Sleeping sickness

Artyicle approval pendingHuman African trypanosomiasis (HAT), or sleeping sickness, is a vector-borne disease that flourishes in impoverished, rural parts of sub-Saharan Africa. It is caused by infection with the protozoan parasite Trypanosoma brucei and is transmitted by tsetse flies of the genus Glossina. The majority of cases are caused by T. b. gambiense, which gives rise to the chronic, anthroponotic endemic disease in Western and Central Africa. Infection with T. b. rhodesiense leads to the acute, zoonotic form of Eastern and Southern Africa. The parasites live and multiply extracellularly in the blood and tissue fluids of their human host. They have elaborated a variety of strategies for invading hosts, to escape the immune system and to take advantage of host growth factors. HAT is a challenging and deadly disease owing to its complex epidemiology and clinical presentation and, if left untreated, can result in high death rates. As one of the most neglected tropical diseases, HAT is characterized by the limited availability of safe and cost-effective control tools. No vaccine against HAT is available, and the toxicity of existing old and cumbersome drugs precludes the adoption of control strategies based on preventive chemotherapy. As a result, the keystones of interventions against sleeping sickness are active and passive case-finding for early detection of cases followed by treatment, vector control and animal reservoir management. New methods to diagnose and treat patients and to control transmission by the tsetse fly are needed to achieve the goal of global elimination of the disease

The origins of a new Trypanosoma brucei rhodesiense sleeping sickness outbreak in eastern Uganda.

BACKGROUND: Sleeping sickness, caused by two trypanosome subspecies, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, is a parasitic disease transmitted by the tsetse fly in sub-Saharan Africa. We report on a recent outbreak of T b rhodesiense sleeping sickness outside the established south-east Ugandan focus, in Soroti District where the disease had previously been absent. Soroti District has been the subject of large-scale livestock restocking activities and, because domestic cattle are important reservoirs of T b rhodesiense, we investigated the role of cattle in the origins of the outbreak. METHODS: We identified the origins of cattle entering the outbreak area in the 4 years preceding the outbreak. A matched case-control study was conducted to assess whether the distance of villages from the main market involved with restocking was a risk factor for sleeping sickness. We investigated the spatial clustering of sleeping sickness cases at the start of the outbreak. FINDINGS: Over 50% (1510 of 2796) of cattle traded at the market were reported to have originated from endemic sleeping sickness areas. The case-control study revealed that distance to the cattle market was a highly significant risk factor for sleeping sickness (p<0.001) and that there was a significant clustering of cases (27 of 28) close to the market at the start of the outbreak (p<0.001). As the outbreak progressed, the average distance of cases moved away from the cattle market (0.014 km per day, 95% CI 0.008-0.020 km per day, p<0.001). INTERPRETATIONS: The results are consistent with the disease being introduced by cattle infected with T b rhodesiense imported to the market from the endemic sleeping sickness focus. The subsequent spread of the disease away from the market suggests that sleeping sickness is becoming established in this new focus. Public health measures directed at controlling the infection in the animal reservoir should be considered to prevent the spread of sleeping sickness

Epidemiology of Trypanosoma brucei rhodesiense sleeping sickness in Eastern Uganda

Sleeping sickness is now recognized as one of the recent re-emerging but neglected diseases. In Uganda and the rest of sub-Saharan Africa, old foci of sleeping sickness persist despite donor-funded projects and there is evidence of expansion of these foci. The World Health Organization acknowledges a high level of undiagnosed sleeping sickness cases and has identified surveillance and treatment as the major control strategy for sleeping sickness. However, to date there have been no clear epidemiological surveillance markers applied for monitoring the burden of the disease at control implementation levels. There is therefore a need to obtain markers for surveillance and to apply these to monitor and improve this important strategy of sleeping sickness control, hence, the objective of this study.Data of sleeping sickness patients from 1987 to 2002 were collected from Tororo, Busia and Soroti districts. Using the ratio of early to late stage patients in an affected population, data from (Livestock Health Research Institute) LIRI hospital in Tororo district were applied to develop a model for estimation of sleeping sickness underdetection. The model was applied to data from a recent outbreak of sleeping sickness in Soroti district to determine the burden of the disease. Geographical information systems (GIS) were applied to quantify the effect of distance from the health units on early detection of sleeping sickness. A semi-structured questionnaire was administered to prospective sleeping sickness patients to determine their treatment seeking behavior. Spatial and temporal trends of sleeping sickness with and without control are described using the SatScan method for spatial temporal clustering. The potential role of remote sensing in surveillance of sleeping sickness was explored using a processed Landsat 7 series satellite image to determine association of land cover classes, vegetation indices, population density, distance to wetlands, distance to the sleeping sickness hospital to the outcome of village scale disease geographical distribution generated using GIS.In the Tororo and Busia area, for every 3 reported patients, 2 went undetected. The Disability Adjusted Life Years (DALYs) for sleeping sickness in the Soroti outbreak are greatly increased when under-detection is taken into account. There is a strong effect of distance to health unit on the surveillance of sleeping sickness. Children and xviii adolescents are less likely to be detected in early stage. During times of low incidence, the proportion of late stage detected patients increases. Most of the delay to diagnosis is attributable to service provider delay and most patients are referred to the sleeping sickness referral hospital by the community and not the health system. Proximity to wetlands and to the sleeping sickness hospital, low population density, vegetation wetness and smaller area of short grassland and larger area of cropland were significantly associated with the distribution of sleeping sickness affected villages in Tororo and Busia districts.Surveillance of sleeping sickness can be monitored by applying the early to late stage ratio of sleeping sickness as an epidemiological tool to determine the level of underdetection and subsequently the burden of disease. Optimal distribution of fixed post diagnostic units will greatly improve rhodesiense sleeping sickness surveillance. Surveillance programmes should regularly update health workers in the primary health care units in the vicinity of sleeping sickness affected populations. Similarly, the affected communities can be resourcefully used to refer sleeping sickness suspects to the appropriate health care facilities. Timely responsive disease surveillance and intervention can prevent spread of sleeping sickness. Remotely sensed maps can assist in accurately describing sleeping sickness foci and therefore, the area requiring application of control interventions

Quantifying the burden of rhodesiense sleeping sickness in Urambo district, Tanzania

Sleeping sickness (human African trypanosomiasis - HAT) is a disease transmitted by tsetse flies and is always fatal if left untreated. The disease occurs in foci affecting poor communities with limited access to health service provision and as such the disease is often left undiagnosed, mistaken for more common afflictions. Even if diagnosed, sleeping sickness is costly to treat, both for health services and patients and their families in terms of costs of diagnosis, transport, hospital care, and the prolonged period of convalescence. Here we estimate the health burden of the acute form T. b. rhodesiense sleeping sickness in Urambo District, Tanzania in terms of Disability Adjusted Life Years (DALYs), the yardstick commonly used by policy makers to prioritize disease management practices, representing a year of healthy life lost to disease. In this single district, the burden of the disease over one year was estimated at 979 DALYs and the estimated monetary costs to health services for the 143 treated patients at US$11,841 and to the patients themselves at US$ 3,673 for direct medical costs and US$ 9,781 for indirect non-medical costs. Sleeping sickness thus places a considerable burden on the affected rural communities and health services

The Dispersal Ecology of Rhodesian Sleeping Sickness Following Its Introduction to a New Area

Tsetse-transmitted human and animal trypanosomiasis are constraints to both human and animal health in sub-Saharan Africa, and although these diseases have been known for over a century, there is little recent evidence demonstrating how the parasites circulate in natural hosts and ecosystems. The spread of Rhodesian sleeping sickness (caused by Trypanosoma brucei rhodesiense) within Uganda over the past 15 years has been linked to the movement of infected, untreated livestock (the predominant reservoir) from endemic areas. However, despite an understanding of the environmental dependencies of sleeping sickness, little research has focused on the environmental factors controlling transmission establishment or the spatially heterogeneous dispersal of disease following a new introduction. In the current study, an annually stratified case-control study of Rhodesian sleeping sickness cases from Serere District, Uganda was used to allow the temporal assessment of correlations between the spatial distribution of sleeping sickness and landscape factors. Significant relationships were detected between Rhodesian sleeping sickness and selected factors, including elevation and the proportion of land which was “seasonally flooding grassland” or “woodlands and dense savannah.” Temporal trends in these relationships were detected, illustrating the dispersal of Rhodesian sleeping sickness into more ‘suitable’ areas over time, with diminishing dependence on the point of introduction in concurrence with an increasing dependence on environmental and landscape factors. These results provide a novel insight into the ecology of Rhodesian sleeping sickness dispersal and may contribute towards the implementation of evidence-based control measures to prevent its further spread

Civil conflict and sleeping sickness in Africa in general and Uganda in particular

Conflict and war have long been recognized as determinants of infectious disease risk. Re-emergence of epidemic sleeping sickness in sub-Saharan Africa since the 1970s has coincided with extensive civil conflict in affected regions. Sleeping sickness incidence has placed increasing pressure on the health resources of countries already burdened by malaria, HIV/AIDS, and tuberculosis. In areas of Sudan, the Democratic Republic of the Congo, and Angola, sleeping sickness occurs in epidemic proportions, and is the first or second greatest cause of mortality in some areas, ahead of HIV/AIDS. In Uganda, there is evidence of increasing spread and establishment of new foci in central districts. Conflict is an important determinant of sleeping sickness outbreaks, and has contributed to disease resurgence. This paper presents a review and characterization of the processes by which conflict has contributed to the occurrence of sleeping sickness in Africa. Conflict contributes to disease risk by affecting the transmission potential of sleeping sickness via economic impacts, degradation of health systems and services, internal displacement of populations, regional insecurity, and reduced access for humanitarian support. Particular focus is given to the case of sleeping sickness in south-eastern Uganda, where incidence increase is expected to continue. Disease intervention is constrained in regions with high insecurity; in these areas, political stabilization, localized deployment of health resources, increased administrative integration and national capacity are required to mitigate incidence. Conflict-related variables should be explicitly integrated into risk mapping and prioritization of targeted sleeping sickness research and mitigation initiatives

Borderlands of Research: Medicine, Empire, and Sleeping Sickness in East Africa, 1902-1914

This dissertation is a history of sleeping sickness research work and prevention programs during the German colonial period in East Africa, focusing on the regions around Lake Victoria and Lake Tanganyika. It examines efforts to study and prevent sleeping sickness, analyzing how both fit into the social, political, and economic dynamics of African life. It covers two phases of German colonial attention to epidemic sleeping sickness between 1902 and 1914: an initial phase of research and scientific expeditions from 1902 to 1906, then a period dominated by the introduction of disease prevention measures in affected areas from 1907 to 1914. Highlighting the local complexity and far-reaching impact of sleeping sickness, I show that sleeping sickness research and prevention emerged from the intersection of tropical medicine expertise, African mobility, and German colonial and African politics. Sleeping sickness, and subsequent efforts toward its treatment and prevention, redefined the boundaries of political power and social influence within African communities during a crucial period of change in the region. By creating new arenas of engagement between African communities and European scientists, specifically in newly-built sleeping sickness camps and among the African medical auxiliaries employed in them, sleeping sickness work created economic relationships, reshaped social and political hierarchies, and set new ground rules for African agriculture and trade. Kings, chiefs, and colonial scientists contended with African communities' demands for treatment, their resistance to examination, and their claims on the use of land and waterways. Further, inter-colonial sleeping sickness research and subsequent prevention programs played a pivotal role in the development of tropical medicine, strengthening disciplinary boundaries and defining the trajectory of future research. My work weaves together narratives of research and disease prevention from metropolitan Europe and East Africa, in contrast to strictly colonial and national histories of health and medicine that have preceded it

Including refugees in disease elimination: challenges observed from a sleeping sickness programme in Uganda.

BACKGROUND: Ensuring equity between forcibly-displaced and host area populations is a key challenge for global elimination programmes. We studied Uganda's response to the recent refugee influx from South Sudan to identify key governance and operational lessons for national sleeping sickness programmes working with displaced populations today. A refugee policy which favours integration of primary healthcare services for refugee and host populations and the availability of rapid diagnostic tests (RDTs) to detect sleeping sickness at this health system level makes Uganda well-placed to include refugees in sleeping sickness surveillance. METHODS: Using ethnographic observations of coordination meetings, review of programme data, interviews with sleeping sickness and refugee authorities and group discussions with health staff and refugees (2013-2016), we nevertheless identified some key challenges to equitably integrating refugees into government sleeping sickness surveillance. RESULTS: Despite fears that refugees were at risk of disease and posed a threat to elimination, six months into the response, programme coordinators progressed to a sentinel surveillance strategy in districts hosting the highest concentrations of refugees. This meant that RDTs, the programme's primary surveillance tool, were removed from most refugee-serving facilities, exacerbating existing inequitable access to surveillance and leading refugees to claim that their access to sleeping sickness tests had been better in South Sudan. This was not intentionally done to exclude refugees from care, rather, four key governance challenges made it difficult for the programme to recognise and correct inequities affecting refugees: (a) perceived donor pressure to reduce the sleeping sickness programme's scope without clear international elimination guidance on surveillance quality; (b) a problematic history of programme relations with refugee-hosting districts which strained supervision of surveillance quality; (c) difficulties that government health workers faced to produce good quality surveillance in a crisis; and (d) reluctant engagement between the sleeping sickness programme and humanitarian structures. CONCLUSIONS: Despite progressive policy intentions, several entrenched governance norms and practices worked against integration of refugees into the national sleeping sickness surveillance system. Elimination programmes which marginalise forced migrants risk unwittingly contributing to disease spread and reinforce social inequities, so new norms urgently need to be established at local, national and international levels

Molecular epidemiology of African sleeping sickness

Human sleeping sickness in Africa, caused by Trypanosoma brucei spp. raises a number of questions. Despite the widespread distribution of the tsetse vectors and animal trypanosomiasis, human disease is only found in discrete foci which periodically give rise to epidemics followed by periods of endemicity A key to unravelling this puzzle is a detailed knowledge of the aetiological agents responsible for different patterns of disease--knowledge that is difficult to achieve using traditional microscopy. The science of molecular epidemiology has developed a range of tools which have enabled us to accurately identify taxonomic groups at all levels (species, subspecies, populations, strains and isolates). Using these tools, we can now investigate the genetic interactions within and between populations of Trypanosoma brucei and gain an understanding of the distinction between human- and nonhuman-infective subspecies. In this review, we discuss the development of these tools, their advantages and disadvantages and describe how they have been used to understand parasite genetic diversity, the origin of epidemics, the role of reservoir hosts and the population structure. Using the specific case of T.b. rhodesiense in Uganda, we illustrate how molecular epidemiology has enabled us to construct a more detailed understanding of the origins, generation and dynamics of sleeping sickness epidemics