Durations of asymptomatic, symptomatic, and care-seeking phases of tuberculosis disease with a Bayesian analysis of prevalence survey and notification data

Background Ratios of bacteriologically-positive tuberculosis (TB) prevalence to notification rates are used to characterise typical durations of TB disease. However, this ignores the clinical spectrum of tuberculosis disease, and potentially-long infectious periods with minimal or no symptoms prior to care-seeking. Methods We developed novel statistical models to estimate progression from initial bacteriological-positivity including smear conversion, symptom onset and initial care-seeking. Case-detection ratios, TB incidence, durations, and other parameters were estimated by fitting the model to tuberculosis prevalence survey and notification data (one subnational and 11 national datasets) within a Bayesian framework using Markov chain Monte Carlo methods. Results Analysis across 11 national datasets found asymptomatic tuberculosis durations in the range 4 - 8 months for African countries; three countries in Asia (Cambodia, Lao PDR, and Philippines) showed longer durations of > 1 year. For the six countries with relevant data, care-seeking typically began half-way between symptom onset and notification. For Kenya and Blantyre, Malawi, individual-level data were available. The sex specific durations of asymptomatic bacteriologically-positive tuberculosis were 9.0 months (95% credible interval [CrI]: 7.2 – 11.2) for men and 8.1 months (95% CrI: 6.2 – 10.3) for women in Kenya, and 4.9 months (95% CrI: 2.6 – 7.9) for men and 3.5 months (95% CrI: 1.3 – 6.2) for women in Blantyre. Age stratified analysis of data for Kenya showed no strong age-dependence in durations. For Blantyre, HIV stratified analysis estimated an asymptomatic duration of 1.3 months (95% CrI: 0.3 – 3.0) for HIV-positive people, shorter than the 8.5 months (95% CrI: 5.0 – 12.7) for HIV-negative people. Additionally, case detection ratios were higher for people living with HIV than HIV-negative people (93% vs 71%). Conclusion Asymptomatic TB disease typically lasts around 6 months. We found no evidence of age-dependence, but much shorter durations among people living with HIV, and longer durations in some Asian settings. To 3 eradicate TB transmission, greater gains may be achieved by proactively screening people without symptoms through active case finding intervention