Elsevier

The Lancet

Volume 390, Issue 10110, 25 November–1 December 2017, Pages 2397-2409
The Lancet

Seminar
Human African trypanosomiasis

https://doi.org/10.1016/S0140-6736(17)31510-6Get rights and content

Summary

Human African trypanosomiasis (sleeping sickness) is a parasitic infection that almost invariably progresses to death unless treated. Human African trypanosomiasis caused devastating epidemics during the 20th century. Thanks to sustained and coordinated efforts over the past 15 years, the number of reported cases has fallen to an historically low level. Fewer than 3000 cases were reported in 2015, and the disease is targeted for elimination by WHO. Despite these recent successes, the disease is still endemic in parts of sub-Saharan Africa, where it is a considerable burden on rural communities, most notably in central Africa. Since patients are also reported from non-endemic countries, human African trypanosomiasis should be considered in differential diagnosis for travellers, tourists, migrants, and expatriates who have visited or lived in endemic areas. In the absence of a vaccine, disease control relies on case detection and treatment, and vector control. Available drugs are suboptimal, but ongoing clinical trials provide hope for safer and simpler treatments.

Introduction

Human African trypanosomiasis is a neglected tropical disease that occurs in sub-Saharan Africa, within the distributional limits of the vector, the tsetse fly. Two forms of the disease exist: the slow-progressing form, caused by Trypanosoma brucei gambiense, which is endemic in western and central Africa; and, the faster-progressing form, caused by Trypanosoma brucei rhodesiense, found in eastern and southern Africa.1

Since the beginning of the 20th century, human African trypanosomiasis has killed millions of people. Today, the disease is rare, thanks to large-scale and efficient deployment of an—albeit incomplete—arsenal of control tools. Yet, cases are reported from more than 20 countries in Africa, where the disease causes substantial morbidity among the affected rural populations, and continues to pose the threat of severe epidemics.2 In a globalised world, cases are also diagnosed outside endemic African countries among travellers, tourists, expatriates, and migrants.3 In this Seminar, we discuss the epidemiology, cause, clinical features, diagnosis, and treatment of human African trypanosomiasis, and touch on epidemiological surveillance and methods of control and elimination.

Section snippets

Epidemiology

The trypanosomes that cause human African trypanosomiasis are classically transmitted by the bite of blood-sucking tsetse flies (Diptera, genus Glossina). T brucei gambiense can also be transmitted congenitally.4, 5, 6 Other routes of transmission are possible but poorly documented, and are thought to be very rare (eg, sexual, laboratory accidents, blood transfusion, and organ transplantation).6, 7, 8, 9

In the early 20th century, devastating epidemics occurred in, among other places, Uganda,

Parasite and vector

T brucei belongs to the Trypanosomatidae family of exclusively parasitic organisms found in vertebrates and insects worldwide.23 These unicellular parasites have co-evolved with their hosts to such an extent that most are commensal rather than pathogenic.24 T brucei includes three morphologically indistinguishable subspecies (figure 2): T brucei brucei, which causes animal African trypanosomiasis, and is not infective to human beings, whereas T brucei rhodesiense and T brucei gambiense can

Clinical features

The clinical presentation of human African trypa-nosomiasis depends on the T brucei subspecies, host response, and disease stage. Variations of virulence and pathogenicity are attributed to different strains of parasite.44, 45 Generally, both forms of the disease lead to death if untreated; although, for T brucei gambiense disease, healthy carriers and self-cure have been described.46 T brucei rhodesiense disease is typically acute, progressing to second-stage disease within a few weeks, and

Diagnosis

Clinical signs and symptoms of human African trypanosomiasis are unspecific and can easily be mistaken for those of other diseases; thus, they are often insufficient for diagnosis.

Reliable serodiagnostic tests exist only for T brucei gambiense infection, and are based on the detection of specific antibodies. The card agglutination test for trypanosomiasis (CATT),62 developed almost 40 years ago, has been pivotal in the control of T brucei gambiense disease. CATT can be done with blood collected

Treatment

Five drugs are routinely used in the treatment of human African trypanosomiasis: pentamidine and suramin to treat first-stage disease, and melarsoprol, eflornithine, and nifurtimox for second-stage disease. All are donated by the manufacturers, and WHO ensures their worldwide distribution free of charge. The drugs can be obtained directly from WHO in Geneva or from the few institutes that stock them (appendix).3 This accessibility means treatment of human African trypanosomiasis is unaffected

Epidemiological surveillance

Surveillance is crucial for control of human African trypanosomiasis because of the disease's focal distribution, occurrence in remote rural areas, and capacity to re-emerge when control activities are relaxed. Control operations are resource-intensive and therefore require careful targeting. Surveillance is carried out by national control programmes, with support from WHO and other partners. Field data are collected through both active and passive case detection, and are assembled, harmonised,

Control and elimination

In the absence of a vaccine or chemoprophylaxis, human African trypanosomiasis is controlled through case detection and treatment, and, to a lesser extent, vector control.

For T brucei gambiense human African trypanosomiasis, the most effective control strategy is case finding and treatment, which reduces the human reservoir and thus decreases T brucei transmission. Cases of T brucei gambiense disease are detected through active screening campaigns by mobile teams, consisting of up to eight

Conclusions

Human African trypanosomiasis has long been a typical neglected tropical disease, characterised by suboptimal control tools and inadequate funding. Over the past 15 years, thanks to the efforts of a broad range of stakeholders, the situation has changed. Today, human African trypanosomiasis is a rare disease that is targeted for elimination. Drugs are available for free thanks to donations of the manufacturers, low-cost rapid diagnostic tests and vector control tools are on the market; safe

Search strategy and selection criteria

We searched PubMed on Dec 1, 2016, for publications written in English or French, using the keywords: “sleeping sickness”, “Trypanosoma brucei gambiense”, “Trypanosoma brucei rhodesiense”, “CATT”, “suramin”, “pentamidine”, “melarsoprol”, “eflornithine”, “tsetse”, “Glossina”, or “human African trypanosomiasis”. Results were limited to those published between 2010 and 2016. Among the almost 3000 references, we selected those we judged relevant, prioritising those reporting applied research. An

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