Development of a safer laboratory vervet monkey model for the study of human African trypanosomiasis

Abstract

BackgroundThere are three subspecies of Trypanosoma brucei: T. b. gambiense, T. b. rhodesiense and T. b. brucei. The first two are infectious to humans, whilst T. b. brucei is not. Identifying an animal model of T. b. brucei that mimics human African trypanosomiasis (HAT) would enable researchers to study HAT without subjecting themselves to undue risks such as accidental infection.ObjectivesThis study assessed the sequential clinical, parasitological and haematological changes in vervet monkeys infected with T. b. brucei.MethodsThree vervet monkeys were infected with a 104 inoculum of T. b. brucei (isolate GUTat 1). Late-stage disease was induced by subcurative treatment with diminazene aceturate 28 days post-infection. The animals were treated curatively with melarsoprol upon relapse. Parasitaemia and clinical signs were monitored daily and, at weekly intervals, the monkeys’ blood and cerebrospinal fluid (CSF) were sampled for haematology and parasitosis assessments, respectively.ResultsThe first-peak parasitaemia was observed between seven and nine days post-infection. Clinical signs associated with the disease included fever, dullness, pallor of mucous membranes, lymphadenopathy, splenomegaly and oedema. Late-stage signs included stiffness of joints and lethargy. The monkeys developed a disease associated with microcytic hypochromic anaemia. There was an initial decline, followed by an increase, in total white blood cell counts from early- to late-stage disease. Trypanosomes were detected in the CSF and there was a significant increase in white cell counts in the CSF during late-stage disease. Infected vervet monkeys displayed classical clinical symptoms, parasitological and haematological trends that were similar to monkeys infected with T.b. rhodesiense.ConclusionThe T. b. brucei vervet monkey model can be used for studying HAT without putting laboratory technicians and researchers at high risk of accidental infection.

Transient Exposure of Humans to Animal Trypanosomes in Communities Highly Exposed to Tsetse Fly Bite

“…However, an insigni cant association was recorded for animal trypanosome ITS1 DNA-positive individuals with elevated glucose, pH and protein levels. Waita et al examined urine parameters such as pH, glucose and leukocytes in vervet monkey models and observed that an elevated pH was associated with a high parasite density in monkeys 32 . Fortunately for the subjects, there were no frameshift mutations in the apoL-1 gene in the animal trypanosome ITS1 DNApositive individuals with high urine pH.…”

“…The research team assessed each participant to ensure that he/she met the inclusion criteria; the participant must have stayed in the community within a month and not taken anti-trypanosomal medication within that period. A total of 2 mL of venous blood and 10 mL of urine samples were collected from 240 participants (Ayekokooso (32); Kwahyia (10); Nkatenkwan (39); Santramor 1 (13) and Zorh ( 146)) for analysis.…”