Inferring transmission heterogeneity using virus genealogies: Estimation and targeted prevention

Spread of HIV typically involves uneven transmission patterns where some individuals spread to a large number of individuals while others to only a few or none. Such transmission heterogeneity can impact how fast and how much an epidemic spreads. Further, more efficient interventions may be achieved by taking such transmission heterogeneity into account. To address these issues, we developed two phylogenetic methods based on virus sequence data: 1) to generally detect if significant transmission heterogeneity is present, and 2) to pinpoint where in a phylogeny high-level spread is occurring. We derive inference procedures to estimate model parameters, including the amount of transmission heterogeneity, in a sampled epidemic. We show that it is possible to detect transmission heterogeneity under a wide range of simulated situations, including incomplete sampling, varying levels of heterogeneity, and including within-host genetic diversity. When evaluating real HIV-1 data from different epidemic scenarios, we found a lower level of transmission heterogeneity in slowly spreading situations and a higher level of heterogeneity in data that included a rapid outbreak, while R0 and Sackin’s index (overall tree shape statistic) were similar in the two scenarios, suggesting that our new method is able to detect transmission heterogeneity in real data. We then show by simulations that targeted prevention, where we pinpoint high-level spread using a coalescence measurement, is efficient when sequence data are collected in an ongoing surveillance system. Such phylogeny-guided prevention is efficient under both single-step contact tracing as well as iterative contact tracing as compared to random intervention.Author summary: Detecting and preventing pathogen outbreaks in the background of steady and slow spread is difficult, yet highly desirable, because such transmission heterogeneity can be a main driver of an epidemic. Hence, detection of transmission heterogeneity may direct prevention efforts and reduce future infections. While incidence and prevalence estimates may give overall indications of an epidemic’s progression, they typically cannot indicate episodic outbreaks or rapid spreads in subpopulations. Likewise, detailed and reliable information about dynamic social networks is rare and not generalizable to detect local outbreaks. HIV sequence data can be used to reconstruct HIV phylogenies, which due to HIV’s high evolutionary rate contain information about both transmission networks and rates of spread. Here, we use HIV phylogenies to first design a general heterogeneity detection method that can signal that there is high-level spreading present. Secondly, we develop a phylogenetic method to pinpoint which individuals that may have been infected by a super-spreader or have been involved in an outbreak. We show that using such phylogeny-guided information to prevent future HIV spread is highly efficient under many epidemiological situations, especially in typical public health situations where samples are collected through time.