Human african trypanosomiasis: current standing and challenges

Human African trypanosomiasis (HAT) caused by the protozoan Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, and transmitted by the tsetse fly (genus Glossina), affects 36 Sub-Saharan African countries with considerable public health impact. Despite approximately 15,000 infected individuals and 70 million at risk, in recent years the World Health Organization has mentioned removal of HAT from the list of Neglected Tropical Diseases by 2020, due to the decrease in cases over the last two decades. When untreated, the disease presents high lethality rates and the available treatments are complicated to administer, highly toxic, and do not guarantee cure, especially in the advanced stages of the disease. Further, there is no prospect for vaccine development in the near future. The present review compiles information on the history of the clinical aspects of HAT, as well as its epidemiology, diagnosis, therapy, and prophylaxis, as well as updating information on the current panorama and perspectives regarding the disease.

Les tests d'agglutination pour le serodiagnostic de l'infection a Tryapnosoma brucei gambiense : bilan et perspectives

Le depistage systematique de la maladie du sommeil a Trypanosoma brucei gambiense dans un foyer endemique necessite la mise en oeuvre de tests serologiques detectant des anticorps specifiques. A cet egard; certains tests d'agglutination relativement simples ont l'avantage de donner une reponse rapide sur le lieu de rencensement meme

Trypanosomiase humaine africaine. Etude d' un score de presomption de diagnostic au Congo

Une enquete cas-temoins a ete realisee au Congo afin de definir une grille de score de presomption de la maladie du sommeil a T.b. gambiense basee sur une selection de criteres cliniques et epidemiologiques de la trypanosomiase; utilisable par les structures sanitaires peripheriques. L'enquete a ete realisee sur 163 cas et 326 temoins. Les signes cliniques et les symptomes retenus sont: fievre; cephalees; prurit et lesions de grattage; diarrhee; odemes; adenopathies cervicales; troubles du sommeil; troubles de l'appetit; troubles sexuels; psychisme; signes neurologiques et autres troubles cliniques mineurs. Les autres criteres retenus sont les antecedents de trypanoso- miase humaine africaine (THA) et /'existence dun cheptel dans la concession. L'analyse des resultats confirme qu'il n'existe pas de critere ou groupe de criteres pathognomo-niques. Aucun des criteres selectionnes n'est suffisamment discriminant pour permettre une selection des trypanosomes parmi des consultants. Une grille de score de presomption semble donc de peu d'utilite au niveau peripherique; ceci est d'autant plus vrai si l'on considere l'augmentation de la charge de travail. Le faible pouvoir discriminant des signes cliniques et des symptomes ainsi que des autres parametres de la trypanosomiase africaine met en evidence la difficulte de mise en place dune strategie d'integration efficiente en temps qu'outil diagnostique precoce

Immunological activities of monoclonal IgG1 antibody against Trypanosoma gambiense.

The present paper deals with the immune reaction between a monoclonal IgG1 antibody and Trypanosoma gambiense. The aggregation of trypanosomes, immune adherence to macrophages and protection against infection are associated with the antibody. IgG1-mediated clumping of trypanosomes is readily dissociated by the addition of complement. Dissociation of the clumped trypanosomes in the equivalence area released approximately fifty percent of previously bound surface antigens. These antigens were capable of binding again to new IgG1 antibody. Complement deposition rendered bivalent IgG1 antibody in the immune complex functionally univalent. Such an event in the presence of complement is of great advantage to the infected host in killing pathogens in vivo, as it allows more antibodies to attach to surface antigens and subsequently to initiate complement activity.

Diversity of complement-mediated immune reaction to Trypanosoma gambiense.

Intact and papain-treated Trypanosoma gambiense clone populations, each expressing special antigens on their cell surfaces, were mixed with rabbit antiserum in the presence of complement. Two distinct types of immune reaction between trypanosomes and antisera were observed: clumping followed by dissociation (CD) and inhibition of aggregation (IA). Special antigens on the cell surface of trypanosomes exposed after papain digestion are implicated in both types of immune reaction. IA was considered to be more effective as an immunological response which would allow the infected host to clear the pathogen without any obstruction of capillaries and impairment of blood flow caused by clumping masses of trypanosomes.

The successful system in long-term cultivation of Trypanosoma gambiense bloodstream forms.

Rat astroglioma cell line (GA-1) was extremely useful for long-term in vitro cultivation of Trypanosoma gambiense blood-stream forms. Parasites could be continuously grown at 37 degrees C for more than 200 days in the culture system, consisted of HEPES-buffered RPMI 1640 (pH 7.2, 300 milliosmole/kg) supplemented with 20% inactivated fetal calf serum in the presence of GA-1 cells. Parasites cultured for more than 200 days still retained not only their virulence for mice but also their original antigenic type. Morphologically, they resembled host infected bloodstream forms by way of having a subterminal kinetoplast and surface coat. The best growth rate of trypanosomes was obtained with 1 X 10(6) GA-1 cells/25 cm2 culture flask. Under this culture condition trypomastigote form populations increased in number up to 7-8 X 10(6) trypanosomes/ml by day 3 after initiation of the culture. The population doubling time in this culture system within the first 24 hours was almost the same as in mice. Most of the cultured trypanosomes were in suspension, but 15-20% of the parasites adhered to the surface of GA-1 cells. The culture system was also shown to be useful for cloning of T. gambiense which is important for separation of mutants.

Reanalyzing the 1900-1920 Sleeping Sickness Epidemic in Uganda

Sleeping sickness has long been a major public health problem in Uganda. From 1900 to 1920; more than 250;000 people died in an epidemic that affected the southern part of the country; particularly the Busoga region. The epidemic has traditionally been ascribed to Trypanosoma brucei gambiense; a parasite now confined to central and western Africa. The Busoga region still reports sleeping sickness; although it is caused by T.b. rhodesiense; commonly believed to have spread to Uganda from Zambia in the 1940s. Our analysis of clinical data recorded in the early 1900s shows that the clinical course of sleeping sickness cases during the 1900-1920 epidemic in Uganda was markedly different from T.b. gambiense cases; but similar to T.b. rhodesiense. These findings suggest that T.b. rhodesiense was present in Uganda and contributed to the epidemic. The historic context is reassessed in the light of these data