Five-year species distribution and antimicrobial susceptibility of non-tuberculous mycobacteria in Malaysia, 2018-2022.

Introduction. Non-tuberculous Mycobacteria (NTM) is a group of mycobacteria distinct from the Mycobacterium tuberculosis complex. They can cause opportunistic infections, especially in immunocompromised individuals.Gap Statement. Over the last few years, there has been a growing concern regarding the distribution and antimicrobial resistance of NTM in Malaysia. however, a comprehensive study to fully grasp the NTM situation has yet to be conducted.Aim. This study aimed to investigate the species distribution and antimicrobial susceptibility patterns of NTM isolated from clinical samples in Malaysia from 2018 to 2022.Methodology. A retrospective analysis was conducted on NTM isolates obtained from various clinical specimens over a span of five years. The isolates were identified using phenotypic and molecular techniques, and antimicrobial susceptibility profiles for clinically significant isolates were determined using minimum inhibitory concentration.Results. The study revealed a diverse distribution of NTM species in Malaysia, with Mycobacteroides abscessus complex and Mycobacterium avium complex emerging as the most predominant. Furthermore, the antimicrobial susceptibility patterns showed varying degrees of resistance to commonly used antibiotics, highlighting the significance of treatment tailored to susceptibility testing results.Conclusion. This study provides valuable perspective into the epidemiology of NTM in Malaysia. The information gained from this study should prove useful for empirically treating serious NTM infections prior to species identification and the availability of antimicrobial susceptibility testing results.

First evaluation of the performance of portable IGRA, QIAreach® QuantiFERON®-TB in intermediate TB incidence setting.

Diagnosis and treatment of tuberculosis infection (TBI) are the core elements of tuberculosis elimination. Interferon gamma release assays have advantages over the tuberculin skin test, although their implementation in low-resource settings is challenging. The performance of a novel digital lateral flow assay QIAreach® QuantiFERON®-TB (QIAreach QFT) against the QuantiFERON®-TB Gold Plus (QFT-Plus) assay was evaluated in an intermediate incidence setting (Malaysia) according to the manufacturer's instructions. Individuals aged 4-82 years, who were candidates for TB infection screening for contact investigation were prospectively recruited. On 196 samples, the QIAreach-QFT showed a positive percent agreement (sensitivity) was 96.5% (CI 87.9-99.6%), a negative percent agreement (specificity) 94.2% (CI 88.4% to 97.6%) and an overall percentage of agreement was 94.9% (95% CI 90.6-97.6%) with a Cohen's κ of 0,88. Out of 196, 5.6% (11/196) samples gave an error result on QIAreach-QFT and 4.1% (8/196) samples gave indeterminate result on QFT-plus. The TTR for QIAreach QFT positive samples varied from 210-1200 seconds (20 min) and significantly correlated with IFN-γ level of QFT-Plus. QIAreach QFT could be considered an accurate and reliable point-of-need test to diagnose TB infection helping to achieve the WHO End TB programme goals even in decentralised settings where laboratory expertise and infrastructure may be limited.

Genomic diversity of SARS-CoV-2 in Malaysia.

BACKGROUND: More than a year after its first appearance in December 2019, the COVID-19 pandemic is still on a rampage in many parts of the world. Although several vaccines have been approved for emergency use, the emergence and rapid spread of new SARS-CoV-2 variants have sparked fears of vaccine failure due to immune evasion. Massive viral genome sequencing has been recommended to track the genetic changes that could lead to adverse consequences. METHODS: We sequenced SARS-CoV-2 respiratory isolates from the National Public Health Laboratory, Malaysia and examined them together with viral genomes deposited in GISAID by other Malaysian researchers, to understand the evolutionary trend of the virus circulating in the country. We studied the distribution of virus lineages and site-wise mutations, analysed genetic clustering with the goeBURST full Minimum Spanning Tree algorithm, examined the trend of viral nucleotide diversity over time and performed nucleotide substitution association analyses. RESULTS: We identified 22 sub-lineages, 13 clonal complexes, 178 sequence types and seven sites of linkage disequilibrium in 277 SARS-CoV-2 genomes sequenced between January and December 2020. B.1.524 was the largest lineage group. The number of mutations per genome ranged from 0 to 19. The mean genomic diversity value over 12 months was 3.26 × 10-4. Of 359 mutations detected, 60.5% of which were non-synonymous, the most frequent were in the ORF1ab (P4715L), S (D614G and A701V) and N (S194L) genes. CONCLUSION: The SARS-CoV-2 virus accumulated an abundance of mutations in the first year of the COVID-19 pandemic in Malaysia. Its overall genetic diversity, however, is relatively low compared to other Asian countries with larger populations. Continuous genomic and epidemiological surveillance will help to clarify the evolutionary processes determining viral diversity and impacting on human health.

Draft Genome Sequences of Local Clinical Isolates of Drug-Resistant and Drug-Sensitive Mycobacterium tuberculosis.

In the battle against tuberculosis (TB), plasticity of the Mycobacterium tuberculosis genome is believed to contribute to the pathogen's virulence and drug resistance. Here, we report 10 draft genome sequences of clinical M. tuberculosis isolated in Malaysia as the basis for understanding the genome plasticity of the M. tuberculosis isolates.

Diversified lineages and drug-resistance profiles of clinical isolates of Mycobacterium tuberculosis complex in Malaysia.

Background: Tuberculosis (TB) is still a major health problem in Malaysia with thousands of cases reported yearly. This is further burdened with the emergence of multidrug-resistant TB (MDR-TB). Whole-genome sequencing (WGS) provides high-resolution molecular epidemiological data for the accurate determination of Mycobacterium tuberculosis complex (MTBC) lineages and prediction of the drug-resistance patterns. This study aimed to investigate the diversity of MTBC in Malaysia in terms of lineage and drug-resistance patterns of the clinical MTBC isolates using WGS approach. Methods: The genomes of 24 MTBC isolated from sputum and pus samples were sequenced. The phenotypic drug susceptibility testing (DST) of the isolates was determined for ten anti-TB drugs. Bioinformatic analysis comprising genome assembly and annotation and single-nucleotide polymorphism (SNP) analysis in genes associated with resistance to the ten anti-TB drugs were done on each sequenced genome. Results: The draft assemblies covered an average of 97% of the expected genome size. Eleven isolates were aligned to the Indo-Oceanic lineage, eight were East-Asian lineage, three were East African-Indian lineage, and one was of Euro-American and Bovis lineages, respectively. Twelve of the 24 MTBC isolates were phenotypically MDR M. tuberculosis: one is polyresistance and another one is monoresistance. Twenty-six SNPs across nine genes associated with resistance toward ten anti-TB drugs were detected where some of the mutations were found in isolates that were previously reported as pan-susceptible using DST. A haplotype consisting of 65 variants was also found among the MTBC isolates with drug-resistance traits. Conclusions: This study is the first effort done in Malaysia to utilize 24 genomes of the local clinical MTBC isolates. The high-resolution molecular epidemiological data obtained provide valuable insights into the mechanistic and epidemiological qualities of TB within the vicinity of Southeast Asia.