Acta Tropica 119 (2011) 14–18
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Acta Tropica
journal homepage: www.elsevier.com/locate/actatropica
Influence of trypanocidal therapy on the haematology of vervet monkeys
experimentally infected with Trypanosoma brucei rhodesiense
Maina Ngotho
a,b,d
, John M. Kagira
b
, Christopher Kariuki
a
, Naomi Maina
c
, John K. Thuita
b
,
David M. Mwangangi
b,e
, Idle O. Farah
a
, Jann Hau
d,∗
a
Institute of Primate Research, P. O. Box 24481 – 00502, Nairobi, Kenya
b
KARI – Trypanosomiasis Research Centre (KARI-TRC), P. O. Box 362, Kikuyu, Kenya
c
Department of Biochemistry, Jomo Kenyatta University of Agriculture& Technology, P. O. Box 62000 – 00200, Nairobi, Kenya
d
Department of Experimental Medicine, University of Copenhagen & University Hospital, 3B Blegdamsvej, DK-2200 Copenhagen N, Denmark
e
Central Veterinary Laboratories Kabete, P.O. Box Private Bag – 00625, Nairobi, Kenya
article info
Article history:
Received 23 February 2010
Received in revised form 17 January 2011
Accepted 27 February 2011
Available online 21 March 2011
Keywords:
HAT
Vervet monkey
Chemotherapy
Haematology
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 fol-
lowing 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.
© 2011 Elsevier B.V. All rights reserved.
1. Introduction
Human African trypanosomiasis (HAT), or sleeping sickness
(SS) is a re-emerging protozoan disease associated with com-
plex haematological changes. Monitoring of the haematological
parameters is important, not only for rapid appraisal of the dis-
ease management, but also in understanding the pathogenesis and
∗
Corresponding author. Tel.: +45 3532 7363; fax: +45 3532 7399.
E-mail address: jhau@SUND.ku.dk (J. Hau).
URL: http://emed.ku.dk (J. Hau).
response to treatment of relapsed infections, when they occur.
The main changes include anaemia, thrombocytopaenia and leu-
cocytopaenia, which intensify as the disease progresses (Stephen,
1986; Robins-Browne et al., 1975). The severity of the haematopoi-
etic changes depends not only on the species of the trypanosome,
but also on the species and physiological state of the host and
acuteness or chronicity of the infection (Jenkins and Facer, 1985;
Stephen, 1986). Recovery of bone marrow haematopoiesis follow-
ing treatment has, however, not been evaluated. It is hypothesised
that the recovery time is dependent on various factors including;
stage of the disease at which treatment is administered, the drug
used for treatment, level of anaemia, and rate of parasite clearance
0001-706X/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.actatropica.2011.02.013