The Epidemic Impact of Therapy for Early Latent Tuberculosis Infection

Abstract

PURPOSE: Contact investigation programs that identify and offer therapy to persons in the early stage of latent tuberculosis (TB) infection may have a substantial impact on the epidemic, since these programs identify individuals who are at high risk of developing active TB. We quantify the impact that treatment of persons with early latent TB infection has on TB incidence and identify the combination of rates of treatment for active TB and treatment for early latent TB infection which will eliminate a TB epidemic. METHODS: A mathematical model of a TB epidemic is formulated which divides infected persons into 3 subgroups: early latent TB infection (early LTBI), long-term latent TB infection (long-term LTBI), and active TB. Infected persons are initially considered to be in the early LTBI phase, from which they can either progress to long-term LTBI, or to active TB. Persons with long-term LTBI also progress to active TB, but at a lower rate. The basic reproductive rate is derived for the model and used to calculate the combinations of therapy for active TB and early LTBI which will eliminate the epidemic. (The basic reproductive rate is defined as the number of secondary cases caused by one infectious case in a population of susceptible persons. When the basic reproductive rate is less than 1, the epidemic will eventually be eliminated.) Computer simulations of the model are used to demonstrate the impact over time of increasing treatment for early LTBI. RESULTS: The model demonstrates that the addition of a program which treats persons with early LTBI will substantially reduce incidence of active TB, and in some cases, may eliminate the epidemic. For example, if the initial annual incidence of active TB in a population is constant at 110 per 100,000 persons, and the current treatment rate for active TB is 80%, then adding a program which treats 20% of persons with early LTBI will reduce the annual incidence of active TB to 42 per 100,000 persons. Under the same initial conditions, the addition of a control program which treats over 33% of persons with early LTBI will lead to eventual elimination of TB. CONCLUSION: Treatment of early latent TB infection is an effective adjunct to treatment of active TB in controlling TB epidemics. Extending programs such as contact investigation which identify persons with recent infection will substantially impact TB epidemics.