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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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Scrub typhus is highly endemic in northern Thailand yet awareness and knowledge are low. We developed a community engagement project to improve awareness in communities at risk of contracting scrub typhus., Methods: We conducted a series of engagement sessions with healthcare workers and community health volunteers so they would, in turn, engage with their communities. We evaluated our activities by assessing the increase in scrub typhus knowledge, using a series of Likert-scale items and open-ended questions. Three to 6 months after the sessions, participants were followed up to collect their experiences training community members., Results: Of 134 participants who took part in eight sessions, 87.3% were community health volunteers. Disease knowledge increased substantially after the sessions and was well maintained for up to 5 mo. Satisfaction was high and, through participant feedback, engagement materials were improved to be more useful to the communities. People with higher education had higher scores and retention., Conclusions: Community engagement was shown to be an effective tool to develop and carry out health-promoting activities in a culturally and context-appropriate manner., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Understanding factors associated with prevalent Mycobacterium tuberculosis infection and prevalent TB disease in household contacts of patients with drug-resistant tuberculosis (TB) may be useful for TB program staff conducting contact investigations., Methods: Using data from a cross-sectional study that enrolled index participants with rifampin-resistant pulmonary TB and their household contacts (HHCs), we evaluated HHCs age ≥15 years for factors associated with two outcomes: Mycobacterium tuberculosis infection and TB disease. Among HHCs who were not already diagnosed with current active TB disease by the TB program, Mycobacterium tuberculosis infection was determined by interferon-gamma release assay (IGRA). TB disease was adjudicated centrally. We fitted logistic regression models using generalized estimating equations., Results: Seven hundred twelve HHCs age ≥15 years enrolled from 279 households in eight high-TB burden countries were a median age of 34 years, 63% female, 22% current smokers and 8% previous smokers, 8% HIV-positive, and 11% previously treated for TB. Of 686 with determinate IGRA results, 471 tested IGRA positive (prevalence 68.8% (95% Confidence Interval: 64.6%, 72.8%)). Multivariable modeling showed IGRA positivity was more common in HHCs aged 25-49 years; reporting prior TB treatment; reporting incarceration, substance use, and/or a period of daily alcohol use in the past 12 months; sharing a sleeping room or more evenings spent with the index participant; living with smokers; or living in a home of materials typical of low socioeconomic status. Forty-six (6.5% (95% Confidence Interval: 4.6%, 9.0%)) HHCs age ≥15 years had prevalent TB disease. Multivariable modeling showed higher prevalence of TB disease among HHCs aged ≥50 years; reporting current or previous smoking; reporting a period of daily alcohol use in the past 12 months; and reporting prior TB treatment., Conclusion: We identified overlapping and distinct characteristics associated with Mycobacterium tuberculosis infection and TB disease that may be useful for those conducting household TB investigations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

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., (© 2023. The Author(s).)

Background: The COPCOV study (chloroquine/ hydroxychloroquine prevention of coronavirus disease), which started recruitment in April 2020, is a multi-country double-blind, randomised, placebo-controlled trial which is being conducted in healthcare facilities involved in COVID-19 case management. Participants are staff employed in facilities managing people with proven or suspected COVID-19. As part of the study, we conducted a series of engagement sessions. The aims were to assess the feasibility of the study, to identify context-specific ethical issues, to understand possible concerns, to fine tune research procedures and to refine the COPCOV information materials. Methods: The COPCOV study was approved by relevant institutional review boards. The sessions described in this paper were part of the study. We conducted a series of engagement sessions, each involving a short presentation of the study, a section where attendees were asked to express their willingness to participate in such a study, which information they would need to change their view and an open Q&A section. Answers were transcribed and coded into themes by two independent investigators. Themes were derived from the data. They complemented other site-specific engagement, communication, and public relation activities such as press releases and websites. Results and conclusions: From 16 th March 2020 to 20 th January 2021, 12 engagement sessions were conducted in Thailand, Laos, Vietnam, Nepal and the UK involving 213 attendees in total. Issues raised revolved around the social value and study rationale; safety of trial medications and risk-benefit balance; study design and commitments. These sessions helped us identify  concerns people had, which helped us refine information materials as well as complement site feasibility assessments. Our experience strongly supports the use of participatory practices prior to conducting clinical trials., Competing Interests: Competing interests: WS, JJC, EAA, SUS, MM, SV, CW, BH, VS, NJW and PYC are investigators or otherwise involved in the COPCOV study; Chloroquine/hydroxychloroquine prevention of coronavirus disease (COVID-19) in the healthcare setting; a randomised, placebo-controlled prophylaxis study (ClinicalTrials.gov; https://clinicaltrials.gov/ct2/show/NCT04303507; 11/03/2021)., (Copyright: © 2022 Perrone C et al.)

In rural areas of South and Southeast Asia malaria is declining but febrile illnesses still account for substantial morbidity and mortality. Village health workers (VHWs) are often the first point of contact with the formal health system, and for patients with febrile illnesses they can provide early diagnosis and treatment of malaria. However, for the majority of febrile patients, VHWs lack the training, support and resources to provide further care. Consequently, treatable bacterial illnesses are missed, antibiotics are overused and poorly targeted, and patient attendance wanes along with declining malaria. This Open Letter announces the start of a new initiative, the Rural Febrile Illness (RFI) project, the first in a series of projects to be implemented as part of the South and Southeast Asian Community-based Trials Network (SEACTN) research programme. This multi-country, multi-site project will run in Bangladesh, Cambodia, Lao PDR, Thailand, and Myanmar. It will define the epidemiological baseline of febrile illness in nine remote and underserved areas of Asia where malaria endemicity is declining and access to health services is limited. The RFI project aims to determine the incidence, causes and outcomes of febrile illness; understand the opportunities, barriers and appetite for adjustment of the role of VHWs to include management of non-malarial febrile illnesses; and establish a network of community healthcare providers and facilities capable of implementing interventions designed to triage, diagnose and treat patients presenting with febrile illnesses within these communities in the future., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Chandna A et al.)

Background: The COPCOV study (chloroquine/ hydroxychloroquine prevention of coronavirus disease), which started recruitment in April 2020, is a multi-country double-blind, randomised, placebo-controlled trial which is being conducted in healthcare facilities involved in COVID-19 case management. COPCOV aims to recruit healthcare workers and other staff employed in facilities managing people with proven or suspected COVID-19. Methods: We conducted a series of engagement sessions, each involving a short presentation of the study, a section where attendees were asked to express if they would be interested in participating in such a study and which information they would need to change their view and an open Q&A section. Answers were transcribed and coded into themes by two independent investigators. Themes were derived from the data. The aims were to assess the feasibility of the study at the respective sites, to identify context-specific ethical issues, to understand concerns potential participants might have, to fine tune research procedures and to refine COPCOV information materials. They complemented other site-specific engagement, communication and public relation activities such as press releases and websites. Results: From 16 th March 2020 to 20 th January 2021, 12 engagement sessions were conducted in Thailand, Laos, Vietnam, Nepal and the UK involving 213 attendees in total. The sessions were designed to encourage potential participants and research professionals not directly involved in the project to interact with those who planned the study and those conducting it. Many attendees were keen to join the study while others had concerns. Questions raised revolved around the social value and study rationale; safety of trial medications and risk-benefit balance; study design and commitments. Conclusions: These sessions helped us refine information materials, identify misunderstandings about the study as well as complement site feasibility assessments. Our experience strongly supports the use of participatory practices prior to conducting clinical trials., Competing Interests: Competing interests: WS, JJC, EAA, SUS, MM, SV, CW, BH, VS, NJW and PYC are investigators or otherwise involved in the COPCOV study; Chloroquine/hydroxychloroquine prevention of coronavirus disease (COVID-19) in the healthcare setting; a randomised, placebo-controlled prophylaxis study (ClinicalTrials.gov; https://clinicaltrials.gov/ct2/show/NCT04303507; 11/03/2021)., (Copyright: © 2021 Perrone C et al.)

Background: Leishmaniasis is an emerging infectious disease reported in the north and south of Thailand of which patients with HIV/AIDS are a high risk group for acquiring the infection. A lack of information regarding prevalence, and the risk association of Leishmania infection among asymptomatic immunocompetent hosts needs further investigation. Information on potential vectors and animal reservoirs in the affected areas is also important to control disease transmission., Methods: An outbreak investigation and a cross-sectional study were conducted following one index case of cutaneous leishmaniasis (CL) caused by L. martiniquensis in an immunocompetent male patient reported in August 2015, Chiang Rai Province, Thailand. From September to November 2015, a total of 392 participants at two study areas who were related to the index case, 130 students at a semi-boarding vocational school and 262 hill tribe villagers in the patient's hometown, were recruited in this study. The nested internal transcribed spacer 1-PCR (ITS1-PCR) was performed to detect Leishmania DNA in buffy coat, and nucleotide sequencing was used to identify species. Antibody screening in plasma was performed using the Direct Agglutination Test (DAT), and associated risk factors were analyzed using a standardized questionnaire. Captured sandflies within the study areas were identified and detected for Leishmania DNA using nested ITS1-PCR. Moreover, the animal reservoirs in the study areas were also explored for Leishmania infection., Results: Of 392 participants, 28 (7.1%) were positive for Leishmania infection of which 1 (4.8%) was L. martiniquensis, 12 (57.1%) were L. orientalis and 8 (38.1%) were Leishmania spp. Of 28, 15 (53.6%) were DAT positive. None showed any symptoms of CL or visceral leishmaniasis. Risk factors were associated with being female (adjusted odds ratio, AOR 2.52, 95%CI 1.01-6.26), increasing age (AOR 1.05, 95%CI 1.02-1.08), having an animal enclosure in a housing area (AOR 3.04, 95%CI 1.13-8.22), being exposed to termite mounds (AOR 3.74, 95%CI 1.11-12.58) and having domestic animals in a housing area (AOR 7.11, 95%CI 2.08-24.37). At the semi-boarding vocational school, six Sergentomyia gemmea samples were PCR positive for DNA of L. orientalis and one S. gemmea was PCR positive for DNA of L. donovani/L. infantum. Additionally, one Phlebotomus stantoni was PCR positive for DNA of L. martiniquensis, and one black rat (Rattus rattus) was PCR positive for DNA of L. martiniquensis., Conclusion: This information could be useful for monitoring Leishmania infection among immunocompetent hosts in affected areas and also setting up strategies for prevention and control. A follow-up study of asymptomatic individuals with seropositive results as well as those with positive PCR results is recommended., Competing Interests: The authors have declared that no competing interests exist.

Whole-genome sequencing (WGS) analysis has great discriminative power for detecting similar molecular fingerprints of suspected tuberculosis (TB) clusters. The proportion of TB cases within clusters and the associated risk factors are important epidemiological parameters guiding appropriate outbreak control strategies in endemic settings. We conducted a hospital-based TB case-cohort study between 2003 and 2011 in the northernmost province of Thailand. We identified TB clusters by Mycobacterium tuberculosis WGS and analysed the risks of TB clustering and the characteristics of large clusters compared with small clusters. Among 1146 TB isolates, we identified 77 clusters with 251 isolates defined by a 5-single-nucleotide variant (SNV) cutoff and 112 clusters with 431 isolates defined by a 12-SNV cutoff. Twelve large clusters with 6 isolates or more in each cluster were identified by a 12-SNV cutoff. Sublineage 2.2.1 (both Ancestral and Modern) strains and imprisonment were independently associated with large clusters. Furthermore, although large clusters of Lineage 2.2.1/Ancestral strains included a high number of prisoners, Lineage 2.2.1/Modern strain clusters were only associated with treatment failures and drug resistance. Heterogeneity among lineage strains was observed with respect to large-cluster characteristics. Patients with an increased TB-transmission tendency should be priority targets for contact investigations and outbreak interventions to prevent ongoing transmission., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Global sodium intake remains above the recommended levels to control blood pressure (BP). We aimed to evaluate the efficacy of a dietary intervention on BP through salt reduction among community-dwelling participants with high risk of cardiovascular disorders (CVD)., Methods: This cluster randomized trial (February 2012 to January 2013) included cooking instruction using the pocket salt meter among patients with diabetes and/or hypertension who were treated at health center in Thailand. Based on health centers, 8 clusters of eligible participants were randomly allocated to the 4 intervention and 4 control groups. Dietary intervention was performed at baseline, 1 month, and 3 months in intervention group. In both groups, systolic and diastolic BPs, and estimated 24 hours salt intake based on overnight urine samples were measured at baseline, 6 months, and 12 months., Results: A total of 753 participants were enrolled (374 in the intervention group and 379 in the control group). In the mixed-effects model, there were significant difference in SBP and estimated salt intake after adjusting covariates at 6 months (adjusted differences between groups [95% CI]; -7.55 [-5.61 to -9.49] mm Hg P  < .01; -0.66 [-0.40 to -0.92] g/day P  = .03). However, these differences were not observed at 12 months (adjusted differences between groups [95% CI]; -1.83 [0.34 to -4.00] mm Hg P  = .48; -0.42 [-0.17 to -0.67] g/day P  = .16). There were no differences in DBP in both follow-ups., Conclusions: These results may suggest the effectiveness of a visually based dietary intervention targeting salt intake reduction in short term, but the effectiveness discontinued in long term.Clinical trial number: The International Standard Randomized Controlled Trial Number Register (ISRCTN39416277) on January 3, 2012., Competing Interests: The authors have no conflicts of interest to declare., (© 2020 The Authors. Journal of General and Family Medicine published by John Wiley & Sons Australia, Ltd on behalf of Japan Primary Care Association.)

Background: Scrub typhus, caused by Orientia tsutsugamushi, is a major cause of acute febrile illness in children in the rural tropics., Methods: We recruited 60 febrile pediatric patients with a positive scrub typhus rapid diagnostic test result and 40 healthy controls from Chiang Rai Province in northern Thailand. Diagnosis was confirmed by the detection of (1) O. tsutsugamushi-specific DNA in blood or eschar samples with a polymerase chain reaction assay, (2) a fourfold rise in immunoglobulin M (IgM) titer to ≥1:3200 in paired plasma samples with an indirect immunofluorescence assay (IFA), or (3) a single IgM titer of ≥1:3200 in an acute plasma sample with an IFA. Demographic, clinical, and laboratory data were collected, and patients were followed up for 1 year., Results: Diagnosis was confirmed in 35 (58%) of 60 patients, and all controls tested negative for scrub typhus. Patients with confirmed scrub typhus had clinical symptoms, including fever (35 of 35 [100%]), eschar (21 of 35 [60%]), cough (21 of 35 [60%]), tachypnea (16 of 35 [46%]), lymphadenopathy (15 of 35 [43%]), and headache (14 of 35 [40%]). Only 4 (11%) of 35 patients received appropriate antibiotic treatment for scrub typhus before admission. The median fever-clearance time was 36 hours (interquartile range, 24-53 hours). Complications observed include hepatitis (9 of 35 [26%]), severe thrombocytopenia (7 of 35 [20%]), pneumonitis (5 of 35 [14%]), circulatory shock (4 of 35 [11%]), and acute respiratory distress syndrome (3 of 35 [9%]). Treatment failure, defined by failure to defervesce within 72 hours of antibiotic treatment initiation, was noted in 8 (23%) of 35 patients, and 1 (3%) of the 35 patients died. No evidence of relapse or reinfection was found., Conclusion: Pediatric scrub typhus in northern Thailand is often severe and potentially fatal with delays in treatment a likely contributing factor. Additional studies to investigate the bacterial, pharmacologic, and immunologic factors related to treatment outcome along with measures to improve public awareness should be prioritized., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

Background: Scrub typhus is a major cause of acute febrile illness in the tropics and is endemic over large areas of the Asia Pacific region. The national and global burden of scrub typhus remains unclear due to limited data and difficulties surrounding diagnosis., Methodology/principal Findings: Scrub typhus reporting data from 2003-2018 were collected from the Thai national disease surveillance system. Additional information including the district, sub-district and village of residence, population, geographical, meteorological and satellite imagery data were also collected for Chiangrai, the province with the highest number of reported cases from 2003-2018. From 2003-2018, 103,345 cases of scrub typhus were reported with the number of reported cases increasing substantially over the observed period. There were more men than women, with agricultural workers the main occupational group affected. The majority of cases occurred in the 15-64 year old age group (72,144/99,543, 72%). Disease burden was greatest in the northern region, accounting for 53% of the total reported cases per year (mean). In the northern region, five provinces-Chiangrai, Chiangmai, Tak, Nan and Mae Hong Son-accounted for 84% (46,927/55,872) of the total cases from the northern region or 45% (46,927/103,345) of cases nationally. The majority of cases occurred from June to November but seasonality was less marked in the southern region. In Chiangrai province, elevation, rainfall, temperature, population size, habitat complexity and diversity of land cover contributed to scrub typhus incidence., Interpretation: The burden of scrub typhus in Thailand is high with disease incidence rising significantly over the last two decades. However, disease burden is not uniform with northern provinces particularly affected. Agricultural activity along with geographical, meteorological and land cover factors are likely to contribute to disease incidence. Our report, along with existing epidemiological data, suggests that scrub typhus is the most clinically important rickettsial disease globally., Competing Interests: We declare no competing interests.

Many microbial species have been recognized as enteropathogens for humans. Here, we predicted the causative agents of acute diarrhea using data from multiplex quantitative PCR (qPCR) assays targeting 19 enteropathogens. For this, a case-control study was conducted at eight hospitals in Thailand. Stool samples and clinical data were collected from 370 hospitalized patients with acute diarrhea and 370 non-diarrheal controls. Multiple enteropathogens were detected in 75.7% and 13.0% of diarrheal stool samples using multiplex qPCR and bacterial culture methods, respectively. Asymptomatic carriers of enteropathogens were found among 87.8% and 45.7% of individuals by qPCR and culture methods, respectively. These results suggested the complexity of identifying causative agents of diarrhea. An analysis using the quantification cut-off values for clinical relevance drastically reduced pathogen-positive stool samples in control subjects from 87.8% to 0.5%, whereas 48.9% of the diarrheal stool samples were positive for any of the 11 pathogens. Among others, rotavirus, norovirus GII, Shigella/EIEC, and Campylobacter were strongly associated with acute diarrhea (P-value < 0.001). Characteristic clinical symptoms, epidemic periods, and age-related susceptibility to infection were observed for some enteropathogens. Investigations based on qPCR approaches covering a broad array of enteropathogens might thus improve our understanding of diarrheal disease etiology and epidemiological trends.

Problem: Despite implementation of universal health coverage in Thailand, gaps remain in the system for screening contacts of tuberculosis patients., Approach: We designed broader criteria for contact investigation and new screening practices and assessed the approach in a programme-based operational research study in 2017-2018. Clinic staff interviewed 100 index patients and asked them to give household and non-household contacts an invitation for a free screening and chest X-ray. Contact persons who attended received 250 Thai baht (about 8 United States dollars) allowance for transport., Local Setting: Chiang Rai province, Thailand, has high rates of tuberculosis notification and a high number of people living in poverty. The coverage of contact investigation in under 5-year-olds was only 33.2% (222 screened out of 668 contacts) over 2011-2015., Relevant Changes: Index patients identified 440 contacts in total and gave invitation cards to 227 of them. The contact investigation coverage was 81.1% (184/227) and tuberculosis detection among contacts screened was 6.0% (11/184). Of the 11 contacts with active tuberculosis, three did not have tuberculosis symptoms, three were non-household contacts and three were contacts of non-smear-positive tuberculosis patients. The contact investigation coverage of the contacts younger than 5 years was 100% (14/14) and the yield of tuberculosis detection in this age group was 21.4% (3/14)., Lessons Learnt: High coverage of contact investigation with a high yield of tuberculosis detection among contacts can be achieved by applying broader criteria for contact investigation and providing financial support for transportation., ((c) 2020 The authors; licensee World Health Organization.)

Pharyngitis is usually caused by a viral infection for which antibiotics are often unnecessarily prescribed, adding to the burden of antimicrobial resistance. Identifying who needs antibiotics is challenging; microbiological confirmation and clinical scores are used but have limitations. In a cross-sectional study nested within a randomized controlled trial, we estimated the prevalence and antibiotic susceptibility profiles of group A Streptococcus (GAS) in patients presenting to primary care with a sore throat and fever in northern Thailand. We then evaluated the use of C-reactive protein (CRP) and clinical scores (Centor and FeverPAIN) to identify the presence of GAS. One hundred sixty-nine patients were enrolled, of whom 35 (20.7%) had β-hemolytic Streptococci (BHS) isolated from throat swab culture, and 11 (6.5%) had GAS. All GAS isolates were sensitive to penicillin G. The median CRP of those without BHS isolation was 10 mg/L (interquartile range [IQR] ≤ 8-18), compared with 18 mg/L (IQR 9-71, P = 0.0302) for those with GAS and 14 mg/L (IQR ≤ 8-38, P = 0.0516) for those with any BHS isolated. However, there were no significant relationships between CRP > 8 mg/L ( P = 0.112), Centor ≥ 3 ( P = 0.212), and FeverPAIN ≥ 4 ( P = 1.000), and the diagnosis of GAS compared with no BHS isolation. Identifying who requires antibiotics for pharyngitis remains challenging and necessitates further larger studies. C-reactive protein testing alone, although imperfect, can reduce prescribing compared with routine care. Targeted CRP testing through clinical scoring may be the most cost-effective approach to ruling out GAS infection.

Background: Medication non-adherence in tuberculosis (TB) patients is an obstacle to TB treatment. Directly observed treatment to monitor and ensure adherence still has some limitations in high TB-burden countries. Most digital adherence technologies emphasize medication-taking reminder functions; however, a bi-directional communication platform to provide patient-health workers with an interface that focuses on enhancing medication adherence is likely to improve medical adherence. A budgeted mobile-based system called CARE-call providing both functions was developed and evaluated concerning whether it could enhance medication adherence. Design: Mixed methods combined quantitative and qualitative approaches. One hundred TB patients were randomized into intervention or control groups. Medication adherence rates between the two groups were compared. A focus group discussion was conducted to obtain in-depth perspectives from the patients. Results: At a 90% adherence level, the number of non-adherence patients in the intervention group was significantly lower than that of the control group (7.5% vs. 27.5%, p = .037). The participants were satisfied with the functions provided by the system, especially the confidentiality of the monitoring process, which did not involve monitoring by imaging or video recording. The bi-directional communication enabled them to contact health staff when concerns arose during the treatment course. Poor mobile phone signals and fast battery drain were reported as major technical problems of the system. Conclusions: The CARE-call system was able to prevent non-adherence in this rural setting in Thailand. However, further investigation with a larger sample size should be conducted on whether the system can also improve successful TB treatment outcome.

Background: Household contacts (HHCs) of individuals with multidrug-resistant tuberculosis (MDR-TB) are at high risk of infection and subsequent disease. There is limited evidence on the willingness of MDR-TB HHCs to take MDR-TB preventive therapy (MDR TPT) to decrease their risk of TB disease., Methods: In this cross-sectional study of HHCs of MDR-TB and rifampicin-resistant tuberculosis (RR-TB) index cases from 16 clinical research sites in 8 countries, enrollees were interviewed to assess willingness to take a hypothetical, newly developed MDR TPT if offered. To identify factors associated with willingness to take MDR TPT, a marginal logistic model was fitted using generalized estimating equations to account for household-level clustering., Results: From 278 MDR-TB/RR-TB index case households, 743 HHCs were enrolled; the median age of HHCs was 33 (interquartile range, 22-49) years, and 62% were women. HHC willingness to take hypothetical MDR TPT was high (79%) and remained high even with the potential for mild side effects (70%). Increased willingness was significantly associated with current employment or schooling (adjusted odds ratio [aOR], 1.83 [95% confidence interval {CI}, 1.07-3.13]), appropriate TB-related knowledge (aOR, 2.22 [95% CI, 1.23-3.99]), confidence in taking MDR TPT (aOR, 7.16 [95% CI, 3.33-15.42]), and being comfortable telling others about taking MDR TPT (aOR, 2.29 [95% CI, 1.29-4.06])., Conclusions: The high percentage of HHCs of MDR-TB/RR-TB index cases willing to take hypothetical MDR TPT provides important evidence for the potential uptake of effective MDR TPT when implemented. Identified HHC-level variables associated with willingness may inform education and counseling efforts to increase HHC confidence in and uptake of MDR TPT., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: We assessed multidrug-resistant tuberculosis (MDR-TB) cases and their household contacts (HHCs) to inform the development of an interventional clinical trial., Methods: We conducted a cross-sectional study of adult MDR-TB cases and their HHCs in 8 countries with high TB burdens. HHCs underwent symptom screenings, chest radiographies, sputum TB bacteriologies, TB infection (TBI) testing (tuberculin skin test [TST] and interferon gamma release assay [IGRA]), and human immunodeficiency virus (HIV) testing., Results: From October 2015 to April 2016, 1016 HHCs from 284 MDR-TB cases were enrolled. At diagnosis, 69% of MDR-TB cases were positive for acid-fast bacilli sputum smears and 43% had cavitary disease; at study entry, 35% remained smear positive after a median MDR-TB treatment duration of 8.8 weeks. There were 9 HHCs that were diagnosed with TB prior to entry and excluded. Of the remaining 1007 HHCs, 41% were male and the median age was 25 years. There were 121 (12%) HHCs that had new cases of TB identified: 17 (2%) were confirmed, 33 (3%) probable, and 71 (7%) possible TB cases. The TBI prevalence (defined as either TST or IGRA positivity) was 72% and varied by age, test used, and country. Of 1007 HHCs, 775 (77%) were considered high-risk per these mutually exclusive groups: 102 (10%) were aged <5 years; 63 (6%) were aged ≥5 and were infected with HIV; and 610 (61%) were aged ≥5 years, were negative for HIV or had an unknown HIV status, and were TBI positive. Only 21 (2%) HHCs were on preventive therapy., Conclusions: The majority of HHCs in these high-burden countries were at high risk of TB disease and infection, yet few were receiving routine preventive therapy. Trials of novel, preventive therapies are urgently needed to inform treatment policy and practice., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Global Mycobacterium tuberculosis population comprises 7 major lineages. The Beijing strains, particularly the ones classified as Modern groups, have been found worldwide, frequently associated with drug resistance, younger ages, outbreaks and appear to be expanding. Here, we report analysis of whole genome sequences of 1170 M. tuberculosis isolates together with their patient profiles. Our samples belonged to Lineage 1-4 (L1-L4) with those of L1 and L2 being equally dominant. Phylogenetic analysis revealed several new or rare sublineages. Differential associations between sublineages of M. tuberculosis and patient profiles, including ages, ethnicity, HIV (human immunodeficiency virus) infection and drug resistance were demonstrated. The Ancestral Beijing strains and some sublineages of L4 were associated with ethnic minorities while L1 was more common in Thais. L2.2.1.Ancestral 4 surprisingly had a mutation that is typical of the Modern Beijing sublineages and was common in Akha and Lahu tribes who have migrated from Southern China in the last century. This may indicate that the evolutionary transition from the Ancestral to Modern Beijing sublineages might be gradual and occur in Southern China, where the presence of multiple ethnic groups might have allowed for the circulations of various co-evolving sublineages which ultimately lead to the emergence of the Modern Beijing strains.

SETTING: This study was conducted among tuberculosis (TB) patients in a highly endemic Thai province. OBJECTIVE: To evaluate the association between different Mycobacterium tuberculosis lineages and clinical characteristics, especially mortality. DESIGN: We enrolled 1,304 TB patients registered from 2002-2011 with culture isolates whose lineages were identified by specific regions of deletion. Data on mortality within 1 year of follow-up were extracted from the registration system and hospital records. Mortality-associated risk factors, including bacterial lineages, as independent variables were analysed using Cox regression models. RESULTS: Of 1,304 isolates, 521 (40.0%) and 582 (44.6%) belonged to Indo-Oceanic and East-Asian lineages, respectively. Indo-Oceanic strains significantly increased the mortality risk compared with East-Asian strains (adjusted hazard ratio [aHR] 1.42, 95%CI 1.02-1.99) or modern lineages (aHR 1.49, 95%CI 1.08-2.06) in the 172 patients who died within 1 year after TB diagnosis. The former also caused significantly higher mortality than modern lineages among patients who died within 6 months after TB diagnosis (aHR 1.62, 95%CI 1.12-2.35). No significant association was found between drug resistance and death. CONCLUSION: In Thailand, the Indo-Oceanic lineage of M. tuberculosis increased mortality risk compared with modern lineages or the East-Asian lineage, the latter being considered highly virulent in previous studies.

Introduction: Low-income and middle-income countries (LMICs) are crucial in the global response to antimicrobial resistance (AMR), but diverse health systems, healthcare practices and cultural conceptions of medicine can complicate global education and awareness-raising campaigns. Social research can help understand LMIC contexts but remains under-represented in AMR research., Objective: To (1) Describe antibiotic-related knowledge, attitudes and practices of the general population in two LMICs. (2) Assess the role of antibiotic-related knowledge and attitudes on antibiotic access from different types of healthcare providers., Design: Observational study: cross-sectional rural health behaviour survey, representative of the population level., Setting: General rural population in Chiang Rai (Thailand) and Salavan (Lao PDR), surveyed between November 2017 and May 2018., Participants: 2141 adult members (≥18 years) of the general rural population, representing 712 000 villagers., Outcome Measures: Antibiotic-related knowledge, attitudes and practices across sites and healthcare access channels., Findings: Villagers were aware of antibiotics (Chiang Rai: 95.7%; Salavan: 86.4%; p<0.001) and drug resistance (Chiang Rai: 74.8%; Salavan: 62.5%; p<0.001), but the usage of technical concepts for antibiotics was dwarfed by local expressions like 'anti-inflammatory medicine' in Chiang Rai (87.6%; 95% CI 84.9% to 90.0%) and 'ampi' in Salavan (75.6%; 95% CI 71.4% to 79.4%). Multivariate linear regression suggested that attitudes against over-the-counter antibiotics were linked to 0.12 additional antibiotic use episodes from public healthcare providers in Chiang Rai (95% CI 0.01 to 0.23) and 0.53 in Salavan (95% CI 0.16 to 0.90)., Conclusions: Locally specific conceptions and counterintuitive practices around antimicrobials can complicate AMR communication efforts and entail unforeseen consequences. Overcoming 'knowledge deficits' alone will therefore be insufficient for global AMR behaviour change. We call for an expansion of behavioural AMR strategies towards 'AMR-sensitive interventions' that address context-specific upstream drivers of antimicrobial use (eg, unemployment insurance) and complement education and awareness campaigns., Trial Registration Number: Clinicaltrials.gov identifier NCT03241316., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Antituberculosis drug-induced liver injury (ATDILI) is a common side effect leading to tuberculosis (TB) treatment disruption. The mechanism of the disease remains poorly understood. We conducted a genomewide association study (GWAS) to investigate all possible genetic factors of ATDILI in Thai patients. This study was carried out in Thai TB patients, including 79 ATDILI cases and 239 tolerant controls from our network hospitals in Thailand. Nearly 1 million single-nucleotide polymorphisms (SNPs) were genotyped across the whole genome using an Illumina OmniExpress Exome BeadChip array. In the discovery stage, we identified strong association signals on chromosome 8 originating from the N -acetyltransferase ( NAT2 ) region. The A allele of rs1495741, the top SNP in the intergenic region of NAT2 and PSD3 (14 kb from NAT2 ), was significantly associated with ATDILI (recessive model, odds ratio of 6.01 [95% confidence interval, 3.42 to 10.57]; P  = 6.86E-11). This particular SNP was reported as a tag SNP for NAT2 inferred phenotypes. The AA, AG, and GG genotypes represented NAT2 slow acetylators, intermediate acetylators, and fast acetylators, respectively. The tag SNP genotypes demonstrated a concordance rate of 94.98% with NAT2 acetylator phenotypes. This GWAS shows that NAT2 is the most important risk factor for ATDILI in the Thai population., (Copyright © 2019 American Society for Microbiology.)

Background: In southeast Asia, antibiotic prescription in febrile patients attending primary care is common, and a probable contributor to the high burden of antimicrobial resistance. The objective of this trial was to explore whether C-reactive protein (CRP) testing at point of care could rationalise antibiotic prescription in primary care, comparing two proposed thresholds to classify CRP concentrations as low or high to guide antibiotic treatment., Methods: We did a multicentre, open-label, randomised, controlled trial in participants aged at least 1 year with a documented fever or a chief complaint of fever (regardless of previous antibiotic intake and comorbidities other than malignancies) recruited from six public primary care units in Thailand and three primary care clinics and one outpatient department in Myanmar. Individuals were randomly assigned using a computer-based randomisation system at a ratio of 1:1:1 to either the control group or one of two CRP testing groups, which used thresholds of 20 mg/L (group A) or 40 mg/L CRP (group B) to guide antibiotic prescription. Health-care providers were masked to allocation between the two intervention groups but not to the control group. The primary outcome was the prescription of any antibiotic from day 0 to day 5 and the proportion of patients who were prescribed an antibiotic when CRP concentrations were above and below the 20 mg/L or 40 mg/L thresholds. The primary outcome was analysed in the intention-to-treat and per-protocol populations. The trial is registered with ClinicalTrials.gov, number NCT02758821, and is now completed., Findings: Between June 8, 2016, and Aug 25, 2017, we recruited 2410 patients, of whom 803 patients were randomly assigned to CRP group A, 800 to CRP group B, and 807 to the control group. 598 patients in CRP group A, 593 in CRP group B, and 767 in the control group had follow-up data for both day 5 and day 14 and had been prescribed antibiotics (or not) in accordance with test results (per-protocol population). During the trial, 318 (39%) of 807 patients in the control group were prescribed an antibiotic by day 5, compared with 290 (36%) of 803 patients in CRP group A and 275 (34%) of 800 in CRP group B. The adjusted odds ratio (aOR) of 0·80 (95% CI 0·65-0·98) and risk difference of -5·0 percentage points (95% CI -9·7 to -0·3) between group B and the control group were significant, although lower than anticipated, whereas the reduction in prescribing in group A compared with the control group was not significant (aOR 0·86 [0·70-1·06]; risk difference -3·3 percentage points [-8·0 to 1·4]). Patients with high CRP concentrations in both intervention groups were more likely to be prescribed an antibiotic than in the control group (CRP ≥20 mg/L: group A vs control group, p<0·0001; CRP ≥40 mg/L: group B vs control group, p<0·0001), and those with low CRP concentrations were more likely to have an antibiotic withheld (CRP <20 mg/L: group A vs control group, p<0·0001; CRP <40 mg/L: group B vs control group, p<0·0001). 24 serious adverse events were recorded, consisting of 23 hospital admissions and one death, which occurred in CRP group A. Only one serious adverse event was thought to be possibly related to the study (a hospital admission in CRP group A)., Interpretation: In febrile patients attending primary care, testing for CRP at point of care with a threshold of 40 mg/L resulted in a modest but significant reduction in antibiotic prescribing, with patients with high CRP being more likely to be prescribed an antibiotic, and no evidence of a difference in clinical outcomes. This study extends the evidence base from lower-income settings supporting the use of CRP tests to rationalise antibiotic use in primary care patients with an acute febrile illness. A key limitation of this study is the individual rather than cluster randomised study design which might have resulted in contamination between the study groups, reducing the effect size of the intervention., Funding: Wellcome Trust Institutional Strategic Support Fund grant (105605/Z/14/Z) and Foundation for Innovative New Diagnostics (FIND) funding from the Australian Government., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Setting: The household contacts (HHCs) of multidrug-resistant tuberculosis (MDR-TB) index cases are at high risk of tuberculous infection and disease progression, particularly if infected with the human immunodeficiency virus (HIV). HIV testing is important for risk assessment and clinical management., Methods: This was a cross-sectional, multi-country study of adult MDR-TB index cases and HHCs. All adult and child HHCs were offered HIV testing if never tested or if HIV-negative >1 year previously when last tested. We measured HIV testing uptake and used logistic regression to evaluate predictors., Results: A total of 1007 HHCs of 284 index cases were enrolled in eight countries. HIV status was known at enrolment for 226 (22%) HHCs; 39 (4%) were HIV-positive. HIV testing was offered to 769 (98%) of the 781 remaining HHCs; 544 (71%) agreed to testing. Of 535 who were actually tested, 26 (5%) were HIV-infected. HIV testing uptake varied by site (median 86%, range 0-100%; P < 0.0001), and was lower in children aged <18 years than in adults (59% vs. 78%; adjusted for site P < 0.0001)., Conclusions: HIV testing of HHCs of MDR-TB index cases is feasible and high-yield, with 5% testing positive. Reasons for low test uptake among children and at specific sites-including sites with high HIV prevalence-require further study to ensure all persons at risk for HIV are aware of their status.

Tuberculosis presents a global health challenge. Mycobacterium tuberculosis is divided into several lineages, each with a different geographical distribution. M. tuberculosis lineage 1 (L1) is common in the high-burden areas in East Africa and Southeast Asia. Although the founder effect contributes significantly to the phylogeographic profile, co-evolution between the host and M. tuberculosis may also play a role. Here, we reported the genomic analysis of 480 L1 isolates from patients in northern Thailand. The studied bacterial population was genetically diverse, allowing the identification of a total of 18 sublineages distributed into three major clades. The majority of isolates belonged to L1.1 followed by L1.2.1 and L1.2.2. Comparison of the single nucleotide variant (SNV) phylogenetic tree and the clades defined by spoligotyping revealed some monophyletic clades representing EAI2&#95;MNL, EAI2&#95;NTM and EAI6&#95;BGD1 spoligotypes. Our work demonstrates that ambiguity in spoligotype assignment could be partially resolved if the entire DR region is investigated. Using the information to map L1 diversity across Southeast Asia highlighted differences in the dominant strain-types in each individual country, despite extensive interactions between populations over time. This finding supported the hypothesis that there is co-evolution between the bacteria and the host, and have implications for tuberculosis disease control.

Introduction: Antibiotic use in low-income and middle-income countries continues to rise despite the knowledge that antibiotic overuse can lead to antimicrobial resistance. There is a paucity of detailed data on the use of antibiotics in primary care in low-resource settings., Objective: To describe the presentation of acute infections and the indications for antibiotic prescription., Design: A 2-year retrospective review of routinely collected data., Setting: All 32 primary care units in one district in northern Thailand., Participants: Patients attending primary care with a history of fever, documented temperature, International Statistical Classification of Diseases 10 code for infection or prescribed a systemic antibiotic. Patients attending after the initiation of a study on C-reactive protein testing in four centres were excluded., Outcome Measures: The proportion of patients prescribed an antibiotic and the frequency of clinical presentations., Results: 762 868 patients attended the health centres, of whom 103 196 met the inclusion criteria, 5966 were excluded resulting in 97 230 attendances consisting of 83 661 illness episodes.46.9% (39 242) of the patients were prescribed an antibiotic during their illness. Indications for antibiotic prescription in the multivariable logistic regression analysis included male sex (adjusted OR (aOR) 1.21 (95% CI 1.16 to 1.28), p<0.001), adults (aOR 1.77 (95% CI 1.57 to 2), p<0.001) and a temperature >37.5°C (aOR 1.24 (95% CI 1.03 to 1.48), p=0.020). 77.9% of the presentations were for respiratory-related problems, of which 98.6% were upper respiratory tract infections. The leading infection diagnoses were common cold (50%), acute pharyngitis (18.9%) and acute tonsillitis (5%) which were prescribed antibiotics in 10.5%, 88.7% and 87.1% of cases, respectively. Amoxicillin was the most commonly prescribed antibiotic., Conclusions: Nearly half of the patients received an antibiotic, the majority of whom had a respiratory infection. The results can be used to plan interventions to improve the rational use of antibiotics. Further studies in private facilities, pharmacies and dental clinics are required., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.)

Background: Antimicrobial resistance (AMR) is a global health priority. Leading UK and global strategy papers to fight AMR recognise its social and behavioural dimensions, but current policy responses to improve the popular use of antimicrobials (eg, antibiotics) are limited to education and awareness-raising campaigns. In response to conceptual, methodological and empirical weaknesses of this approach, we study people's antibiotic-related health behaviour through three research questions.RQ1: What are the manifestations and determinants of problematic antibiotic use in patients' healthcare-seeking pathways?RQ2: Will people's exposure to antibiotic awareness activities entail changed behaviours that diffuse or dissipate within a network of competing healthcare practices?RQ3: Which proxy indicators facilitate the detection of problematic antibiotic behaviours across and within communities?, Methods: We apply an interdisciplinary analytical framework that draws on the public health, medical anthropology, sociology and development economics literature. Our research involves social surveys of treatment-seeking behaviour among rural dwellers in northern Thailand (Chiang Rai) and southern Lao PDR (Salavan). We sample approximately 4800 adults to produce district-level representative and social network data. Additional 60 cognitive interviews facilitate survey instrument development and data interpretation. Our survey data analysis techniques include event sequence analysis (RQ1), multilevel regression (RQ1-3), social network analysis (RQ2) and latent class analysis (RQ3)., Discussion: Social research in AMR is nascent, but our unprecedentedly detailed data on microlevel treatment-seeking behaviour can contribute an understanding of behaviour beyond awareness and free choice, highlighting, for example, decision-making constraints, problems of marginalisation and lacking access to healthcare and competing ideas about desirable behaviour., Trial Registration Number: NCT03241316; Pre-results.

Tuberculosis (TB) is known to be affected by host genetic factors. We reported a specific genetic risk factor through a genome-wide association study (GWAS) that focused on young age onset TB. In this study, we further focused on the heterogeneity of Mycobacterium tuberculosis (M. tb) lineages and assessed its possible interaction with age at onset on host genetic factors. We identified the pathogen lineage in 686 Thai TB cases and GWAS stratified by both infected pathogen lineage information and age at onset revealed a genome-wide significant association of one single-nucleotide polymorphism (SNP) on chromosome 1p13, which was specifically associated with non-Beijing lineage-infected old age onset cases (P=2.54E-08, OR=1.74 (95% CI=1.43-2.12)), when we compared them to the population-matched healthy controls. This SNP locates near the CD53 gene, which encodes a leukocyte surface glycoprotein. Interestingly, the expression of CD53 was also correlated with the patients' active TB status. This is the first report of a pathogen lineage-based genome-wide association study. The results suggested that host genetic risk in TB is depended upon the pathogen genetic background and demonstrate the importance of analyzing the interaction between host and pathogen genomes in TB.

Tuberculosis (TB) occurs as a result of complex interactions between the host immune system and pathogen virulence factors. Human leukocyte antigen (HLA) class II molecules play an important role in the host immune system. However, no study has assessed the association between HLA class II genes and susceptibility to TB caused by specific strains. This study investigated the possible association of HLA class II genes with TB caused by modern and ancient Mycobacterium tuberculosis (MTB). The study included 682 patients with TB and 836 control subjects who were typed for HLA-DRB1 and HLA-DQB1 alleles. MTB strains were classified using a large sequence polymorphism typing method. Association analysis was performed using common HLA alleles and haplotypes in different MTB strains. HLA association analysis of patients infected with modern MTB strains showed significant association for HLA-DRB1*09:01 (odds ratio [OR] = 1.82; P-value = 9.88 × 10 -4 ) and HLA-DQB1*03:03 alleles (OR = 1.76; P-value = 1.31 × 10 -3 ) with susceptibility to TB. Haplotype analysis confirmed that these alleles were in strong linkage disequilibrium and did not exert an interactive effect. Thus, the results of this study showed an association between HLA class II genes and susceptibility to TB caused by modern MTB strains, suggesting the importance of strain-specific analysis to determine susceptibility genes associated with TB., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Anti-tuberculosis drug-induced liver injury (AT-DILI) is one of the most common forms of drug-induced liver injury (DILI) in high tuberculosis (TB) burden countries. Among anti-tuberculosis drugs, isoniazid is the main cause of hepatotoxicity in patients with AT-DILI., Objective: To investigate the association of AT-DILI with N-acetyltransferase 2 (NAT2) genotype status in Thai TB patients., Methods: We enrolled 53 patients diagnosed with AT-DILI and 85 patients who tolerated anti-tuberculosis treatment as controls. Acetylator status was determined based on the inferred NAT2 haplotypes from four common single-nucleotide polymorphisms (SNPs) in Thais using Sanger sequencing., Results: Phenotype frequencies of the NAT2 acetylator in AT-DILI patients were respectively 71.7%, 22.6% and 5.7% for slow, intermediate and rapid acetylators. Among slow, intermediate, and rapid acetylators in treatment tolerant controls, phenotype frequencies were respectively 22.4%, 62.4% and 15.3%. Slow NAT2 acetylators demonstrated a significant association with risk of AT-DILI. The odds ratio of comparing slow NAT2 acetylator in DILI patients and tolerance was 8.80 (95%CI 4.01-19.31, P = 1.53 × 10 -8 )., Conclusions: Slow acetylator status in the NAT2 genotype is a significant risk factor for DILI in Thai patients with TB. This evidence provides confirmatory data in support of the role of NAT2 in AT-DILI in the Thai population.

This cross-sectional study (February 2012 to March 2013) was conducted to estimate daily salt intake and basic characteristics among 793 community-dwelling participants at high risk of cardiovascular disease (Framingham risk score >15%), who had visited diabetes or hypertension clinics at health centres in the Muang district, Chiang Rai, Thailand. We performed descriptive analysis of baseline data and used an automated analyser to estimate the average of 24-hour salt intake estimated from 3 days overnight urine collection. Participants were divided into two groups based on median estimated daily salt intake. Mean age and proportion of males were 65.2 years and 37.6% in the higher salt intake group (>=10.0 g/day, n=362), and 67.5 years and 42.7% in the lower salt intake group (<10.0 g/day, n=431), respectively (p=0.01, p<0.01). The higher salt intake group comprised more patients with a family history of hypertension, antihypertensive drug use, less ideal body mass index (18.5-24.9), higher exercise frequency (>=2 times weekly) and lower awareness of high salt intake. Among higher salt intake participants, those with lower awareness of high salt intake were younger and more often had a family history of hypertension, relative to those with more awareness. Our data indicated that families often share lifestyles involving high salt intake, and discrepancies between actual salt intake and awareness of high salt intake may represent a need for salt reduction intervention aiming at family level. Awareness of actual salt intake should be improved for each family.

Tuberculosis (TB) is a major global health problem. Routine laboratory tests or newly developed molecular detection are limited to the quality of sputum sample. Here we selected genes specific to TB by a minimum redundancy-maximum relevancy package using publicly available microarray data and determine level of selected genes in blood collected from a Thai TB cohort of 40 active TB patients, 38 healthy controls and 18 previous TB patients using quantitative real-time PCR. FCGR1A, FCGR1B variant 1, FCGR1B variant 2, APOL1, GBP5, PSTPIP2, STAT1, KCNJ15, MAFB and KAZN had significantly higher expression level in active TB individuals as compared with healthy controls and previous TB cases (P<0.01). A mathematical method was applied to calculate TB predictive score, which contains the level of expression of seven genes and this score can identify active TB cases with 82.5% sensitivity and 100% specificity as compared with conventional culture confirmation. In addition, TB predictive scores in active TB patients were reduced to normal after completion of standard short-course therapy, which was mostly in concordant with the disease outcome. These finding suggested that blood gene expression measurement and TB Sick Score could have potential value in terms of diagnosis of TB and anti-TB treatment monitoring.

There is an urgent need for simple, rapid, and affordable diagnostic tests for tuberculosis (TB) to combat the great burden of the disease in developing countries. The microscopic observation drug susceptibility assay (MODS) is a promising tool to fill this need, but it is not widely used due to concerns regarding its biosafety and efficiency. This study evaluated the automated MODS (Auto-MODS), which operates on principles similar to those of MODS but with several key modifications, making it an appealing alternative to MODS in resource-limited settings. In the operational setting of Chiang Rai, Thailand, we compared the performance of Auto-MODS with the gold standard liquid culture method in Thailand, mycobacterial growth indicator tube (MGIT) 960 plus the SD Bioline TB Ag MPT64 test, in terms of accuracy and efficiency in differentiating TB and non-TB samples as well as distinguishing TB and multidrug-resistant (MDR) TB samples. Sputum samples from clinically diagnosed TB and non-TB subjects across 17 hospitals in Chiang Rai were consecutively collected from May 2011 to September 2012. A total of 360 samples were available for evaluation, of which 221 (61.4%) were positive and 139 (38.6%) were negative for mycobacterial cultures according to MGIT 960. Of the 221 true-positive samples, Auto-MODS identified 212 as positive and 9 as negative (sensitivity, 95.9%; 95% confidence interval [CI], 92.4% to 98.1%). Of the 139 true-negative samples, Auto-MODS identified 135 as negative and 4 as positive (specificity, 97.1%; 95% CI, 92.8% to 99.2%). The median time to culture positivity was 10 days, with an interquartile range of 8 to 13 days for Auto-MODS. Auto-MODS is an effective and cost-sensitive alternative diagnostic tool for TB diagnosis in resource-limited settings., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Problem: The 2008 tuberculosis (TB) surveillance of Chiang Rai Hospital, Chiang Rai, Thailand reported that 8.4% of Thai, 22.7% of hill tribe minority and 25% of migrant patients (n = 736) defaulted from treatment., Context: TB patient management in Chiang Rai is complicated due to poverty and HIV stigma. A previous study shows unaffordable travel expense was one of the reasons of patient default., Action: We engaged Chiang Rai women's organizations whose members are of high socioeconomic status to support poor TB patients financially and socially. A group of women formed a team to support these TB patients (n = 192) by raising and sustaining funds and providing home visits (n = 37). TB surveillance and patient-fund register data were used to evaluate TB treatment outcomes., Outcome: THE SUCCESS OF TB TREATMENT WAS SIGNIFICANTLY HIGHER FOR PATIENTS RECEIVING FINANCIAL SUPPORT (RELATIVE RISK [RR]: 1.351; 95% confidence interval [CI] 1.20-1.53; P < 0.000). Lower death rates in all groups were observed among patients receiving financial support. However, financial assistance alone did not improve treatment outcomes for migrant patients. Thirty-seven patients (25 Thai, eight hill tribe, four migrants) who were visited by women volunteers at home achieved 95% TB treatment success., Discussion: It is possible to involve volunteers to support poor TB patients. Willingness to support TB patients was driven by presenting provincial TB epidemiology information, research data on the experience of poor patients and the inspiring experiences of other women volunteers. Future research should investigate the reasons for the high treatment success among patients who received home visits.

Background: Decreasing salt consumption can prevent cardiovascular diseases (CVD). Practically, it is difficult to promote people's awareness of daily salt intake and to change their eating habits in terms of reducing salt intake for better cardiovascular health. Health education programs visualizing daily dietary salt content and intake may promote lifestyle changes in patients at high risk of cardiovascular diseases., Methods/design: This is a cluster randomized trial. A total of 800 high-CVD-risk patients attending diabetes and hypertension clinics at health centers in Muang District, Chiang Rai province, Thailand, will be studied with informed consent. A health center recruiting 100 participants is a cluster, the unit of randomization. Eight clusters will be randomized into intervention and control arms and followed up for 1 year. Within the intervention clusters the following will be undertaken: (1) salt content in the daily diet will be measured and shown to study participants; (2) 24-hour salt intake will be estimated in overnight-collected urine and the results shown to the participants; (3) a dietician will assist small group health education classes in cooking meals with less salt. The primary outcome is blood pressure change at the 1-year follow-up. Secondary outcomes at the 1-year follow-up are estimated 24-hoursalt intake, incidence of CVD events and CVD death. The intention-to-treat analysis will be followed.Blood pressure and estimated 24-hour salt intake will be compared between intervention and control groups at the cluster and individual level at the 1-year follow-up. Clinical CVD events and deaths will be analyzed by time-event analysis. Retinal blood vessel calibers of CVD-risk patients will be assessed cross-sectionally. Behavioral change to reduce salt intake and the influencing factors will be determined by structured equation model (SEM). Multilevel regression analyses will be applied. Finally, the cost effectiveness of the intervention will be analyzed., Discussion: This study is unique as it will recruit the individuals most vulnerable to CVD morbidity and mortality by applying the general Framingham CVD risk scoring system. Dietary salt reduction will be applied as a prioritized, community level intervention for the prevention of CVD in a developing country., Trial Registration: ISRCTN39416277.

Background and Setting: Thailand is one of the highest tuberculosis (TB)-burdened countries. Chiang Rai, the northernmost province of Thailand has high tuberculosis and human immunodeficiency virus (HIV) prevalence and the laboratory workload for TB culture and drug susceptibility testing is increasing., Objectives: To evaluate the simply modified microscopic-observation drug-susceptibility assay (MODS) in the setting of a developing country., Methods: In this cross-sectional diagnostic study, a total of 202 sputum samples of clinically diagnosed TB patients were used to test the performance of MODS assay in reference to gold standard BACTEC™ MGIT™ 960 liquid culture system and Ogawa solid culture. Sputum samples were collected from clinically diagnosed TB patients. Culture growth rate and time to culture positivity were compared among three methods. Performance of modified MODS assay was evaluated for detection of mycobacterium drug resistance in reference to MGIT antimicrobial susceptibility test (AST)., Result: Median time to culture positivity by MODS, solid, and liquid culture were 12, 30, and 6 days respectively. Compared to the drug susceptibility test (DST) result of reference liquid culture, the sensitivity and specificity of MODS for detection of multidrug-resistant tuberculosis (MDR-TB) was 85.7% and 97.5% respectively. MODS assay has a positive predicative value of 80% and negative predictive value of 96.5% for isoniazid resistance, 70% and 100% for rifampicin resistance, and 66.7% and 99.1% for MDR-TB., Conclusion: MODS is a highly effective screening test for detection of MDR-TB.

Purpose: Northern Thailand is a tuberculosis (TB) endemic area with a high TB death rate. We aimed to establish the time of highest death risk during TB treatment, and to identify the risk factors taking place during that period of high risk., Patients and Methods: We explored the TB surveillance data of the Chiang Rai province, Northern Thailand, retrospectively for 12 years. A total of 19,174 TB patients (including 5,009 deaths) were investigated from 1997 to 2008, and the proportion of deaths in each month of TB treatment was compared. Furthermore, multiple logistic regression analysis was performed to identify the characteristics of patients who died in the first month of TB treatment. A total of 5,626 TB patients from 2005 to 2008 were included in this regression analysis., Result: The numbers of deaths in the first month of TB treatment were 38%, 39%, and 46% in the years 1997-2000, 2001-2004, and 2005-2008, respectively. The first month of TB treatment is the time of the maximum number of deaths. Moreover, advancing age, HIV infection, and being a Thai citizen were significant factors contributing to these earlier deaths in the course of TB treatment., Conclusion: Our findings have pointed to the specific time period and patients at higher risk for TB death. These findings would be useful for prioritizing interventions in order to diminish TB-related deaths globally. Studies based on these findings are necessary for the introduction of newer intervention strategies.

Objective: To determine liver cancer trends in Sa Kaeo Province, Thailand., Methods: Death certificate (1993-2003) and hospital records (1999-2003) were reviewed and compared to national averages and other provinces., Results: According to data from death certificates, liver cancer mortality in Sa Kaeo Province increased from 3.1 to 26.1 per 100,000 population between 1993 and 2003. In Thailand overall rates increased from 9.0 to 19.8 per 100,000 population between 1996 and 2003. According to electronic hospital records, the total number of patient encounters (in-patient admissions and out-patient visits) for liver cancer in the two main hospitals in Sa Kaeo Province increased 56% (14% annually) between 1999 and 2003. The number of cases of hepatocellular carcinoma increased from 42 in 2001 to 73 in 2003, while the number of cases of cholangiocarcinoma showed little change., Conclusions: Thailand as a whole and Sa Kaeo Province specifically have a high burden of liver cancer, which appears to have increased substantially in the past 10 years. Demonstrating the impact of ongoing strategies aimed at reducing risk factors for liver cancer, such as universal hepatitis B vaccination of infants, will require reliable data describing liver cancer disease burden and etiology. Rapid investigations using available data from death certificates, electronic admissions records, and patient charts can provide valuable insights on disease burden and trends.

We studied the risk factors for default in isoniazid preventative therapy (IPT) against tuberculosis in 412 people living with HIV (PLWH) in Mae Chan Hospital, Thailand. Default rates decreased from 57% in 1995 to 17% in 1999. Female sex, residence inside Mae Chan District, and registered in the PLWH group at enrollment of IPT were associated with lower default rates. The integration of IPT into the PLWH day care centre activities over the years might contribute to improvements.