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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.
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Análisis Costo-Beneficio , Ensayos de Liberación de Interferón gamma , Tuberculosis Latente , Prueba de Tuberculina , Tuberculosis Pulmonar , Humanos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Tuberculosis Latente/economía , Tailandia/epidemiología , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/economía , Prueba de Tuberculina/economía , Ensayos de Liberación de Interferón gamma/economía , Masculino , Femenino , Años de Vida Ajustados por Calidad de Vida , Adulto , Persona de Mediana Edad , Tamizaje Masivo/economía , Tamizaje Masivo/métodos , Cadenas de MarkovRESUMEN
Data on immunogenicity induced by SARS-CoV-2 infection and its sustainability are essential to inform COVID-19 vaccine schedule. A prospective cohort study was conducted among adults at-risk for COVID-19 during the Omicron variant-dominant epidemic. All were followed up for anti-spike RBD levels on days 0, 14, 90 and 180 after enrollment. Of the 871 individuals included, 264 (30.3 %) had COVID-19. Those with COVID-19 had significantly lower baseline geometric mean level of anti-spike RBD than those without COVID-19 (326 vs. 989; P < 0.001). Among the COVID-19 patients, anti-spike RBD level significantly increased the most at 14 days after infection and dropped significantly at day 90 and day 180. Giving a booster dose during 91-180 days after infection induced high level of anti-spike RBD through 180 days. These findings suggest high level but short-lived immunity induced by SARS-CoV-2 infection while sustained immunity required a booster dose administered from 90 days after the infection.
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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.
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Costo de Enfermedad , Composición Familiar , Gastos en Salud , Tuberculosis , Humanos , Tailandia/epidemiología , Femenino , Masculino , Adulto , Tuberculosis/economía , Tuberculosis/terapia , Persona de Mediana Edad , Estudios Transversales , Gastos en Salud/estadística & datos numéricos , Encuestas y Cuestionarios , Adulto Joven , Adolescente , Anciano , Tuberculosis Resistente a Múltiples Medicamentos/economía , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Costos de la Atención en SaludRESUMEN
Mycobacterium tuberculosis is considered by many to be the deadliest microbe, with the estimated annual cases numbering more than 10 million. The bacteria, including Mycobacterium africanum, are classified into nine major lineages and hundreds of sublineages, each with different geographical distributions and levels of virulence. The phylogeographic patterns can be a result of recent and early human migrations as well as coevolution between the bacteria and various human populations, which may explain why many studies on human genetic factors contributing to tuberculosis have not been replicable in different areas. Moreover, several studies have revealed the significance of interactions between human genetic variations and bacterial genotypes in determining the development of tuberculosis, suggesting coadaptation. The increased availability of whole-genome sequence data from both humans and bacteria has enabled a better understanding of these interactions, which can inform the development of vaccines and other control measures.
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Genoma Bacteriano , Mycobacterium tuberculosis , Tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidad , Tuberculosis/microbiología , Tuberculosis/genética , Genómica , Variación Genética , Filogenia , Genotipo , Evolución Molecular , Filogeografía , Interacciones Huésped-Patógeno/genéticaRESUMEN
The southernmost part of Thailand is a unique and culturally diverse region that has been greatly affected by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak during the coronavirus disease-2019 pandemic. To gain insights into this situation, we analyzed 1942 whole-genome sequences of SARS-CoV-2 obtained from the five southernmost provinces of Thailand between April 2021 and March 2022, together with those publicly available in the Global Initiative on Sharing All Influenza Data database. Our analysis revealed evidence for transboundary transmissions of the virus in and out of the five southernmost provinces during the study period, from both domestic and international sources. The most prevalent viral variant in our sequence dataset was the Delta B.1.617.2.85 variant, also known as the Delta AY.85 variant, with many samples carrying a non-synonymous mutation F306L in their spike protein. Protein-protein docking and binding interface analyses suggested that the mutation may enhance the binding between the spike protein and host cell receptor protein angiotensin-converting enzyme 2, and we found that the mutation was significantly associated with an increased fatality rate. This mutation has also been observed in other SARS-CoV-2 variants, suggesting that it is of particular interest and should be monitored.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiología , COVID-19/genética , Tailandia/epidemiología , Glicoproteína de la Espiga del Coronavirus/genética , MutaciónRESUMEN
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.
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Lupus Eritematoso Sistémico , Trastornos de los Cromosomas Sexuales del Desarrollo Sexual , Trisomía , Humanos , Masculino , Femenino , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/genética , Predisposición Genética a la Enfermedad , Tailandia/epidemiología , Aberraciones Cromosómicas Sexuales , Cromosomas Humanos X/genética , China , Proteínas de la MembranaRESUMEN
Whole genome sequencing (WGS) of Mycobacterium tuberculosis offers valuable insights for tuberculosis (TB) control. High throughput platforms like Illumina and Oxford Nanopore Technology (ONT) are increasingly used globally, although ONT is known for higher error rates and is less established for genomic studies. Here we present a study comparing the sequencing outputs of both Illumina and ONT platforms, analysing DNA from 59 clinical isolates in highly endemic TB regions of Thailand. The resulting sequence data were used to profile the M. tuberculosis pairs for their lineage, drug resistance and presence in transmission chains, and were compared to publicly available WGS data from Thailand (n = 1456). Our results revealed isolates that are predominantly from lineages 1 and 2, with consistent drug resistance profiles, including six multidrug-resistant strains; however, analysis of ONT data showed longer phylogenetic branches, emphasising the technologies higher error rate. An analysis incorporating the larger dataset identified fifteen of our samples within six potential transmission clusters, including a significant clade of 41 multi-drug resistant isolates. ONT's extended sequences also revealed strain-specific structural variants in pe/ppe genes (e.g. ppe50), which are candidate loci for vaccine development. Despite some limitations, our results show that ONT sequencing is a promising approach for TB genomic research, supporting precision medicine and decision-making in areas with less developed infrastructure, which is crucial for tackling the disease's significant regional burden.
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Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Humanos , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Antituberculosos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Filogenia , Tuberculosis/tratamiento farmacológico , Secuenciación Completa del Genoma/métodos , Pruebas de Sensibilidad MicrobianaRESUMEN
Background: The HLA-B alleles have been used as a marker to predict drug-induced adverse reactions and as a major contributor to hypersensitivity reactions. We examined the feasibility of HLA-B alleles as pharmacogenomic markers of drug-induced hypersensitivity in an Indonesian Malay Ethnic. Methods: Fifty-eight Indonesian individuals of Malay ethnicity were enrolled in this study. HLA-B alleles were determined using reverse sequence-specific oligonucleotide probe coupled with xMAP technology. Results: HLA-B*15:02 (15.52%), HLA-B*35:05 (9.48%), and HLA-B*07:05 (7.76%) were frequent alleles in the Indonesian Malay ethnic populations. We discovered at least eight pharmacogenomics markers of drug-induced hypersensitivity: HLA-B*15:02, HLA-B*15:21, HLA-B*13:01, HLA-B*35:05, HLA-B*38:02, HLA-B*51:01, HLA-B*57:01, and HLA-B*58:01. HLA-B*15:02 was in the same serotype group with HLA-B*15:21, which is a B-75 serotype associated with genetic predisposition for carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis. The Indonesian population, represented by Malay, Javanese, and Sundanese ethnicities, was similar to South East Asian, Han Chinese, and Taiwanese populations based on HLA-B*15:02 frequency as the most common allele found in Malay ethnics. Conclusion: We provided valuable information on the frequency of drug hypersensitivity-associated HLA-B alleles in Indonesian Malay ethnic population, which can improve treatment safety.
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Thailand experienced five waves of coronavirus disease 2019 (COVID-19) between 2020 and 2022, with the Bangkok Metropolitan Region (BMR) being at the centre of all outbreaks. The molecular evolution of the causative agent of the disease, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has previously been characterized in Thailand, but a detailed spatiotemporal analysis is still lacking. In this study, we comprehensively reviewed the development and timelines of the five COVID-19 outbreaks in Thailand and the public health responses, and also conducted a phylogenetic analysis of 27â913 SARS-CoV-2 genomes from Thailand, together with 7330 global references, to investigate the virus's spatiotemporal evolution during 2020 and 2022, with a particular focus on the BMR. Limited cross-border transmission was observed during the first four waves in 2020 and 2021, but was common in 2022, aligning well with the timeline of change in the international travel restrictions. Within the country, viruses were mostly restricted to the BMR during the first two waves in 2020, but subsequent waves in 2021 and 2022 saw extensive nationwide transmission of the virus, consistent with the timeline of relaxation of disease control measures employed within the country. Our results also suggest frequent epidemiological connections between Thailand and neighbouring countries during 2020 and 2021 despite relatively stringent international travel controls. The overall sequencing rate of the viruses circulating in the BMR was ~0.525â%, meeting the recommended benchmark, and our analysis supports that this is sufficient for tracking of the trend of the virus burden and genetic diversity. Our findings reveal insights into the local transmission dynamics of SARS-CoV-2 in Thailand, and provide a valuable reference for planning responses to future outbreaks.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiología , Filogenia , Tailandia/epidemiología , Brotes de EnfermedadesRESUMEN
This study aimed to characterize whole-genome sequencing (WGS) information of Mycobacterium tuberculosis (Mtb) in the Mandalay region of Myanmar. It was a cross-sectional study conducted with 151 Mtb isolates obtained from the fourth nationwide anti-tuberculosis (TB) drug-resistance survey. Frequency of lineages 1, 2, 3, and 4 were 55, 65, 9, and 22, respectively. The most common sublineage was L1.1.3.1 (n = 31). Respective multi-drug resistant tuberculosis (MDR-TB) frequencies were 1, 1, 0, and 0. Four clusters of 3 (L2), 2 (L4), 2 (L1), and 2 (L2) isolates defined by a 20-single-nucleotide variant (SNV) cutoff were detected. Simpson's index for sublineages was 0.0709. Such high diversity suggests that the area probably had imported Mtb from many geographical sources. Relatively few genetic clusters and MDR-TB suggest there is a chance the future control will succeed if it is carried out properly.
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Multi-stage tuberculosis (TB) vaccines composed of active- and dormancy-associated antigens are promising to trigger the immune protection against all TB stages. However, scientists are still in quest of the suitable vaccine candidates. In this study, we identified the potential targets for this vaccine in a high TB burden country, Thailand. Peptide microarray was applied to gauge IgA and IgG antibodies specific to 16,730 linear epitopes of 52 dormancy-associated Mycobacterium tuberculosis (M. tb) proteins in three study groups: active tuberculosis (ATB), latent tuberculosis infection (LTBI) and endemic healthy control (EHC). Preferential IgA recognition against epitopes of dormancy-associated proteins was identified in LTBI group. Validation of these findings revealed that LTBI subjects exhibited the greater levels of Rv2659c- and Rv1738-specific IgA than those of household contacts, but less than did ATB subjects. Frequencies of IFNγ-producing CD4+ and CD8+ T cells induced by proteins Rv2659c and Rv1738 were higher in LTBI than ATB individuals. The results indicated that LTBI group in a high TB burden country demonstrated cell-mediated immune response to proteins Rv2659c and Rv1738 stronger than those of ATB. These immune responses likely contribute to natural protection against dormant M. tb and might be potential targets for a multi-stage TB vaccine.
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Tuberculosis Latente , Mycobacterium tuberculosis , Tuberculosis , Humanos , Linfocitos T CD8-positivos , Tailandia , Antígenos Bacterianos , Tuberculosis/microbiología , Péptidos , Inmunidad Celular , Inmunoglobulina ARESUMEN
The genetics underlying tuberculosis (TB) pathophysiology are poorly understood. Human genome-wide association studies have failed so far to reveal reproducible susceptibility loci, attributed in part to the influence of the underlying Mycobacterium tuberculosis (Mtb) bacterial genotype on the outcome of the infection. Several studies have found associations of human genetic polymorphisms with Mtb phylo-lineages, but studies analysing genome-genome interactions are needed. By implementing a phylogenetic tree-based Mtb-to-human analysis for 714 TB patients from Thailand, we identify eight putative genetic interaction points (P < 5 × 10-8) including human loci DAP and RIMS3, both linked to the IFNγ cytokine and host immune system, as well as FSTL5, previously associated with susceptibility to TB. Many of the corresponding Mtb markers are lineage specific. The genome-to-genome analysis reveals a complex interactome picture, supports host-pathogen adaptation and co-evolution in TB, and has potential applications to large-scale studies across many TB endemic populations matched for host-pathogen genomic diversity.
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Mycobacterium tuberculosis , Tuberculosis , Humanos , Estudio de Asociación del Genoma Completo , Filogenia , Tuberculosis/microbiología , Mycobacterium tuberculosis/genética , Genoma , Interacciones Huésped-Patógeno/genéticaRESUMEN
To determine contributions of previously incarcerated persons to tuberculosis (TB) transmission in the community, we performed a healthcare facility-based cohort study of TB patients in Thailand during 2017-2020. We used whole-genome sequencing of Mycobacterium tuberculosis isolates from patients to identify genotypic clusters and assess the association between previous incarceration and TB transmission in the community. We identified 4 large genotype clusters (>10 TB patients/cluster); 28% (14/50) of the patients in those clusters were formerly incarcerated. Formerly incarcerated TB patients were more likely than nonincarcerated patients to be included in large clusters. TB patients within the large genotype clusters were geographically dispersed throughout Chiang Rai Province. Community TB transmission in the community was associated with the presence of formerly incarcerated individuals in Thailand. To reduce the risk for prison-to-community transmission, we recommend TB screening at the time of entry and exit from prisons and follow-up screening in the community.
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Mycobacterium tuberculosis , Tuberculosis , Humanos , Prisiones , Estudios de Cohortes , Tailandia , Tuberculosis/diagnóstico , Mycobacterium tuberculosis/genéticaRESUMEN
Background: There is known to be significant genetic involvement in persistent pulmonary hypertension of the newborn (PPHN), but to date there is not a clear understanding of this situation, and clarifying that involvement would be of considerable assistance in devising effective treatments for the disease. This case-control study was undertaken to search for genetic variants associated with PPHN in the Thai population using a genome-wide association study (GWAS). Methods: A 659,184 single nucleotide polymorphisms from 387 participants (54 PPHN cases and 333 healthy participants) were genotyped across the human genome using an Illumina Asian Screening Array-24 v1.0 BeadChip Array. After quality control, we obtained 443,063 autosomal SNPs for the GWAS analysis. The FaST-LMM and R packages were used for all statistical analyses. Results: For the case-control analysis, the genomic inflation factor (λ) was 1.016, rs149768622 T>C in the first intron of WWC2 gene showed the strongest association with a P value of 3.76E-08 and odds ratio (OR) of 13.24 (95% CI: 3.91-44.78). The variants at the LOC102723906/LOC105377599, CADM4, GPM6A, CIT, RIMBP2, LOC105374510, LOC105375193, PTPRN2, CDK14, and LCORL loci showed suggestive evidence of associations with PPHN (P<1E-05). Conclusions: This GWAS found that rs149768622 T>C in the WWC2 gene was possibly associated with PPHN. However, replication and functional studies are needed to validate this association and further explore the role(s) of the WWC2 gene in PPHN.
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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.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Prueba de COVID-19 , Pandemias , Sistemas de Atención de Punto , Sistemas CRISPR-Cas/genética , Edición GénicaRESUMEN
Due to the widespread Omicron variant of SARS-CoV-2 in Thailand, the effectiveness of COVID-19 vaccines has become a major issue. The primary objective of this study is to examine the real-world effectiveness of COVID-19 vaccines based on secondary data acquired under normal circumstances in a real-world setting, to protect against treatment with invasive ventilation of pneumonia during January to April 2022, a period when Omicron was predominant. We conducted a nationwide test-negative case-control study. The case and control were matched with a ratio of 1:4 in terms of age, date of specimen collection, and hospital collection specimen and the odds ratio was calculated using conditional logistic regression. Overall, there was neither a distinction between mix-and-match regimens and homologous mRNA regimens against severe symptoms, nor was there a decline of the protective effect over the study period. The third and fourth dose boosters with ChAdOx1 nCoV-19 or mRNA vaccines provided high levels of protection against severe outcomes, approximately 87% to 100%, whereas two doses provided a moderate degree (70%). Thus, this study concludes that current national vaccine strategies provide favourable protective benefits against the Omicron variant. All Thais should receive at least two doses, while high-risk or vulnerable groups should be administered at least three doses.
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Between the first case of COVID-19 in January 2020 and the end of 2021, Thailand experienced four waves of the epidemic. The third and fourth waves were caused by the alpha and delta strains from April 2021 to November 2021. Serosurveillance studies provide snapshots of the true scale of the outbreak, including the asymptomatic infections that could not be fully captured by a hospital-based case detection system. We aimed to investigate the distribution of SARs-CoV-2 seroprevalence in unvaccinated adults after the delta wave outbreak. From November to December 2021, we conducted a cross-sectional survey study in 12 public health areas (PHAs) across Thailand. A total of 26,717 blood samples were collected and tested for SARs-CoV-2 antibodies (anti-S IgG) using a qualitative immunoassay. The results showed that seropositive prevalence in this cohort was 1.4% (95% CI: 1.24 to 1.52). The lowest prevalence was in the northern region (PHA 1) and in central Thailand (PHA 3) at 0.4% (95% CI: 0.15 to 0.95), while the highest was in the southern region of Thailand (PHA 12) at 5.8% (95% CI: 4.48 to 7.29). This seropositive prevalence was strikingly lower than the reports from other countries. Our serosurveillance results suggest that the vaccination of unvaccinated groups should be accelerated, especially in the public health areas with the lowest seroprevalence.
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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.
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Tenofovir disoproxil fumarate (TDF) associates with renal tubular dysfunction (RTD) in some people living with HIV (PLWH). We studied clinical and genetic factors associated with RTD in Thai PLWH receiving TDF. RTD was diagnosed in 13 of 65 (20%) patients. The median (interquartile range) age and CD4 cell counts were 43.8 (40.4-50.9) years and 554 (437-716) cells/mm3, respectively. The median duration of TDF use was 46.9 (31.5-54.1) months. Univariate logistic regression demonstrated body mass index (BMI), concomitant use of protease inhibitor (PI), hyperlipidemia, and homozygous C/C SNP rs1059751 of ABCC4 gene as predisposing factors of RTD. In multivariate model, concomitant use of PI [adjusted odds ratio (aOR) 11.39; 95% confidence interval (CI), 1.59- 81.56; P = 0.015], hyperlipidemia (aOR 8.59; 95% CI, 1.46-50.40; P = 0.017), and BMI (aOR 0.76; 95% CI, 0.59-0.98; P = 0.037) remained associated with RTD in patients receiving TDF. PLWH receiving TDF with the presence of these factors should be closely monitored for RTD.
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Fármacos Anti-VIH , Infecciones por VIH , Humanos , Tenofovir/efectos adversos , Fármacos Anti-VIH/efectos adversos , Tailandia/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Factores de RiesgoRESUMEN
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.