranges were estimated by country and epidemiological region based on reported incidence, underreporting rates if available, and the judgment of national and international experts. Based on these estimates, approximately 0.2 to 0.4 cases and 0.7 to 1.2 million VL and CL cases, respectively, occur each year. More than 90% of global VL cases occur in six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. Cutaneous leishmaniasis is more widely distributed, with about one-third of cases occurring in each of three epidemiological regions, the Americas, the Mediterranean basin, and western Asia from the Middle East to Central Asia. The ten countries with the highest estimated case counts, Afghanistan, Algeria, Colombia, Brazil, Iran, Syria, Ethiopia, North Sudan, Costa Rica and Peru, together account for 70 to 75% of global estimated CL incidence. Mortality data were extremely sparse and generally represent hospital-based deaths only. Using an overall case-fatality rate of 10%, we reach a tentative estimate of 20,000 to 40,000 leishmaniasis deaths per year. Although the information is very poor in a number of countries, this is the first in-depth exercise to better estimate the real impact of leishmaniasis. These data should help to define control strategies and reinforce leishmaniasis advocacy.

Human African trypanosomiasis in non-endemic countries (2000-2010).

BACKGROUND: Human African trypanosomiasis (HAT) can affect travelers to sub-Saharan Africa, as well as migrants from disease endemic countries (DECs), posing diagnosis challenges to travel health services in non-disease endemic countries (non-DECs). METHODS: Cases reported in journals have been collected through a bibliographic research and complemented by cases reported to the World Health Organization (WHO) during the process to obtain anti-trypanosome drugs. These drugs are distributed to DECs solely by WHO. Drugs are also provided to non-DECs when an HAT case is diagnosed. However, in non-DEC pentamidine can also be purchased in the market due to its indication to treat Pneumocystis and Leishmania infections. Any request for drugs from non-DECs should be accompanied by epidemiological and clinical data on the patient. RESULTS: During the period 2000 to 2010, 94 cases of HAT were reported in 19 non-DECs. Seventy-two percent of them corresponded to the Rhodesiense form, whereas 28% corresponded to the Gambiense. Cases of Rhodesiense HAT were mainly diagnosed in tourists after short visits to DECs, usually within a few days of return. The majority of them were in first stage. Initial misdiagnosis with malaria or tick-borne diseases was frequent. Cases of Gambiense HAT were usually diagnosed several months after initial examination and subsequent to a variety of misdiagnoses. The majority were in second stage. Patients affected were expatriates living in DECs for extended periods and refugees or economic migrants from DECs. CONCLUSIONS: The risk of HAT in travelers and migrants, albeit low, cannot be overlooked. In non-DECs, rarity, nonspecific symptoms, and lack of knowledge and awareness in health staff make diagnosis difficult. Misdiagnosis is frequent, thus leading to invasive diagnosis methods, unnecessary treatments, and increased risk of fatality. Centralized distribution of drugs for HAT by WHO enables an HAT surveillance system for non-DECs to be maintained. This system provides valuable information on disease transmission and complements data collected in DECs.