Enhancing the public health impact of latent tuberculosis infection diagnosis and treatment (ACT4): protocol for a cluster randomised trial.

INTRODUCTION: Treatment of latent tuberculosis (TB) infection (LTBI) is an important component of the End-TB strategy. However, the number of individuals who successfully complete LTBI treatment remains low as there are losses at all steps in the LTBI 'cascade-of-care'. The reasons for these losses are variable and highly dependent on the setting. We have planned a trial of a standardised public health approach to strengthen the management of household contacts (HHCs) of newly diagnosed patients with pulmonary TB. Assessing costs related to approach is a secondary objective of the study. METHODS AND ANALYSIS: A cluster randomised trial will be conducted in 24 randomisation units (health facilities or groups of health facilities) in five countries. In Phase 1, at intervention sites, we will conduct a standardised assessment of the current LTBI programme, with a focus on cascade-of-care endpoints. Standardised open-ended questionnaires on practices, knowledge, attitudes and beliefs regarding TB prevention are then administered to key patient groups and healthcare workers. At each site, local stake-holders will review study findings and select solutions based on their acceptability, cost and effectiveness. In Phase 2, intervention clinics will implement the selected solutions, along with contact measurement registries and regular in-service LTBI management training. Control sites will continue their usual LTBI care with no explicit evaluation, strengthening or training activities. The primary study outcome is the number of HHC initiating LTBI treatment per newly diagnosed active TB patient, within 3 months of diagnosis of the index patient. An intention-to-treat analysis will be performed, using a Poisson regression approach. ETHICS AND DISSEMINATION: Ethics approval from the MUHC ethical review board (ERB) was obtained in November 2015. During the study standardised tools will be developed and made publicly available. Key study findings and novel methodologic contributions will be detailed in publications and other dissemination activities. TRIAL REGISTRATION NUMBER: NCT02810678; Pre-Results.

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 .

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.