Household-Contact Investigation for Detection of Tuberculosis in Vietnam.

BACKGROUND: Active case finding is a top priority for the global control of tuberculosis, but robust evidence for its effectiveness in high-prevalence settings is lacking. We sought to evaluate the effectiveness of household-contact investigation, as compared with standard, passive measures alone, in Vietnam. METHODS: We performed a cluster-randomized, controlled trial at clinics in 70 districts (local government areas with an average population of approximately 500,000 in urban areas and 100,000 in rural areas) in eight provinces of Vietnam. Health workers at each district clinic or hospital were assigned to perform either household-contact intervention plus standard passive case finding (intervention group) or passive case finding alone (control group). In the intervention districts, household contacts of patients with positive results for tuberculosis on sputum smear microscopy (smear-positive tuberculosis) were invited for clinical assessment and chest radiography at baseline and at 6, 12, and 24 months. The primary outcome was the cumulative incidence of registered cases of tuberculosis among household contacts of patients with tuberculosis during a 2-year period. RESULTS: In 70 selected districts, we enrolled 25,707 household contacts of 10,964 patients who had smear-positive pulmonary tuberculosis. In the 36 districts that were included in the intervention group, 180 of 10,069 contacts were registered as having tuberculosis (1788 cases per 100,000 population), as compared with 110 of 15,638 contacts (703 per 100,000) in the control group (relative risk of the primary outcome in the intervention group, 2.5; 95% confidence interval [CI], 2.0 to 3.2; P<0.001); the relative risk of smear-positive disease among household contacts in the intervention group was 6.4 (95% CI, 4.5 to 9.0; P<0.001). CONCLUSIONS: Household-contact investigation plus standard passive case finding was more effective than standard passive case finding alone for the detection of tuberculosis in a high-prevalence setting at 2 years. (Funded by the Australian National Health and Medical Research Council; ACT2 Australian New Zealand Clinical Trials Registry number, ACTRN12610000600044 .).

Validation of the GenoType MTBDRplus assay for diagnosis of multidrug resistant tuberculosis in South Vietnam.

BACKGROUND: To control multidrug resistant tuberculosis (MDR-TB), the drug susceptibility profile is needed to guide therapy. Classical drug susceptibility testing (DST) may take up to 2 to 4 months. The GenoType MTBDRplus test is a commercially available line-probe assay that rapidly detects Mycobacterium tuberculosis (MTB) complex, as well as the most common mutations associated with rifampin and isoniazid resistance.We assessed sensitivity and specificity of the assay by using a geographically representative set of MTB isolates from the South of Vietnam. METHODS: We re-cultured 111 MTB isolates that were MDR, rifampin-resistant or pan-susceptible according to conventional DST and tested these with the GenoType MTBDRplus test. RESULTS: By conventional DST, 55 strains were classified as MDR-TB, four strains were rifampicin mono-resistant and 52 strains were susceptible to all first-line drugs. The sensitivity of the GenoType MTBDRplus was 93.1% for rifampicin, 92.6% for isoniazid and 88.9% for the combination of both; its specificity was 100%. The positive predictive value of the GenoType MTBDRplus test for MDR-TB was 100% and the negative predictive value 90.3%. CONCLUSIONS: We found a high specificity and positive predictive value of the GenoType MTBDRplus test for MDR-TB which merits its use in the MDR-TB treatment program in Vietnam.

Mortality and failure among tuberculosis patients who did not complete treatment in Vietnam: a cohort study.

BACKGROUND: Tuberculosis treatment failure and death rates are low in the Western Pacific Region, including Vietnam. However, failure or death may also occur among patients who did not complete treatment, i.e. reported as default or transfer-out. We aimed to assess the proportion failures and deaths among new smear-positive pulmonary tuberculosis patients with reported default or transfer-out. Treatment outcomes rates were 1.4% default, 3.0% transfer-out, 0.4% failure and 2.6% death in northern Vietnam in 2003. METHODS: Tuberculosis patients in 32 randomly selected district tuberculosis units in northern Vietnam were followed up 1 to 3 years after treatment initiation for survival, recent treatment history and bacteriologically confirmed tuberculosis. RESULTS: Included were 85 transferred patients and 42 who defaulted. No information was available of 41 (32%), 28 (22%) had died. Fifty-eight were available for follow-up (46%); all had sputum smear results. Tuberculosis was recorded in 11 (13%), including 6 (7%) with positive sputum smears, 3 (3%) with negative smears but positive culture and 2 (2%) who had started re-treatment for bacteriologically confirmed tuberculosis. Fifteen (17%, 95%CI 10-27%) had died within 8 months after treatment initiation. Of 86 patients with known study outcomes, 39 (45%, 95%CI 35-56%) had died or had bacteriologically confirmed tuberculosis. This was recorded for 29/53 (55%, 95%CI 40-68%) transferred patients and 10/33 (30%, 95%CI 16-49%) patients who defaulted. CONCLUSION: The total failure and death rates are 0.6% and 0.8% higher than based on routine reporting in northern Vietnam. Although this was a large proportion of treatment failures and deaths, failure and death rates were low. Defaulting and transfer carry a high risk of failure and in particular death.

High mortality during tuberculosis treatment does not indicate long diagnostic delays in Vietnam: a cohort study.

BACKGROUND: Delay in tuberculosis diagnosis and treatment initiation may increase disease severity and mortality. In evaluations of tuberculosis control programmes high fatality rates during tuberculosis treatment, are used as an indicator of long delays in low HIV-prevalence settings. However, data for this presumed association between delay and fatality are lacking. We assessed the association between diagnostic delay and mortality of new smear-positive pulmonary tuberculosis patients in Vietnam. METHODS: Follow-up of a patient cohort included in a survey of diagnostic delay in 70 randomly selected districts. Data on diagnosis and treatment were extracted from routine registers. Patients who had died during the course of treatment were compared to those with reported cure, completed treatment or failure (survivors). RESULTS: Complete data were available for 1881/2093 (89.9%) patients, of whom 82 (4.4%) had died. Fatality was 4.5% for patients with < or = 4 weeks delay, 5.0% for 5- < or = 8 weeks delay (aOR 1.11, 95%CI 0.67-1.84) and 3.2% for > 9 weeks delay (aOR 0.69, 95%CI 0.37-1.30). Fatality tended to decline with increasing delay but this was not significant. Fatality was not associated with median diagnostic delay at district level (Spearman's rho = -0.08, P = 0.5). CONCLUSION: Diagnostic delay is not associated with treatment mortality in Vietnam at individual nor district level, suggesting that high case fatality should not be used as an indicator of long diagnostic delay in national tuberculosis programmes.