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Title: Clinical studies on naturally acquired plasmodium knowlesi infections in humans
Author: Daneshvar, Cyrus
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2013
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The non-human primate malaria species, Plasmodium knowlesi, was rarely thought infect humans in nature. In Sarawak, Malaysian Borneo, where infect ions with "Plasmodium malariae" were unusually common and causing acute clinical syndromes, it was discovered that these infections were due to naturally acquired infections with P. knowlesi. It was then established that this species of Plasmodium was the leading cause of malaria in certain geographical regions in Southeast Asia, and it is now accepted as the fifth cause of malaria in humans. This thesis describes a series of clinical field studies conducted prospectively to evaluate i) the clinical and laboratory features of human P. knowlesi infections and ii) the in-vivo parasitic and clinical response to treatment. This prospective study, in adults presenting with acute malaria infections, found single knowlesi malaria infections in 113 of 179 (63%) cases in the Kapit region. The mean age was 44.9±14.9 years, and 56.1% were male, with I in 4 patients reporting previous episodes of malaria. A history of jungle/jungle fringe exposure was present in R7% of cases "' most through fanning and logging. The median duration of illness was 4 [interquartile range (IQR) 3-6] days, with symptoms of fever, chills, rigors, malaise, anorexia, myalgia occurring in >80% of cases. Cough and abdominal pain were present in 56% and 52% of patients respectively. On examination, the median temperature was 37.6 [37-38.5] degc. The liver and spleen were palpable in 26 (24%) and 16 (15%) cases respectively. Thrombocytopenia was present in all cases during admission, and recovered following treatment. Altered renal (29.9%), electrolyte (29%) and liver function tests (46.7%) were observed, recovering with clearance of parasitaemia. Acute renal failure was present in 3 (2.8%) patients. Severe kl10wlesi malaria was present in 10 (9.3%) patients and the case fatality was 1.8% (95% confidence intervals: 0.2% to 6.6%). In uncomplicated knowlesi infections, treatment with chloroquine was very effective. The fever clearance time was 26.5 [16-34] hours and time to clear 50% and 90% of parasites was 3.1 (2.84-3.43) and 10.3 (9.4-11.4) hours respectively. Parasite clearance times were faster than for vivax malaria (p=0.02). There was no evidence of recrudescence or treatment failure. The spectrum of disease in knowlesi malaria ranges from a mild febrile illness associated with low parasitaemia and thrombocytopenia, to severe disease with multiple organ involvement which can be fatal. Similarities with severe falciparum infection were noted, however cerebral malaria was not observed. The use of chloroquine for the treatment of uncomplicated knowlesi malaria infections was found to be highly effective, with rapid parasite clearance times and no evidence of parasite resistance or recrudescence. Further studies addressing optimal management strategies for severe knowlesi malaria arc urgently needed, including those that will accurately classify severe knowlesi disease and define the most effective anti-malarial treatment.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available