Coinfections by noninteracting pathogens are not independent and require new tests of interaction

PLoS Biol. 2019 Dec 3;17(12):e3000551. doi: 10.1371/journal.pbio.3000551. eCollection 2019 Dec.

Abstract

If pathogen species, strains, or clones do not interact, intuition suggests the proportion of coinfected hosts should be the product of the individual prevalences. Independence consequently underpins the wide range of methods for detecting pathogen interactions from cross-sectional survey data. However, the very simplest of epidemiological models challenge the underlying assumption of statistical independence. Even if pathogens do not interact, death of coinfected hosts causes net prevalences of individual pathogens to decrease simultaneously. The induced positive correlation between prevalences means the proportion of coinfected hosts is expected to be higher than multiplication would suggest. By modelling the dynamics of multiple noninteracting pathogens causing chronic infections, we develop a pair of novel tests of interaction that properly account for nonindependence between pathogens causing lifelong infection. Our tests allow us to reinterpret data from previous studies including pathogens of humans, plants, and animals. Our work demonstrates how methods to identify interactions between pathogens can be updated using simple epidemic models.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Coinfection / epidemiology*
  • Cross-Sectional Studies
  • Epidemics / statistics & numerical data
  • Host-Pathogen Interactions / physiology*
  • Humans
  • Infections / epidemiology*
  • Models, Biological
  • Prevalence

Grants and funding

This work was initiated during the Multiscale Vectored Plant Viruses Working Group at the National Institute for Mathematical and Biological Synthesis, supported by the National Science Foundation through NSF Award \#DBI-1300426 (LJG), with additional support from The University of Tennessee, Knoxville (LJG). This material is based upon research supported by the Thomas Jefferson Fund of the Embassy of France in the United States (FMH and VAB), the FACE Foundation (FMH and VAB), and Girton College, University of Cambridge (NJC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.