From sentinel surveillance for sleeping sickness treatment failure to the development of a pharmacovigilance approach

Abstract

In the late 1990’s a disturbing trend of geographically distinct melarsoprol treatment failures accompanied a dramatic resurgence of Human African Trypanosomiasis. These studies present results from a sentinel surveillance network (HATSENTINEL) that was established at nine sites in five countries in response to this crisis, recommendations on the need for continued trypanosome specimen collection and a call for pharmacovigilance. Seven sites are located in Democratic Republic of the Congo (DRC), Angola, or Sudan, where T. b. gambiense is endemic and two sites are located in Uganda and Tanzania, areas endemic for T. b. rhodesiense. The facilities included health centers and hospitals operated by ministries of health and nongovernmental organizations. The HATSENTINEL network addressed the lack of standard diagnostic and treatment protocols used for HAT in African facilities by using a standardized form to collect data about the specific diagnostic methods and treatment regimens in use at the sentinel facilities. The melarsoprol failure rates detected by HATSENTINEL in northern Angola (98%) and in East Kasai Province of DRC (61%) are substantially higher than previously reported. There was no evidence of geographic spread of melarsoprol-refractory infection. The drug remained effective at a site in DRC during the 6 years of surveillance, despite its proximity to the northern Angola site. The failure rates did prompt the MOHs to switch protocols to an alternative drug, eflornithine. The four centers that used eflornithine as first line treatment for Stage II patients had failure rates ranging from 2.3% to 3.9%; this led to overall reductions in the number of cases. The study attempted to isolate and investigate parasite strains resistant to melarsoprol but the limited results did not find this to be the case. The investigation for resistant strains should continue. The results from the HATSENTINEL network has reinforced the need for continued sentinel surveillance. This has also revealed the need for improved pharmacovigilance. There will be many barriers to establishing a reliable pharmacovigilance network, yet these challenges do not mean that pharmacovigilance is not possible in Africa or should be set to a lower standard. In the case of human African trypanosomiasis we argue that the most rigorous approaches advocated by WHO should be embraced.