Browsing by Author "Mahasirimongkol S."

Filter results by typing the first few letters
Now showing 1 - 20 of 37
  • No Thumbnail Available
    ItemMetadata only
    A large geno-spatial cluster of multi-drug resistant tuberculosis outbreak in a western district of Thailand
    (2025-03-01) Thipkrua N.; Disrathakit A.; Chongsuvivatwong V.; Mahasirimongkol S.; Ruangchai W.; Palittapongarnpim P.; Chaiprasert A.; Pungrassami P.; Kamolwat P.; Suthum K.; Tossapornpong K.; Sriplung H.; Thipkrua N.; Mahidol University
    The growing issue of drug resistance, particularly multidrug-resistant TB (MDR-TB), has exacerbated this problem. The rise of drug resistance TB is a severe global health concern. In Thailand, a persistent community outbreak of primary MDR-TB has been confirmed in the Tha Maka district of Kanchanaburi province, with an increasing prevalence of MDR-TB among newly diagnosed pulmonary tuberculosis cases. It was the first site in Thailand where a cluster of MDR-TB, caused by the Asian African 3 Modern Beijing strain, and XDR-TB, caused by L2.1, outbreaks were reported. This study aims to assess the MDR-TB outbreak in detail by characterizing the genomic profiles of the prevalent MDR-TB strains and examining their geographical distribution within the affected district. Through whole-genome sequencing (WGS) and bioinformatic analysis of 188 MTB isolates, the study identified three major phylogenetic lineages: the East Asian lineage (L2, 92 %), the Indo-Oceanic lineage (L1, 5.9 %), and the Euro-American lineage (L4, 2.1 %). The detailed sub-lineage distribution offers valuable insights into the predominant genetic clusters of M. tuberculosis within the sampled population. Notably, Lineage 2, specifically the L2.2.M3 sub-lineage, stood out as the dominant strain of MDR-TB, accounting for 77.7 % of the isolates. This finding underscores the significant prevalence of the L2.2.M3 sub-lineage and its potential role in the local transmission dynamics of tuberculosis. The high proportion and genetic homogeneity of the L2.2.M3 cluster among MDR-TB patients may indicate the strain's adaptation for more effective transmission within the Thai population. The increasing prevalence of this pathogenic strain could significantly impact tuberculosis control programs. Early diagnosis and contact tracing with chemotherapeutic preventive therapy for MDR-TB will be essential in inhibiting the spread and reactivation of these strains. Additionally, further studies are needed to prospectively identify transmission routes through contact tracing and real-time genotypic methods. It will also be crucial to ensure that future vaccines and/or recommended chemoprophylaxis therapy for MDR-TB will provide protection against these emerging strains.
  • No Thumbnail Available
    ItemMetadata only
    A Multiplexed Cas13-Based Assay with Point-of-Care Attributes for Simultaneous COVID-19 Diagnosis and Variant Surveillance
    (2023-04-01) Patchsung M.; Homchan A.; Aphicho K.; Suraritdechachai S.; Wanitchanon T.; Pattama A.; Sappakhaw K.; Meesawat P.; Wongsatit T.; Athipanyasilp A.; Jantarug K.; Athipanyasilp N.; Buahom J.; Visanpattanasin S.; Niljianskul N.; Chaiyen P.; Tinikul R.; Wichukchinda N.; Mahasirimongkol S.; Sirijatuphat R.; Angkasekwinai N.; Crone M.A.; Freemont P.S.; Joung J.; Ladha A.; Abudayyeh O.; Gootenberg J.; Zhang F.; Chewapreecha C.; Chanarat S.; Horthongkham N.; Pakotiprapha D.; Uttamapinant C.; Mahidol University
    Point-of-care (POC) nucleic acid detection technologies are poised to aid gold-standard technologies in controlling the COVID-19 pandemic, yet shortcomings in the capability to perform critically needed complex detection - such as multiplexed detection for viral variant surveillance - may limit their widespread adoption. Herein, we developed a robust multiplexed clustered regularly interspaced short palindromic repeats (CRISPR)-based detection using LwaCas13a and PsmCas13b to simultaneously diagnose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and pinpoint the causative SARS-CoV-2 variant of concern (VOC) - including globally dominant VOCs Delta (B.1.617.2) and Omicron (B.1.1.529) - all the while maintaining high levels of accuracy upon the detection of multiple SARS-CoV-2 gene targets. The platform has several attributes suitable for POC use: premixed, freeze-dried reagents for easy use and storage; convenient direct-to-eye or smartphone-based readouts; and a one-pot variant of the multiplexed detection. To reduce reliance on proprietary reagents and enable sustainable use of such a technology in low- and middle-income countries, we locally produced and formulated our own recombinase polymerase amplification reaction and demonstrated its equivalent efficiency to commercial counterparts. Our tool - CRISPR-based detection for simultaneous COVID-19 diagnosis and variant surveillance that can be locally manufactured - may enable sustainable use of CRISPR diagnostics technologies for COVID-19 and other diseases in POC settings.
  • No Thumbnail Available
    ItemMetadata only
    Altered IL-6 signalling and risk of tuberculosis: a multi-ancestry mendelian randomisation study
    (2024-01-01) Hamilton F.; Schurz H.; Yates T.A.; Gilchrist J.J.; Möller M.; Naranbhai V.; Ghazal P.; Timpson N.J.; Akhtar S.; Anwar M.; Asgar O.; Ashraf S.; Bidi S.; Breen G.; Broster J.; Chung R.; Collier D.; Curtis C.J.; Chaudhary S.; Colligan G.; Deloukas P.; Durham C.; Durrani F.; Eto F.; Finer S.; Gafton J.; Angel A.; Griffiths C.; Harvey J.; Heng T.; Hodgson S.; Huang Q.Q.; Hurles M.; Hunt K.A.; Hussain S.; Islam K.; Iyer V.; Jacobs B.M.; Kalantzis G.; Khan A.; Langenberg C.; Lavery C.; Lee S.H.; MacArthur D.; Malik S.; Malawsky D.; Martin H.; Mason D.; Mathur R.; Mazid M.B.; McDermott J.; Morton C.; Newman B.; Owor E.; Qureshi A.; Ramachandrappa S.; Raza M.; Russell J.; Safa N.; Samuel M.; Siddiqui M.; Simpson M.; Solly J.; Spreckley M.; Stow D.; Taylor M.; Trembath R.C.; Tricker K.; van Heel D.A.; Walter K.; Winckley C.; Wood S.; Wright J.; Zengeya I.; Zöllner J.; Parks T.; Dodd P.J.; Hoal E.G.; Morris A.P.; Hill A.V.S.; van Crevel R.; van Laarhoven A.; Ottenhoff T.H.M.; Metspalu A.; Magi R.; Meyer C.G.; Ellis M.; Thye T.; Mahasirimongkol S.; Pasomsub E.; Tokunaga K.; Omae Y.; Yanai H.; Mushiroda T.; Kubo M.; Takahashi A.; Kamatani Y.; Alisjahbana B.; Liu W.; Sheng A.d.; Hamilton F.; Mahidol University
    Background: The role of IL-6 responses in human tuberculosis risk is unknown. IL-6 signalling inhibitors, such as tocilizumab, are thought to increase the risk of progression to tuberculosis, and screening for latent Mycobacterium tuberculosis infection before using these drugs is widely recommended. We used single nucleotide polymorphisms (SNPs) in and near the IL-6 receptor gene (IL6R), including the non-synonymous variant, rs2228145, for which the C allele contributes to reduced classic (cis) IL-6 signalling activity, to test the hypothesis that altered IL-6 signalling is causally associated with the risk of developing tuberculosis. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) published in English from database inception to Jan 1, 2024. GWAS were identified from the European Bioinformatics Institute, MRC Integrative Epidemiology Unit catalogues, and MEDLINE, selecting publicly available studies for which tuberculosis was an outcome and that included the IL6R rs2228145 SNP. Using each study's population-level summary statistics, effect estimates were extracted for each additional copy of the C allele of rs2228145. We used these estimates to perform multi-ancestry, two-sample mendelian randomisation analyses to estimate the causal effect of reduced IL-6 signalling on tuberculosis. Our primary analyses used rs2228145-C as a genetic instrument, weighted on C-reactive protein (CRP) reduction as a measure of the effect on IL-6 signalling. We also took an alternative, ancestry-specific, multiple SNP approach using IL-6 receptor plasma protein as an exposure. Additionally, we compared the effects of rs2228145 in tuberculosis with those in critical COVID-19, rheumatoid arthritis, Crohn's disease, and coronary artery disease using the summary statistics extracted from GWAS. Findings: 17 GWAS were included, collating data for 19 302 individuals with tuberculosis (cases) and 1 019 821 population controls across multiple ancestries. For each additional rs2228145-C allele, the odds of tuberculosis reduced (odds ratio [OR] 0·94 [95% CI 0·92–0·97]; p=6·8 × 10–6). Multi-ancestry mendelian randomisation analyses supported these findings, with decreased odds of tuberculosis associated with readouts of reduced IL-6 signalling (0·52 [0·39–0·69] for each natural log CRP decrease; p=6·8 × 10–6), with weak evidence of heterogeneity (I2=0·315; p=0·11). Ancestry-specific, multiple SNP mendelian randomisation using increase in IL-6 receptor plasma protein as an exposure revealed a similar reduced risk of tuberculosis (OR 0·94 [95% CI 0·93–0·96]; p=2·4 × 10–10). The protective effects on tuberculosis seen with rs2228145-C were similar in size and direction to those observed in critical COVID-19 (0·66 [0·50–0·86]), Crohn's disease (0·57 [0·44–0·74]), and rheumatoid arthritis (0·45 [0·36–0·58]), all of which benefit from the therapeutic effects of IL-6 antagonism. Interpretation: Our findings propose a causal relationship between reduced IL-6 signalling and lower risk of tuberculosis, akin to the effect seen in other IL-6 mediated diseases. This study suggests that IL-6 antagonists do not increase the risk of tuberculosis but rather should be investigated as therapeutic adjuncts in its treatment. Funding: UK National Institute for Health and Care Research, Wellcome Trust, EU European Regional Development Fund, the Welsh Government, and UK Research and Innovation.
  • No Thumbnail Available
    ItemMetadata only
    Analysis of complete genomes of Mycobacterium tuberculosis sublineage 2.1 (Proto-Beijing) revealed the presence of three pe_pgrs3-pe_pgrs4-like genes
    (2024-12-01) Davies-Bolorunduro O.F.; Jaemsai B.; Ruangchai W.; Noppanamas T.; Boonbangyang M.; Bodharamik T.; Sawaengdee W.; Mahasirimongkol S.; Palittapongarnpim P.; Davies-Bolorunduro O.F.; Mahidol University
    Mycobacterium tuberculosis Complex (MTBC), the etiological agent of tuberculosis (TB), demonstrates considerable genotypic diversity with distinct geographic distributions and variable virulence profiles. The pe-ppe gene family is especially noteworthy for its extensive variability and roles in host immune response modulation and virulence enhancement. We sequenced an Mtb genotype L2.1 isolate from Chiangrai, Northern Thailand, using second and third-generation sequencing technologies. Comparative genomic analysis with two additional L2.1 isolates and two L2.2.AA3 (Asia Ancestral 3 Beijing) isolates revealed significant pe-ppe gene variations. Notably, all L2.1 isolates harbored three copies of pe_pgrs3-pe_pgrs4-like genes (pe_pgrs3*, pe_pgrs4*, and pe_pgrs4), different from L2.2.AA3 and H37Rv strains. Additionally, ppe53 was duplicated in all but H37Rv, and ppe50 was deleted in L2.1 isolates, contrasting with an extended ppe50 in an L2.2 isolate (Mtb 18b), which contains an additional SVP motif. Complete deletion of ppe66 and loss of wag22 were observed in L2.1 isolates. These findings highlight the high structural variability of the pe-ppe gene family, emphasizing its complex roles in Mtb-host immune interactions. This genetic complexity offers potentially critical insights into mycobacterial pathogenesis, with significant implications for vaccine development and diagnostics.
  • No Thumbnail Available
    ItemMetadata only
    Association between the CYP2B6 polymorphisms and nonnucleoside reverse transcriptase inhibitors drug-induced liver injury: a systematic review and meta-analysis
    (2024-12-01) Chanhom N.; Sonjan J.; Inchai J.; Udomsinprasert W.; Chaikledkaew U.; Suvichapanich S.; Mahasirimongkol S.; Jittikoon J.; Chanhom N.; Mahidol University
    Nevirapine (NVP) and Efavirenz (EFV) can cause antiretroviral drug-induced liver injury (ARVDILI). The objectives of this study were to summarize and analyze existing data on pharmacogenomics associated with nonnucleoside reverse transcriptase inhibitors drug-induced liver injury using systematic review and meta-analysis. This study systematically searched the relevant studies regarding pharmacogenes related to ARVDILI from online databases. Genes-encoding proteins were further analyzed using the STRING program to determine the protein-protein interactions (PPI). CYP2B6 polymorphisms were further meta-analyzed. Seventeen genes have been shown to be significantly associated with ARVDILI. Illustration from STRING analysis, CYP2B6, CYP1A1, and CYP2D6 enzymes have been recognized as central proteins linked to all other analyzed proteins. Meta-analysis illustrated that CYP2B6 *1/*6 (OR = 1.83; 95% CI: 1.15–2.90; P = 0.01), *6/*6 (OR = 2.48; 95% CI: 1.28–4.79; P = 0.007), and *1/*6 plus *6/*6 (OR = 1.94; 95% CI: 1.24–3.01; P = 0.003) were associated with risks of EFV-induced liver injury. Moreover, CYP2B6 *1/*6 (OR = 0.44; 95% CI: 0.22–0.91; P = 0.03) and a group combining individuals with either *1/*6 or *6/*6 (OR = 0.42; 95% CI: 0.21–0.84; P = 0.01) were associated with reduced risks of NVP-induced liver injury. This meta-analysis revealed an association between CYP2B6 genetic polymorphism and susceptibility to ARVDILI.
  • No Thumbnail Available
    ItemMetadata only
    Association of genetic variation on X chromosome with systemic lupus erythematosus in both Thai and Chinese populations
    (2024-03-08) Tangtanatakul P.; Lei Y.; Jaiwan K.; Yang W.; Boonbangyang M.; Kunhapan P.; Sodsai P.; Mahasirimongkol S.; Pisitkun P.; Yang Y.; Eu-Ahsunthornwattana J.; Aekplakorn W.; Jinawath N.; Neelapaichit N.; Hirankarn N.; Wang Y.F.; Tangtanatakul P.; Mahidol University
    Objectives X chromosome has been considered as a risk factor for SLE, which is a prototype of autoimmune diseases with a significant sex difference (female:male ratio is around 9:1). Our study aimed at exploring the association of genetic variants in X chromosome and investigating the influence of trisomy X in the development of SLE. Methods X chromosome-wide association studies were conducted using data from both Thai (835 patients with SLE and 2995 controls) and Chinese populations (1604 patients with SLE and 3324 controls). Association analyses were performed separately in females and males, followed by a meta-analysis of the sex-specific results. In addition, the dosage of X chromosome in females with SLE were also examined. Results Our analyses replicated the association of TMEM187-IRAK1-MECP2, TLR7, PRPS2 and GPR173 loci with SLE. We also identified two loci suggestively associated with SLE. In addition, making use of the difference in linkage disequilibrium between Thai and Chinese populations, a synonymous variant in TMEM187 was prioritised as a likely causal variant. This variant located in an active enhancer of immune-related cells, with the risk allele associated with decreased expression level of TMEM187. More importantly, we identified trisomy X (47,XXX) in 5 of 2231 (0.22%) females with SLE. The frequency is significantly higher than that found in the female controls (0.08%; two-sided exact binomial test P=0.002). Conclusion Our study confirmed previous SLE associations in X chromosome, and identified two loci suggestively associated with SLE. More importantly, our study indicated a higher risk of SLE for females with trisomy X.
  • No Thumbnail Available
    ItemMetadata only
    Association of NAT2 promoter hypermethylation with susceptibility to hepatotoxicity due to antituberculosis drugs and biomarker potential
    (2025-12-01) Jittikoon J.; Saengsiwaritt W.; Chanhom N.; Chaikledkaew U.; Wattanapokayakit S.; Mahasirimongkol S.; Udomsinprasert W.; Jittikoon J.; Mahidol University
    This study aimed to determine whether promoter methylation of N-acetyltransferase 2 (NAT2), a metabolic enzyme responsible for drug metabolism and detoxification, was correlated with clinical parameters indicating anti-tuberculosis drug-induced liver injury (ATDILI) in tuberculosis patients and might emerge as an ATDILI biomarker. NAT2 promoter methylation in blood leukocyte of 102 tuberculosis patients (49 ATDILI cases and 53 non-ATDILI cases) and 100 healthy controls were quantified using quantitative real-time methylation-specific polymerase chain reaction. Compared to healthy volunteers, tuberculosis patients had significantly reduced NAT2 demethylation index. Compared with non-ATDILI patients, NAT2 demethylation index was significantly decreased in ATDILI patients. An independent association was found between lower NAT2 demethylation index and increased susceptibility to ATDILI. NAT2 demethylation index quantified after starting treatment within 1–7 days was negatively correlated with serum aminotransferases measured within 8–60 days of treatment. ROC curve analysis uncovered that NAT2 demethylation index was found to be a more sensitive and specific biomarker for ATDILI when compared to serum aminotransferases measured following treatment initiation within 1–7 days. Kaplan–Meier analysis unveiled a notable association between lower NAT2 demethylation index and a higher incidence of ATDILI in tuberculosis patients, as confirmed by Cox regression analysis while accounting for confounding variables. A reduction in NAT2 demethylation index could reflect ATDILI progression and potentially be used as a new, specific biomarker for ATDILI.
  • No Thumbnail Available
    ItemMetadata only
    Author Correction: Pathogen genomic surveillance status among lower resource settings in Asia (Nature Microbiology, (2024), 9, 10, (2738-2747), 10.1038/s41564-024-01809-4)
    (2024-01-01) Getchell M.; Wulandari S.; de Alwis R.; Agoramurthy S.; Khoo Y.K.; Mak T.M.; Moe L.; Stona A.C.; Pang J.; Momin M.H.F.H.A.; Amir A.; Andalucia L.R.; Azzam G.; Chin S.; Chookajorn T.; Arunkumar G.; Hung D.T.; Ikram A.; Jha R.; Karlsson E.A.; Le Thi M.Q.; Mahasirimongkol S.; Malavige G.N.; Manning J.E.; Munira S.L.; Trung N.V.; Nisar I.; Qadri F.; Qamar F.N.; Robinson M.T.; Saloma C.P.; Setk S.; Shirin T.; Tan L.V.; Dizon T.J.R.; Thayan R.; Thu H.M.; Tissera H.; Xangsayarath P.; Zaini Z.; Lim J.C.W.; Maurer-Stroh S.; Smith G.J.D.; Wang L.F.; Pronyk P.; Getchell M.; Mahidol University
    Correction to: Nature Microbiologyhttps://doi.org/10.1038/s41564-024-01809-4, published online 24 September 2024. In the version of the article initially published, Thanat Chookajorn was mistakenly listed as an additional corresponding author. The HTML and PDF versions of the article have now been amended so that Ruklanthi de Alwis remains the sole corresponding author.
  • No Thumbnail Available
    ItemMetadata only
    Catastrophic costs incurred by tuberculosis affected households from Thailand’s first national tuberculosis patient cost survey
    (2024-12-01) Youngkong S.; Kamolwat P.; Wongrot P.; Thavorncharoensap M.; Chaikledkaew U.; Nateniyom S.; Pungrassami P.; Praditsitthikorn N.; Mahasirimongkol S.; Jittikoon J.; Nishikiori N.; Baena I.G.; Yamanaka T.; Youngkong S.; Mahidol University
    Tuberculosis (TB) causes an economic impact on the patients and their households. Although Thailand has expanded the national health benefit package for TB treatment, there was no data on out-of-pocket payments and income losses due to TB from patients and their household perspectives. This national TB patient cost survey was conducted to examine the TB-related economic burden, and assess the proportion of TB patients and their households facing catastrophic total costs because of TB disease. A cross-sectional TB patient cost survey was employed following WHO methods. Structured interviews with a paper-based questionnaire were conducted from October 2019 to July 2021. Both direct and indirect costs incurred from the patient and their household perspective were valued in 2021 and estimated throughout pre- and post-TB diagnosis episodes. We assessed the proportion of TB-affected households facing costs > 20% of household expenditure due to TB. We analyzed 1400 patients including 1382 TB (first-line treatment) and 18 drug-resistant TB patients (DR-TB). The mean total costs per TB episode for all study participants were 903 USD (95% confident interval; CI 771–1034 USD). Of these, total direct non-medical costs were the highest costs (mean, 402 USD, and 95%CI 334–470 USD) incurred per TB-affected household followed by total indirect costs (mean, 393 USD, and 95%CI 315–472 USD) and total direct medical costs (mean, 107 USD, and 95%CI 81–133 USD, respectively. The proportion of TB-affected households facing catastrophic costs was 29.5% (95%CI 25.1–34.0%) for TB (first-line), 61.1% (95%CI 29.6–88.1%) for DR-TB and 29.9% (95%CI 25.6–34.4%) overall. This first national survey highlighted the economic burden on TB-affected households. Travel, food/nutritional supplementation, and indirect costs contribute to a high proportion of catastrophic total costs. These suggest the need to enhance financial and social protection mechanisms to mitigate the financial burden of TB-affected households.
  • No Thumbnail Available
    ItemMetadata only
    Comparison of safety and immunogenicity of CoronaVac and ChAdOx1 against the SARS-CoV-2 circulating variants of concern (Alpha, Delta, Beta) in Thai healthcare workers
    (2022-04-01) Angkasekwinai N.; Sewatanon J.; Niyomnaitham S.; Phumiamorn S.; Sukapirom K.; Sapsutthipas S.; Sirijatuphat R.; Wittawatmongkol O.; Senawong S.; Mahasirimongkol S.; Trisiriwanich S.; Chokephaibulkit K.; Mahidol University
    Background: Inactivated vaccine (CoronaVac) and chimpanzee adenovirus-vector vaccine (ChAdOx1) have been widely used in resource-limited settings. However, the information on the reactogenicity and immunogenicity of these two vaccines in the same setting are limited. Methods: Healthy health care workers (HCWs) aged 18 years or older were randomly assigned to receive either two doses of CoronaVac at 4 weeks interval or two doses of ChAdOx1 at 10 weeks interval. Self-reported adverse events (AEs) were collected for 7 days following each vaccination. Immunogenicity was determined by IgG antibodies levels against receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S1 subunit) and the 50% plaque reduction neutralization titers against various strains. Results: Of the 360 HCWs, 180 in each vaccine group, the median (interquartile range: IQR) age was 35 (29–44) years old and 84.2% were female. Participants who received ChAdOx1 reported higher frequency of AEs than those received CoronaVac after both the first dose (84.4% vs. 66.1%, P < 0.001) and second dose (75.6% vs. 60.6%, P = 0.002), with more AEs in those younger than 30 years of age for both vaccines. The seroconversion rates were 75.6% and 100% following the first dose of CoronaVac and ChAdOx1, respectively. All participants were seropositive at 2 weeks after the second dose. The anti-SARS-CoV-2 RBD IgG levels induced by CoronaVac was lower than ChAdOX1 with geometric means of 164.4 and 278.5 BAU/mL, respectively (P = 0.0066). Both vaccines induced similar levels of neutralizing antibodies against the Wuhan strain, with the titers of 337.4 and 331.2; however, CoronaVac induced significantly lower GMT against Alpha (23.1 vs. 92.5), Delta (21.2 vs. 69.7), and Beta (10.2 vs. 43.6) variants, respectively. Conclusion: CoronaVac induces lower measurable antibodies against circulating variants but with lower frequency of AEs than ChAdOx1. An earlier boosting to prevent breakthrough infections may be needed.
  • No Thumbnail Available
    ItemMetadata only
    Comprehensive analysis of Mycobacterium tuberculosis genomes reveals genetic variations in bacterial virulence
    (2024-01-01) Worakitchanon W.; Yanai H.; Piboonsiri P.; Miyahara R.; Nedsuwan S.; Imsanguan W.; Chaiyasirinroje B.; Sawaengdee W.; Wattanapokayakit S.; Wichukchinda N.; Omae Y.; Palittapongarnpim P.; Tokunaga K.; Mahasirimongkol S.; Fujimoto A.; Worakitchanon W.; Mahidol University
    Tuberculosis, a disease caused by Mycobacterium tuberculosis (Mtb), is a significant health problem worldwide. Here, we developed a method to detect large insertions and deletions (indels), which have been generally understudied. Leveraging this framework, we performed a comprehensive analysis of single nucleotide variants and small and large indels across 1,960 Mtb clinical isolates. Comparing the distribution of variants demonstrated that gene disruptive variants are underrepresented in genes essential for bacterial survival. An evolutionary analysis revealed that Mtb genomes are enriched in partially deleterious mutations. Genome-wide association studies identified small and large deletions in eccB2 significantly associated with patient prognosis. Additionally, we unveil significant associations with antibiotic resistance in 23 non-canonical genes. Among these, large indels are primarily found in genetic regions of Rv1216c, Rv1217c, fadD11, and ctpD. This study provides a comprehensive catalog of genetic variations and highlights their potential impact for the future treatment and risk prediction of tuberculosis.
  • No Thumbnail Available
    ItemMetadata only
    Cost-Benefit Analysis of Genetic Testing as a Prenatal Diagnostic Tool for Thalassemia: A Single-Center Study From Central Thailand
    (2025-01-01) Malasai K.; Jittikoon J.; Udomsinprasert W.; Talungchit P.; Youngkong S.; Sangroongruangsri S.; Mahasirimongkol S.; Chaikledkaew U.; Malasai K.; Mahidol University
    Purpose: This study aimed to evaluate the costs and benefits of genetic testing, specifically mutation analysis and prenatal diagnostic testing, for the confirmation of thalassemia in at-risk pregnancies in Thailand, providing crucial insights to inform public health policy decision-making. Patients and Methods: We analyzed the costs and benefits of following standard screening guidelines, which included a sequence of tests such as mean corpuscular volume (MCV)/mean corpuscular hemoglobin (MCH) with dichlorophenol indophenol precipitation (DCIP), hemoglobin (Hb) typing, genetic testing, and amniocentesis. A decision-tree model was employed for this analysis. The study compared the scenarios with and without genetic testing, adopting a societal perspective that accounted for costs during pregnancy and the lifetime of a child born with thalassemia. Both one-way and probabilistic sensitivity analyses were conducted to account for uncertainties in the parameters used. Results: The results revealed that adhering to the standard screening program with genetic testing resulted in a cost-savings of approximately 490 USD per prevented thalassemia case. Among the diagnostic methods, the specificity of the MCV/MCH with DCIP showed a higher degree of sensitivity relative to other testing methods, significantly influencing the outcomes. From a governmental perspective, with a full uptake of genetic testing, the incremental budget required was estimated to be 3.7 million USD (131 million THB) for one year. Conclusion: These findings are particularly valuable for policymakers, as they provide robust evidence supporting potential revisions to the reimbursement structure within Thailand’s Universal Health Coverage benefit package, facilitating better management of thalassemia and improving prenatal care.
  • No Thumbnail Available
    ItemMetadata only
    Cost-Utility Analysis of Molecular Testing for Tuberculosis Diagnosis in Suspected Pulmonary Tuberculosis in Thailand
    (2022-01-01) Chitpim N.; Jittikoon J.; Udomsinprasert W.; Mahasirimongkol S.; Chaikledkaew U.; Mahidol University
    Purpose: Given the lack of economic evaluation study of molecular testing in Thailand, this study aimed to evaluate the cost-utility of molecular testing algorithms including Xpert MTB/RIF and the loop-mediated isothermal amplification (TB-LAMP) in the general population suspected of having pulmonary TB based on a societal perspective. Methods: A hybrid decision tree Markov model using a 1-month cycle length was used to evaluate costs and outcomes of five TB diagnostic algorithms: 1) sputum smear microscopy (SSM) with culture and drug susceptibility testing (DST), 2) Xpert MTB/RIF addon, 3) Xpert MTB/RIF initial, 4) TB-LAMP add-on, and 5) TB-LAMP initial during a lifetime period. All costs were calculated in 2021 Baht, and results were presented as an incremental cost-effectiveness ratio (ICER) for molecular testing compared with SSM with culture. One-way sensitivity and probability analyses were used to evaluate uncertainty input parameters. Results: TB-LAMP was less expensive overall (6565 Baht) than Xpert MTB/RIF (7010 Baht) and SSM with culture (6845 Baht). Molecular testing was projected to improve quality adjusted life year (QALY) by 0.53 to 0.94 years. In comparison to SSM with culture and DST, providing an initial TB-LAMP test was the most preferred choice. Xpert MTB/RIF Initial had the lowest ICER (197 Baht per QALY gained), followed by TB-LAMP Add-on (993 Baht per QALY gained) and Xpert MTB/RIF Add-on (3940 Baht per QALY gained). One-way sensitivity analysis uncovered that sensitivity of TB-LAMP was greater than that of other parameters. Conclusion: Providing molecular testing including Xpert MTB/RIF and TB-LAMP as either initial or add-on test for TB diagnosis was more cost-effective than SSM with culture and DST in the general population with suspected pulmonary TB in Thailand. Our study could provide useful evidence to policymakers advocating for inclusion of molecular testing in the universal health coverage benefit package in Thailand.
  • No Thumbnail Available
    ItemMetadata only
    Distribution of Mycobacterium tuberculosis Lineages and Drug Resistance in Upper Myanmar
    (2022-12-01) Phyu A.N.; Aung S.T.; Palittapongarnpim P.; Htet K.K.K.; Mahasirimongkol S.; Aung H.L.; Chaiprasert A.; Chongsuvivatwong V.; Mahidol University
    Mycobacterium tuberculosis complex (MTBC) is divided into 9 whole genome sequencing (WGS) lineages. Among them, lineages 1–4 are widely distributed. Multi-drug resistant tuberculosis (MDR-TB) is a major public health threat. For effective TB control, there is a need to obtain genetic information on lineages of Mycobacterium tuberculosis (Mtb) and to understand distribution of lineages and drug resistance. This study aimed to describe the distribution of major lineages and drug resistance patterns of Mtb in Upper Myanmar. This was a cross-sectional study conducted with 506 sequenced isolates. We found that the most common lineage was lineage 2 (n = 223, 44.1%). The most common drug resistance mutation found was streptomycin (n = 44, 8.7%). Lineage 2 showed a higher number of MDR-TB compared to other lineages. There were significant associations between lineages of Mtb and drug resistance patterns, and between lineages and geographical locations of Upper Myanmar (p value < 0.001). This information on the distribution of Mtb lineages across the geographical areas will support a lot for the better understanding of TB transmission and control in Myanmar and other neighboring countries. Therefore, closer collaboration in cross border tuberculosis control is recommended.
  • No Thumbnail Available
    ItemMetadata only
    Early treatment of Favipiravir in COVID-19 patients without pneumonia: a multicentre, open-labelled, randomized control study
    (2022-01-01) Sirijatuphat R.; Manosuthi W.; Niyomnaitham S.; Owen A.; Copeland K.K.; Charoenpong L.; Rattanasompattikul M.; Mahasirimongkol S.; Wichukchinda N.; Chokephaibulkit K.; Mahidol University
    We investigated Favipiravir (FPV) efficacy in mild cases of COVID-19 without pneumonia and its effects towards viral clearance, clinical condition, and risk of COVID-19 pneumonia development. PCR-confirmed SARS-CoV-2-infected patients without pneumonia were enrolled (2:1) within 10 days of symptomatic onset into FPV and control arms. The former received 1800 mg FPV twice-daily (BID) on Day 1 and 800 mg BID 5–14 days thereafter until negative viral detection, while the latter received only supportive care. The primary endpoint was time to clinical improvement, defined by a National Early Warning Score (NEWS) of ≤1. 62 patients (41 female) comprised the FPV arm (median age: 32 years, median BMI: 22 kg/m²) and 31 patients (19 female) comprised the control arm (median age: 28 years, median BMI: 22 kg/m²). The median time to sustained clinical improvement, by NEWS, was 2 and 14 days for FPV and control arms, respectively (adjusted hazard ratio (aHR) of 2.77, 95% CI 1.57–4.88, P <.001). The FPV arm also had significantly higher likelihoods of clinical improvement within 14 days after enrolment by NEWS (79% vs. 32% respectively, P <.001). 8 (12.9%) and 7 (22.6%) patients in FPV and control arms developed mild pneumonia at a median (range) of 6.5 (1–13) and 7 (1–13) days after treatment, respectively (P =.316). All recovered well without complications. We can conclude that early treatment of FPV in symptomatic COVID-19 patients without pneumonia was associated with faster clinical improvement. Trial registration: Thai Clinical Trials Registry identifier: TCTR20200514001.
  • No Thumbnail Available
    ItemMetadata only
    Economic analysis of pharmacogenetics testing for human leukocyte antigen-based adverse drug reactions
    (2023-01-01) Yuliwulandari R.; Chaikledkaew U.; Prayuni K.; Zahroh H.; Mahasirimongkol S.; Turongkaravee S.; Jittikoon J.; Wattanapokayakit S.; Patrinos G.P.; Mahidol University
    Adverse drug reactions (ADRs) can cause treatment interruptions as well as disability and sometimes death. Recent developments in genetics have shown that some ADRs could be avoided by using pharmacogenetic tests before treatment initiation. However, due to their novelty, many countries, especially in Asia, are yet to implement pre-emptive genetic screenings in clinical settings. Several studies have been published on the cost-effectiveness of genetics screening before treatment initiation. This chapter discusses the potential pharmacoeconomic implications of human leukocyte antigen (HLA) typing associated with some well-known and studied ADRs and the associated implementation into routine care.
  • No Thumbnail Available
    ItemMetadata only
    Economic evaluation of diagnosis and treatment for latent tuberculosis infection among contacts of pulmonary tuberculosis patients in Thailand
    (2024-12-01) Yoopetch P.; Wu O.; Jittikoon J.; Thavorncharoensap M.; Youngkong S.; Praditsitthikorn N.; Mahasirimongkol S.; Anothaisintawee T.; Udomsinprasert W.; Chaikledkaew U.; Yoopetch P.; Mahidol University
    Currently, interferon-gamma release assay (IGRA) is costly and not included as latent tuberculosis infection (LTBI) screening test strategy in Thailand’s Universal Coverage Scheme (UCS) benefit package. The objective of this study was to assess the cost-utility of LTBI screening strategies among tuberculosis (TB) contacts in Thailand. A hybrid decision tree and Markov model was developed to compare the lifetime costs and health outcomes of tuberculin skin test (TST) and IGRA, in comparison to no screening, based on a societal perspective. Health outcomes were the total number of TB cases averted and quality-adjusted life years (QALYs), with results presented as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to explore uncertainties in all parameters. The ICER of TST compared with no screening was 27,645 baht per QALY gained, while that of IGRA compared to TST was 851,030 baht per QALY gained. In a cohort of 1000 TB contacts, both TST and IGRA strategies could avert 282 and 283 TB cases, respectively. At the Thai societal willingness-to-pay threshold of 160,000 baht per QALY gained, TST was deemed cost-effective, whereas IGRA would not be cost-effective, unless the cost of IGRA was reduced to 1,434 baht per test.
  • No Thumbnail Available
    ItemMetadata only
    Economic evaluation of diagnostic tests for Thai patients with tuberculosis: A dynamic transmission model approach
    (2025-03-01) Chitpim N.; Praditsitthikorn N.; White L.J.; Meeyai A.; Jittikoon J.; Bunwong K.; Youngkong S.; Thavorncharoensap M.; Mahasirimongkol S.; Udomsinprasert W.; Chaikledkaew U.; Chitpim N.; Mahidol University
    Conventional tuberculosis (TB) diagnosis is time-consuming, while newer molecular assays such as Xpert MTB/RIF and loop-mediated amplification test for TB (TB-LAMP) provide faster results but at a higher cost compared to sputum smear microscopy (SSM) with culture and drug susceptibility testing (DST) in Thailand. This study assessed the cost-utility of TB diagnostic algorithms as either initial or add-on tests from a societal perspective for TB diagnosis in the general Thai population. A dynamic transmission model was employed to evaluate five TB diagnostic algorithms over a 15-year period. Costs were calculated in 2023 Thai Baht, with results presented as incremental cost-effectiveness ratios (ICERs) compared to SSM with culture and DST. One-way and probability sensitivity analyses were conducted to assess parameter uncertainty. Compared to SSM with culture and DST, the ICER values (Baht per QALY gained) of TB-LAMP Add-On (3,563), Xpert MTB/RIF Add-On (3,670), and TB-LAMP Initial (6,429) indicated that these algorithms were cost-effective, while Xpert MTB/RIF Initial emerged as a cost-saving option. One-way sensitivity analysis results revealed that the utility of the first-line treatment exhibited the highest variability in ICERs, followed by the unit cost of Xpert MTB/RIF. The results supported the adoption of Xpert MTB/RIF as an initial test for the general Thai population. These findings provide evidence for policymakers to integrate molecular testing into Thailand’s Universal Coverage Scheme benefit package, aligning with national TB strategies to reduce TB incidence and mortality.
  • No Thumbnail Available
    ItemMetadata only
    Economic Evaluation of Screening Strategy for Latent Tuberculosis Infection (LTBI) in Contacts of Tuberculosis Patients: Systematic Review and Quality Assessment
    (2022-10-01) Yoopetch P.; Chitpim N.; Jittikoon J.; Udomsinprasert W.; Thavorncharoensap M.; Youngkong S.; Praditsitthikorn N.; Mahasirimongkol S.; Chaikledkaew U.; Mahidol University
    A tuberculin skin test (TST) or interferon-gamma release assay (IGRA) can be used to screen for latent tuberculosis infection (LTBI). Due to its low cost, TST has been used particularly in underdeveloped countries. The limitations of TST were poor specificity in populations with a high prevalence of Bacille Calmette-Guérin (BCG) vaccination and variability of test readers. IGRA is used as an alternative to TST in settings where higher costs can be supported. The lack of studies conducted in high TB incidence countries since previous review, and using relevant assessment tools of the quality appraisal make the need for updated studies and a more comprehensive systematic review. This study aimed to conduct a systematic review of published economic evaluations of screening strategies for LTBI in contacts of TB patients, assess the quality of these studies, and compare the assessment results related to a country’s income level in order to provide information to other countries. The databases were searched in January 2022 including MEDLINE and Scopus. Two independent reviewers evaluated the included studies based on eligibility criteria, data extraction, and quality assessment. Eleven economic evaluations of LTBI diagnostic tests in TB contacts were included. Most studies were conducted in high-income countries (91%) and used cost-effectiveness analysis methods (73%). The quality assessment of reporting and data sources was appropriate, ranging from 71% to 89%. Interventions varied from study to study. The outcomes were cost per life years gained (27%), cost per quality-adjusted life year gained (27%), cost per TB case prevented (36%), and cost per close contact case (10%). In high-income countries which were not countries with high TB burden, the use of IGRA alone for screening TB contacts was cost-effective, whereas TST was cost-effective in only two studies. In comparison to TST, IGRA could reduce false-positive results, resulting in fewer patients undergoing TB treatment and preventive treatment.
  • No Thumbnail Available
    ItemMetadata only
    Genetic basis of sudden death after COVID-19 vaccination in Thailand
    (2022-11-01) Ittiwut C.; Mahasirimongkol S.; Srisont S.; Ittiwut R.; Chockjamsai M.; Durongkadech P.; Sawaengdee W.; Khunphon A.; Larpadisorn K.; Wattanapokayakit S.; Wetchaphanphesat S.; Arunotong S.; Srimahachota S.; Pittayawonganon C.; Thammawijaya P.; Sutdan D.; Doungngern P.; Khongphatthanayothin A.; Kerr S.J.; Shotelersuk V.; Mahidol University
    Background: Severe acute respiratory syndrome coronavirus 2 vaccination reduces morbidity and mortality associated with coronavirus disease 2019 (COVID-19); unfortunately, it is associated with serious adverse events, including sudden unexplained death (SUD). Objective: We aimed to study the genetic basis of SUD after COVID-19 vaccination in Thailand. Methods: From April to December 2021, cases with natural but unexplained death within 7 days of COVID-19 vaccination were enrolled for whole exome sequencing. Results: Thirteen were recruited, aged between 23 and 72 years; 10 (77%) were men, 12 were Thai; and 1 was Australian. Eight (61%) died after receiving the first dose of vaccine, and 7 (54%) died after receiving ChAdOx1 nCoV-19; however, there were no significant correlations between SUD and either the number or the type of vaccine. Fever was self-reported in 3 cases. Ten (77%) and 11 (85%) died within 24 hours and 3 days of vaccination, respectively. Whole exome sequencing analysis revealed that 5 cases harbored SCN5A variants that had previously been identified in patients with Brugada syndrome, giving an SCN5A variant frequency of 38% (5 of 13). This is a significantly higher rate than that observed in Thai SUD cases occurring 8–30 days after COVID-19 vaccination during the same period (10% [1 of 10]), in a Thai SUD cohort studied before the COVID-19 pandemic (12% [3 of 25]), and in our in-house exome database (12% [386 of 3231]). Conclusion: These findings suggest that SCN5A variants may be associated with SUD within 7 days of COVID-19 vaccination, regardless of vaccine type, number of vaccine dose, and presence of underlying diseases or postvaccine fever.