The potential impact of preventive therapy against tuberculosis in the WHO South-East Asian Region: a modelling approach

Abstract

Background The prevention of tuberculosis (TB) is key for accelerating current, slow declines in TB burden. The 2018 World Health Organization (WHO) guidelines on eligibility for preventive therapy to treat latent TB infection (LTBI) include people living with human immunodeficiency virus (PLHIV), household contacts of TB patients including children, and those with clinical conditions including silicosis, dialysis, transplantation, etc. and other country-specific groups. We aimed to estimate the potential impact of full implementation of these guidelines in the WHO South-East Asian (SEA) Region, which bears the largest burden of TB and LTBI amongst the WHO regions. Methods We developed mathematical models of TB transmission dynamics, calibrated individually to each of the 11 countries in the region. We modelled preventive therapy in the absence of other TB interventions. As an alternative comparator, reflecting ongoing developments in TB control in the region, we also simulated improvements in the treatment cascade for active TB, including private sector engagement and intensified case-finding. Relative to both scenarios, for each country in the region, we projected TB cases and deaths averted between 2020 and 2030, by full uptake of preventive therapy, defined as comprehensive coverage amongst eligible populations as per WHO guidelines, and assuming outcomes consistent with clinical trials. We also performed sensitivity analysis to illustrate impact under less-than-optimal conditions. Results At the regional level, full uptake of preventive therapy amongst identified risk groups would reduce annual incidence rates in 2030 by 8.30% (95% CrI 6.48–10.83) relative to 2015, in the absence of any additional interventions. If implemented against a backdrop of improved TB treatment cascades, preventive therapy would achieve an incremental 6.93 percentage points (95% CrI 5.81–8.51) of reduction in annual incidence rates, compared to 2015. At the regional level, the numbers of individuals with latent TB infection that need to be treated to avert 1 TB case is 64 (95% CrI 55–74). Sensitivity analysis illustrates that results for impact are roughly proportional to ‘effective coverage’ (the product of actual coverage and effectiveness of the regimen). Conclusions Full implementation of WHO guidelines is important for ending TB in the SEA Region. Although future strategies will need to be expanded to the population level, to achieve large declines in TB incidence, the uptake of current tools can offer a valuable step in this direction.

Costs of TB services in India (No 1)

“…This study responds to the appeal for recent and comprehensive data on TB services and interventions required for current and upcoming scale-up of TB preventive therapy in the South East Asia region, 16 and other resource needs assessments in India and surrounding regions. Units costs generated from this study can equip planners and economists, understand resource allocation and financial needs using standardised unit costs across key services and interventions delivered to patients affected with TB.…”

Modelling the global burden of drug-resistant tuberculosis avertable by a post-exposure vaccine

“…In addition to mass vaccination, supplementary immunisation approaches may also have an important impact, for example, vaccination of close contacts of diagnosed TB cases. Recent modelling work (albeit in the context of preventive therapy) suggests that preventing 60% of incident TB amongst household contacts of TB cases in the WHO South-East Asian Region could reduce annual incidence rates in the Region by ~8%, by 2030 30 . That analysis assumed preventive therapy to be ineffective amongst those with drug-resistant infection; a vaccine in place of preventive therapy, therefore, might be expected to have a similar impact on RR-TB, if not higher.…”

Estimating the population at high risk for tuberculosis through household exposure in high-incidence countries: a model-based analysis

“…These estimates provide country-specific information to help reach this goal in the 20 countries that had more than 80% of the global total of new TB cases in 2019. As estimated for child household contacts globally or in the WHO Southeast Asia region, future modeling studies could build on this work by estimating the impact of reaching household contacts of all ages in averting TB disease and death and the associated cost [ 22 , 33 ]. Household contact investigation studies continue to show the benefit of TPT among household contacts of all ages, including the recent study by Paradkar et al reporting that 2% of household contacts at study sites in India developed TB in the first 24 months of follow-up [34] .…”