title: Modelling the performance of isoniazid preventive therapy for reducing tuberculosis in HIV endemic settings: the effects of network structure.
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.
authors.affiliation: Bristol Centre for Complexity Sciences, University of Bristol, Bristol, UK. harriet.l.mills@gmail.com
authors.forename: H L
authors.initials: HL
authors.lastname: Mills
authors.forename: T
authors.initials: T
authors.lastname: Cohen
authors.forename: C
authors.initials: C
authors.lastname: Colijn
mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000627:therapeutic use; D003198:Computer Simulation; D016358:Contact Tracing / Q000379:methods*; D019353:Endemic Diseases; D015658:HIV Infections / Q000150:complications* / Q000453:epidemiology; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage* / Q000627:therapeutic use*; D008954:Models, Biological; D013997:Time Factors; D014376:Tuberculosis / Q000453:epidemiology / Q000517:prevention & control*
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid