Factors that are associated with the risk of acquiringPlasmodium knowlesimalaria in Sabah, Malaysia: a case-control study protocol

Abstract

IntroductionPlasmodium knowlesi has long been present in Malaysia, and is now an emerging cause of zoonotic human malaria. Cases have been confirmed throughout South-East Asia where the ranges of its natural macaque hosts and Anopheles leucosphyrus group vectors overlap. The majority of cases are from Eastern Malaysia, with increasing total public health notifications despite a concurrent reduction in Plasmodium falciparum and P. vivax malaria. The public health implications are concerning given P. knowlesi has the highest risk of severe and fatal disease of all Plasmodium spp in Malaysia. Current patterns of risk and disease vary based on vector type and competence, with individual exposure risks related to forest and forest-edge activities still poorly defined. Clustering of cases has not yet been systematically evaluated despite reports of peri-domestic transmission and known vector competence for human-to-human transmission.Methods and analysisA population-based case–control study will be conducted over a 2-year period at two adjacent districts in north-west Sabah, Malaysia. Confirmed malaria cases presenting to the district hospital sites meeting relevant inclusion criteria will be requested to enrol. Three community controls matched to the same village as the case will be selected randomly. Study procedures will include blood sampling and administration of household and individual questionnaires to evaluate potential exposure risks associated with acquisition of P. knowlesi malaria. Secondary outcomes will include differences in exposure variables between P. knowlesi and other Plasmodium spp, risk of severe P. knowlesi malaria, and evaluation of P. knowlesi case clustering. Primary analysis will be per protocol, with adjusted ORs for exposure risks between cases and controls calculated using conditional multiple logistic regression models.EthicsThis study has been approved by the human research ethics committees of Malaysia, the Menzies School of Health Research, Australia, and the London School of Hygiene and Tropical Medicine, UK.

Seasonal and Spatial Dynamics of the Primary Vector of Plasmodium knowlesi within a Major Transmission Focus in Sabah, Malaysia

“…knowlesi cases in the past few years especially in Kudat district, it is hypothesized that people are only getting infected when they visit forested areas. Within our current study sites, the number of malaria cases occurring over the sampling period ranged from 1.9 to 2.5 cases per 100 people [48]. As positive An .…”

Phylogenetic analysis of simian Plasmodium spp. infecting Anopheles balabacensis Baisas in Sabah, Malaysia

“…Hitherto, this simian malaria has not become zoonotic to humans yet although it has been proven experimentally to be infective to monkey through the bites of An . dirus [29]. The infection rate of P .…”

Association between Landscape Factors and Spatial Patterns ofPlasmodium knowlesiInfections in Sabah, Malaysia

“…Consequently, uncertainty in diagnosis resulted in some infections being recorded as P. malariae or P. malariae/knowlesi . To estimate the true proportion of P. knowlesi , we calculated the sensitivity and specificity of microscopy diagnosis of P. malariae for a subset of 539 malaria patients for whom both microscopy and molecularly confirmed results were available, including all patients from Kudat and Kota Marudu hospitals who were referred to a tertiary care hospital during this period and all patients recruited at these hospitals during 2013 and 2014 ( 22 , 26 ). The proportion of malaria cases reported as P. knowlesi per village per year was adjusted for this sensitivity and specificity by using a Bayesian estimation of true incidence from apparent incidence obtained by testing individual samples ( 27 ).…”

“…Travel time to the clinic from each village was estimated by using travel times reported in community interviews and by patients recruited as part of a population-based case–control study ( 26 ). …”