Relapse following chemotherapy of human and animal African trypanosomoses: a review

Abstract

An effective treatment regimen depends on detecting cases of African trypanosomosis, is a highly desirable and dependable control options. The last new veterinary drug, diminazene aceturate (Berenil) and that for treating human African trypanosomosis, alpha-Difluoromethylornithine or eflorthine (α-DFMO) that were patented 55 and 40 years ago, respectively showed the dearth of anti-trypanosome drugs. A major setback is ineffectiveness of treatment often attributed to the following factors: (i) wide spread resistance, which cut across the disease ecological areas involving all the pathogenic trypanosome species and available trypanocides. The increasing reports of multiple and cross resistance could worsen the already deplorable situation with very few drugs of choice, and (ii) parasites are shielded from trypanocidal drug actions in “privileged” sites; eyes, testes adipose tissue and brain. Advances in molecular biology have afforded the application of polymorphism to identify drug resistant genes. Lately, RNA interference used in gene silencing have allowed more insight into mode of drug actions and mechanism of resistance. Most trypanocides (excluding tryparsamide, melamingly arsenicals, nitrofuran and DFMO cannot cross the bloodtight (the blood-brain/blood-cerebrospinal fluid) barriers. Similarly, the lack of detectable levels of drugs in adipose tissue, spleen, skeletal muscle and lungs could result in relapse. Occult infection with amastigote and sphaeromastigote stages of Trypanosoma brucei lodged in the choroids plexus has remained controversial. Strict adherence to established protocol for rational drug use has been advocated as possible panacea to limit emergence and spread of induced drug resistance. Effective management of HAT cases will depend on accurate diagnosis and clinical staging of the disease, will inform using pentamidine and suramin or merlasoprol or a combination of these drugs for early and late stage infections. Other operational factors that promote occurrence of relapse includes increase in defective or adulterated drugs, inappropriate handling resulting in under dosage and pharmacokinetic limitations. The areas requiring research attentions and ways to minimize relapse are highlighted.

Keywords: Cryptic infection, Drug-resistance, Privileged sites, Recrudescence, Relapse, Trypanocides, Trypanosomosis