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Fulltext SARS-CoV-2 multiplex RT-PCR to detect variants of concern (VOCs) in Malaysia, between January to May 2021

Fu JYL, Chong YM, Sam IC, Chan YF

J Virol Methods, 2022 Mar;301:114462.
PMID: 35026305 DOI: 10.1016/j.jviromet.2022.114462

Emerging SARS-CoV-2 variants of concern (VOC) have been associated with enhanced transmissibility and immune escape. Next-generation sequencing (NGS) of the whole genome is the gold standard for variant identification for surveillance but is time-consuming and costly. Rapid and cost-effective assays that detect SARS-CoV-2 variants are needed. We evaluated Allplex SARS-CoV-2 Master Assay and Variants I Assay to detect HV69/70 deletion, Y144 deletion, E484K, N501Y, and P681H spike mutations in 248 positive samples collected in Kuala Lumpur, Malaysia, between January and May 2021. Spike variants were detected in 78/248 (31.5 %), comprising 60 VOC B.1.351 (beta) and 18 B.1.1.7 (alpha). With NGS as reference for 115 samples, the sensitivity for detecting the spike mutations was 98.7 % with the Master Assay and 100 % with the Variants I Assay. The emergence of beta variants correlated with increasing COVID-19 infections in Malaysia. The prevalence of alpha VOC and lineage B.1.466.2 was low. These assays detect mutations present in alpha, beta and gamma VOCs. Of the VOCs which have subsequently emerged, the assays should detect omicron (B.1.1.529) but not B.1.617.2 (delta). In conclusion, spike variant PCR assays can be used to rapidly monitor selected SARS-CoV-2 VOCs in resource-limited settings, but require updates as new variants emerge.
An amino acid change in nsP4 of chikungunya virus confers fitness advantage in human cell lines rather than in Aedes albopictus

Fu JYL, Chua CL, Vythilingam I, Sulaiman WYW, Wong HV, Chan YF, et al.

J Gen Virol, 2019 11;100(11):1541-1553.
PMID: 31613205 DOI: 10.1099/jgv.0.001338

Chikungunya virus (CHIKV) has caused large-scale epidemics of fever, rash and arthritis since 2004. This unprecedented re-emergence has been associated with mutations in genes encoding structural envelope proteins, providing increased fitness in the secondary vector Aedes albopictus. In the 2008-2013 CHIKV outbreaks across Southeast Asia, an R82S mutation in non-structural protein 4 (nsP4) emerged early in Malaysia or Singapore and quickly became predominant. To determine whether this nsP4-R82S mutation provides a selective advantage in host cells, which may have contributed to the epidemic, the fitness of infectious clone-derived CHIKV with wild-type nsP4-82R and mutant nsP4-82S were compared in Ae. albopictus and human cell lines. Viral infectivity, dissemination and transmission in Ae. albopictus were not affected by the mutation when the two variants were tested separately. In competition, the nsP4-82R variant showed an advantage over nsP4-82S in dissemination to the salivary glands, but only in late infection (10 days). In human rhabdomyosarcoma (RD) and embryonic kidney (HEK-293T) cell lines coinfected at a 1 : 1 ratio, wild-type nsP4-82R virus was rapidly outcompeted by nsP4-82S virus as early as one passage (3 days). In conclusion, the nsP4-R82S mutation provides a greater selective advantage in human cells than in Ae. albopictus, which may explain its apparent natural selection during CHIKV spread in Southeast Asia. This is an unusual example of a naturally occurring mutation in a non-structural protein, which may have facilitated epidemic transmission of CHIKV.
Fulltext Susceptibility of Aedes albopictus, Ae. aegypti and human populations to Ross River virus in Kuala Lumpur, Malaysia

Fu JYL, Chua CL, Abu Bakar AS, Vythilingam I, Wan Sulaiman WY, Alphey L, et al.

PLoS Negl Trop Dis, 2023 Jun;17(6):e0011423.
PMID: 37307291 DOI: 10.1371/journal.pntd.0011423

BACKGROUND: Emerging arboviruses such as chikungunya and Zika viruses have unexpectedly caused widespread outbreaks in tropical and subtropical regions recently. Ross River virus (RRV) is endemic in Australia and has epidemic potential. In Malaysia, Aedes mosquitoes are abundant and drive dengue and chikungunya outbreaks. We assessed risk of an RRV outbreak in Kuala Lumpur, Malaysia by determining vector competence of local Aedes mosquitoes and local seroprevalence as a proxy of human population susceptibility.
METHODOLOGY/PRINCIPAL FINDINGS: We assessed oral susceptibility of Malaysian Ae. aegypti and Ae. albopictus by real-time PCR to an Australian RRV strain SW2089. Replication kinetics in midgut, head and saliva were determined at 3 and 10 days post-infection (dpi). With a 3 log10 PFU/ml blood meal, infection rate was higher in Ae. albopictus (60%) than Ae. aegypti (15%; p<0.05). Despite similar infection rates at 5 and 7 log10 PFU/ml blood meals, Ae. albopictus had significantly higher viral loads and required a significantly lower median oral infectious dose (2.7 log10 PFU/ml) than Ae. aegypti (4.2 log10 PFU/ml). Ae. albopictus showed higher vector competence, with higher viral loads in heads and saliva, and higher transmission rate (RRV present in saliva) of 100% at 10 dpi, than Ae. aegypti (41%). Ae. aegypti demonstrated greater barriers at either midgut escape or salivary gland infection, and salivary gland escape. We then assessed seropositivity against RRV among 240 Kuala Lumpur inpatients using plaque reduction neutralization, and found a low rate of 0.8%.
CONCLUSIONS/SIGNIFICANCE: Both Ae. aegypti and Ae. albopictus are susceptible to RRV, but Ae. albopictus displays greater vector competence. Extensive travel links with Australia, abundant Aedes vectors, and low population immunity places Kuala Lumpur, Malaysia at risk of an imported RRV outbreak. Surveillance and increased diagnostic awareness and capacity are imperative to prevent establishment of new arboviruses in Malaysia.
Changing predominant SARS-CoV-2 lineages drives successive COVID-19 waves in Malaysia, February 2020 to March 2021

Sam IC, Chong YM, Abdullah A, Fu JYL, Hasan MS, Jamaluddin FH, et al.

J Med Virol, 2021 Nov 10.
PMID: 34757638 DOI: 10.1002/jmv.27441

Malaysia has experienced three waves of coronavirus disease 2019 (COVID-19) as of March 31, 2021. We studied the associated molecular epidemiology and SARS-CoV-2 seroprevalence during the third wave. We obtained 60 whole-genome SARS-CoV-2 sequences between October 2020 and January 2021 in Kuala Lumpur/Selangor and analyzed 989 available Malaysian sequences. We tested 653 residual serum samples collected between December 2020 to April 2021 for anti-SARS-CoV-2 total antibodies, as a proxy for population immunity. The first wave (January 2020) comprised sporadic imported cases from China of early Pango lineages A and B. The second wave (March-June 2020) was associated with lineage B.6. The ongoing third wave (from September 2020) was propagated by a state election in Sabah. It is due to lineage B.1.524 viruses containing spike mutations D614G and A701V. Lineages B.1.459, B.1.470, and B.1.466.2 were likely imported from the region and confined to Sarawak state. Direct age-standardized seroprevalence in Kuala Lumpur/Selangor was 3.0%. The second and third waves were driven by super-spreading events and different circulating lineages. Malaysia is highly susceptible to further waves, especially as alpha (B.1.1.7) and beta (B.1.351) variants of concern were first detected in December 2020/January 2021. Increased genomic surveillance is critical.
Fulltext Antibody Response Following COVID-19 Vaccination in Malaysian Cancer Patients and Healthy Individuals

Song CV, Ahmad Bustamam RS, Gin Gin G, Saad M, Abdul Satar NF, Ramasamy AM, et al.

Cureus, 2024 Nov;16(11):e73528.
PMID: 39669806 DOI: 10.7759/cureus.73528

INTRODUCTION: There is a lack of real-world evidence on direct comparisons between COVID-19 vaccines in multiethnic low- and middle-income settings. Cancer patients have an impaired vaccine response due to the disease itself or the effects of treatment. Hence, identifying the best vaccine to use for cancer patients is important. We aimed to compare the antibody response between cancer patients and healthy individuals following COVID-19 vaccination and assess seroconversion rates, vaccine efficacy, and the impact of sex on antibody response, as well as document adverse events in cancer patients.
MATERIALS AND METHODS: A prospective cohort study of cancer patients and healthy individuals receiving vaccines was conducted in Malaysia. All participants were aged 18 or above at recruitment and received at least two doses of vaccine. We excluded patients who had missing serum antibody data post-first dose and post-second dose. Sociodemographic and clinical data were collected at baseline, prior to vaccination. Data on self-reported breakthrough infection was collected at six months. Multivariable linear mixed-effects regression models were used to investigate the association between the type of vaccine and serum IgG titer.
RESULTS: A total of 389 patients with solid (n=276, 71.0%) or hematologic cancers (n=113, 29.0%) were included, along with 246 healthy individuals. Most cancer patients received BNT162b2 (n=358, 92.0%), followed by AZ1222 (n=19, 4.9%) and Coronavac (n=12, 3.1%). Most healthy individuals received BNT162b2 (n=151, 61.4%), followed by Coronavac (n=95, 38.6%). Vaccination, after adjustment for confounders (pre-vaccine infection, age, ethnicity, comorbidity, timepoint, income, cancer type, and booster), with Coronavac was associated with lower log IgG titer (-3.09 U/ml, 95% confidence interval=-4.37 to -1.80, p<0.01) than that of BNT162b2 in patients with cancer and also lower log IgG titer (-2.64 U/ml, 95% confidence interval=-2.97 to -2.30, p<0.01) than that of BNT162b2 in healthy individuals. No effect modification by sex was observed. Among the cancer cohort, 76 patients (19.5%) reported breakthrough infections after vaccination, while 33 (13.4%) participants in the healthy cohort reported breakthrough infections after vaccination. Coronavac was associated with greater odds of breakthrough infection among healthy individuals (odds ratio=7.34 compared to BNT162b2, confidence interval=1.40 to 33.49, p=0.02).
CONCLUSION: Vaccination with BNT162b2 yields higher IgG titer than Coronavac in all groups and fewer breakthrough infections in healthy subjects. The effect of vaccination is not modified by sex.
Fulltext SARS-CoV-2 genomic surveillance in Malaysia: displacement of B.1.617.2 with AY lineages as the dominant Delta variants and the introduction of Omicron during the fourth epidemic wave

Azami NAM, Perera D, Thayan R, AbuBakar S, Sam IC, Salleh MZ, et al.

Int J Infect Dis, 2022 Dec;125:216-226.
PMID: 36336246 DOI: 10.1016/j.ijid.2022.10.044

OBJECTIVES: This study reported SARS-CoV-2 whole genome sequencing results from June 2021 to January 2022 from seven genome sequencing centers in Malaysia as part of the national surveillance program.
METHODS: COVID-19 samples that tested positive by reverse transcription polymerase chain reaction and with cycle threshold values <30 were obtained throughout Malaysia. Sequencing of SARS-CoV-2 complete genomes was performed using Illumina, Oxford Nanopore, or Ion Torrent platforms. A total of 6163 SARS-CoV-2 complete genome sequences were generated over the surveillance period. All sequences were submitted to the Global Initiative on Sharing All Influenza Data database.
RESULTS: From June 2021 to January 2022, Malaysia experienced the fourth wave of COVID-19 dominated by the Delta variant of concern, including the original B.1.617.2 lineage and descendant AY lineages. The B.1.617.2 lineage was identified as the early dominant circulating strain throughout the country but over time, was displaced by AY.59 and AY.79 lineages in Peninsular (west) Malaysia, and the AY.23 lineage in east Malaysia. In December 2021, pilgrims returning from Saudi Arabia facilitated the introduction and spread of the BA.1 lineage (Omicron variant of concern) in the country.
CONCLUSION: The changing trends of circulating SARS-CoV-2 lineages were identified, with differences observed between west and east Malaysia. This initiative highlighted the importance of leveraging research expertise in the country to facilitate pandemic response and preparedness.