Combination interventions to control the tuberculosis epidemic in the Karamoja subregion of Uganda: A modelling analysis

The Karamoja subregion in northeastern Uganda is disproportionately affected by tuberculosis (TB), with an estimated TB prevalence >3 times the national average. Recently introduced health systems strengthening (HSS) interventions, including active symptom screening campaigns covering approximately 20% of the population annually, have substantially increased the number of people initiated on TB treatment, improved TB treatment completion and increased uptake of TB preventive therapy. However, to achieve further reductions in TB incidence and mortality, additional interventions are needed. We aimed to assess the impact of four additional interventions, layered onto existing HSS interventions, on TB incidence and mortality. We developed a dynamic compartmental model calibrated to TB epidemiology in Karamoja (population 1.4 million, 50% children <15 years old, 34% undernourished; estimated annual TB incidence 670 per 100,000). In addition to the existing HSS interventions, we modelled four interventions: adding chest X-ray with computer aided detection to current case-finding campaigns; increased home-based contact investigation to cover all persons diagnosed with TB plus nutritional support for undernourished persons with TB; community-wide testing and treatment of TB infection; and nutritional support to undernourished persons with TB infection. We estimated the number of TB disease episodes and deaths averted over 20 years. Over 20 years, continued implementation of HSS would reduce TB incidence by 2.4% per year to 339/100,000 (95% UI 222-475) and TB mortality by 3.2% per year to 13/100,000 (95% UI 6-20), compared to current incidence and mortality. Implementation of all four additional interventions could accelerate impact, bringing TB incidence to 161/100,000 (95% UI 61-299) and TB mortality to 5/100,000 (95% UI 2-10), thereby averting 47,450 (95% UI 18,030-76,640) TB episodes and 2,880 (95% UI 1,040-3980) TB deaths compared to HSS alone. Combination interventions to reduce undernutrition and find people with TB disease and infection can have a meaningful epidemiological impact in Karamoja.