Control and surveillance of human African trypanosomiasis.

In the 1960s, it appeared that human African trypanosomiasis (HAT) could be effectively controlled, but by the beginning of the twenty-first century several decades of neglect had led to alarming numbers of reported new cases, with an estimated 300 000 people infected. The World Health Organization (WHO) responded with a series of initiatives aimed at bringing HAT under control again. Since 2001, the pharmaceutical companies that produce drugs for HAT have committed themselves to providing them free of charge to WHO for distribution for the treatment of patients. In addition, funds have been provided to WHO to support national sleeping sickness control programmes to boost control and surveillance of the disease. That, coupled with bilateral cooperation and the work of nongovernmental organizations, helped reverse the upward trend in HAT prevalence. By 2012, the number of reported cases was fewer than 8000. This success in bringing HAT under control led to its inclusion in the WHO Roadmap for eradication, elimination and control of neglected tropical diseases, with a target set to eliminate the disease as a public health problem by 2020. A further target has been set, by countries in which HAT is endemic, to eliminate gambiense HAT by reducing the incidence of infection to zero in a defined geographical area. This report provides information about new diagnostic approaches, new therapeutic regimens and better understanding of the distribution of the disease with high-quality mapping. The roles of human and animal reservoirs and the tsetse fly vectors that transmit the parasites are emphasized. The new information has formed the basis for an integrated strategy with which it is hoped that elimination of gambiense HAT will be achieved. The report also contains recommendations on the approaches that will lead to elimination of the disease.

Evaluation of the micro-CATT, CATT/Trypanosoma brucei gambiense, and LATEX/T b gambiense methods for serodiagnosis and surveillance of human African trypanosomiasis in West and Central Africa.

OBJECTIVE: To evaluate the performance of serological tests using dried blood on filter-papers (micro-card agglutination test for trypanosomiasis (micro-CATT)) performed under field and laboratory conditions and using whole blood ((CATT/T.b. gambiense) (wb-CATT) and latex agglutination (LATEX/T.b. gambiense) (wb-LATEX)) for the serodiagnosis and surveillance of human African trypanosomiasis in West and Central Africa. METHODS: We evaluated the micro-CATT, wb-CATT and wb-LATEX methods in Côte d'Ivoire and the Central African Republic by screening 940 people. Sensitivity and specificity were calculated for each serological test; only patients with the confirmed presence of trypanosomes in the blood or lymph aspirate were considered true positives. Positive and negative predictive values were also calculated. FINDINGS: Each of the tests showed a lower sensitivity in the Central African Republic than in Côte d'Ivoire. CONCLUSION: The results confirmed the efficiency of the classic wb-CATT to detect sleeping sickness patients. The micro-CATT method can be used for human African trypanosomiasis surveillance if the test is performed on the same day as the blood collection, or if samples are stored at 4 degrees C. Otherwise, micro-CATT can be used when absolute sensitivity is not required. wb-LATEX should only be used for high-specificity screening.

Cysteine proteinases of trypanosome parasites: novel targets for chemotherapy.

The protozoan parasites, Trypanosoma brucei and T. cruzi, that cause sleeping sickness in sub-Saharan Africa and Chagas' Disease in Latin America, respectively, exert significant morbidity and mortality in man. Combinations of toxicity and differential efficacy of current drugs provide an urgent need to develop novel, cheap and effective chemotherapies. Research over the last decade with cultured trypanosomes and mice experimentally infected with these parasites has demonstrated that trypanosome cysteine proteinases are valid targets for the rational design of new drugs. In particular, potent peptidyl and peptidomimetic inhibitors of brucipain (a.k.a. trypanopain-Tb) and cruzain (a.k.a. cruzipain), the respective cysteine proteinases of T. brucei and T. cruzi, have proved trypanocidal. Efforts are ongoing to develop more specific non-toxic inhibitors of various chemistries with improved biological half-lives and biovailability characteristics. Here, the biochemical and biological properties together with the history, current status and perceived directions on the development of specific inhibitors of trypanosome cysteine proteinases will be reviewed.