Screening and rapid molecular diagnosis of tuberculosis in prisons in Russia and Eastern Europe: a cost-effectiveness analysis

Abstract

Background: Prisons of the former Soviet Union (FSU) have high rates of multidrug-resistant tuberculosis (MDR-TB) and are thought to drive general population tuberculosis (TB) epidemics. Effective prison case detection, though employing more expensive technologies, may reduce long-term treatment costs and slow MDR-TB transmission.

Methods and findings: We developed a dynamic transmission model of TB and drug resistance matched to the epidemiology and costs in FSU prisons. We evaluated eight strategies for TB screening and diagnosis involving, alone or in combination, self-referral, symptom screening, mass miniature radiography (MMR), and sputum PCR with probes for rifampin resistance (Xpert MTB/RIF). Over a 10-y horizon, we projected costs, quality-adjusted life years (QALYs), and TB and MDR-TB prevalence. Using sputum PCR as an annual primary screening tool among the general prison population most effectively reduced overall TB prevalence (from 2.78% to 2.31%) and MDR-TB prevalence (from 0.74% to 0.63%), and cost US$543/QALY for additional QALYs gained compared to MMR screening with sputum PCR reserved for rapid detection of MDR-TB. Adding sputum PCR to the currently used strategy of annual MMR screening was cost-saving over 10 y compared to MMR screening alone, but produced only a modest reduction in MDR-TB prevalence (from 0.74% to 0.69%) and had minimal effect on overall TB prevalence (from 2.78% to 2.74%). Strategies based on symptom screening alone were less effective and more expensive than MMR-based strategies. Study limitations included scarce primary TB time-series data in FSU prisons and uncertainties regarding screening test characteristics.

Conclusions: In prisons of the FSU, annual screening of the general inmate population with sputum PCR most effectively reduces TB and MDR-TB prevalence, doing so cost-effectively. If this approach is not feasible, the current strategy of annual MMR is both more effective and less expensive than strategies using self-referral or symptom screening alone, and the addition of sputum PCR for rapid MDR-TB detection may be cost-saving over time.

Figure 1. Natural history, diagnosis, and treatment of TB.

Simplified diagram of the health states and transitions in our model. Screening and diagnostic alternatives affect the rate of transition from undetected to detected active disease, represented here by a dashed arrow. Death from all states is not shown. See Figures S1 and S2 for more detail regarding the model structure.

Figure 2. Diagnosis of non-MDR-TB and MDR-TB and the development of acquired (treatment-associated) MDR-TB.

Diagram showing the detection of non-MDR-TB and MDR-TB. Individuals with MDR-TB transition through a state in which they are treated with standard first-line (DOTS) therapy before the multidrug resistance of their strain is detected. This rate of transition is substantially accelerated in strategies using sputum PCR (Xpert MTB/RIF). Individuals developing acquired (treatment-associated) MDR-TB also transition through a state in which they are treated with standard first-line treatment before the multidrug resistance of their strain is detected. The rate of detection for these individuals is unaffected by the choice of case finding strategy. tx, treatment.

Figure 3. The effects of alternative screening and diagnostic strategies on TB and MDR-TB prevalence.

(A) Prevalence of TB (both non-MDR-TB and MDR-TB) among prison population over 10-y time horizon. (B) Prevalence of MDR-TB among prison population over 10-y time horizon. Strategy 1 (S1), self-referral only (no screening), is not shown.

Figure 4. Base case cost-effectiveness frontier.

Total costs and total QALYs are shown for each strategy. The cost-effectiveness frontier, illustrated by the dashed line, indicates the strategies with the lowest cost per QALY. The ICER gives the cost in US dollars for each additional QALY gained, as one chooses more costly and effective alternatives along the cost-effectiveness frontier. The black dot denotes no screening; dark blue symbols denote strategies using MMR screening alone; red symbols denote strategies using annual symptom screening alone; light blue symbols denote strategies using sputum PCR screening; purple symbols denote strategies using combined MMR and symptom screening. Star-shaped symbols denote strategies where sputum PCR is used only for rapid MDR-TB detection among individuals who screen positive for TB.

Figure 5. Outcomes for country-specific analysis.

Overall TB prevalence rates (A–C), MDR-TB prevalence rates (D–F), and cost-effectiveness frontiers (G–I) over 10 y within prisons in three countries. These outcomes reflect model prisons in Tajikistan (A, D, and G), the Russian Federation (B, E, and H), and Latvia (C, F, and I). Strategy 1 (S1), self-referral only (no screening), is not shown in tracings of overall and MDR-TB prevalence (A–F).

Figure 6. Results of two-way sensitivity analyses.

(A) Test sensitivities of MMR and of symptom screening are varied from 0% to 100%. Colored regions indicate combinations of test sensitivities for which sputum PCR screening (maroon), symptom screening (yellow), and MMR (blue) are the least costly of the three screening strategies evaluated. (B) Test sensitivities of MMR and of symptom screening are varied from 0% to 100%. Colored regions indicate the ICER of sputum PCR screening compared with the next best strategy, divided into the following: cost-saving (yellow), non-dominated and ICER

Figure 7. Results of the probabilistic sensitivity analysis.

Ten thousand parameter combinations were randomly selected, and the NMB was calculated for each strategy in each parameter combination. The likelihood that each strategy is preferred (has the highest NMB) at willingness-to-pay thresholds from US$0 to US$15,000 is shown.