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

Abstract

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 eradicate TB transmission, greater gains may be achieved by proactively screening people without symptoms through active case finding interventions

Understanding drivers of phylogenetic clustering and terminal branch lengths distribution in epidemics of Mycobacterium tuberculosis

“…To show this I tested three different sampling rates: ε= 0.5, 1, and 2, corresponding to a median infectious period of ~16.6, 8.3, and 4.2 months, respectively. These values cover well the possible length of the symptomatic period estimated in different countries ( Ku et al, 2021 ). For each value of ε, I considered three different transmission rates leading to three scenarios: a shrinking epidemic with R0=0.9, a stable epidemic with R0=1, and a growing epidemic with R0=1.1.…”

“…However, the epidemiological characteristics of circulating MTB strains are normally not known, and the differences in latency and clock rates used here are possible. The length of the latent period and the clock rates are well within the range of values estimated with different data sets ( Menardo et al, 2019 ; Ku et al, 2021 ). Overall, these results show that the standard interpretation of clustering results and TBL distributions can potentially be misleading in some epidemiological settings.…”

“…Given the uncertainty about the length of the latent period I tested three different rates of progression to infectiousness ψ= 0.5, 1, 2, corresponding to a median latent period of ~16.6, 8.3, and 4.2 months, respectively. These values represent the range of duration of asymptomatic infection estimated in different countries ( Ku et al, 2021 ). All other parameters were constant in all simulations (π=8 × 10 –8 ; σ = ε= 0.5; λ=1, sampling period = 10 years).…”

“…However, there can be confounding factors, such as the migration of strains from other regions. Finally, the length of the infectious and latent period can be estimated (with some assumptions) from prevalence surveys and notification data ( Ku et al, 2021 ). Usually this is done at the population level, the same analysis on individual lineages, or clones, could provide useful insights on the heterogeneity of MTB populations.…”

Reimagining the status quo: How close are we to rapid sputum-free tuberculosis diagnostics for all?

“…Tests to diagnose subclinical (asymptomatic) TB are lacking. This state (bacteriologically-positive TB in those reporting no symptoms and typically not seeking healthcare) is more prevalent than previously estimated, with highly variable duration (six months to beyond five years) 35 , 36 and may be responsible for more than half of TB transmission. 16 The detection of Mtb bacilli or DNA in aerosols has been facilitated by the development of face masks, with capture filters or absorbent materials, or blow tubes with a capture filter.…”