AbstractThe simian parasite Plasmodium knowlesi is a common cause of human malaria in Malaysian Borneo, and can cause severe and fatal disease. Substantial knowledge gaps exist in regards to the epidemiology, clinical features, diagnosis, and pathophysiology of knowlesi malaria, and the overall aim of this thesis was to enhance understanding in these areas.
First, two retrospective studies were conducted at Kudat District Hospital, northeast Sabah, with these studies confirming that P. knowlesi was the most common cause of malaria among adults and children at this hospital. A wide age-distribution among patients with knowlesi malaria was described, and two family clusters were identified. Second, Sabah Department of Health malaria notification data were reviewed, with this study demonstrating that, while notifications of P. falciparum and P. vivax had decreased markedly over the past 20 years, over the past decade notifications of “P. malariae/P. knowlesi” increased significantly. Third, a prospective observational study was conducted, involving all malaria patients admitted to Queen Elizabeth Hospital (QEH), a tertiary-referral hospital in Sabah, from September 2010 to October 2011. This study found that P. knowlesi was the most common cause of severe malaria at QEH, and was associated with a 3-fold increased risk of severity compared to P. falciparum. Parasite count was the major independent risk factor for severe knowlesi malaria, with risk increasing 11-fold with parasitemia >20,000/μL and 28-fold with parasitemia >100,000/μL. Artesunate therapy was highly effective for severe malaria, and no deaths from any species occurred in this study. This study also evaluated the accuracy of microscopy, and the sensitivity of two rapid diagnostic tests, for the diagnosis of knowlesi malaria. Finally, in the first of a series of pathophysiological studies conducted at QEH, red cell deformability among patients with knowlesi malaria was investigated. These studies have confirmed the importance of knowlesi malaria as a public health problem in Sabah, and have extended the existing information regarding the epidemiological and clinical features, as well as diagnosis and treatment, of knowlesi malaria. Future research priorities are identified in order to enhance our understanding of this emerging disease.
Note: Please note that published article : Barber BE, William T, Grigg MJ, Menon J, Auburn S, Marfurt J, Anstey NM, Yeo TW. 'A prospective comparative study of knowlesi, falciparum, and vivax malaria in Sabah, Malaysia: high proportion with severe disease from Plasmodium knowlesi and Plasmodium vivax but no mortality with early referral and artesunate therapy'. Clinical Infectious Diseases 2013; 56(3):383-97 - listed in "Published manuscripts forming the basis of this thesis" on page xvi, is only available on CD ROM.
|Date of Award||Jul 2013|
|Supervisor||Nicholas Anstey (Supervisor) & Tsin Yeo (Supervisor)|