Sputum monitoring during tuberculosis treatment for predicting outcome: systematic review and meta-analysis.

WHO has previously recommended sputum-smear examination at the end of the second month of treatment in patients with recently diagnosed pulmonary tuberculosis, and, if positive, extension of the intensive therapy phase. We did a systematic review and meta-analysis to assess the accuracy of a positive sputum smear or culture during treatment for predicting failure or relapse in pulmonary tuberculosis. We searched PubMed, Embase, and the Cochrane Library for studies published in English through December, 2009. We included randomised controlled trials, cohort, and case-control studies of previously untreated pulmonary tuberculosis patients who had received a standardised regimen with rifampicin in the initial phase. Accuracy results were summarised in forest plots and pooled by use of a hierarchical regression approach. 15 papers (28 studies) met the inclusion criteria. The pooled sensitivities for both 2-month smear (24% [95% CI 12-42%], six studies) and culture (40% [95% CI 25-56%], four studies) to predict relapse were low. Corresponding specificities (85% [95% CI 72-90%] and 85% [95% CI 77-91%]) were higher, but modest. For failure, 2-month smear (seven studies) had low sensitivity (57% [95% CI 41-73%]) and higher, although modest, specificity (81% [95% CI 72-87%]). Both sputum-smear microscopy and mycobacterial culture during tuberculosis treatment have low sensitivity and modest specificity for predicting failure and relapse. Although we pooled a diverse group of patients, the individual studies had similar performance characteristics. Better predictive markers are needed.

Cost-effectiveness of alternative strategies for tuberculosis screening before kindergarten entry.

OBJECTIVE: We undertook a decision analysis to evaluate the economic and health effects and incremental cost-effectiveness of using targeted tuberculin skin testing, compared with universal screening or no screening, before kindergarten. METHODS: We constructed a decision tree to determine the costs and clinical outcomes of using targeted testing compared with universal screening or no screening. Baseline estimates for input parameters were taken from the medical literature and from California health jurisdiction data. Sensitivity analyses were performed to determine plausible ranges of associated outcomes and costs. We surveyed California health jurisdictions to determine the prevalence of mandatory universal tuberculin skin testing. RESULTS: In our base-case scenario, the cost to prevent an additional case of tuberculosis by using targeted testing, compared with no screening, was $524,897. The cost to prevent an additional case by using universal screening, compared with targeted testing, was $671,398. The incremental cost of preventing a case through screening remained above $100,000 unless the prevalence of tuberculin skin testing positivity increased to >10%. More than 51% of children entering kindergarten in California live where tuberculin skin testing is mandatory. CONCLUSIONS: The cost to prevent a case of tuberculosis by using either universal screening or targeted testing of kindergarteners is high. If targeted testing replaced universal tuberculin skin testing in California, then $1.27 million savings per year would be generated for more cost-effective strategies to prevent tuberculosis. Improving the positive predictive value of the risk factor tool or applying it to groups with higher prevalence of latent tuberculosis would make its use more cost-effective. Universal tuberculin skin testing should be discontinued, and targeted testing should be considered only when the prevalence of risk factor positivity and the prevalence of tuberculin skin testing positivity among risk factor-positive individuals are high enough to meet acceptable thresholds for cost-effectiveness.

Cost-effectiveness of tuberculosis evaluation and treatment of newly-arrived immigrants.

BACKGROUND: Immigrants to the U.S. are required to undergo overseas screening for tuberculosis (TB), but the value of evaluation and treatment following entry to the U.S. is not well understood. We determined the cost-effectiveness of domestic follow-up of immigrants identified as tuberculosis suspects through overseas screening. METHODS: Using a stochastic simulation for tuberculosis reactivation, transmission, and follow-up for a hypothetical cohort of 1000 individuals, we calculated the incremental cost-effectiveness of follow-up and evaluation interventions. We utilized published literature, California Reports of Verified Cases of Tuberculosis (RVCTs), demographic estimates from the California Department of Finance, Medicare reimbursement, and Medi-Cal reimbursement rates. Our target population was legal immigrants to the United States, our time horizon is twenty years, and our perspective was that of all domestic health-care payers. We examined the intervention to offer latent tuberculosis therapy to infected individuals, to increase the yield of domestic evaluation, and to increase the starting and completion rates of LTBI therapy with INH (isoniazid). Our outcome measures were the number of cases averted, the number of deaths averted, the incremental dollar cost (year 2004), and the number of quality-adjusted life-years saved. RESULTS: Domestic follow-up of B-notification patients, including LTBI treatment for latently infected individuals, is highly cost-effective, and at times, cost-saving. B-notification follow-up in California would reduce the number of new tuberculosis cases by about 6-26 per year (out of a total of approximately 3000). Sensitivity analysis revealed that domestic follow-up remains cost-effective when the hepatitis rates due to INH therapy are over fifteen times our best estimates, when at least 0.4 percent of patients have active disease and when hospitalization of cases detected through domestic follow-up is no less likely than hospitalization of passively detected cases. CONCLUSION: While the current immigration screening program is unlikely to result in a large change in case rates, domestic follow-up of B-notification patients, including LTBI treatment, is highly cost-effective. If as many as three percent of screened individuals have active TB, and early detection reduces the rate of hospitalization, net savings may be expected.