I undertook a PubMed search using the keywords “human African trypanosomiasis”, “sleeping sickness”, “trypanosomiasis”, “trypanosomes”, “diagnosis”, “treatment”, “CNS”, “T b rhodesiense”, and “T b gambiense” from 1970 to September, 2012. Keywords were used both individually and in combination; for example, “sleeping sickness and diagnosis”. I also referred to my personal database of papers and information. From the available data and resources, I selected sources that had particular relevance
ReviewClinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness)
Introduction
Human African trypanosomiasis (HAT), which is also known as sleeping sickness, is one of the world's neglected diseases. Caused by protozoan parasites of the genus Trypanosoma and transmitted by the bite of the blood-sucking tsetse fly of the genus Glossina, about 60 million people are estimated to be at risk of the disease between latitudes 14° north and 29° south throughout many countries in sub-Saharan Africa.1, 2, 3 HAT is almost always fatal if untreated or inadequately treated and is a substantial cause of both mortality and morbidity in affected regions, where it also has a substantial effect on livestock production. The problem of the disease is compounded by the extent of tsetse fly infestation, which covers about 10 million km2 of the landmass of Africa.2
There are two forms of HAT, the more common west African disease caused by Trypanosoma brucei gambiense (T b gambiense) and the less common east African disease caused by T b rhodesiense.1, 2 Although about 97% of cases of HAT are due to the T b gambiense variant, the T b rhodesiense variant, which is responsible for only about 3% of cases,4 causes a more acute and severe illness, and it can be a substantial hazard in travellers from Europe and the USA returning from visits to east African game parks.5, 6
For centuries there had been a general awareness of the existence of a severe wasting disease called nagana occurring in cattle in sub-Saharan latitudes and also of a fatal sleep disorder of human beings occurring in those areas.7, 8 The cause of nagana was finally identified in 1899 by David Bruce, who showed that the disease was caused by a trypanosome that became known eponymously as Trypanosoma brucei, with his subsequent studies proving that it was the tsetse fly that transmitted the disease from wild to domestic animals.7, 8 During the following decade, several other discoveries were made, including the identification by Dutton of a subspecies in a European individual, which was termed T b gambiense; the first identification by Castellani of trypanosomes in the blood and CSF in a patient with HAT; and the identification by Stephens and Fantham of a subspecies called T b rhodesiense.7, 8, 9 Although animals such as cattle are the main reservoirs of trypanosomes causing T b rhodesiense disease, human beings are the main reservoir for trypanosomes causing T b gambiense HAT.3, 10 Figure 1 shows the distribution of these two HAT variants. In Uganda, both types of HAT exist, raising the possibility that some patients can become co-infected with both T b gambiense and T b rhodesiense.8, 12 The existence of these two variants in the same region raises the problematic issue of patient treatment, which would be different for both diseases, especially because microscopy alone is not sufficient to distinguish between the two subspecies.
Section snippets
Epidemiology
The epidemiology of HAT shows a history of epidemics and disease resurgences over the past century. Around the time that these seminal discoveries about the disease were being made (1896–1906), HAT caused the deaths of many hundreds of thousands of people in affected regions in major epidemics.1, 8 However, with strong measures, including an initial mass animal cull and eradication of large forested regions of sub-Saharan Africa, followed by advances in insect vector control and intensive human
Parasite, vector, and host
Details of trypanosome biology and parasite–host interactions have been described elsewhere.1, 2, 3 In brief, the trypanosome genome, which has now been sequenced, contains about 9000 genes, of which 10% encode variant surface glycoproteins, which are present on the surface of the trypanosome and anchored to its outer membrane by a glycosylphosphatidylinositol anchor.1, 2 A crucial feature is that only one variant surface glycoprotein gene is expressed at a time, and there is a rapid switching
Clinical features
Traditionally, symptoms of HAT are described as occurring in early or late stages. However, distinguishing between these stages on the basis of clinical features alone can be very difficult and the two stages can seem to merge into each other, which is why more objective criteria are needed to differentiate them.
Diagnostic aspects of HAT
Obtaining a positive diagnosis of HAT is essential in view of the grim outcome of the natural disease and the toxicity of the drugs used for its treatment. Time spent in the sub-Saharan location where HAT is endemic, as well as a suggestive clinical presentation, will point to the possibility of infection, especially in patients from east Africa. Alternative diagnoses or coexisting diseases that need to be investigated and excluded include malaria, HIV infection, leishmaniasis, tuberculosis,
Pharmacological treatment of HAT
The treatment of HAT has been unsatisfactory for many years, with all four of the main drugs used for early-stage and late-stage disease being unavailable orally, often toxic, and sometimes ineffective (table).57 These limited treatment options are a result of a 50-year period of underinvestment by governments and the pharmaceutical industry into a disease for which even widespread treatment promised little or no prospect of financial returns. However, over the past decade, the situation has
Conclusions
Despite the formidable reputation of sleeping sickness for over a century as one of Africa's major deadly diseases, there has been substantial progress over the past 10–15 years, both in terms of reduction in the number of people infected with the disease and in the development of better treatment regimens and potentially more effective and orally administered drugs. Despite these advances, the outlook for the smaller number of patients with T b rhodesiense infection is less optimistic than for
Search strategy and selection criteria
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