TY - JOUR
T1 - Individual-level factors associated with the risk of acquiring human Plasmodium knowlesi malaria in Malaysia
T2 - A case-control study
AU - Grigg, Matthew
AU - Cox, Jonathan
AU - WILLIAM, Timothy
AU - Jelip, Jenarun
AU - Fornace, Kimberly M.
AU - Brock, Patrick M
AU - von Seidlein,, Lorenz
AU - Barber, Bridget
AU - Anstey, Nicholas
AU - Yeo, Tsin
AU - Drakeley, Christopher J.
PY - 2017/6
Y1 - 2017/6
N2 - Background: The 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.
Methods: We 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.
Findings: From 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.
Interpretation: Adult 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.
AB - Background: The 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.
Methods: We 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.
Findings: From 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.
Interpretation: Adult 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.
UR - http://www.scopus.com/inward/record.url?scp=85042939038&partnerID=8YFLogxK
U2 - 10.1016/S2542-5196(17)30031-1
DO - 10.1016/S2542-5196(17)30031-1
M3 - Article
C2 - 28758162
VL - 1
SP - e97-e104
JO - The Lancet Planetary Health
JF - The Lancet Planetary Health
SN - 2542-5196
IS - 3
ER -