Research Article: The Burden of Human African Trypanosomiasis

Date Published: December 23, 2008

Publisher: Public Library of Science

Author(s): Eric M. Fèvre, Beatrix v. Wissmann, Susan C. Welburn, Pascal Lutumba, Simon Brooker

Abstract: Human African trypanosomiasis (HAT, or sleeping sickness) is a protozoan parasitic infection caused by Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense. These are neglected tropical diseases, and T.b. rhodesiense HAT is a zoonosis. We review current knowledge on the burden of HAT in sub-Saharan Africa, with an emphasis on the disability-adjusted life year (DALY), data sources, and methodological issues relating to the use of this metric for assessing the burden of this disease. We highlight areas where data are lacking to properly quantify the impact of these diseases, mainly relating to quantifying under-reporting and disability associated with infection, and challenge the HAT research community to tackle the neglect in data gathering to enable better evidence-based assessments of burden using DALYs or other appropriate measures.

Partial Text: Human African trypanosomiasis (HAT)—also known as sleeping sickness—is caused by infection with one of two parasites: Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense. These organisms are extra-cellular protozoan parasites that are transmitted by insect vectors in the genus Glossina (tsetse flies). As with a few other human pathogens (e.g., tuberculosis caused by Myobacterium tuberculosis and M. bovis), HAT shares the confusion that two different causative organisms cause a similar clinical disease. The parasites can be distinguished through molecular methods [1],[2], but not parasitologically; the geographic range of the parasites has been a key component of the differential diagnosis of HAT, as T.b. gambiense occurs in West and Central Africa, and T.b. rhodesiense occurs only in East Africa, though there are concerns that an overlap may now have occurred in their ranges [3]. To understand the epidemiology of HAT, as well as its disease and economic burden, it is essential to understand the distinction between the diseases caused by the two parasites.

T.b. rhodesiense is a zoonosis [5],[6], with a number of wildlife [7] and domestic animal species known to act as reservoirs. Where wildlife is not abundant, domestic species, particularly cattle, are the main reservoir [8], with livestock demography driving outbreaks [9]. T.b. gambiense is generally not considered zoonotic—it can be isolated from animal hosts [10],[11], but large-scale control campaigns targeting only the human reservoir (active screening and treatment of human cases) are able to locally eliminate transmission [12],[13], and theoretical assessments of control options [14] confirm that from an epidemiological perspective, the presence of animal hosts is unlikely to mean they serve as a reservoir of infection for humans [15] (such hosts and their potential as a source for re-introduction of the parasite to the human population would need to be considered if ever aiming for total elimination of the disease, however). The transmission of HAT occurs primarily in rural areas (with a few exceptions, including peri-urban Kinshasa [16]), in areas at the furthest extremities of the formal health system, creating particular problems for patients to access health care [17],[18], for control campaigns to have an effective outreach [19], and, importantly, in the assessment of the burden of infections, hindering efforts to collect data on how many people are at risk, how many people are infected, and what the impact of the disease is on the social environment. These are not issues restricted to HAT (of either form), but are general among many of the neglected tropical diseases and neglected zoonotic diseases [20],[21].

Quantifying the impact of a disease—its burden—is a necessity in providing an evidence base for effective decision making in relation to planning of control and interventions [32]. Burden can be measured in terms of impact at a range of scales—the individual, family groups, society at large. For decision-making at the societal level (e.g., government policy, national or regional budgetary allocation, etc.), a societal, or population-based approach, is most appropriate. For this, a range of tools are available [33],[34]; the DALY is a useful and now well-established measure [35]–[37]. Proper quantification matters greatly to the neglected diseases, because a primary reason for their neglect is that their true impact on society is not known. For focal diseases such as HAT, it is necessary to choose an appropriate scale at which the assessment of burden is carried out—in many sub-Saharan African countries, the national level burden of malaria, for example, will exceed, by orders of magnitude, that of HAT, leishmaniasis [38], cysticercosis [39], or many other neglected infections. However, within a province or district, where transmission of a neglected disease occurs, it may assume a much greater importance; as budgetary decisions are increasingly made at such decentralised levels [40],[41], it is also appropriate to measure the burden of disease at this level [42],[43]. Scientific research at a range of geographic scales that uses recognised health metrics as an outcome can therefore assist in the development of effective policy.

Akin to the challenges involved in the assessment of burden of most neglected tropical diseases, data on HAT incidence, morbidity, and mortality is incomplete and fragmented at present. Under-reporting of HAT, exacerbated by insufficient access to health care by patients, as well as confounding with concurrent endemic diseases such as malaria and HIV/AIDS, is a significant obstacle. Methods to quantify levels of under-reporting of both T.b. gambiense and T.b. rhodesiense[59],[85] need to be validated and extended to foci in different countries. As well as estimating mortality, those living in HAT foci must be enumerated to provide a denominator for incidence figures; estimates of the population at risk, validated by field data, are urgently required. This would enable the limited resources available for data collection and public health interventions to be deployed as efficiently as possible. We have seen that morbidity associated with HAT is currently represented by single, average disability weightings in global comparative assessments. This does not reflect the dual causation of HAT (gambiense and rhodesiense), the distinction between early and late stages (and the reduction in the societal burden that can be achieved by early detection of cases), or treatment-associated morbidity. While alternative disability weightings for use in DALY calculations have been proposed and used [44], a wider consultative exercise is necessary to reach a data-driven consensus.



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