The use of sputum PCR as an annual, primary screen for TB in the general prison population of former Soviet countries was the most effective strategy for reducing both TB and MDR-TB prevalence, and provided health benefit at a cost well below their average per-capita GDP. The Commission on Macroeconomics and Health considers an intervention whose cost per QALY gained is below a country's per-capita GDP to be very cost-effective 
. Though it would require significant investment, expanding case finding efforts in prisons with high prevalence of MDR-TB to include screening with sputum PCR will likely lead to substantially improved TB disease control, with the increased costs offset by decreased expenditures on MDR-TB treatment.
In settings where the implementation of sputum PCR screening is not feasible, combined MMR and symptom screening is a cost-effective alternative that produces substantial reductions in TB and MDR-TB prevalence, at low cost per QALY compared with per-capita GDP. In Tajikistan, where the cost of labor is low, this strategy was cost-saving over the 10-y time horizon considered. In other settings, MMR-based strategies were cost-saving.
The highly attractive cost-per-QALY-gained profile of sputum PCR is driven by three features of the populations and settings we consider: the high prevalence of TB, the high proportion of MDR-TB cases, and the availability of both first-line and second-line treatment regimens. In our country-specific analysis for Tajikistan, the poorest of the three countries specifically modeled, the incremental cost per QALY of sputum PCR screening was lower than for Russia, Latvia, or the FSU in general, despite the higher estimated per-test cost there. This is explained by the higher than average prevalence of TB and MDR-TB in Tajikistan, relative to the other settings. In prison settings with TB/MDR-TB prevalence lower than those considered here, the incremental cost per QALY gained for sputum PCR screening is likely substantially higher. Importantly, even in lower prevalence settings, if the cost of MDR-TB therapy could be reduced, the ICER of sputum PCR screening would be further improved: reducing the costs of MDR-TB drugs themselves and avoiding overuse of precautionary hospitalization of MDR-TB cases are potentially policy-relevant approaches to achieving lower MDR-TB therapy costs. Because much of the benefits of sputum PCR screening come from detecting MDR-TB cases that can be effectively treated, it is not appropriate to apply our findings to prison settings without a functioning MDR-TB treatment program.
Studying disease control in places of incarceration presents important challenges. Security concerns often predominate over public health threats in the daily operations of prisons and other detention facilities, and the public perception of inmates can lower prison health as a research priority for government funding agencies. Therefore, a major limitation of our study was the availability of primary data regarding TB epidemiology and control in prisons in the FSU. This required us to make multiple simplifying assumptions about the biology and treatment of TB and to draw from a variety of heterogeneous data sources to estimate model inputs. Despite this heterogeneity and uncertainty, our many sensitivity and scenario analyses suggest that the main results—that sputum PCR is cost-effective when used as a primary screening tool for TB in prisons of high prevalence—was robust. However, time-series data against which to calibrate or validate the model were not available, so we cannot be sure which parameter combinations best match reality. While we performed multiple sensitivity and uncertainty analyses, including probabilistic sensitivity analyses, for which the large majority supported the robustness of the findings in the main analysis, the potential still remains that the type of correlation structure present in the joint posterior distribution of model parameters determined via empirical calibration could lead to different conclusions regarding robustness.
Very little prospective data exist regarding the test characteristics of MMR. We conducted a systematic review of the literature on MMR to identify all relevant articles for our estimates of its sensitivity and specificity (Text S1
). We also conducted two-way sensitivity analyses across the entire range of possible values for MMR's sensitivity to determine thresholds for cost-effectiveness. In these analyses, MMR screening maintains a favorable ratio cost per QALY gained as long as it maintains a sensitivity of >60% for pulmonary TB (). Finally, because of the possibility that MMR's performance differs between smear-positive and smear-negative cases in ways that are difficult to adjust for via verification bias adjustments, we conducted two sensitivity analyses where we assumed either that (1) MMR sensitivity for smear-negative cases was equal to that of smear-positive cases or (2) MMR sensitivity for smear-positive cases was at the upper bound of its confidence interval and smear-negative sensitivity was at the lower bound of its confidence interval. In both cases, the results remained consistent with those in the main analysis.
Our estimates of test characteristics are further complicated by the lack of a functional “gold standard” for TB diagnosis. While culture positivity is considered to be the “gold standard” case definition for epidemiological studies, a significant proportion of smear-negative TB cases as defined clinically on the basis of nonresponse to broad spectrum antibiotics are culture-negative. More invasive methods such as bronchoalveolar lavage can show a meaningful proportion of these individuals to have bacteriologically positive disease 
. Since a clinical diagnosis is usually used as the basis for treatment, we included a proportion of such “abacillary cases” in our estimates of sensitivity and specificity for the diagnostic tools considered in the analysis (Text S1
). A scenario analysis in which test characteristic estimates included only bacteriologically positive cases resulted in the same conclusions as our main analysis (Table S4
Our study did not explicitly model HIV, given data limitations and the complexity of HIV-TB co-infections. However, it is well known that HIV affects the susceptibility for and clinical presentation of TB in ways relevant to the screening methods we have examined. In most former Soviet republics, estimates of HIV prevalence in places of incarceration range from 0% to 4.76%, but higher rates have been reported in select prisons in Ukraine and the Baltic states 
. Our analysis is likely less accurate for these settings, though it is difficult to predict how including HIV might have affected our results, given that HIV disease can impact both the radiographic appearance and the bacillary load of sputum in individuals co-infected with TB 
Another important limitation of our model is the absence of a separate compartment for individuals who default from treatment. In prisons of the FSU, treatment default is most often due either to early release or to transfer to another facility. In our model, default was incorporated into treatment outcomes by assuming these individuals would remain on treatment until treatment success, treatment failure, death, or release. A scenario analysis in which treatment outcomes immediately after release were worse than those reported—accounting for a lapse in treatment—did not substantially impact the results (Table S4
Our estimates of the cost-effectiveness of more sensitive screening strategies are likely conservative because, while we did model morbidity, mortality, and costs resulting from active disease occurring after release from prison, we did not model post-release transmission in the general, non-prison population and do not capture the consequent benefits and averted costs of better TB control in prisons reducing such transmission. Therefore, the cost-effectiveness of strategies reducing TB and MDR-TB prevalence among inmates may be underestimated.
As global TB control efforts expand to cover comprehensive treatment for MDR-TB, the efficient use of scarce healthcare resources is paramount. The use of interventions, including sputum PCR for case finding and rapid MDR-TB detection, that maximally interrupt the cycle of transmission in prisons where TB is prevalent and MDR-TB strains are concentrated may save resources while promoting a culture of human rights for prison residents and averting preventable deaths both inside and outside prison walls.