Elsevier

The Lancet

Volume 362, Issue 9394, 1 November 2003, Pages 1469-1480
The Lancet

Seminar
The trypanosomiases

https://doi.org/10.1016/S0140-6736(03)14694-6Get rights and content

Summary

The trypanosomiases consist of a group of important animal and human diseases caused by parasitic protozoa of the genus Trypanosoma. In sub-Saharan Africa, the final decade of the 20th century witnessed an alarming resurgence in sleeping sickness (human African trypanosomiasis). In South and Central America, Chagas' disease (American trypanosomiasis) remains one of the most prevalent infectious diseases. Arthropod vectors transmit African and American trypanosomiases, and disease containment through insect control programmes is an achievable goal. Chemotherapy is available for both diseases, but existing drugs are far from ideal. The trypanosomes are some of the earliest diverging members of the Eukaryotae and share several biochemical peculiarities that have stimulated research into new drug targets. However, differences in the ways in which trypanosome species interact with their hosts have frustrated efforts to design drugs effective against both species. Growth in recognition of these neglected diseases might result in progress towards control through increased funding for drug development and vector elimination.

Section snippets

The parasites and their vectors

Superficially, there are many similarities between trypanosome species and the diseases they cause (table). Both are single-celled flagellates (figure 2) that are transmitted by insect vectors (figure 3). They share phases of local multiplication in their human host followed by dissemination and localisation in target organs, in which they cause potentially lethal damage. However, key differences between the organisms exist, which can account for why clinical manifestations and susceptibility

Evolutionary history

Comparison of 18S rRNA gene sequences from multiple trypanosome species obtained from diverse hosts, combined with other molecular approaches, suggests that the genus Trypanosoma is monophyletic.5 By superimposing estimates with the molecular clock on vicariance biogeography, it is suggested that T brucei and T cruzi shared a common ancestor around 100 million years ago.6

This prehistoric dating indicates that human beings were exposed to African trypanosomes concomitantly with their evolution.

Epidemiology and transmission

T brucei and T cruzi are transmitted by biting insects, but a fundamental difference between the means of transmission has been incorporated into the classification of these organisms. T brucei are known as salivaria because they are transmitted in tsetse saliva. T cruzi belongs to the stercoraria because transmission is via vector faeces.

Transmission of both species can also be via blood transfusion, contaminated needles, or the congenital route. Rarely, transmission of T cruzi by

Trypanosoma brucei

Trypanosoma brucei is divided into three subspecies. Only two cause human African trypanosomiasis.9 In west and central Africa, T brucei gambiense causes a chronic form of sleeping sickness. In east and southern Africa, T brucei rhodesiense causes an acute form. Natural tsetse-mediated transmission of both subspecies happens only in Uganda. Infection with either subspecies is uniformly fatal if untreated. T brucei brucei is not infectious to human beings.

Results of molecular studies are

Trypanosoma cruzi

In 1985, WHO estimated that about 100 million people in Latin America were at risk of acquiring Chagas' disease, with a prevalence of human T cruzi infection estimated at 18 million cases.8, 22 Since 15–30% of the infected population develops overt clinical manifestations, about 5 million people can be assumed to have clinical changes attributable to Chagas' disease today. Successful programmes in vector control have led to a decline in transmission in recent years (see later).

T cruzi is

The diseases

Human African trypanosomiasis and Chagas' disease are both chronic diseases that undergo distinct stages in their natural course. Both are potentially fatal. Sterilising acquired immunity does not exist after natural infection, and there are no vaccines.

Any pathogen must evade host-cell immunity to establish infection. In the mammalian host, by contrast with T cruzi and many other pathogenic protozoa that adopt an intracellular existence, which protects them from humoral immunity, African

Human African trypanosomiasis

This disorder is classed as stage 1 or 2 depending on whether parasites have become manifest in the cerebrospinal fluid. The pathology has been reviewed elsewhere.2, 36, 37, 38

Prospects for disease management through insect control

The epidemiological features of sleeping sickness and Chagas' disease are defined largely by the insect vectors that carry the parasites. Tsetse flies and triatominae differ ecologically. Tsetse flies are highly mobile winged dipterans needing special conditions of temperature, humidity, and vegetation. Triatominae usually crawl within peridomestic environments. Generally speaking, people are bitten by tsetse flies while active outside and by triatomines while asleep indoors. However, both

Outlook

Optimism that similarities in the biochemistry and ecological features of the trypanosome parasites may point to general control strategies has yet to bear fruit because of differences in relations between host, parasite, and the vector arthropods. In human African trypanosomiasis and Chagas' disease, control of transmission through efforts aimed at reducing the prevalence of insect vectors or mammalian reservoirs clearly works. It is essential to establish workable guidelines by which

Search strategy and selection criteria

PubMed Central and ISI Web of Science were searched, with the keywords: ‘trypanosomiasis’, ‘sleeping sickness’, ‘Chagas disease’, ‘T brucei’, and ‘T cruzi’. Preference was given to reviews that encompassed much of the primary published work on the findings that have led to the prevailing picture of these diseases. WHO websites for Chagas' disease (http://www.who.int/ctd/chagas/index.html; accessed Aug 20, 2003) and human African trypanosomiasis (http://www.who.int/health-topics/afrtryps.htm;

References (125)

  • AC Frasch

    Functional diversity in the trans-sialidase and mucin families in Trypanosoma cruzi.

    Parasitol Today

    (2000)
  • A Acosta-Serrano et al.

    The mucin-like glycoprotein super-family of Trypanosoma cruzi: structure and biological roles

    Mol Biochem Parasitol

    (2001)
  • GD Pollevick et al.

    Trypanosoma cruzi surface mucins with exposed variant epitopes

    J Biol Chem

    (2000)
  • L Penchenier et al.

    Diagnosis of human trypanosomiasis, due to Trypanosoma brucei gambiense in central Africa, by the polymerase chain reaction

    Trans R Soc Trop Med Hyg

    (2000)
  • VW Pentreath

    Trypanosomiasis and the nervous system: pathology and immunology

    Trans R Soc Trop Med Hyg

    (1995)
  • A Buguet et al.

    The duality of sleeping sickness: focusing on sleep

    Sleep Med Rev

    (2001)
  • MO Jauberteau et al.

    Galactocerebrosides are antigens for immunoglobulins in sera of an experimental model of trypanosomiasis in sheep

    J Neurol Sci

    (1991)
  • N Girones et al.

    Etiology of Chagas disease myocarditis: autoimmunity, parasite persistence, or both?

    Trends Parasitol

    (2003)
  • DM Engman et al.

    Pathogenesis of Chagas heart disease: role of autoimmunity

    Acta Trop

    (2002)
  • JS Leon et al.

    Autoimmunity in Chagas heart disease

    Int J Parasitol

    (2001)
  • RL Tarleton

    Parasite persistence in the aetiology of Chagas disease

    Int J Parasitol

    (2001)
  • GE Marcon et al.

    Use of a nested polymerase chain reaction (N-PCR) to detect Trypanosoma cruzi in blood samples from chronic chagasic patients and patients with doubtful serologies

    Diagn Microbiol Infect Dis

    (2002)
  • J Pepin et al.

    The treatment of human African trypanosomiasis

    Adv Parasitol

    (1994)
  • J Keiser et al.

    New drugs for the treatment of human African trypanosomiasis: research and development

    Trends Parasitol

    (2001)
  • D Legros et al.

    Treatment of human African trypanosomiasis: present situation and needs for research and development

    Lancet Infect Dis

    (2002)
  • J Pepin et al.

    African trypanosomiasis and drug-induced encephalopathy: risk factors and pathogenesis

    Trans R Soc Trop Med Hyg

    (1991)
  • C Burri et al.

    Efficacy of new, concise schedule for melarsoprol in treatment of sleeping sickness caused by Trypanosoma brucei gambiense: a randomised trial

    Lancet

    (2000)
  • FW Jennings

    Combination chemotherapy of CNS trypanosomiasis

    Acta Trop

    (1993)
  • FW Jennings et al.

    Human African trypanosomiasis: potential therapeutic benefits of an alternative suramin and melarsoprol regimen

    Parasitol Int

    (2002)
  • D Legros et al.

    Risk factors for treatment failure after melarsoprol for Trypanosoma brucei gambiense trypanosomiasis in Uganda

    Trans R Soc Trop Med Hyg

    (1999)
  • MP Barrett et al.

    The biochemical basis of arsenical-diamidine crossresistance in African trypanosomes

    Parasitol Today

    (1999)
  • P Trouiller et al.

    Drug development for neglected diseases: a deficient market and a public-health policy failure

    Lancet

    (2002)
  • A Stich et al.

    Waking up to sleeping sickness

    Trends Parasitol

    (2003)
  • WM Degrave et al.

    Parasite genome initiatives

    Int J Parasitol

    (2001)
  • DJ LaCount et al.

    RNA interference in African trypanosomes

    Protist

    (2001)
  • PA Michels et al.

    Metabolic aspects of glycosomes in trypanosomatidae: new data and views

    Parasitol Today

    (2000)
  • CL Verlinde et al.

    Glycolysis as a target for the design of new anti-trypanosome drugs

    Drug Resist Updat

    (2001)
  • MP Barrett

    The pentose phosphate pathway and parasitic protozoa

    Parasitol Today

    (1997)
  • S Muller et al.

    Targeting polyamines of parasitic protozoa in chemotherapy

    Trends Parasitol

    (2001)
  • KS Paul et al.

    Fatty acid synthesis in African trypanosomes: a solution to the myristate mystery

    Trends Parasitol

    (2001)
  • WHO

    The World Health Report, 2002

    (2002)
  • C Burri et al.

    Human African trypanosomiasis

  • M Miles

    American trypanosomiasis (Chagas disease)

  • JR Stevens et al.

    The molecular evolution of Trypanosomatidae

    Adv Parasitol

    (2001)
  • JR Stevens et al.

    The ancient and divergent origins of the human pathogenic trypanosomes, Trypanosoma brucei and T cruzi

    Parasitology

    (1999)
  • F Guhl et al.

    Chagas disease and human migration

    Mem Inst Oswaldo Cruz

    (2000)
  • A MacLeod et al.

    The population genetics of Trypanosoma brucei and the origin of human infectivity

    Philos Trans R Soc Lond B Biol Sci

    (2001)
  • A MacLeod et al.

    Minisatellite marker analysis of Trypanosoma brucei: reconciliation of clonal, panmictic, and epidemic population genetic structures

    Proc Natl Acad Sci USA

    (2000)
  • KM Hager et al.

    Mechanism of resistance of African trypanosomes to cytotoxic human HDL

    Nature

    (1997)
  • L Vanhamme et al.

    Apolipoprotein L-I is the trypanosome lytic factor of human serum

    Nature

    (2003)
  • Cited by (0)

    View full text