Community engagement around scrub typhus in northern Thailand: a pilot project.

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.

Factors associated with prevalent Mycobacterium tuberculosis infection and disease among adolescents and adults exposed to rifampin-resistant tuberculosis in the household.

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.

Genome-wide host-pathogen analyses reveal genetic interaction points in tuberculosis disease.

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.

Risk for Prison-to-Community Tuberculosis Transmission, Thailand, 2017-2020.

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.

Prevalence and associated risk factors of Leishmania infection among immunocompetent hosts, a community-based study in Chiang Rai, Thailand.

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.

An impact of dietary intervention on blood pressures among diabetic and/or hypertensive patients with high cardiovascular disorders risk in northern Thailand by cluster randomized trial.

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.

Defining the burden of febrile illness in rural South and Southeast Asia: an open letter to announce the launch of the Rural Febrile Illness project.

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.

Good participatory practice for coronavirus disease 2019 (COVID-19) research: the case of a COVID-19 prevention study.

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 coronavirus disease 2019 (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.

Risk factors associated with large clusters of tuberculosis patients determined by whole-genome sequencing in a high-tuberculosis-burden country.

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.

The estimated burden of scrub typhus in Thailand from national surveillance data (2003-2018).

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.

Etiologic features of diarrheagenic microbes in stool specimens from patients with acute diarrhea in Thailand.

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.

Contact tracing for tuberculosis, Thailand.

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.

Prevalence of Group A Streptococcus in Primary Care Patients and the Utility of C-Reactive Protein and Clinical Scores for Its Identification in Thailand.

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 ß-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.

Feasibility of Identifying Household Contacts of Rifampin-and Multidrug-resistant Tuberculosis Cases at High Risk of Progression to Tuberculosis Disease.

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.

Clinical Characteristics and Outcome of Children Hospitalized With Scrub Typhus in an Area of Endemicity.

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.

Willingness to Take Multidrug-resistant Tuberculosis (MDR-TB) Preventive Therapy Among Adult and Adolescent Household Contacts of MDR-TB Index Cases: An International Multisite Cross-sectional Study.

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.

Ensuring tuberculosis treatment adherence with a mobile-based CARE-call system in Thailand: a pilot study.

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.

A novel Ancestral Beijing sublineage of Mycobacterium tuberculosis suggests the transition site to Modern Beijing sublineages.

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.

Antibiotic knowledge, attitudes and practices: new insights from cross-sectional rural health behaviour surveys in low-income and middle-income South-East Asia.

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.

Genomewide Association Study Confirming the Association of NAT2 with Susceptibility to Antituberculosis Drug-Induced Liver Injury in Thai Patients.

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.