Do Cryptic Reservoirs Threaten Gambiense-Sleeping Sickness Elimination?

Trypanosoma brucei gambiense causes human African trypanosomiasis (HAT). Between 1990 and 2015, almost 440000 cases were reported. Large-scale screening of populations at risk, drug donations, and efforts by national and international stakeholders have brought the epidemic under control with <2200 cases in 2016. The World Health Organization (WHO) has set the goals of gambiense-HAT elimination as a public health problem for 2020, and of interruption of transmission to humans for 2030. Latent human infections and possible animal reservoirs may challenge these goals. It remains largely unknown whether, and to what extend, they have an impact on gambiense-HAT transmission. We argue that a better understanding of the contribution of human and putative animal reservoirs to gambiense-HAT epidemiology is mandatory to inform elimination strategies.

Monitoring the elimination of human African trypanosomiasis: Update to 2014.

BACKGROUND: The World Health Organization (WHO) has targeted the elimination of Human African trypanosomiasis (HAT) 'as a public health problem' by 2020. The selected indicators of elimination should be monitored every two years, and we provide here a comprehensive update to 2014. The monitoring system is underpinned by the Atlas of HAT. RESULTS: With 3,797 reported cases in 2014, the corresponding milestone (5,000 cases) was surpassed, and the 2020 global target of 'fewer than 2,000 reported cases per year' seems within reach. The areas where HAT is still a public health problem (i.e. > 1 HAT reported case per 10,000 people per year) have halved in less than a decade, and in 2014 they corresponded to 350 thousand km2. The number and potential coverage of fixed health facilities offering diagnosis and treatment for HAT has expanded, and approximately 1,000 are now operating in 23 endemic countries. The observed trends are supported by sustained surveillance and improved reporting. DISCUSSION: HAT elimination appears to be on track. For gambiense HAT, still accounting for the vast majority of reported cases, progress continues unabated in a context of sustained intensity of screening activities. For rhodesiense HAT, a slow-down was observed in the last few years. Looking beyond the 2020 target, innovative tools and approaches will be increasingly needed. Coordination, through the WHO network for HAT elimination, will remain crucial to overcome the foreseeable and unforeseeable challenges that an elimination process will inevitably pose.

Developing a Progressive Control Pathway for African Animal Trypanosomosis.

Progressive control pathways (PCPs) are stepwise approaches for the reduction, elimination, and eradication of human and animal diseases. They provide systematic frameworks for planning and evaluating interventions. Here we outline a PCP for tsetse-transmitted animal trypanosomosis, the scourge of poor livestock keepers in tropical Africa. Initial PCP stages focus on the establishment of national coordination structures, engagement of stakeholders, development of technical capacities, data collection and management, and pilot field interventions. The intermediate stage aims at a sustainable and economically profitable reduction of disease burden, while higher stages target elimination. The mixed-record of success and failure in past efforts against African animal trypanosomosis (AAT) makes the development of this PCP a high priority.

Did Neoliberalizing West African Forests Produce a New Niche for Ebola?

A recent study introduced a vaccine that controls Ebola Makona, the Zaire ebolavirus variant that has infected 28,000 people in West Africa. We propose that even such successful advances are insufficient for many emergent diseases. We review work hypothesizing that Makona, phenotypically similar to much smaller outbreaks, emerged out of shifts in land use brought about by neoliberal economics. The epidemiological consequences demand a new science that explicitly addresses the foundational processes underlying multispecies health, including the deep-time histories, cultural infrastructure, and global economic geographies driving disease emergence. The approach, for instance, reverses the standard public health practice of segregating emergency responses and the structural context from which outbreaks originate. In Ebola's case, regional neoliberalism may affix the stochastic "friction" of ecological relationships imposed by the forest across populations, which, when above a threshold, keeps the virus from lining up transmission above replacement. Export-led logging, mining, and intensive agriculture may depress such functional noise, permitting novel spillovers larger forces of infection. Mature outbreaks, meanwhile, can continue to circulate even in the face of efficient vaccines. More research on these integral explanations is required, but the narrow albeit welcome success of the vaccine may be used to limit support of such a program.

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.

Developing a continental atlas of the distribution and trypanosomal infection of tsetse flies (Glossina species).

BACKGROUND: Tsetse flies (Genus: Glossina) are the sole cyclical vectors of African trypanosomoses. Despite their economic and public health impacts in sub-Saharan Africa, it has been decades since the latest distribution maps at the continental level were produced. The Food and Agriculture Organization of the United Nations is trying to address this shortcoming through the Atlas of tsetse and African animal trypanosomosis. METHODS: For the tsetse component of the Atlas, a geospatial database is being assembled which comprises information on the distribution and trypanosomal infection of Glossina species. Data are identified through a systematic literature review. Field data collected since January 1990 are included, with a focus on occurrence, apparent density and infection rates of tsetse flies. Mapping is carried out at the level of site/location. For tsetse distribution, the database includes such ancillary information items as survey period, trap type, attractant (if any), number of traps deployed in the site and the duration of trapping (in days). For tsetse infection, the sampling and diagnostic methods are also recorded. RESULTS: As a proof of concept, tsetse distribution data for three pilot countries (Ethiopia, Kenya and Uganda) were compiled from 130 peer-reviewed publications, which enabled tsetse occurrence to be mapped in 1266 geographic locations. Maps were generated for eight tsetse species (i.e. G. brevipalpis, G. longipennis, G. fuscipes fuscipes, G. tachinoides, G. pallidipes, G. morsitans submorsitans, G. austeni and G. swynnertoni). For tsetse infection rates, data were identified in 25 papers, corresponding to 91 sites. CONCLUSIONS: A methodology was developed to assemble a geo-spatial database on the occurrence, apparent density and trypanosomal infection of Glossina species, which will enable continental maps to be generated. The methodology is suitable for broad brush mapping of all tsetse species of medical and veterinary public health importance. For a few tsetse species, especially those having limited economic importance and circumscribed geographic distribution (e.g. fusca group), recently published information is scanty or non-existent. Tsetse-infested countries can adopt and adapt this approach to compile national Atlases, which ought to draw also on the vast amount of unpublished information.

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.

Assembling a geospatial database of tsetse-transmitted animal trypanosomosis for Africa.

BACKGROUND: African animal trypanosomosis (AAT), or nagana, is widespread within the tsetse-infested belt of sub-Saharan Africa. Although a wealth of information on its occurrence and prevalence is available in the literature, synthesized and harmonized data at the regional and continental scales are lacking. To fill this gap the Food and Agriculture Organization of the United Nations (FAO) launched the Atlas of tsetse and AAT, jointly implemented with the International Atomic Energy Agency (IAEA) in the framework of the Programme Against African Trypanosomosis (PAAT). METHODS: The Atlas aims to build and regularly update a geospatial database of tsetse species occurrence and AAT at the continental level. The present paper focuses on the methodology to assemble a dynamic database of AAT, which hinges on herd-level prevalence data as estimated using various diagnostic techniques. A range of ancillary information items is also included (e.g. trypanosome species, survey period, species and breed of animals, husbandry system, etc.). Input data were initially identified through a literature review. RESULTS: Preliminary results are presented for Ethiopia, Kenya and Uganda in East Africa: 122 papers were identified and analyzed, which contained field data collected from January 1990 to December 2013. Information on AAT was extracted and recorded for 348 distinct geographic locations. The presented distribution maps exemplify the range of outputs that can be directly generated from the AAT database. CONCLUSIONS: Activities are ongoing to map the distribution of AAT in all affected countries and to develop the tsetse component of the Atlas. The presented methodology is also being transferred to partners in affected countries, with a view to developing capacity and strengthening data management, harmonization and sharing. In the future, geospatial modelling will enable predictions to be made within and beyond the range of AAT field observations. This variety of information layers will inform decisions on the most appropriate, site-specific strategies for intervention against AAT. Data on the occurrence of human-infective trypanosomes in non-human hosts will also provide valuable information for sleeping sickness control and elimination.

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.

The sequential aerosol technique: a major component in an integrated strategy of intervention against Riverine Tsetse in Ghana.

BACKGROUND: An integrated strategy of intervention against tsetse flies was implemented in the Upper West Region of Ghana (9.62°-11.00° N, 1.40°-2.76° W), covering an area of ≈18,000 km(2) within the framework of the Pan-African Tsetse and Trypanosomosis Eradication Campaign. Two species were targeted: Glossina tachinoides and Glossina palpalis gambiensis. METHODOLOGY/PRINCIPAL FINDINGS: The objectives were to test the potentiality of the sequential aerosol technique (SAT) to eliminate riverine tsetse species in a challenging subsection (dense tree canopy and high tsetse densities) of the total sprayed area (6,745 km(2)) and the subsequent efficacy of an integrated strategy including ground spraying (≈100 km(2)), insecticide treated targets (20,000) and insecticide treated cattle (45,000) in sustaining the results of tsetse suppression in the whole intervention area. The aerial application of low-dosage deltamethrin aerosols (0.33-0.35 g a.i/ha) was conducted along the three main rivers using five custom designed fixed-wings Turbo thrush aircraft. The impact of SAT on tsetse densities was monitored using 30 biconical traps deployed from two weeks before until two weeks after the operations. Results of the SAT monitoring indicated an overall reduction rate of 98% (from a pre-intervention mean apparent density per trap per day (ADT) of 16.7 to 0.3 at the end of the fourth and last cycle). One year after the SAT operations, a second survey using 200 biconical traps set in 20 sites during 3 weeks was conducted throughout the intervention area to measure the impact of the integrated control strategy. Both target species were still detected, albeit at very low densities (ADT of 0.27 inside sprayed blocks and 0.10 outside sprayed blocks). CONCLUSIONS/SIGNIFICANCE: The SAT operations failed to achieve elimination in the monitored section, but the subsequent integrated strategy maintained high levels of suppression throughout the intervention area, which will contribute to improving animal health, increasing animal production and fostering food security.

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.

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.

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.

Towards the Atlas of human African trypanosomiasis.

BACKGROUND: Updated, accurate and comprehensive information on the distribution of human African trypanosomiasis (HAT), also known as sleeping sickness, is critically important to plan and monitor control activities. We describe input data, methodology, preliminary results and future prospects of the HAT Atlas initiative, which will allow major improvements in the understanding of the spatial distribution of the disease. METHODS: Up-to-date as well as historical data collected by national sleeping sickness control programmes, non-governmental organizations and research institutes have been collated over many years by the HAT Control and Surveillance Programme of the World Health Organization. This body of information, unpublished for the most part, is now being screened, harmonized, and analysed by means of database management systems and geographical information systems (GIS). The number of new HAT cases and the number of people screened within a defined geographical entity were chosen as the key variables to map disease distribution in sub-Saharan Africa. RESULTS: At the time of writing, over 600 epidemiological reports and files from seventeen countries were collated and included in the data repository. The reports contain information on approximately 20,000 HAT cases, associated to over 7,000 different geographical entities. The oldest epidemiological records considered so far date back to 1985, the most recent having been gathered in 2008. Data from Cameroon, Central African Republic, Chad, Congo, Equatorial Guinea and Gabon from the year 2000 onwards were fully processed and the preliminary regional map of HAT distribution is presented. CONCLUSION: The use of GIS tools and geo-referenced, village-level epidemiological data allow the production of maps that substantially improve on the spatial quality of previous cartographic products of similar scope. The significant differences between our preliminary outputs and earlier maps of HAT transmission areas demonstrate the strong need for this systematic approach to mapping sleeping sickness and point to the inaccuracy of any calculation of population at risk based on previous maps of HAT transmission areas. The Atlas of HAT will lay the basis for novel, evidence-based methodologies to estimate the population at risk and the burden of disease, ultimately leading to more efficient targeting of interventions. Also, the Atlas will help streamline future field data collection in those parts of Africa that still require it.