dc.contributor.author |
Ichagichu, James Maina |
|
dc.date.accessioned |
2016-02-15T13:41:08Z |
|
dc.date.available |
2016-02-15T13:41:08Z |
|
dc.date.issued |
2016-02-15 |
|
dc.identifier.uri |
http://hdl.handle.net/123456789/1914 |
|
dc.description |
A thesis Submitted in partial fulfillment for the Degree of Master of
Science in Molecular Medicine in the Jomo Kenyatta University of
Agriculture and Technology
2009 |
en_US |
dc.description.abstract |
New and affordable interventions are required for malaria control. The exploitation of
old drugs originally designed against other diseases presents an attractive alternative
since it limits the cost of drug discovery. Methotrexate (MTX) is one such drug. This
drug is used in high intolerable doses (9–20 g/kg body weight) for cancer treatment and
low safe doses (7.5-25 mg/kg body weight) for arthritis. The low doses are beyond
MTX concentrations required to kill drug-resistant P. falciparum strains in vitro with an
50 % inhibitory concentration (IC 50) of less than 50 nM. This study reports on the
toxicity and efficacy of MTX in the olive baboon (Papio anubis) infected with
Plasmodium knowlesi.
Twelve baboons were randomly allocated to 3 treatment groups of 4 animals each.
Group 3 (non-infected animals) were administered with MTX at a doses of 1.0
mg/kg/day for 5 days. Each animal in group 1 and 2 was infected with 1 x 106 P.
knowlesi blood stage parasites. All animals in groups 1 and 2 were administered with
MTX at single doses of 1.0 and 0.35 mg/kg/day for 5 days respectively. Due to stringent
ethical obligations and high cost of using non-human primates in biomedical research,
retrospective data was used for the positive (n = 4, infected and treated with
pyrimethamine at 1.0 mg/kg/day for 5 days) and negative (n = 4, infected non-treated)
control groups. Pre-infection and pre-treatment baseline data was used for the noninfected,
non-treated controls. Baseline samples were collected from animals in the
present study once weekly for 3 weeks prior to infection and drug administration. All
animals were followed up for 42 days. Clinical chemistry assays, postmortem and
histopathological examinations were conducted for all animals.
Group 3 animals remained clinically healthy throughout the experiment. Their clinical
chemistry and blood profile parameters fluctuated within the baseline range. Postmortem
and histological studies conducted at the end of follow-up period did not show
drug-related pathology. In infected animals, there was a significant increase in
parasitaemia from the inception to cessation of MTX administration (Group 1: p =
0.0131; Group 2: p = 0.0141). Infected baboons were euthanized to alleviate suffering.
Outcome of infected animals revealed changes consistent with the negative controls.
These findings indicate that MTX, at the dosages used in this study, is safe in the
baboon but not efficacious against P. knowlesi in vivo. |
en_US |
dc.description.sponsorship |
Dr. Simon Karanja
JKUAT, Kenya.
Dr. Hastings Ozwara
Institute of Primate Research, Kenya.
Dr. Joseph Mwatha
KEMRI, Kenya. |
en_US |
dc.language.iso |
en |
en_US |
dc.publisher |
JKUAT, Molecular Medicine |
en_US |
dc.subject |
Molecular Medicine |
en_US |
dc.title |
Study of Efficacy of Methotrexate against Plasmodium knowlesi and its Adverse Effects in Papio Anubis (Olive Baboon) |
en_US |
dc.type |
Thesis |
en_US |