Abstract
BackgroundTuberculosis (TB) is the leading cause of death in South Africa. The burden of disease varies by age, with peaks in TB notification rates in the HIV-negative population at ages 0−5, 20−24, and 45−49 years. There is little variation between age groups in the rates in the HIV-positive population. The drivers of this age pattern remain unknown. MethodsWe developed an age-structured simulation model of Mycobacterium tuberculosis (Mtb) transmission in Cape Town, South Africa. We considered five states of TB progression: susceptible, infected (latent TB), active TB, treated TB, and treatment default. Latently infected individuals could be re-infected; a previous Mtb infection slowed progression to active disease. We further considered three states of HIV progression: HIV negative, HIV positive, on antiretroviral therapy. To parameterize the model, we analysed treatment outcomes from the Cape Town electronic TB register, social mixing patterns from a Cape Town community and used literature estimates for other parameters. To investigate the main drivers behind the age patterns, we conducted sensitivity analyses on all parameters related to the age structure. ResultsThe model replicated the age patterns in HIV-negative TB notification rates of Cape Town in 2009. Simulated TB notification rate in HIV-negative patients was 1000/100,000 person-years (pyrs) in children aged <5 years and decreased to 51/100,000 in children 5−15 years. The peak in early adulthood occurred at 25−29 years (463/100,000 pyrs). After a subsequent decline, simulated TB notification rates gradually increased from the age of 30 years. Sensitivity analyses showed that the dip after the early adult peak was due to the protective effect of latent TB and that retreatment TB was mainly responsible for the rise in TB notification rates from the age of 30 years. ConclusionThe protective effect of a first latent infection on subsequent infections and the faster progression in previously treated patients are the key determinants of the age-structure of TB notification rates in Cape Town.
Highlights
The HIV and Tuberculosis (TB) epidemics in South Africa (SA) are among the worst in the world
Sensitivity analyses showed that the dip after the early adult peak was due to the protective effect of latent TB and that retreatment TB was mainly responsible for the rise in TB notification rates from the age of 30 years
The protective effect of a first latent infection on subsequent infections and the faster progression in previously treated patients are the key determinants of the age-structure of TB notification rates in Cape Town
Summary
The HIV and Tuberculosis (TB) epidemics in South Africa (SA) are among the worst in the world. Tuberculosis (TB) is the leading cause of natural death in South Africa (Statistics South Africa, 2014a). The HIVassociated TB epidemic partly explains the failure of DOTS to reduce the TB prevalence in SA (Wood et al, 2011b), since about 65% of TB patients in South Africa are co-infected with HIV (WHO, 2014a). Tuberculosis (TB) is the leading cause of death in South Africa. The burden of disease varies by age, with peaks in TB notification rates in the HIV-negative population at ages 0-5, 20-24 and 45-49 years. There is little variation between age groups in the rates in the HIVpositive population The drivers of this age pattern remain unknown
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