Use of network analysis multidrug-resistant tuberculosis contact investigation in Kanchanaburi, Thailand.

OBJECTIVE: To characterise MDR-TB outbreak and incorporate social network analysis with contact investigation to detect case-contact linkages and clusters. METHODS: MDR-TB cases registered in the district hospital between October 2012 and September 2015 were interviewed and their contacts were investigated. A relationship-based weighted network was constructed. RESULTS: Among 43 interviewed MDR-TB cases, 20 (47%) were male, five (12%) were asymptomatic (and discovered incidentally) and 22 (51%) had underlying diseases. From the documented 115 contacts, 61 (53%) were household contacts and 49 (43%) were close (non-household) contacts; 70 (61%) were screened for TB using various tests. In this network, we prioritised 37 contacts connected with more than one MDR-TB patient. The largest cluster was identified in the pharmacy unit of the hospital. CONCLUSION: This investigation yielded a significant number of MDR-TB contacts, and social network analysis facilitated the prioritisation for screening. Social network analysis is useful and feasible in this program setting and complements MDR-TB contact investigation.

OBJECTIF: Caractériser une épidémie de TB-MDR et incorporer une analyse du réseau social avec une investigation sur les contacts pour détecter les liens et les regroupements cas-contacts. MÉTHODES: Les cas de TB-MR enregistrés à l'hôpital de district entre octobre 2012 et septembre 2015 ont été interrogés et leurs contacts ont été investigués. Un réseau pondéré sur base de la relation a été construit. RÉSULTATS: Sur 43 cas de TB-MDR interviewés, 20 (47%) étaient des hommes, cinq (12%) étaient asymptomatiques (et ont été découverts fortuitement) et 22 (51%) avaient des maladies sous-jacentes. Parmi les 115 contacts recensés, 61 (53%) étaient des contacts dans le ménage et 49 (43%) étaient des contacts proches (hors ménage); 70 (61%) ont été dépistés pour la TB à l'aide de divers tests. Dans ce réseau, nous avons priorisé 37 contacts reliés à plus d'un patient atteint de TB-MR. Le regroupement le plus important a été identifié dans l'unité de pharmacie de l'hôpital. CONCLUSION: Cette investigation a abouti à un nombre important de contacts avec la TB-MDR et l'analyse du réseau social a facilité l'établissement des priorités pour le dépistage. L'analyse du réseau social est utile et réalisable dans le cadre de ce programme et complète l'investigation sur les contacts de TB-MDR.

Treatment success among Myanmar migrants with TB in Thailand.

SETTING: Two facilities, one providing clinic-based care and another providing residential care to Myanmar migrants with TB, in a Thailand-Myanmar border area.OBJECTIVE: To determine the effects of health insurance, total delay and the model of care on treatment success of TB.METHODS: A prospective study was conducted among adult Myanmar migrants under treatment for newly diagnosed TB. Effects of health insurance, total delay and model of care on treatment success at completion of 6-month treatment were analysed using multiple logistic regression models.RESULTS: Of 191 Myanmar migrants with TB, 167 (87.4%) had treatment success. Median time delays from symptom onset to treatment initiation among migrants with health insurance receiving clinic-based care were significantly shorter than those without health insurance. Those who received residential care had higher odds of treatment success than those under clinic-based care (aOR 6.0, 95% CI 1.5-23.3); having health insurance (aOR 1.0, 95% CI 0.3-2.9) and total delay (aOR 1.7, 95% CI 0.7-4.2) were not significantly associated with treatment success.CONCLUSIONS: A high treatment success rate was associated with receiving residential care among Myanmar migrants with TB on the Thai-Myanmar border. The residential care model, implemented under a non-governmental organisation, was feasible and effective for the migrant population.

Diagnostic performance of whole-genome sequencing for identifying drug-resistant TB in Thailand.

BACKGROUND: Whole-genome sequencing (WGS) is a promising tool for the detection of drug-resistant TB (DR-TB). To date, there have been few comparisons of diagnostic performance of WGS and phenotypic drug susceptibility testing (DST) in DR-TB.METHODS: We compared drug resistance-conferring mutations identified by WGS analysis using TB-Profiler and Mykrobe with phenotypic DST profiles based on the Löwenstein-Jensen proportion method using drug-resistant Mycobacterium tuberculosis (n = 537) isolates from across Thailand. Based on available phenotypic DST results, diagnostic performance was analysed for resistance against isoniazid, rifampicin, ethambutol (EMB), streptomycin, ethionamide (ETH), kanamycin, capreomycin (CPM), para-aminosalicylic acid, ofloxacin and levofloxacin.RESULTS: High agreement between the two methods was observed for most drugs (>91%), except EMB (57%, 95% CI 53-61) and ETH (70%, 95% CI 66-74). Also, low specificity was observed for EMB (49%, 95% CI 44-54) and ETH (66%, 95% CI 61-71). Sensitivity was high for most drugs (range 83-98%), except CPM (77%, 95% CI 59-88).CONCLUSION: Low agreement between WGS and phenotypic tests for drug resistance was found for EMB and ETH. The current genomic database is insufficient for the identification of CPM resistance. Challenges remain for routine usage of WGS-based DST, especially for second-line anti-TB drugs.

Effect of Global Fund financial support for patients with multidrug-resistant tuberculosis.

SETTING: The Global Fund provides financial support for patients with multidrug-resistant tuberculosis (MDR-TB), patients' families and hospitals providing services for these patients in Thailand, but the impact of this support has not been evaluated.OBJECTIVE: To assess the impact of Global Fund financial support on drug adherence, out-of-pocket (OOP) payments, sputum culture conversion and the perception of the usefulness of this support.DESIGN: A retrospective cohort study was conducted in eight provincial hospitals with and without financial support in four regions of Thailand. MDR-TB patients aged ≥15 years registered in 2015-2016 who received treatment at these hospitals for at least 6 months were included.RESULTS: There was no significant difference in drug adherence rates. The OOP payments during treatment were significantly lower in patients who received financial support (P < 0.001). Although the supported group had higher positive culture rates at the beginning of treatment, sputum converted at a faster rate than for the unsupported group (P = 0.034). More than 80% of both groups perceived financial support as being useful, leading to faster diagnosis and improving follow-up compliance.CONCLUSION: Financial support for MDR-TB patients has a positive impact on treatment and should be continued.

Under- and over-consumption intermittent TB treatment among rural TB patients in south-west China.

OBJECTIVE: To assess adherence to intermittent directly observed treatment (DOT) during the 2-month intensive phase of tuberculosis (TB) treatment in south-west rural China. DESIGN: A cross-sectional study was conducted in Simao Prefecture, Yunnan Province, China. One hundred and thirty new TB patients registered under DOTS and treated during the 2-month intensive phase and their observers were separately interviewed at their homes using structured questionnaires. Numbers of packs of TB drugs were checked on the spot. RESULTS: Of 130 visits, the same percentage (3.1%) of patients and their observers reported missing > or =2 consecutive weeks of treatment (prevalence-adjusted kappa = 0.94). The percentages who missed > or =20% of the packs, as reported by patients and observers, were 3.8 and 2.3, respectively (prevalence-adjusted kappa = 0.969). According to the pill count, nine patients (7%) had missed > or =20% of the packs, 10 had over-consumed TB drugs and two had lost respectively five and six packs. Eight of the 10 who had over-consumed had done so due to confusion in the days of the month, and two because they wanted a quicker recovery. CONCLUSIONS: Intermittent regimens in China need to be more carefully monitored to avoid over-consumption of anti-tuberculosis drugs in addition to non-adherence due to under-consumption.

Social impact of tuberculosis in southern Thailand: views from patients, care providers and the community.

BACKGROUND: There is growing recognition that attention to social and behavioral factors in tuberculosis (TB) control needs to complement biomedical emphasis on better drugs, vaccines and new diagnostic tools. METHODS: Using qualitative methods, we conducted 10 focus groups and seven individual interviews to explore how TB is perceived or experienced in southern Thailand. Participants included male and female patients with TB, patients with AIDS, TB care providers, family members of patients with TB, religious leaders (Buddhist and Muslim), and unaffected community members. RESULTS: Responses informed two conceptual frameworks on stigma and social support. The first model dichotomized the meaning of TB into 'good' and 'bad' factors related to social support and stigma, respectively. The second model identified three themes--disease severity, religion, and knowledge of TB--linked to either stigma, social support, or both. CONCLUSION: Social support as a facilitator and stigma as a barrier are diametrically opposed concepts that need to inform TB care and treatment. Interventions to reduce stigma and promote social support at the patient, household, community, and health care system levels should be part of future efforts in the control of TB in Thailand.

Non-communicable diseases increased risk of recurrent tuberculosis in epidemic area of Human Immunodeficiency Virus infection, Thailand.

In recent decades, many countries in Southeast Asia such as Thailand reported an increase of non-communicable diseases (NCDs) and are faced with double burden of NCDs and communicable diseases such as tuberculosis. Recurrent tuberculosis (TB) has been reported in association with Human Immunodeficiency Virus infection (HIV) and diabetes mellitus, however the association between recurrent TB and other NCDs has not been well investigated in this region. A retrospective cohort study was conducted to determine risk of recurrent TB associated with NCDs in an endemic area of HIV in Thailand. Of 1,444 pulmonary TB patients who are registered and had completed a course of treatment during 2003-2012, 99 were diagnosed for recurrent TB (1.954 per 100 TB cases-year). After adjusting for HIV, age, sex, and previous TB treatment outcome, Poisson regression revealed significant risk of recurrent TB among patient with diabetes mellitus (RR=2.76; 95% CI=1.66-4.59), with chronic obstructive pulmonary disease (RR=2.16; 95% CI=1.33-3.49) and with liver cirrhosis (RR=4.45; 95% CI=2.23-8.87). Regular routine screening for TB among patients with liver cirrhosis, diabetes mellitus and chronic obstructive pulmonary disease should be established to improve prevention and control of TB in endemic areas of TB and HIV.

Deteriorated tuberculosis drugs and management system problems in lower southern Thailand.

SETTINGS: Three institutes, 11 hospitals and 38 community hospitals in southern Thailand. OBJECTIVES: To assess the quality of tuberculosis (TB) drugs used in TB treatment facilities in southern Thailand and their TB drug management systems. DESIGN: Cross-sectional study utilising interviews, document review, inspection of drug storage, visual examination of TB drugs, and laboratory analysis of samples of isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA) and ethambutol (EMB). RESULTS: No stock-out of TB drugs was found at any level. Thirteen (25%) hospitals/institutes removed coated EMB tablets from their foil packages for daily dose packing. Eleven (21%) hospitals/institutes bisected 400 mg coated EMB tablets before dispensing as a non-available 200 mg tablet. On the day of inspection grossly deteriorated EMB was observed in 44% of hospitals/institutes. All samples, except 14% of EMB, passed content assay tests. All INH and EMB samples passed the dissolution tests, but 62% of RMP samples and 26% of PZA samples failed. CONCLUSIONS: Sub-standard deteriorated TB drugs are a serious problem for TB control. TB drugs examined in the study area were not managed properly. Education on TB drug packaging and storage, and non-destructive systems in TB drug distribution, storage, inventory control, quality assurance and supervision are essential interventions.

Practice of directly observed treatment (DOT) for tuberculosis in southern Thailand: comparison between different types of DOT observers.

SETTING: A government health system in southern Thailand where the directly observed treatment, short-course (DOTS) strategy has been implemented. OBJECTIVE: To compare the practice of actual directly observed treatment (DOT) and the observer sustainability for different types of observer. METHODS: During 1999-2000, 411 patients with new smear-positive pulmonary tuberculosis were followed up. The patients and/or their observers were interviewed about the presence of any person with the patient during drug intake and the practice of watching the patient swallowing the medicine (actual DOT). Data were recorded monthly and analysed by Cox and logistic regression models. RESULTS: For health personnel (HP), community member (CM), and family member (FM) observers, the proportions who did not practise actual DOT were respectively 11%, 23%, and 35%, and the proportions who changed to no observer or self administration were respectively 11%, 1%, and 2%, during the first 9 months of treatment. Health personnel had the lowest risk of not practising actual DOT (odds ratio HP/FM 0.1, 95%CI 0.1-0.2; CM/FM 0.9, 95%CI 0.5-1.6) but the highest risk for change to self administration. CONCLUSION: To increase the coverage of actual DOT, strategies are needed to maintain health personnel as the DOT observers and to promote actual DOT among family member observers.

Study of tuberculosis and AIDS stigma as barriers to tuberculosis treatment adherence using validated stigma scales.

BACKGROUND: Adherence to tuberculosis (TB) treatment is important for TB control. The effect of stigma on adherence has not been well quantified. OBJECTIVE: To identify the effects of TB and acquired immune-deficiency syndrome (AIDS) stigma on missed doses during TB treatment. DESIGN: Validated TB and AIDS stigma scales assessing perceived and experienced/felt stigma were administered in a prospective cohort of 459 TB patients at TB treatment initiation and after 2 months. Repeated measures and multivariable models estimated the effects of stigma on the rate of missed doses. RESULTS: Fifty-six per cent of patients missed no doses, and associations between stigma and missed doses were minimal. Heterogeneity of effects was observed, how- ever, with higher experienced and felt TB stigma increasing missed doses among women (adjusted RR 1.22, 95%CI 1.10-1.34) and human immunodeficiency virus (HIV) co-infected patients (aRR 1.39, 95%CI 1.13-1.72). Experienced and felt AIDS stigma also increased missed doses among HIV co-infected patients (aRR 1.43, 95%CI 1.31-1.56). CONCLUSION: Stigma has a minimal effect in this population with good adherence. Among women and HIV co-infected patients, however, experienced and felt stigma, and not perceived stigma, increased the rate of missed doses. Further research is needed to determine if stigma or coping interventions among these subgroups would improve adherence.

Tuberculosis and AIDS stigma among patients who delay seeking care for tuberculosis symptoms.

BACKGROUND: Delay in presentation to a health facility is an important concern for tuberculosis (TB) control. The effect of stigma on delay in seeking care for TB symptoms is not well studied, especially in the context of the human immunodeficiency virus (HIV) co-epidemic. OBJECTIVE: To estimate the association of TB and acquired immune-deficiency syndrome (AIDS) stigma on delay in seeking care for TB symptoms. METHODS: For 480 newly diagnosed patients with TB, time from first TB symptom to the first visit to a qualified provider was calculated. Stigma scales were administered to each patient to obtain a stigma score. RESULTS: Among men, those with higher TB stigma had a small increase in delay times, while women had a small decrease in delay. Among patients presenting with hemoptysis, higher TB stigma was associated with a small increase in delay, while among patients presenting with fever or extra-pulmonary symptoms only, higher TB and AIDS stigma resulted in shorter delay times. CONCLUSION: In a population with a relatively short median delay (26 days), the impact of TB and AIDS stigma translates into a minimal change in delay time. This suggests that stigma does not have a clinically relevant effect on TB patient delay in southern Thailand.