Individual-level factors associated with the risk of acquiring human Plasmodium knowlesi malaria in Malaysia: a case-control study

Abstract

SummaryBackgroundThe emergence of human malaria due to the monkey parasite Plasmodium knowlesi threatens elimination efforts in southeast Asia. Changes in land use are thought to be driving the rise in reported P knowlesi cases, but the role of individual-level factors is unclear. To address this knowledge gap we assessed human and environmental factors associated with zoonotic knowlesi malaria risk.MethodsWe did this population-based case-control study over a 2 year period in the state of Sabah in Malaysia. We enrolled cases with microscopy-positive, PCR-confirmed malaria who presented to two primary referral hospitals serving the adjacent districts of Kudat and Kota Marudu. We randomly selected three malaria-negative community controls per case, who were matched by village within 2 weeks of case detection. We obtained questionnaire data on demographics, behaviour, and residential malaria risk factors, and we also assessed glucose-6-phosphate dehydrogenase (G6PD) enzyme activity. We used conditional logistic regression models to evaluate exposure risk between P knowlesi cases and controls, and between P knowlesi and human-only Plasmodium spp malaria cases.FindingsFrom Dec 5, 2012, to Jan 30, 2015, we screened 414 patients and subsequently enrolled 229 cases with P knowlesi malaria mono-infection and 91 cases with other Plasmodium spp infection. We enrolled 953 matched controls, including 683 matched to P knowlesi cases and 270 matched to non-P knowlesi cases. Age 15 years or older (adjusted odds ratio [aOR] 4·16, 95% CI 2·09–8·29, p<0·0001), male gender (4·20, 2·54–6·97, p<0·0001), plantation work (3·50, CI, 1·34–9·15, p=0·011), sleeping outside (3·61, 1·48–8·85, p=0·0049), travel (2·48, 1·45–4·23, p=0·0010), being aware of the presence of monkeys in the past 4 weeks (3·35, 1·91–5·88, p<0·0001), and having open eaves or gaps in walls (2·18, 1·33–3·59, p=0·0021) were independently associated with increased risk of symptomatic P knowlesi infection. Farming occupation (aOR 1·89, 95% CI 1·07–3·35, p=0·028), clearing vegetation (1·89, 1·11–3·22, p=0·020), and having long grass around the house (2·08, 1·25–3·46, p=0·0048) increased risk for P knowlesi infection but not other Plasmodium spp infection. G6PD deficiency seemed to be protective against P knowlesi (aOR 0·20, 95% CI 0·04–0·96, p=0·045), as did residual insecticide spraying of household walls (0·52, 0·31–0·87, p=0·014), with the presence of young sparse forest (0·35, 0·20–0·63, p=00040) and rice paddy around the house (0·16, 0·03–0·78, 0·023) also associated with decreased risk.InterpretationAdult men working in agricultural areas were at highest risk of knowlesi malaria, although peri-domestic transmission also occurrs. Human behavioural factors associated with P knowlesi transmission could be targeted in future public health interventions.FundingUnited Kingdom Medical Research Council, Natural Environment Research Council, Economic and Social Research Council, and Biotechnology and Biosciences Research Council.

Updates on malaria incidence and profile in Malaysia from 2013 to 2017

“…In general, Sabah and Sarawak contributed more than 75% of the notified malaria cases in Malaysia, whilst the top four states in Peninsular Malaysia namely Selangor, Kelantan, Perak and Pahang reported around 17% of the total malaria cases in combination. Given the high numbers of malaria cases in Sabah and Sarawak, many research and publications [5][6][7][8][12][13][14][15] focused on the epidemiology, patterns and characteristics of notified malaria cases in these two states. Based on recent literature search, as far as is known, this is the most current analysis that described the sociodemographic profile and epidemiology of malaria cases between Peninsular Malaysia and Sabah and Sarawak.…”

“…Throughout the 5 years, indigenous cases contributed the most number of cases (13,487; 81.7%), followed by import A cases (2916; 17.7%). Majority of the cases (16,454; 99.7%) were alive post infection (Table 3).…”

Spatial-temporal Distribution and Demography of Knowlesi Malaria in Peninsular Malaysia, 2011 to 2018

“…This study reveals that P. knowlesi infections were distributed across all age groups with higher prevalence among adults of the age group of 20-39 years, notably males, who likely are more active outdoors and have greater forest exposure to infection due to job opportunities [22]. A small segment of knowlesi malaria cases was observed among children and the elderly which could be associated with limited outdoor activities and lower risk of biting by infected Anopheles mosquito.…”

Local human movement patterns and land use impact exposure to zoonotic malaria in Malaysian Borneo

“…Although P. knowlesi has previously been associated with forest exposure (e.g. (19)) and higher biting rates have been reported in forest interiors (23), this novel approach incorporating both mosquito and human space use data provides a new perspective on peri-domestic transmission, with more than 90% of infectious bites predicted in areas surrounding households at forest edges. This study additionally demonstrates the utility of ecological methods to understand human movement and identify geographical areas associated with higher contact with disease vectors.…”

“…Previous studies of P. knowlesi have relied on questionnaire surveys, identifying self-reported travel to nearby plantations and forest areas as a risk factor for P. knowlesi and other malaria infections (e.g. (19–21)). However, the resultant spatial range and frequency of these movements remain unknown and the definition of different habitat types is entirely subjective.…”