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  1. Mohd Abd Razak MR, Sastu UR, Norahmad NA, Abdul-Karim A, Muhammad A, Muniandy PK, et al.
    PLoS One, 2016;11(3):e0152415.
    PMID: 27023787 DOI: 10.1371/journal.pone.0152415
    Malaysia has a national goal to eliminate malaria by 2020. Understanding the genetic diversity of malaria parasites in residual transmission foci can provide invaluable information which may inform the intervention strategies used to reach elimination targets. This study was conducted to determine the genetic diversity level of P. falciparum isolates in malaria residual foci areas of Sabah. Malaria active case detection was conducted in Kalabakan and Kota Marudu. All individuals in the study sites were screened for malaria infection by rapid diagnostic test. Blood from P. falciparum-infected individuals were collected on filter paper prior to DNA extraction. Genotyping was performed using merozoite surface protein-1 (MSP-1), merozoite surface protein-2 (MSP-2), glutamate rich protein (GLURP) and 10 neutral microsatellite loci markers. The size of alleles, multiplicity of infection (MOI), mean number of alleles (Na), expected heterozygosity (He), linkage disequilibrium (LD) and genetic differentiation (FST) were determined. In Kalabakan, the MSP-1 and MSP-2 alleles were predominantly K1 and FC27 family types, respectively. The GLURP genotype VI (751-800 bp) was predominant. The MOI for MSP-1 and MSP-2 were 1.65 and 1.20, respectively. The Na per microsatellite locus was 1.70. The He values for MSP-1, MSP-2, GLURP and neutral microsatellites were 0.17, 0.37, 0.70 and 0.33, respectively. In Kota Marudu, the MSP-1 and MSP-2 alleles were predominantly MAD20 and 3D7 family types, respectively. The GLURP genotype IV (651-700 bp) was predominant. The MOI for both MSP-1 and MSP-2 was 1.05. The Na per microsatellite locus was 3.60. The He values for MSP-1, MSP-2, GLURP and neutral microsatellites were 0.24, 0.25, 0.69 and 0.30, respectively. A significant LD was observed in Kalabakan (0.495, p<0.01) and Kota Marudu P. falciparum populations (0.601, p<0.01). High genetic differentiation between Kalabakan and Kota Marudu P. falciparum populations was observed (FST = 0.532). The genetic data from the present study highlighted the limited diversity and contrasting genetic pattern of P. falciparum populations in the malaria declining areas of Sabah.
  2. Md Iderus NH, Singh SSL, Ghazali SM, Zulkifli AA, Ghazali NAM, Lim MC, et al.
    Front Public Health, 2023;11:1213514.
    PMID: 37693699 DOI: 10.3389/fpubh.2023.1213514
    BACKGROUND: Globally, the COVID-19 pandemic has affected the transmission dynamics and distribution of dengue. Therefore, this study aims to describe the impact of the COVID-19 pandemic on the geographic and demographic distribution of dengue incidence in Malaysia.

    METHODS: This study analyzed dengue cases from January 2014 to December 2021 and COVID-19 confirmed cases from January 2020 to December 2021 which was divided into the pre (2014 to 2019) and during COVID-19 pandemic (2020 to 2021) phases. The average annual dengue case incidence for geographical and demographic subgroups were calculated and compared between the pre and during the COVID-19 pandemic phases. In addition, Spearman rank correlation was performed to determine the correlation between weekly dengue and COVID-19 cases during the COVID-19 pandemic phase.

    RESULTS: Dengue trends in Malaysia showed a 4-year cyclical trend with dengue case incidence peaking in 2015 and 2019 and subsequently decreasing in the following years. Reductions of 44.0% in average dengue cases during the COVID-19 pandemic compared to the pre-pandemic phase was observed at the national level. Higher dengue cases were reported among males, individuals aged 20-34 years, and Malaysians across both phases. Weekly dengue cases were significantly correlated (ρ = -0.901) with COVID-19 cases during the COVID-19 pandemic.

    CONCLUSION: There was a reduction in dengue incidence during the COVID-19 pandemic compared to the pre-pandemic phase. Significant reductions were observed across all demographic groups except for the older population (>75 years) across the two phases.

  3. Chin AZ, Maluda MCM, Jelip J, Jeffree MSB, Culleton R, Ahmed K
    J Physiol Anthropol, 2020 Nov 23;39(1):36.
    PMID: 33228775 DOI: 10.1186/s40101-020-00247-5
    BACKGROUND: Malaria is a major public-health problem, with over 40% of the world's population (more than 3.3 billion people) at risk from the disease. Malaysia has committed to eliminate indigenous human malaria transmission by 2020. The objective of this descriptive study is to understand the epidemiology of malaria in Malaysia from 2000 through 2018 and to highlight the threat posed by zoonotic malaria to the National Malaria Elimination Strategic Plan.

    METHODS: Malaria is a notifiable infection in Malaysia. The data used in this study were extracted from the Disease Control Division, Ministry of Health Malaysia, contributed by the hospitals and health clinics throughout Malaysia. The population data used in this study was extracted from the Department of Statistics Malaysia. Data analyses were performed using Microsoft Excel. Data used for mapping are available at EPSG:4326 WGS84 CRS (Coordinate Reference System). Shapefile was obtained from igismap. Mapping and plotting of the map were performed using QGIS.

    RESULTS: Between 2000 and 2007, human malaria contributed 100% of reported malaria and 18-46 deaths per year in Malaysia. Between 2008 and 2017, indigenous malaria cases decreased from 6071 to 85 (98.6% reduction), while during the same period, zoonotic Plasmodium knowlesi cases increased from 376 to 3614 cases (an 861% increase). The year 2018 marked the first year that Malaysia did not report any indigenous cases of malaria caused by human malaria parasites. However, there was an increasing trend of P. knowlesi cases, with a total of 4131 cases reported in that year. Although the increased incidence of P. knowlesi cases can be attributed to various factors including improved diagnostic capacity, reduction in human malaria cases, and increase in awareness of P. knowlesi, more than 50% of P. knowlesi cases were associated with agriculture and plantation activities, with a large remainder proportion linked to forest-related activities.

    CONCLUSIONS: Malaysia has entered the elimination phase of malaria control. Zoonotic malaria, however, is increasing exponentially and becoming a significant public health problem. Improved inter-sectoral collaboration is required in order to develop a more integrated effort to control zoonotic malaria. Local political commitment and the provision of technical support from the World Health Organization will help to create focused and concerted efforts towards ensuring the success of the National Malaria Elimination Strategic Plan.

  4. Montini Maluda MC, Jelip J, Ibrahim MY, Suleiman M, Jeffree MS, Binti Aziz AF, et al.
    Am J Trop Med Hyg, 2020 08;103(2):864-868.
    PMID: 32524958 DOI: 10.4269/ajtmh.19-0928
    Japanese encephalitis (JE) is endemic in Malaysia. Although JE vaccination is practiced in the neighboring state of Sarawak for a long time, little is known about JE in Sabah state in Borneo. As a result, informed policy formulation for JE in Sabah has not been accomplished. In the present study, we have analyzed JE cases that have been reported to the Sabah State Health Department from 2000 to 2018. A total of 92 JE cases were reported during 19 years, and three-fourths of the cases were attributed to children. The estimated mean incidence for JE cases is 0.161/100,000 population. Japanese encephalitis was predominant in Sabah during June, July, and August, peaking in July. In most cases, pigs were absent within a 400-m radius of the place of residence. We could not establish any relationship between the mapping of JE cases and the number of piggeries in each district. We could not establish a relationship between average rainfall and JE cases, either. We propose the cases reported are possibly showing the tip of an iceberg and continuous surveillance is needed, as JE is a public health challenge in Sabah.
  5. Fornace KM, Drakeley CJ, Lindblade KA, Jelip J, Ahmed K
    Nat Commun, 2023 Sep 16;14(1):5750.
    PMID: 37717079 DOI: 10.1038/s41467-023-41546-6
    Increasing numbers of human zoonotic malaria cases are reported globally. Current malaria control measures cannot eliminate transmission from wildlife reservoirs, leaving many countries with no pathway to malaria elimination certification. New policies are needed to redefine elimination goals and certification.
  6. Barber BE, Bird E, Wilkes CS, William T, Grigg MJ, Paramaswaran U, et al.
    J Infect Dis, 2015 Apr 1;211(7):1104-10.
    PMID: 25301955 DOI: 10.1093/infdis/jiu562
    BACKGROUND: Plasmodium knowlesi is the commonest cause of malaria in Malaysia, but little is known regarding infection during pregnancy.
    METHODS: To investigate comparative risk and consequences of knowlesi malaria during pregnancy, we reviewed (1) Sabah Health Department malaria-notification records created during 2012-2013, (2) prospectively collected data from all females with polymerase chain reaction (PCR)-confirmed malaria who were admitted to a Sabah tertiary care referral hospital during 2011-2014, and (3) malaria microscopy and clinical data recorded at a Sabah tertiary care women and children's hospital during 2010-2014.
    RESULTS: During 2012-2013, 774 females with microscopy-diagnosed malaria were notified, including 252 (33%), 172 (20%), 333 (43%), and 17 (2%) with Plasmodium falciparum infection, Plasmodium vivax infection, Plasmodium malariae/Plasmodium knowlesi infection, and mixed infection, respectively. Among females aged 15-45 years, pregnancy was reported in 18 of 124 (14.5%), 9 of 93 (9.7%), and 4 of 151 (2.6%) P. falciparum, P. vivax, and P. malariae/P. knowlesi notifications respectively (P = .002). Three females with knowlesi malaria were confirmed as pregnant: 2 had moderate anemia, and 1 delivered a preterm low-birth-weight infant. There were 17, 7, and 0 pregnant women with falciparum, vivax, and knowlesi malaria, respectively, identified from the 2 referral hospitals.
    CONCLUSIONS: Although P. knowlesi is the commonest malaria species among females in Sabah, P. knowlesi infection is relatively rare during pregnancy. It may however be associated with adverse maternal and pregnancy outcomes.
    KEYWORDS: Plasmodium knowlesi; malaria; maternal anemia; pregnancy; preterm delivery
  7. Grigg MJ, William T, Piera KA, Rajahram GS, Jelip J, Aziz A, et al.
    Malar J, 2018 Dec 10;17(1):463.
    PMID: 30526613 DOI: 10.1186/s12936-018-2593-x
    BACKGROUND: Spreading Plasmodium falciparum artemisinin drug resistance threatens global malaria public health gains. Limited data exist to define the extent of P. falciparum artemisinin resistance southeast of the Greater Mekong region in Malaysia.

    METHODS: A clinical efficacy study of oral artesunate (total target dose 12 mg/kg) daily for 3 days was conducted in patients with uncomplicated falciparum malaria and a parasite count 

  8. Abdullah NR, Barber BE, William T, Norahmad NA, Satsu UR, Muniandy PK, et al.
    PLoS One, 2013;8(12):e82553.
    PMID: 24358203 DOI: 10.1371/journal.pone.0082553
    Despite significant progress in the control of malaria in Malaysia, the complex transmission dynamics of P. vivax continue to challenge national efforts to achieve elimination. To assess the impact of ongoing interventions on P. vivax transmission dynamics in Sabah, we genotyped 9 short tandem repeat markers in a total of 97 isolates (8 recurrences) from across Sabah, with a focus on two districts, Kota Marudu (KM, n = 24) and Kota Kinabalu (KK, n = 21), over a 2 year period. STRUCTURE analysis on the Sabah-wide dataset demonstrated multiple sub-populations. Significant differentiation (F ST  = 0.243) was observed between KM and KK, located just 130 Km apart. Consistent with low endemic transmission, infection complexity was modest in both KM (mean MOI  = 1.38) and KK (mean MOI  = 1.19). However, population diversity remained moderate (H E  = 0.583 in KM and H E  = 0.667 in KK). Temporal trends revealed clonal expansions reflecting epidemic transmission dynamics. The haplotypes of these isolates declined in frequency over time, but persisted at low frequency throughout the study duration. A diverse array of low frequency isolates were detected in both KM and KK, some likely reflecting remnants of previous expansions. In accordance with clonal expansions, high levels of Linkage Disequilibrium (I A (S) >0.5 [P<0.0001] in KK and KM) declined sharply when identical haplotypes were represented once (I A (S)  = 0.07 [P = 0.0076] in KM, and I A (S) = -0.003 [P = 0.606] in KK). All 8 recurrences, likely to be relapses, were homologous to the prior infection. These recurrences may promote the persistence of parasite lineages, sustaining local diversity. In summary, Sabah's shrinking P. vivax population appears to have rendered this low endemic setting vulnerable to epidemic expansions. Migration may play an important role in the introduction of new parasite strains leading to epidemic expansions, with important implications for malaria elimination.
  9. William T, Jelip J, Menon J, Anderios F, Mohammad R, Awang Mohammad TA, et al.
    Malar J, 2014;13:390.
    PMID: 25272973 DOI: 10.1186/1475-2875-13-390
    While Malaysia has had great success in controlling Plasmodium falciparum and Plasmodium vivax, notifications of Plasmodium malariae and the microscopically near-identical Plasmodium knowlesi increased substantially over the past decade. However, whether this represents microscopic misdiagnosis or increased recognition of P. knowlesi has remained uncertain.
  10. William T, Rahman HA, Jelip J, Ibrahim MY, Menon J, Grigg MJ, et al.
    PLoS Negl Trop Dis, 2013;7(1):e2026.
    PMID: 23359830 DOI: 10.1371/journal.pntd.0002026
    BACKGROUND: The simian parasite Plasmodium knowlesi is a common cause of human malaria in Malaysian Borneo and threatens the prospect of malaria elimination. However, little is known about the emergence of P. knowlesi, particularly in Sabah. We reviewed Sabah Department of Health records to investigate the trend of each malaria species over time.

    METHODS: Reporting of microscopy-diagnosed malaria cases in Sabah is mandatory. We reviewed all available Department of Health malaria notification records from 1992-2011. Notifications of P. malariae and P. knowlesi were considered as a single group due to microscopic near-identity.

    RESULTS: From 1992-2011 total malaria notifications decreased dramatically, with P. falciparum peaking at 33,153 in 1994 and decreasing 55-fold to 605 in 2011, and P. vivax peaking at 15,857 in 1995 and decreasing 25-fold to 628 in 2011. Notifications of P. malariae/P. knowlesi also demonstrated a peak in the mid-1990s (614 in 1994) before decreasing to ≈ 100/year in the late 1990s/early 2000s. However, P. malariae/P. knowlesi notifications increased >10-fold between 2004 (n = 59) and 2011 (n = 703). In 1992 P. falciparum, P. vivax and P. malariae/P. knowlesi monoinfections accounted for 70%, 24% and 1% respectively of malaria notifications, compared to 30%, 31% and 35% in 2011. The increase in P. malariae/P. knowlesi notifications occurred state-wide, appearing to have begun in the southwest and progressed north-easterly.

    CONCLUSIONS: A significant recent increase has occurred in P. knowlesi notifications following reduced transmission of the human Plasmodium species, and this trend threatens malaria elimination. Determination of transmission dynamics and risk factors for knowlesi malaria is required to guide measures to control this rising incidence.

  11. Cooper DJ, Rajahram GS, William T, Jelip J, Mohammad R, Benedict J, et al.
    Clin Infect Dis, 2020 01 16;70(3):361-367.
    PMID: 30889244 DOI: 10.1093/cid/ciz237
    BACKGROUND: Malaysia aims to eliminate malaria by 2020. However, while cases of Plasmodium falciparum and Plasmodium vivax have decreased substantially, the incidence of zoonotic malaria from Plasmodium knowlesi continues to increase, presenting a major challenge to regional malaria control efforts. Here we report incidence of all Plasmodium species in Sabah, including zoonotic P. knowlesi, during 2015-2017.

    METHODS: Microscopy-based malaria notification data and polymerase chain reaction (PCR) results were obtained from the Sabah Department of Health and State Public Health Laboratory, respectively, from January 2015 to December 2017. From January 2016 this was complemented by a statewide prospective hospital surveillance study. Databases were matched, and species was determined by PCR, or microscopy if PCR was not available.

    RESULTS: A total of 3867 malaria cases were recorded between 2015 and 2017, with PCR performed in 93%. Using PCR results, and microscopy if PCR was unavailable, P. knowlesi accounted for 817 (80%), 677 (88%), and 2030 (98%) malaria cases in 2015, 2016, and 2017, respectively. P. falciparum accounted for 110 (11%), 45 (6%), and 23 (1%) cases and P. vivax accounted for 61 (6%), 17 (2%), and 8 (0.4%) cases, respectively. Of those with P. knowlesi, the median age was 35 (interquartile range: 24-47) years, and 85% were male.

    CONCLUSIONS: Malaysia is approaching elimination of the human-only Plasmodium species. However, the ongoing increase in P. knowlesi incidence presents a major challenge to malaria control and warrants increased focus on knowlesi-specific prevention activities. Wider molecular surveillance in surrounding countries is required.

  12. Fong MY, Lau YL, Jelip J, Ooi CH, Cheong FW
    J Genet, 2019 Sep;98.
    PMID: 31544794
    Plasmodium knowlesi contributes to the majority of human malaria incidences in Malaysia. Its uncontrollable passage among the natural monkey hosts can potentially lead to zoonotic outbreaks. The merozoite of this parasite invades host erythrocytes through interaction between its erythrocyte-binding proteins (EBPs) and their respective receptor on the erythrocytes. The regionII of P. knowlesi EBP, P. knowlesi beta (PkβII) protein is found to be mediating merozoite invasion into monkey erythrocytes by interacting with sialic acid receptors. Hence, the objective of this study was to investigate the genetic diversity, natural selection and haplotype grouping of PkβII of P. knowlesi isolates in Malaysia. Polymerase chain reaction amplifications of PkβII were performed on archived blood samples from Malaysia and 64 PkβII sequences were obtained. Sequence analysis revealed length polymorphism, and its amino acids at critical residues indicate the ability of PkβII to mediate P. knowlesi invasion into monkey erythrocytes. Low genetic diversity (π = 0.007) was observed in the PkβII of Malaysia Borneo compared to Peninsular Malaysia (π = 0.015). The PkβII was found to be under strong purifying selection to retain infectivity in monkeys and it plays a limited role in the zoonotic potential of P. knowlesi. Its haplotypes could be clustered into Peninsular Malaysia and Malaysia Borneo groups, indicating the existence of two distinct P. knowlesi parasites in Malaysia as reported in an earlier study.
  13. Hawkes FM, Manin BO, Cooper A, Daim S, R H, Jelip J, et al.
    Sci Rep, 2019 09 16;9(1):13312.
    PMID: 31527622 DOI: 10.1038/s41598-019-49842-2
    In lowland areas of Malaysia, Plasmodium knowlesi infection is associated with land use change and high proportions of the vector Anopheles balabacensis. We conducted a 15-month study in two Malaysian villages to determine the effect of habitat on vector populations in understudied high-altitude, high-incidence districts. Anopheles mosquitoes were sampled in human settlements, plantations and forest edges, and screened for Plasmodium species by PCR. We report the first An. donaldi positive for P. knowlesi. This potential vector was associated with habitat fragmentation measured as disturbed forest edge:area ratio, while An. balabacensis was not, indicating fragmented land use could favour An. donaldi. Anopheline species richness and diversity decreased from forest edge, to plantation, to human settlement. Greater numbers of An. balabacensis and An. donaldi were found in forest edges compared to human settlements, suggesting exposure to vectors and associated zoonoses may be greater for people entering this habitat.
  14. Suleiman M, Muhammad J, Jelip J, William T, Chua TH
    PMID: 29644840
    The horseshoe crab (Carcinoscorpius rotundicauda) is consumed by those
    residing near the coastal areas of Kota Marudu District in Malaysia, as it is considered
    a delicacy. During June to August, 2011 thirty cases of tetrodotoxin poisoning
    were reported from Kota Marudu District following ingestion of horseshoe
    crabs caught in Kota Marudu Bay. The purpose of this study is to describe this
    case series in order to determine risk factors to prevent further outbreaks. There
    were six confirmed and 24 probable cases of tetrodotoxin poisoning identified in
    the study area during the study period as diagnosed by clinical presentation and
    laboratory findings. Symptoms included dizziness (80%), circumoral and lingual
    numbness (80%), hand and feet numbness (63.3%), nausea and vomiting (30%)
    and weakness and difficulty in breathing (26.6%). Three cases (10%) died while 27
    cases recovered. Forty-seven percent of the cases had onset of symptoms within
    30 minutes of ingestion and 14% 31-60 minutes after ingestion of horseshoe crab
    meat. Urine samples were collected from the cases, while horseshoe crabs, cockles
    and sea water from the epidemic area were also taken for analysis. Tetrodotoxin
    was detected in the urine of six cases; the highest concentrations recorded were
    among the three cases who died. High tetrodotoxin concentrations were found
    in the hepatic cecum and eggs of the tested horseshoe crabs. Dinoflagellates were
    not detected in the sea water or cockle samples. Intensive health education was
    initiated quickly to stop other members of the Marudu Bay community from
    consuming the horseshoe crabs. This is the first documented epidemic of tetrodotoxin
    poisoning in Sabah.
  15. Hawkes FM, Manin BO, Cooper A, Daim S, R H, Jelip J, et al.
    Sci Rep, 2019 Nov 20;9(1):17510.
    PMID: 31745193 DOI: 10.1038/s41598-019-53744-8
    An amendment to this paper has been published and can be accessed via a link at the top of the paper.
  16. Suleiman M, Jelip J, Rundi C, Chua TH
    Am J Trop Med Hyg, 2017 Dec;97(6):1731-1736.
    PMID: 29016314 DOI: 10.4269/ajtmh.17-0589
    During the months of January-February and May-June 2013 coinciding with the red tide occurrence in Kota Kinabalu, Sabah, Malaysia, six episodes involving 58 cases of paralytic shellfish poisoning (PSP) or saxitoxin (STX) poisoning and resulting in four deaths were reported. Many of them were intoxicated from consuming shellfish purchased from the markets, whereas others were intoxicated from eating shellfish collected from the beach. Levels of STX in shellfish collected from the affected areas were high (mean 2,920 ± 780 and 360 ± 140 µg STX equivalents/100 g shellfish meat respectively for the two periods). The count of toxic dinoflagellates (Pyrodinium bahamense var compressum) of the sea water sampled around the coast was also high (mean 34,200 ± 10,300 cells/L). Species of shellfish containing high levels of STX were Atrina fragilis, Perna viridis, and Crassostrea belcheri. The age of victims varied from 9 to 67 years. Symptoms presented were typical of PSP, such as dizziness, numbness, vomiting, and difficulty in breathing. Recommended steps to prevent or reduce PSP in future red tide season include better monitoring of red tide occurrence, regular sampling of shellfish for determination of STX level, wider dissemination of information on the danger of eating contaminated shellfish among the communities, fishermen, and fishmongers.
  17. Grigg MJ, William T, Drakeley CJ, Jelip J, von Seidlein L, Barber BE, et al.
    BMJ Open, 2014 Aug 22;4(8):e006004.
    PMID: 25149186 DOI: 10.1136/bmjopen-2014-006004
    INTRODUCTION: Plasmodium 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 ANALYSIS: A 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.

    ETHICS: This 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.

  18. Fornace KM, Topazian HM, Routledge I, Asyraf S, Jelip J, Lindblade KA, et al.
    Nat Commun, 2023 Jun 01;14(1):2945.
    PMID: 37263994 DOI: 10.1038/s41467-023-38476-8
    Reported incidence of the zoonotic malaria Plasmodium knowlesi has markedly increased across Southeast Asia and threatens malaria elimination. Nonzoonotic transmission of P. knowlesi has been experimentally demonstrated, but it remains unknown whether nonzoonotic transmission is contributing to increases in P. knowlesi cases. Here, we adapt model-based inference methods to estimate RC, individual case reproductive numbers, for P. knowlesi, P. falciparum and P. vivax human cases in Malaysia from 2012-2020 (n = 32,635). Best fitting models for P. knowlesi showed subcritical transmission (RC  1) was estimated historically for P. falciparum and P. vivax, with declines in RC estimates observed over time consistent with local elimination. Together, this suggests sustained nonzoonotic P. knowlesi transmission is highly unlikely and that new approaches are urgently needed to control spillover risks.
  19. Grigg MJ, Cox J, William T, Jelip J, Fornace KM, Brock PM, et al.
    Lancet Planet Health, 2017 Jun 09;1(3):e97-e104.
    PMID: 28758162 DOI: 10.1016/S2542-5196(17)30031-1
    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.

    FUNDING: United Kingdom Medical Research Council, Natural Environment Research Council, Economic and Social Research Council, and Biotechnology and Biosciences Research Council.

  20. Phang WK, Hamid MHA, Jelip J, Mudin RN, Chuang TW, Lau YL, et al.
    PMID: 33322414 DOI: 10.3390/ijerph17249271
    The life-threatening zoonotic malaria cases caused by Plasmodium knowlesi in Malaysia has recently been reported to be the highest among all malaria cases; however, previous studies have mainly focused on the transmission of P. knowlesi in Malaysian Borneo (East Malaysia). This study aimed to describe the transmission patterns of P. knowlesi infection in Peninsular Malaysia (West Malaysia). The spatial distribution of P. knowlesi was mapped across Peninsular Malaysia using Geographic Information System techniques. Local indicators of spatial associations were used to evaluate spatial patterns of P. knowlesi incidence. Seasonal autoregressive integrated moving average models were utilized to analyze the monthly incidence of knowlesi malaria in the hotspot region from 2012 to 2017 and to forecast subsequent incidence in 2018. Spatial analysis revealed that hotspots were clustered in the central-northern region of Peninsular Malaysia. Time series analysis revealed the strong seasonality of transmission from January to March. This study provides fundamental information on the spatial distribution and temporal dynamic of P. knowlesi in Peninsular Malaysia from 2011 to 2018. Current control policy should consider different strategies to prevent the transmission of both human and zoonotic malaria, particularly in the hotspot region, to ensure a successful elimination of malaria in the future.
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