Risk Factors for Tuberculosis (TB) Among Household Contacts of Patients With Smear-Positive TB in 8 Provinces of Vietnam: A Nested Case-Control Study.

BACKGROUND: Tuberculosis (TB) continues to account for significant morbidity and mortality annually. Household contacts (HHCs) of persons with TB are a key population for targeting prevention and control interventions. We aimed to identify risk factors associated with developing TB among HHCs. METHODS: We conducted a nested case-control study among HHCs in 8 provinces in Vietnam enrolled in a randomized controlled trial of active case finding for TB. Cases were any HHCs diagnosed and registered with TB within the Vietnam National TB Program during 2 years of follow-up. Controls were selected by simple random sampling from the remaining HHCs. Risk factor data were collected at enrollment and during follow-up. A logistic regression model was developed to determine predictors of TB among HHCs. RESULTS: We selected 1254 HHCs for the analysis: 214 cases and 1040 controls. Underlying characteristics varied between both groups; cases were older, more likely to be male, with a higher proportion of reported previous TB and diabetes. Risk factors associated with a TB diagnosis included being male (adjusted odds ratio [aOR], 1.4; 95% confidence interval [CI], 1.03-2.0), residing in an urban setting (aOR, 1.8; 1.3-2.5), prior TB (aOR, 4.6; 2.5-8.7), history of diabetes (aOR, 3.1; 1.7-5.8), current smoking (aOR, 3.1; 2.2-4.4), and prolonged history of coughing in the index case at enrollment (OR , 1.6; 1.1-2.3). CONCLUSIONS: Household contacts remain an important key population for TB prevention and control. TB programs should ensure effective contact investigations are implemented for household contacts, particularly those with additional risk factors for developing TB.

[Diabetes among new cases of pulmonary tuberculosis in Hanoï, Vietnam]. / Diabète chez les nouveaux cas de tuberculose pulmonaire à Hanoï, Vietnam.

The aim of this study was to analyze all new pulmonary tuberculosis cases and to assess the frequency and consequences of associated diabetes mellitus. Although apparently distinct, these two diseases could be linked, as suspected since decades. The context is the persistent endemicity of tuberculosis and the recent emergence of diabetes, two major health events for developing countries. The study was conducted at National TB hospital in Hanoï, Vietnam, and retrospectively included tuberculosis patients, cases with diabetes and controls without diabetes, collected during a three-year period 2006-2008. Cases associated with HIV infection or other comorbidities potentially affecting mortality were excluded. Among 2867 new pulmonary TB cases, 254 (8.8%) had associated diabetes. Eighty-six cases and 86 matched controls were included. Among cases mean blood glucose at admission was 14.4 mmol/dl, and patients were mostly urban (50% cases vs 32.5% controls, p=0.03). Clinical symptoms were similar in both groups. However, chest X-Ray cavitary images were significantly more frequent among cases (38.3% vs 16.3%, p=0.002, OR=4.1), as did infiltrative images (78% vs 62%, p=0.017, OR=2.55) and positive sputum smears (67.4% vs 47.8%, p=0.014, OR=2.21). In Vietnam, DM is found in quasi 9% of patients with a new diagnosis of primary pulmonary TB. The diabetes-TB patients may have more severe radiologic findings and a higher smear positivity rate. We suggest that in addition to the systematic HIV screening, all new TB patients should also be screened for diabetes.

Barriers to adherence with tuberculosis contact investigation in six provinces of Vietnam: a nested case-control study.

BACKGROUND: Close contacts of patients with tuberculosis (TB) have a substantial risk of developing the disease, particularly during the first year after exposure. Household contact investigation has recently been recommended as a strategy to enhance case detection in high-burden countries. However the barriers to its implementation in these settings remain poorly understood. METHODS: A nested case-control study was conducted in Vietnam within the context of a large cluster randomised controlled trial of active screening for TB in household contacts of patients with pulmonary TB. The study population comprised contacts (and their index patients) from 12 Districts in six provinces throughout the country. Cases were contacts (and their index patients) that did not attend the scheduled screening appointment. Controls were those who did attend. We assessed relevant knowledge, attitudes and practices in cases and controls. RESULTS: The acceptability of contact investigation was high among both cases (n = 109) and controls (n = 194). Both cases (47%) and controls (36%) commonly reported discrimination against people with TB. Cases were less likely than controls to understand that sharing sleeping quarters with a TB patient increased their risk of disease (OR 0.46, 0.27 - 0.78) or recognise TB as an infectious disease (OR 0.65, 0.39 - 1.08). A higher proportion of cases than controls held the mistaken traditional belief that a non-infectious form of TB caused the disease (OR 1.69, 1.02 - 2.78). CONCLUSIONS: The knowledge, attitudes and practices of contacts and TB patients influence their ongoing participation in contact investigation. TB case detection policies in high-prevalence settings can be strengthened by systematically evaluating and addressing locally important barriers to attendance. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12610000600044 .

Polymorphisms of SP110 are associated with both pulmonary and extra-pulmonary tuberculosis among the Vietnamese.

BACKGROUND: Tuberculosis (TB) is an infectious disease that remains a major cause of morbidity and mortality worldwide, yet the reasons why only 10% of people infected with Mycobacterium tuberculosis go on to develop clinical disease are poorly understood. Genetically determined variation in the host immune response is one factor influencing the response to M. tuberculosis. SP110 is an interferon-responsive nuclear body protein with critical roles in cell cycling, apoptosis and immunity to infection. However association studies of the gene with clinical TB in different populations have produced conflicting results. METHODS: To examine the importance of the SP110 gene in immunity to TB in the Vietnamese we conducted a case-control genetic association study of 24 SP110 variants, in 663 patients with microbiologically proven TB and 566 unaffected control subjects from three tertiary hospitals in northern Vietnam. RESULTS: Five SNPs within SP110 were associated with all forms of TB, including four SNPs at the C terminus (rs10208770, rs10498244, rs16826860, rs11678451) under a dominant model and one SNP under a recessive model, rs7601176. Two of these SNPs were associated with pulmonary TB (rs10208770 and rs16826860) and one with extra-pulmonary TB (rs10498244). CONCLUSION: SP110 variants were associated with increased susceptibility to both pulmonary and extra-pulmonary TB in the Vietnamese. Genetic variants in SP110 may influence macrophage signaling responses and apoptosis during M. tuberculosis infection, however further research is required to establish the mechanism by which SP110 influences immunity to tuberculosis infection.

Household contact investigation for tuberculosis in Vietnam: study protocol for a cluster randomized controlled trial.

BACKGROUND: Tuberculosis is an infectious disease that continues to cause considerable morbidity and mortality globally. Only 65% of patients worldwide are currently diagnosed. Contact investigation is a strategy that aims to increase case detection and reduce transmission of tuberculosis, yet there is little evidence to show its effectiveness. METHODS/DESIGN: We will conduct a cluster randomized controlled trial of contact investigation within the national tuberculosis control program of Vietnam. Household contacts of patients with smear-positive pulmonary tuberculosis will be invited to attend district tuberculosis units for symptom screening, examination, and chest radiography on four occasions over a two-year period. The primary endpoint is clinically confirmed tuberculosis among contacts during the 24 months of follow-up, ascertained using capture-recapture analysis. Microbiologically proven tuberculosis and treatment completion rates among contacts diagnosed with tuberculosis will be secondary endpoints. The incremental cost-effectiveness ratio will be estimated. The study will have 80% power to detect a 50% increase in the primary endpoint in the active intervention arm compared with the control arm. The study will include 8,829 contacts in each of the active screening and control groups, within 70 districts in 8 provinces in Vietnam, in both rural and urban settings. DISCUSSION: The effectiveness of contact investigation as a tool for improved tuberculosis case finding has not been established. This cluster randomized trial will provide valuable operational information for national tuberculosis programs in high-prevalence countries, in order to select the most cost-effective strategies to improve tuberculosis case detection. TRIAL REGISTRATION: The ACT2 study has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12610000600044).

Contact investigation in households of patients with tuberculosis in Hanoi, Vietnam: a prospective cohort study.

SETTING: Existing tuberculosis control strategies in Vietnam are based on symptomatic patients attending health services for investigation. This approach has not resulted in substantial reductions in the prevalence of tuberculosis disease, despite the National Tuberculosis Program achieving high treatment completion rates. Alternative approaches are being considered. OBJECTIVE: To determine the feasibility and yield of contact investigation in households of patients with smear positive pulmonary tuberculosis among household members of tuberculosis patients in Hanoi, Vietnam. METHODS: Household contacts of patients with smear positive pulmonary tuberculosis were recruited at four urban and rural District Tuberculosis Units in Hanoi. Clinical and radiological screening was conducted at baseline, six months and 12 months. Sputum microscopy and culture was performed in contacts suspected of having tuberculosis. MIRU-VNTR molecular testing was used to compare the strains of patients and their contacts with disease. RESULTS: Among 545 household contacts of 212 patients, four were diagnosed with tuberculosis at baseline (prevalence 734 cases per 100,000 persons, 95% CI 17-1451) and one was diagnosed with tuberculosis during the subsequent 12 months after initial screening (incidence 180 cases per 100,000 person-years, 95% CI 44-131). Two of these cases were culture positive for M. tuberculosis and both had identical or near-identical MIRU-VNTR strain types. CONCLUSION: Household contacts of patients with potentially infectious forms of tuberculosis have a high prevalence of disease. Household contact investigation is feasible in Vietnam. Further research is required to investigate its effectiveness.

National survey of tuberculosis prevalence in Viet Nam.

OBJECTIVE: To estimate the prevalence of tuberculosis in Viet Nam with data from a population-based survey, compare it with the prevalence estimated by the World Health Organization, and identify major demographic determinants of tuberculosis prevalence. METHODS: A cross-sectional survey with multistage cluster sampling, stratified by urban, rural and remote areas, was done in 2006-2007 in 70 communes. All inhabitants aged > or = 15 years were invited for cough and chest X-ray examination. Participants with findings suggestive of tuberculosis provided sputum specimens for smear examination and culture. Point prevalence estimates, 95% confidence intervals and design effects were calculated. Confidence intervals and P-values were adjusted for the cluster design. FINDINGS: Of 114,389 adult inhabitants, 94 179 (82.3%) were screened. Of 87,314 (92.7%) screened by both questionnaire and chest X-ray, 3522 (4.0%) had productive cough, 518 (0.6%) had a recent history of tuberculosis and 2972 (3.4%) had chest X-ray abnormalities suggestive of tuberculosis. Sputum tests were done for 7648 participants. Sputum test, bacterial culture or both confirmed 269 tuberculosis cases, 174 of which were smear-positive. The prevalence rate of smear-positive tuberculosis was 145 per 100,000 (95% confidence interval: 110-180) assuming no tuberculosis in persons aged < 15 years. Prevalence was 5.1 times as high in men as in women, increased with age, was higher in rural than in urban or remote areas and showed a north-to-south gradient. CONCLUSION: In Viet Nam, the tuberculosis prevalence rate based on positive sputum smear tests was 1.6 times as high as previously estimated. Age and sex patterns were consistent with notification data. Tuberculosis control should remain a high priority in Viet Nam.

HIV-associated TB in An Giang Province, Vietnam, 2001-2004: epidemiology and TB treatment outcomes.

BACKGROUND: Mortality is high in HIV-infected TB patients, but few studies from Southeast Asia have documented the benefits of interventions, such as co-trimoxazole (CTX), in reducing mortality during TB treatment. To help guide policy in Vietnam, we studied the epidemiology of HIV-associated TB in one province and examined factors associated with outcomes, including the impact of CTX use. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively abstracted data for all HIV-infected persons diagnosed with TB from 2001-2004 in An Giang, a province in southern Vietnam in which TB patients receive HIV counseling and testing. We used standard WHO definitions to classify TB treatment outcomes. We conducted multivariate analysis to identify risk factors for the composite outcome of death, default, or treatment failure during TB treatment. From 2001-2004, 637 HIV-infected TB patients were diagnosed in An Giang. Of these, 501 (79%) were male, 321 (50%) were aged 25-34 years, and the most common self-reported HIV risk factor was sex with a commercial sex worker in 221 (35%). TB was classified as smear-positive in 531 (83%). During TB treatment, 167 (26%) patients died, 9 (1%) defaulted, and 6 (1%) failed treatment. Of 454 patients who took CTX, 116 (26%) had an unsuccessful outcome compared with 33 (70%) of 47 patients who did not take CTX (relative risk, 0.4; 95% confidence interval [CI], 0.3-0.5). Adjusting for male sex, rural residence, TB smear status and disease location, and the occurrence of adverse events during TB treatment in multivariate analysis, the benefit of CTX persisted (adjusted odds ratio for unsuccessful outcome 0.1; CI, 0.1-0.3). CONCLUSIONS/SIGNIFICANCE: In An Giang, Vietnam, HIV-associated TB was associated with poor TB treatment outcomes. Outcomes were significantly better in those taking CTX. This finding suggests that Vietnam should consider applying WHO recommendations to prescribe CTX to all HIV-infected TB patients.