Peer Review Report For: Impact of effective contact rate and post treatment immune status on population tuberculosis infection and disease using a mathematical model [version 1; peer review: 1 approved with reservations, 1 not approved]

Résumé

Background: Tuberculosis (TB) disease burden is determined by both infection and progression rate to disease. Progression rate varies by immune status, with prior infection in high burdened settings significantly reducing the progression to disease from subsequent reinfections and completion of successful treatment associated with increased risk of subsequent TB disease. Novel studies of TB vaccines are now underway targeting high risk individuals who have completed successful combination TB chemotherapy for active TB. Methods: In our study, we explored the impact of effective contact rate (β) and post-treatment immune status on population TB burden using a mathematical model incorporating five immunological states; susceptible, newly infected, reinfected, active TB and treated TB. Results: We found that the number of newly infected individuals increased with increasing values of β< 10yr -1 , but declined when β> 10yr -1 . Corresponding numbers of reinfected individuals increased with increasing values of β irrespective of post-treatment immune status. Furthermore, we noted that the number of active TB cases decreased by 7 - 17% when treated individuals moved to either newly infected or reinfected immune states, respectively, rather than to the fully susceptible state at values of β< 10yr -1 . The corresponding declines in TB burden were only 2 - 7% at values of β> 10yr -1 . Results show that TB prevalence in high burden settings is primarily driven by effective contact rates, which are significantly modified by pre- and post-treatment immune factors. Conclusions: The observation that impact of post-treatment immune status modification on population burden may be diminished in very high burdened settings will be important for vaccine design.

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