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Fulltext Zoonotic malaria requires new policy approaches to malaria elimination

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.
Fulltext Vector compositions change across forested to deforested ecotones in emerging areas of zoonotic malaria transmission in Malaysia

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

Hussin N, Lim YA, Goh PP, William T, Jelip J, Mudin RN

Malar J, 2020 Jan 31;19(1):55.
PMID: 32005228 DOI: 10.1186/s12936-020-3135-x

BACKGROUND: To date, most of the recent publications on malaria in Malaysia were conducted in Sabah, East Malaysia focusing on the emergence of Plasmodium knowlesi. This analysis aims to describe the incidence, mortality and case fatality rate of malaria caused by all Plasmodium species between Peninsular Malaysia and East Malaysia (Sabah and Sarawak) over a 5-year period (2013-2017).
METHODS: This is a secondary data review of all diagnosed and reported malaria confirmed cases notified to the Ministry of Health, Malaysia between January 2013 and December 2017.
RESULTS: From 2013 to 2017, a total of 16,500 malaria cases were notified in Malaysia. The cases were mainly contributed from Sabah (7150; 43.3%) and Sarawak (5684; 34.4%). Majority of the patients were male (13,552; 82.1%). The most common age group in Peninsular Malaysia was 20 to 29 years (1286; 35.1%), while Sabah and Sarawak reported highest number of malaria cases in age group of 30 to 39 years (2776; 21.6%). The top two races with malaria in Sabah and Sarawak were Bumiputera Sabah (5613; 43.7%) and Bumiputera Sarawak (4512; 35.1%), whereas other ethnic group (1232; 33.6%) and Malays (1025; 28.0%) were the two most common races in Peninsular Malaysia. Plasmodium knowlesi was the commonest species in Sabah and Sarawak (9902; 77.1%), while there were more Plasmodium vivax cases (1548; 42.2%) in Peninsular Malaysia. The overall average incidence rate, mortality rate and case fatality rates for malaria from 2013 to 2017 in Malaysia were 0.106/1000, 0.030/100,000 and 0.27%, respectively. Sarawak reported the highest average incidence rate of 0.420/1000 population followed by Sabah (0.383/1000). Other states in Peninsular Malaysia reported below the national average incidence rate with less than 0.100/1000.
CONCLUSIONS: There were different trends and characteristics of notified malaria cases in Peninsular Malaysia and Sabah and Sarawak. They provide useful information to modify current prevention and control measures so that they are customised to the peculiarities of disease patterns in the two regions in order to successfully achieve the pre-elimination of human-only species in the near future.
Fulltext The effects of the COVID-19 pandemic on dengue cases in Malaysia

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.
Fulltext Spatial distribution of Plasmodium knowlesi cases and their vectors in Johor, Malaysia: in light of human malaria elimination

Pramasivan S, Ngui R, Jeyaprakasam NK, Liew JWK, Low VL, Mohamed Hassan N, et al.

Malar J, 2021 Oct 29;20(1):426.
PMID: 34715864 DOI: 10.1186/s12936-021-03963-0

BACKGROUND: Plasmodium knowlesi, a simian malaria parasite infection, increases as Plasmodium falciparum and Plasmodium vivax infections decrease in Johor, Malaysia. Therefore, this study aimed to identify the distribution of vectors involved in knowlesi malaria transmission in Johor. This finding is vital in estimating hotspot areas for targeted control strategies.
METHODS: Anopheles mosquitoes were collected from the location where P. knowlesi cases were reported. Cases of knowlesi malaria from 2011 to 2019 in Johor were analyzed. Internal transcribed spacers 2 (ITS2) and cytochrome c oxidase subunit I (COI) genes were used to identify the Leucosphyrus Group of Anopheles mosquitoes. In addition, spatial analysis was carried out on the knowlesi cases and vectors in Johor.
RESULTS: One hundred and eighty-nine cases of P. knowlesi were reported in Johor over 10 years. Young adults between the ages of 20-39 years comprised 65% of the cases. Most infected individuals were involved in agriculture and army-related occupations (22% and 32%, respectively). Four hundred and eighteen Leucosphyrus Group Anopheles mosquitoes were captured during the study. Anopheles introlatus was the predominant species, followed by Anopheles latens. Spatial analysis by Kriging interpolation found that hotspot regions of P. knowlesi overlapped or were close to the areas where An. introlatus and An. latens were found. A significantly high number of vectors and P. knowlesi cases were found near the road within 0-5 km.
CONCLUSIONS: This study describes the distribution of P. knowlesi cases and Anopheles species in malaria-endemic transmission areas in Johor. Geospatial analysis is a valuable tool for studying the relationship between vectors and P. knowlesi cases. This study further supports that the Leucosphyrus Group of mosquitoes might be involved in transmitting knowlesi malaria cases in Johor. These findings may provide initial evidence to prioritize diseases and vector surveillance.
Fulltext Spatial and Temporal Analysis of Plasmodium knowlesi Infection in Peninsular Malaysia, 2011 to 2018

Phang WK, Hamid MHA, Jelip J, Mudin RN, Chuang TW, Lau YL, et al.

Int J Environ Res Public Health, 2020 12 11;17(24).
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.
Fulltext Severe Plasmodium knowlesi malaria in a tertiary care hospital, Sabah, Malaysia

William T, Menon J, Rajahram G, Chan L, Ma G, Donaldson S, et al.

Emerg Infect Dis, 2011 Jul;17(7):1248-55.
PMID: 21762579 DOI: 10.3201/eid1707.101017

The simian parasite Plasmodium knowlesi causes severe human malaria; the optimal treatment remains unknown. We describe the clinical features, disease spectrum, and response to antimalarial chemotherapy, including artemether-lumefantrine and artesunate, in patients with P. knowlesi malaria diagnosed by PCR during December 2007-November 2009 at a tertiary care hospital in Sabah, Malaysia. Fifty-six patients had PCR-confirmed P. knowlesi monoinfection and clinical records available for review. Twenty-two (39%) had severe malaria; of these, 6 (27%) died. Thirteen (59%) had respiratory distress; 12 (55%), acute renal failure; and 12, shock. None experienced coma. Patients with uncomplicated disease received chloroquine, quinine, or artemether-lumefantrine, and those with severe disease received intravenous quinine or artesunate. Parasite clearance times were 1-2 days shorter with either artemether-lumefantrine or artesunate treatment. P. knowlesi is a major cause of severe and fatal malaria in Sabah. Artemisinin derivatives rapidly clear parasitemia and are efficacious in treating uncomplicated and severe knowlesi malaria.
Risk factors of tuberculosis among health care workers in Sabah, Malaysia

Jelip J, Mathew GG, Yusin T, Dony JF, Singh N, Ashaari M, et al.

Tuberculosis (Edinb), 2004;84(1-2):19-23.
PMID: 14670342

Tuberculosis (TB) is one of the main public health problems in Sabah; 30% of the total number of TB cases reported in Malaysia every year occur in Sabah. The average incidence of TB among health care workers over the past 5 years is 280.4 per 100,000 population (1, Annual Report of Sabah State TB Control Programme, 1998). At present, there are no specific measures for the prevention of TB transmission in health care facilities. A case-control study was conducted among health care workers in Sabah in 2000-2001. Cases were health care workers with TB diagnosed between January 1990 and June 2000. Controls were health care workers without TB and working in the same facility as cases during the disease episode. The study attempted to identify risk factors for TB among the study population. Data were collected through structured interviews and review of patients' records. The notification rate of TB among health care workers was significantly higher than that to the general population (Z=4.893, p<0.01). The average notification rate of TB among health care workers over the last 5 years was two times higher than in the general population (280.4/100,000 compared to 153.9/100,000). Regression results showed that ethnicity, designation, family contact and TB related knowledge did not significantly contribute to the risk of contracting TB in this study. However, after controlling for the above factors, age, gender, history of TB contact outside the workplace (other than family contact), duration of service and failure to use respiratory protection when performing high-risk procedures, were the main risk factors of TB among health care workers. This study succeeded in identifying some of the risk factors of TB among health care workers. We managed to include the large ratio of controls to case (3:1) and those cases spanned over a period of 10 years. However, the findings from the study have to be applied with caution due to the limitations of this study, which include recall bias, dropouts, and small sample size. Based on the study findings, we recommend that health care workers in the first 10 years of service should take extra precautions, such as using respiratory protection when performing procedures that are considered to be of high risk with respect to TB infection. They should also undergo TB screening at least once every 2 years and, if symptomatic, offered prophylactic treatment. The Respiratory Protection Programme should be fully implemented to help reduce the risk of TB among health care workers in Sabah.
Recombinase-Aided Loop-Mediated Isothermal Amplification on Human Plasmodium knowlesi

Lai MY, Abdul Hamid MH, Jelip J, Mudin RN, Lau YL

Am J Trop Med Hyg, 2024 Apr 03;110(4):648-652.
PMID: 38412548 DOI: 10.4269/ajtmh.23-0572

Loop-mediated isothermal amplification (LAMP) is a nucleic acid amplification technique that can amplify specific nucleic acids at a constant temperature (63-65°C) within a short period (<1 hour). In this study, we report the utilization of recombinase-aided LAMP to specifically amplify the 18S sRNA of Plasmodium knowlesi. The method was built on a conventional LAMP assay by inclusion of an extra enzyme, namely recombinase, into the master mixture. With the addition of recombinase into the LAMP assay, the assay speed was executed within a time frame of less than 28 minutes at 65°C. We screened 55 P. knowlesi samples and 47 non-P. knowlesi samples. No cross-reactivity was observed for non-P. knowlesi samples, and the detection limit for recombinase-aided LAMP was one copy for P. knowlesi after LAMP amplification. It has been reported elsewhere that LAMP can be detected through fluorescent readout systems. Although such systems result in considerable limits of detection, the need for sophisticated equipment limits their use. Hence, we used here a colorimetric detection platform for the evaluation of the LAMP assay's performance. This malachite green-based recombinase-aided LAMP assay enabled visualization of results with the naked eye. Negative samples were observed by a change in color from green to colorless, whereas positive samples remained green. Our results demonstrate that the LAMP assay developed here is a convenient, sensitive, and useful diagnostic tool for the rapid detection of knowlesi malaria parasites. This method is suitable for implementation in remote healthcare settings, where centralized laboratory facilities, funds, and clinicians are in short supply.
Fulltext Prevalence of Plasmodium falciparum Molecular Markers of Antimalarial Drug Resistance in a Residual Malaria Focus Area in Sabah, Malaysia

Norahmad NA, Mohd Abd Razak MR, Abdullah NR, Sastu UR, Imwong M, Muniandy PK, et al.

PLoS One, 2016;11(10):e0165515.
PMID: 27788228 DOI: 10.1371/journal.pone.0165515

Chloroquine (CQ) and fansidar (sulphadoxine-pyrimethamine, SP) were widely used for treatment of Plasmodium falciparum for several decades in Malaysia prior to the introduction of Artemisinin-based Combination Therapy (ACT) in 2008. Our previous study in Kalabakan, located in south-east coast of Sabah showed a high prevalence of resistance to CQ and SP, suggesting the use of the treatment may no longer be effective in the area. This study aimed to provide a baseline data of antimalarial drug resistant markers on P. falciparum isolates in Kota Marudu located in the north-east coast of Sabah. Mutations on genes associated with CQ (pfcrt and pfmdr1) and SP (pfdhps and pfdhfr) were assessed by PCR amplification and restriction fragment length polymorphism. Mutations on the kelch13 marker (K13) associated with artemisinin resistance were determined by DNA sequencing technique. The assessment of pfmdr1 copy number variation associated with mefloquine resistant was done by real-time PCR technique. A low prevalence (6.9%) was indicated for both pfcrt K76T and pfmdr1 N86Y mutations. All P. falciparum isolates harboured the pfdhps A437G mutation. Prevalence of pfdhfr gene mutations, S108N and I164L, were 100% and 10.3%, respectively. Combining the different resistant markers, only two isolates were conferred to have CQ and SP treatment failure markers as they contained mutant alleles of pfcrt and pfmdr1 together with quintuple pfdhps/pfdhfr mutation (combination of pfdhps A437G+A581G and pfdhfr C59R+S108N+I164L). All P. falciparum isolates carried single copy number of pfmdr1 and wild type K13 marker. This study has demonstrated a low prevalence of CQ and SP resistance alleles in the study area. Continuous monitoring of antimalarial drug efficacy is warranted and the findings provide information for policy makers in ensuring a proper malaria control.
Fulltext Prevalence of Asymptomatic and/or Low-Density Malaria Infection among High-Risk Groups in Peninsular Malaysia

Noordin NR, Lee PY, Mohd Bukhari FD, Fong MY, Abdul Hamid MH, Jelip J, et al.

Am J Trop Med Hyg, 2020 09;103(3):1107-1110.
PMID: 32618263 DOI: 10.4269/ajtmh.20-0268

Asymptomatic and/or low-density malaria infection has been acknowledged as an obstacle to achieving a malaria-free country. This study aimed to determine the prevalence of asymptomatic and/or low-density malaria infection in previously reported malarious localities using nested PCR in four states, namely, Johor, Pahang, Kelantan, and Selangor, between June 2019 and January 2020. Blood samples (n = 585) were collected and were extracted using a QIAamp blood kit. The DNA was concentrated and subjected to nested PCR. Thin and thick blood smears were examined as well. Of the 585 samples collected, 19 were positive: 10 for Plasmodium knowlesi, eight for Plasmodium vivax, and one for Plasmodium ovale. Asymptomatic and/or low-density malaria infection is a threat to malaria elimination initiatives. Eliminating countries should develop guidance policy on the importance of low-density malaria infection which includes detection and treatment policy.
Fulltext Predicting Plasmodium knowlesi transmission risk across Peninsular Malaysia using machine learning-based ecological niche modeling approaches

Phang WK, Hamid MHBA, Jelip J, Mudin RNB, Chuang TW, Lau YL, et al.

Front Microbiol, 2023;14:1126418.
PMID: 36876062 DOI: 10.3389/fmicb.2023.1126418

The emergence of potentially life-threatening zoonotic malaria caused by Plasmodium knowlesi nearly two decades ago has continued to challenge Malaysia healthcare. With a total of 376 P. knowlesi infections notified in 2008, the number increased to 2,609 cases in 2020 nationwide. Numerous studies have been conducted in Malaysian Borneo to determine the association between environmental factors and knowlesi malaria transmission. However, there is still a lack of understanding of the environmental influence on knowlesi malaria transmission in Peninsular Malaysia. Therefore, our study aimed to investigate the ecological distribution of human P. knowlesi malaria in relation to environmental factors in Peninsular Malaysia. A total of 2,873 records of human P. knowlesi infections in Peninsular Malaysia from 1st January 2011 to 31st December 2019 were collated from the Ministry of Health Malaysia and geolocated. Three machine learning-based models, maximum entropy (MaxEnt), extreme gradient boosting (XGBoost), and ensemble modeling approach, were applied to predict the spatial variation of P. knowlesi disease risk. Multiple environmental parameters including climate factors, landscape characteristics, and anthropogenic factors were included as predictors in both predictive models. Subsequently, an ensemble model was developed based on the output of both MaxEnt and XGBoost. Comparison between models indicated that the XGBoost has higher performance as compared to MaxEnt and ensemble model, with AUCROC values of 0.933 ± 0.002 and 0.854 ± 0.007 for train and test datasets, respectively. Key environmental covariates affecting human P. knowlesi occurrence were distance to the coastline, elevation, tree cover, annual precipitation, tree loss, and distance to the forest. Our models indicated that the disease risk areas were mainly distributed in low elevation (75-345 m above mean sea level) areas along the Titiwangsa mountain range and inland central-northern region of Peninsular Malaysia. The high-resolution risk map of human knowlesi malaria constructed in this study can be further utilized for multi-pronged interventions targeting community at-risk, macaque populations, and mosquito vectors.
Fulltext Plasmodium vivax population structure and transmission dynamics in Sabah Malaysia

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.
Fulltext Plasmodium knowlesi malaria during pregnancy

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
Fulltext Plasmodium knowlesi Malaria in Sabah, Malaysia, 2015-2017: Ongoing Increase in Incidence Despite Near-elimination of the Human-only Plasmodium Species

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.
Fulltext Plasmodium falciparum artemisinin resistance monitoring in Sabah, Malaysia: in vivo therapeutic efficacy and kelch13 molecular marker surveillance

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
Fulltext Phylogeographic Evidence for 2 Genetically Distinct Zoonotic Plasmodium knowlesi Parasites, Malaysia

Yusof R, Ahmed MA, Jelip J, Ngian HU, Mustakim S, Hussin HM, et al.

Emerg Infect Dis, 2016 Aug;22(8):1371-80.
PMID: 27433965 DOI: 10.3201/eid2208.151885

Infections of humans with the zoonotic simian malaria parasite Plasmodium knowlesi occur throughout Southeast Asia, although most cases have occurred in Malaysia, where P. knowlesi is now the dominant malaria species. This apparently skewed distribution prompted an investigation of the phylogeography of this parasite in 2 geographically separated regions of Malaysia, Peninsular Malaysia and Malaysian Borneo. We investigated samples collected from humans and macaques in these regions. Haplotype network analyses of sequences from 2 P. knowlesi genes, type A small subunit ribosomal 18S RNA and cytochrome c oxidase subunit I, showed 2 genetically distinct divergent clusters, 1 from each of the 2 regions of Malaysia. We propose that these parasites represent 2 distinct P. knowlesi types that independently became zoonotic. These types would have evolved after the sea-level rise at the end of the last ice age, which separated Malaysian Borneo from Peninsular Malaysia.
Fulltext No evidence of sustained nonzoonotic Plasmodium knowlesi transmission in Malaysia from modelling malaria case data

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.
Fulltext Nineteen Years of Japanese Encephalitis Surveillance in Sabah, Malaysian Borneo

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.
Fulltext Mutations of pvdhfr and pvdhps genes in vivax endemic-malaria areas in Kota Marudu and Kalabakan, Sabah

Sastu UR, Abdullah NR, Norahmad NA, Saat MN, Muniandy PK, Jelip J, et al.

Malar J, 2016;15:63.
PMID: 26850038 DOI: 10.1186/s12936-016-1109-9

Malaria cases persist in some remote areas in Sabah and Sarawak despite the ongoing and largely successful malaria control programme conducted by the Vector Borne Disease Control Programme, Ministry Of Health, Malaysia. Point mutations in the genes that encode the two enzymes involved in the folate biosynthesis pathway, dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) enzymes confer resistance to pyrimethamine and sulfadoxine respectively, in both Plasmodium falciparum and P. vivax. The aim of the current study was to determine the mutation on both pvdhfr at codon 13, 33, 57, 58, 61, 117, and 173 and pvdhps genes at codon 383 and 553, which are potentially associated with resistance to pyrimethamine and sulfadoxine in P. vivax samples in Sabah.

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