Heterogeneous infectiousness in mathematical models of tuberculosis: A systematic review

TB mathematical models employ various assumptions and approaches in dealing with the heterogeneous infectiousness of persons with active TB. We reviewed existing approaches and considered the relationship between them and existing epidemiological evidence. We searched the following electronic bibliographic databases from inception to 9 October 2018: MEDLINE, EMBASE, Biosis, Global Health and Scopus. Two investigators extracted data using a standardised data extraction tool. We included in the review any transmission dynamic model of M. tuberculosis transmission explicitly simulating heterogeneous infectiousness of person with active TB. We extracted information including: study objective, model structure, number of active TB compartments, factors used to stratify the active TB compartment, relative infectiousness of each active TB compartment and any intervention evaluated in the model. Our search returned 1899 unique references, of which the full text of 454 records were assessed for eligibility, and 99 studies met the inclusion criteria. Of these, 89 used compartmental models implemented with ordinary differential equations, while the most common approach to stratification of the active TB compartment was to incorporate two levels of infectiousness. However, various clinical characteristics were used to stratify the active TB compartments, and models differed as to whether they permitted transition between these states. Thirty-four models stratified the infectious compartment according to sputum smear status or pulmonary involvement, while 18 models stratified based on health care-related factors. Variation in infectiousness associated with drug-resistant M. tuberculosis was the rationale for stratifying active TB in 33 models, with these models consistently assuming that drug-resistant active TB cases were less infectious. Given the evidence of extensive heterogeneity in infectiousness of individuals with active TB, an argument exists for incorporating heterogeneous infectiousness, although this should be considered in light of the objectives of the study and the research question. PROSPERO Registration: CRD42019111936.