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Fulltext Malaria elimination in Malaysia and the rising threat of Plasmodium knowlesi

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.
Fulltext High proportion of norovirus infection and predominance of GII.3 [P12] genotype among the children younger than 5 in Sabah, Malaysian Borneo

John JL, Mori D, Amit LN, Mosiun AK, Chin AZ, Ahmed K

J Clin Virol, 2021 10;143:104968.
PMID: 34509928 DOI: 10.1016/j.jcv.2021.104968

Globally, norovirus (NoV) has become one of the important causes of acute gastroenteritis (AGE) in children. It is responsible for death of children younger than 5 years in developing countries. Although there is limited information and the rate of child mortality caused by diarrhea is low in Malaysia, the burden of diarrhea is high, especially in Sabah. NoV GI, GII and GIV genogroups are known to infect humans, and GII.4 is the predominant genotype distributed worldwide. Better understanding of the etiology of NoV will help to inform policies for prevention and control. The aim of this study was to determine the burden and genotype distribution of NoV in children younger than 5 years with AGE who attended health-care facilities in Sabah, Malaysia. Diarrhea stool samples were collected from 299 children with AGE and NoV was detected by amplifying the capsid and RNA-dependent RNA polymerase gene and reverse transcription-polymerase chain reaction (RT-PCR) analysis. Nucleotide sequencing of the amplicons was used for genotypes and phylogenetic analyses . NoV-positive stool samples were found in 17.7% (53/299) among which 13/53 (24.5%), 38/53 (71.7%), and 2/53 (3.8%) identified as NoV GI, GII and combination of GI and GII, respectively. The most common genotypes were GII.3 [P12] (80%) followed by GII.6 [P7] (13.3%), and GII.17 [P17] (6.7%). In the phylogenetic tree, all Sabahan NoV samples were shown to share ancestry with their respective genotype from predominantly East Asian countries and to some extent Australia and Europe. However, the Sabahan strains formed independent clusters with significant bootstrap values, indicating a clonal spread after the strains had entered Sabah.
Fulltext Emergence of equine-like G3 strains as the dominant rotavirus among children under five with diarrhea in Sabah, Malaysia during 2018-2019

Amit LN, Mori D, John JL, Chin AZ, Mosiun AK, Jeffree MS, et al.

PLoS One, 2021;16(7):e0254784.
PMID: 34320003 DOI: 10.1371/journal.pone.0254784

Rotavirus infection is a dilemma for developing countries, including Malaysia. Although commercial rotavirus vaccines are available, these are not included in Malaysia's national immunization program. A scarcity of data about rotavirus genotype distribution could be partially to blame for this policy decision, because there are no data for rotavirus genotype distribution in Malaysia over the past 20 years. From January 2018 to March 2019, we conducted a study to elucidate the rotavirus burden and genotype distribution in the Kota Kinabalu and Kunak districts of the state of Sabah. Stool specimens were collected from children under 5 years of age, and rotavirus antigen in these samples was detected using commercially available kit. Electropherotypes were determined by polyacrylamide gel electrophoresis of genomic RNA. G and P genotypes were determined by RT-PCR using type specific primers. The nucleotide sequence of the amplicons was determined by Sanger sequencing and phylogenetic analysis was performed by neighbor-joining method. Rotavirus was identified in 43 (15.1%) children with watery diarrhea. The male:female ratio (1.9:1) of the rotavirus-infected children clearly showed that it affected predominantly boys, and children 12-23 months of age. The genotypes identified were G3P[8] (74% n = 31), followed by G1P[8] (14% n = 6), G12P[6](7% n = 3), G8P[8](3% n = 1), and GxP[8] (3% n = 1). The predominant rotavirus circulating among the children was the equine-like G3P[8] (59.5% n = 25) with a short electropherotype. Eleven electropherotypes were identified among 34 strains, indicating substantial diversity among the circulating strains. The circulating genotypes were also phylogenetically diverse and related to strains from several different countries. The antigenic epitopes present on VP7 and VP4 of Sabahan G3 and equine-like G3 differed considerably from that of the RotaTeq vaccine strain. Our results also indicate that considerable genetic exchange is occurring in Sabahan strains. Sabah is home to a number of different ethnic groups, some of which culturally are in close contact with animals, which might contribute to the evolution of diverse rotavirus strains. Sabah is also a popular tourist destination, and a large number of tourists from different countries possibly contributes to the diversity of circulating rotavirus genotypes. Considering all these factors which are contributing rotavirus genotype diversity, continuous surveillance of rotavirus strains is of utmost importance to monitor the pre- and post-vaccination efficacy of rotavirus vaccines in Sabah.
Increase in rotavirus prevalence with the emergence of genotype G9P[8] in replacement of genotype G12P[6] in Sabah, Malaysia

Amit LN, John JL, Mori D, Chin AZ, Mosiun AK, Ahmed K

Arch Virol, 2023 Jun 03;168(6):173.
PMID: 37269384 DOI: 10.1007/s00705-023-05803-9

Rotaviruses are major causative agents of acute diarrhea in children under 5 years of age in Malaysia. However, a rotavirus vaccine has not been included in the national vaccination program. To date, only two studies have been carried out in the state of Sabah, Malaysia, although children in this state are at risk of diarrheal diseases. Previous studies showed that 16%-17% of cases of diarrhea were caused by rotaviruses and that equine-like G3 rotavirus strains are predominant. Because the prevalence of rotaviruses and their genotype distribution vary over time, this study was conducted at four government healthcare facilities from September 2019 through February 2020. Our study revealed that the proportion of rotavirus diarrhea increased significantly to 37.2% (51/137) after the emergence of the G9P[8] genotype in replacement of the G12P[8] genotype. Although equine-like G3P[8] strains remain the predominant rotaviruses circulating among children, the Sabahan G9P[8] strain belonged to lineage VI and was phylogenetically related to strains from other countries. A comparison of the Sabahan G9 strains with the G9 vaccine strains used in the RotaSiil and Rotavac vaccines revealed several mismatches in neutralizing epitopes, indicating that these vaccines might not be effective in Sabahan children. However, a vaccine trial may be necessary to understand the precise effects of vaccination.
Fulltext Emergence of non-classical genotype constellations of G9P[8] rotavirus strains in diarrheic children in Sabah, Malaysia

Fong SY, Akari Y, Amit LN, John JL, Chin AZ, Komoto S, et al.

Infect Genet Evol, 2024 Nov;125:105685.
PMID: 39461399 DOI: 10.1016/j.meegid.2024.105685

G9P[8] has been the predominant rotavirus A (RVA) genotype in Malaysia since the 2000s. However, the overall genetic makeup and evolution of Malaysian G9P[8] strains are still unknown. Therefore, this study aimed to evaluate and characterize the complete genomes of three G9P[8] RVA strains isolated from diarrheic children under five years old in Sabah. Contrary to the classical Wa-like constellation, these strains contained a DS-1-like genotype. Two strains, namely L202 and L234, were genotype G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E2-H1, while one (KN102) was genotype G9-P[8]-I1-R1-C1-M1-A2-N1-T1-E1-H1. Phylogenetic analysis revealed that the NSP4 genes of L202 and L234 strains were closer to that of G9P[8]-E2 strains from Japan, suggesting they might share a common ancestor. The findings from this study provide new insights into the genetic characteristics of circulating G9P[8] strains in Sabah, which are important for rotavirus surveillance and potential vaccine development in the region.
Fulltext Risk factor of plasmodium knowlesi infection in Sabah Borneo Malaysia, 2020: A population-based case-control study

Chin AZ, Avoi R, Atil A, Awang Lukman K, Syed Abdul Rahim SS, Ibrahim MY, et al.

PLoS One, 2021;16(9):e0257104.
PMID: 34506556 DOI: 10.1371/journal.pone.0257104

BACKGROUND: In the Malaysian state of Sabah, P. knowlesi notifications increased from 2% (59/2,741) of total malaria notifications in 2004 to 98% (2030/2,078) in 2017. There was a gap regarding P. knowlesi acquisition risk factors related to practice specifically in working age group. The main objective of this study was to identify the risk factors for acquiring P. knowlesi infection in Sabah among the working age group.
METHODS AND METHODS: This retrospective population-based case-control study was conducted in Ranau district to assess sociodemographic, behavioural and medical history risk factors using a pretested questionnaire. The data were entered and analyzed using IBM SPSS version 23. Bivariate analysis was conducted using binary logistic regression whereas multivariate analysis was conducted using multivariable logistic regression. We set a statistical significance at p-value less than or equal to 0.05.
RESULTS: A total of 266 cases and 532 controls were included in the study. Male gender (AOR = 2.71; 95% CI: 1.63-4.50), spending overnight in forest (AOR = 1.92; 95% CI: 1.20-3.06), not using mosquito repellent (AOR = 2.49; 95% CI: 1.36-4.56) and history of previous malaria infection (AOR = 49.34; 95% CI: 39.09-78.32) were found to be independent predictors of P. knowlesi infection.
CONCLUSIONS: This study showed the need to strengthen the strategies in preventing and controlling P. knowlesi infection specifically in changing the practice of spending overnight in forest and increasing the usage of personal mosquito repellent.