Modelling the performance of isoniazid preventive therapy for reducing tuberculosis in HIV endemic settings: the effects of network structure

J R Soc Interface. 2011 Oct 7;8(63):1510-20. doi: 10.1098/rsif.2011.0160. Epub 2011 Apr 20.

Abstract

Individuals living with HIV experience a much higher risk of progression from latent M. tuberculosis infection to active tuberculosis (TB) disease relative to individuals with intact immune systems. A several-month daily course of a single drug during latent infection (i.e. isoniazid preventive therapy (IPT)) has proved in clinical trials to substantially reduce an HIV-infected individual's risk of TB disease. As a result of these findings and ongoing studies, the World Health Organization has produced strong guidelines for implementing IPT on a community-wide scale for individuals with HIV at risk of TB disease. To date, there has been limited use of IPT at a community-wide level. In this paper, we present a new co-network model for HIV and TB co-epidemics to address questions about how the population-level impact of community-wide IPT may differ from the individual-level impact of IPT offered to selected individuals. In particular, we examine how the effect of clustering of contacts within high-TB incidence communities may affect the rates of re-infection with TB and how this clustering modifies the expected population-level effects of IPT. We find that populations with clustering of respiratory contacts experience aggregation of TB cases and high numbers of re-infection events. While, encouragingly, the overall population-level effects of community-wide IPT appear to be sustained regardless of network structure, we find that in populations where these contacts are highly clustered, there is dramatic heterogeneity in the impact of IPT: in some sub-regions of these populations, TB is nearly eliminated, while in others, repeated re-infection almost completely undermines the effect of IPT. Our findings imply that as IPT programmes are brought to scale, we should expect local heterogeneity of effectiveness as a result of the complex patterns of disease transmission within communities.

MeSH terms

  • Africa South of the Sahara / epidemiology
  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / therapeutic use
  • Computer Simulation
  • Contact Tracing / methods*
  • Endemic Diseases
  • HIV Infections / complications*
  • HIV Infections / epidemiology
  • Humans
  • Isoniazid / administration & dosage*
  • Isoniazid / therapeutic use*
  • Models, Biological*
  • Time Factors
  • Tuberculosis / epidemiology
  • Tuberculosis / prevention & control*

Substances

  • Antitubercular Agents
  • Isoniazid