title: Influence of trypanocidal therapy on the haematology of vervet monkeys experimentally infected with Trypanosoma brucei rhodesiense.
abstract: The aim of this study was to characterise the sequential haematological changes in vervet monkeys infected with Trypanosoma brucei rhodesiense and subsequently treated with sub-curative diminazene aceturate (DA) and curative melarsoprol (MelB) trypanocidal drugs. Fourteen vervet monkeys, on a serial timed-kill pathogenesis study, were infected intravenously with 10(4) trypanosomes of a stabilate T. b. rhodesiense KETRI 2537. They were treated with DA at 28 days post infection (dpi) and with MelB following relapse of infection at 140 dpi. Blood samples were obtained from the monkeys weekly, and haematology conducted using a haematological analyser. All the monkeys developed a disease associated with macrocytic hypochromic anaemia characterised by a reduction in erythrocytes (RBC), haemoglobin (HB), haematocrit (HCT), mean cell volume (MCV), platelet count (PLT), and an increase in the red cell distribution width (RDW) and mean platelet volume (MPV). The clinical disease was characteristic of human African trypanosomiasis (HAT) with a pre-patent period of 3 days. Treatment with DA cleared trypanosomes from both the blood and cerebrospinal fluid (CSF). The parasites relapsed first in the CSF and later in the blood. This treatment normalised the RBC, HCT, HB, PLT, MCV, and MPV achieving the pre-infection values within two weeks while RDW took up to 6 weeks to attain pre-infection levels after treatment. Most of the parameters were later characterised by fluctuations, and declined at one to two weeks before relapse of trypanosomes in the haemolymphatic circulation. Following MelB treatment at 140 dpi, most values recovered within two weeks and stabilised at pre-infection levels, during the 223 days post treatment monitoring period. It is concluded that DA and MelB treatments cause similar normalising changes in the haematological profiles of monkeys infected with T. b. rhodesiense, indicating the efficacy of the drugs. The infection related changes in haematology parameters, further characterise the vervet monkey as an optimal induced animal model of HAT. Serial monitoring of these parameters can be used as an adjunct in the diagnosis and prognosis of the disease outcome in the vervet monkey model.
authors.affiliation: Institute of Primate Research, Nairobi, Kenya.
authors.forename: Maina
authors.initials: M
authors.lastname: Ngotho
authors.forename: John M
authors.initials: JM
authors.lastname: Kagira
authors.forename: Christopher
authors.initials: C
authors.lastname: Kariuki
authors.forename: Naomi
authors.initials: N
authors.lastname: Maina
authors.forename: John K
authors.initials: JK
authors.lastname: Thuita
authors.forename: David M
authors.initials: DM
authors.lastname: Mwangangi
authors.forename: Idle O
authors.initials: IO
authors.lastname: Farah
authors.forename: Jann
authors.initials: J
authors.lastname: Hau
mesh_terms: D000748:Anemia, Macrocytic / Q000469:parasitology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D002555:Cerebrospinal Fluid / Q000469:parasitology; D002522:Chlorocebus aethiops / Q000097:blood / Q000134:cerebrospinal fluid / Q000469:parasitology*; D004133:Diminazene / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006405:Hematology; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D008549:Melarsoprol / Q000494:pharmacology* / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000469:parasitology; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects / Q000469:parasitology*; D014353:Trypanosomiasis, African / Q000188:drug therapy*
chemical_list: C003915:diminazene aceturate; D004133:Diminazene; D008549:Melarsoprol