Research Interests

The impact of human mobility on respiratory virus transmission

During the COVID-19 pandemic, aggregated location data from mobile phones became an important source of information on changes in population-level movements and the effectiveness of non-pharmaceutical interventions (NPIs) in mitigating SARS-CoV-2 spread. I began working with cellphone mobility data in 2020, first to inform forecasts of respiratory virus outbreaks on US military bases for US DoD, and then to retrospectively relate changes in population mobility to healthcare-seeking behavior in South Africa and respiratory virus transmission dynamics in Seattle.

In collaboration with Seattle Flu Alliance investigators, I studied how mobility and COVID-19 NPIs influenced the transmission dynamics of SARS-CoV-2 and 17 endemic respiratory viruses in the greater Seattle region during pre- and post-pandemic years (2018 - 2022) (Perofsky et al. 2024). We found that cellphone mobility is most predictive of respiratory virus transmission during periods of dramatic behavioral change (e.g., Seattle’s stay-at-home orders in March 2020). However, smaller-scale changes in mobility also correlate with increases in transmission at the beginning of epidemic waves and with declines in transmission during shorter interruptions to population movement (e.g., a pre-pandemic snowstorm). Interestingly, the transmission dynamics of endemic viruses had stronger, longer-lasting associations with mobility than pandemic SARS-CoV-2. As an extension of this work, we are using mechanistic transmission models, informed by mobility and serology data, to study the relative impacts of waning immunity and decreased social distancing on the post-pandemic rebound of respiratory syncytial virus (RSV) in Seattle.

I have also collaborated with members of Trevor Bedford’s group (Fred Hutch) to relate cellphone mobility patterns to the genomic epidemiology of SARS-CoV-2 in Seattle-King County and Washington state.

Publications

  • Perofsky, A.C., et al. Impacts of human mobility on the citywide transmission dynamics of 18 respiratory viruses in pre- and post-COVID-19 pandemic years. 2024. Nature Communications, 15, 4164. DOI
  • Paredes, M.I., A.C. Perofsky, et al. Local-scale phylodynamics reveal differential community impact of SARS-CoV-2 in a metropolitan US county. 2024. PLOS Pathogens, 20(3), e1012117. DOI
  • Tran-Kiem, C., M.I. Paredes, A.C. Perofsky, et al. Fine-scale spatial and social patterns of SARS-CoV-2 transmission from identical pathogen sequences. 2024. medRxiv, 2024.05.24.24307811. Preprint
  • Perofsky, A.C., et al. The direct and indirect effects of the COVID-19 pandemic on private healthcare utilization in South Africa. 2022. Clinical Infectious Diseases, 75(1), e1000-e1010. DOI

Ecological and evolutionary drivers of influenza outbreaks in human and animal populations

The effects of antigenic drift on annual influenza epidemics in the United States

Collaborators: Cécile Viboud (NIH), John Huddleston (Fred Hutch), Trevor Bedford (Fred Hutch), Florian Krammer (Mt. Sinai), WHO Global Influenza Surveillance and Response System (GISRS) Collaborating Centers in Atlanta, London, Melbourne, and Tokyo

Influenza viruses continually accumulate genetic changes in epitopes of two major surface proteins, hemagglutinin (HA) and neuraminidase (NA), in a process known as “antigenic drift.” Antigenic drift helps the virus to escape immune recognition, leaving previously exposed individuals susceptible to reinfection and necessitating regular updates to the flu vaccine. Antigenic drift is expected to lead to more susceptible individuals and flu cases, in turn leading to earlier, larger, or more severe epidemics. However, prior evidence for the impact of antigenic drift on seasonal influenza outbreaks is conflicting. In a recent eLife article, we systematically compared experimental and sequence-based measures of A(H3N2) evolution in predicting regional epidemic dynamics in the US across 22 seasons, from 1997 to 2019. We also considered the effects of other co-circulating flu viruses, prior immunity, and vaccine-related parameters on A(H3N2) incidence.

We found that evolution in both major surface proteins contributes to variability in epidemic magnitude across seasons, though viral evolution appears to be secondary to subtype interference in shaping annual outbreaks. When comparing the predictive performance of different evolutionary indicators, genetic changes in broad sets of epitope sites had stronger, more consistent relationships with different measures of epidemic dynamics than the serological assays traditionally used to measure how flu viruses change from season to season. These findings have implications for the surveillance of evolutionary indicators that are most relevant for population impact and for the prediction of influenza burden on inter-annual time frames.

We are currently extending this research to assess the effects of antigenic drift and prior population immunity on A(H3N2) vaccine effectiveness in the US.

Publications

  • Perofsky, A.C., et al. Antigenic drift and subtype interference shape A(H3N2) epidemic dynamics in the United States. 2024. eLife 13:RP91849. DOI
  • Perofsky, A.C. and M.I. Nelson. Seasonal influenza: The challenges of vaccine strain selection. 2020. eLife 9:e62955. DOI (Insight article)

Influenza transmission dynamics among exhibition swine in the United States Midwest

Collaborators: Martha Nelson (NIH) and Andrew Bowman’s group (Ohio State)

Every summer in the US, youths attending agricultural fairs are exposed to genetically diverse influenza A viruses (IAVs) circulating in exhibition swine, resulting in hundreds of lab-confirmed zoonotic infections since 2010. Exhibition swine represent a small, defined population (1.5% of the U.S. herd), presenting a realistic opportunity to mitigate a pandemic threat. We analyzed virologic surveillance data collected from thousands of pigs attending 350 national, state, and local swine exhibitions across several states during 2016–2018.

Key findings include:

  • An early-season national show played a key role in the propagation and spatial dissemination of a specific virus (H1 δ-2) that became dominant among exhibition swine and was associated with the majority of zoonotic infections in 2018.
  • The earlier timing of jackpot shows and long-distance travel for repeated showing of individual pigs provides a pathway for the introduction of influenza into county fairs. Jackpot shows are held to specifically to show swine and do not include the community festival attractions found at state and county fairs.

Understanding the evolutionary origins of zoonotic IAVs and which types of exhibition shows are likely to have downstream effects on disease transmission can inform public health mitigation strategies to reduce zoonotic transmission and the risk of pandemic IAV emergence.

Publications

  • McBride, D. S.†, Perofsky, A. C.†, et al. Tracing the Source of Influenza A Virus Zoonoses in Interconnected Circuits of Swine Exhibitions. 2021. Journal of Infectious Diseases, 224(3), 458-468. DOI †Co-first authors
  • Nelson, M. I., Perofsky, A., et al. A Heterogeneous Swine Show Circuit Drives Zoonotic Transmission of Influenza A Viruses in the United States. 2020. Journal of Virology, 94(24). DOI

Operational involvement in the COVID-19 pandemic response and disease predictions

Submitted articles and reports

  • Mathis, S.M., A.E. Webber, …, A.C. Perofsky, … et al. (110 authors) Evaluation of FluSight influenza forecasting in the 2021-22 and 2022-23 seasons with a new target laboratory-confirmed influenza hospitalizations. 2023. medRxiv, 2023.12.08.23299726. Preprint
  • COVID-19 Private Consultations Excess Respiratory Encounters Reports, National Institute for Communicable Diseases, South Africa. Reports were updated on a biweekly or monthly basis from September 2020 to April 2022.

Doctoral research: Ecological, evolutionary, and behavioral determinants of gut microbiomes in Malagasy mammals.

Advisor: Lauren Ancel Meyers (UT-Austin); Collaborators: Rebecca Lewis (UT-Austin), Anthony Di Fiore (UT-Austin)

Mammalian gut microbial communities govern host development, metabolism, immune function, and physiology, through interactions that range from commensal and mutualistic to pathogenic. However, the relative contributions of vertical, horizontal, and environmental transmission to gut microbiome composition are not well understood. For my PhD research, I integrated field-collected data, molecular analyses, and computational and statistical approaches to study how social networks and proximity to other host species influence bacteria transmission and gut microbiome composition in the wild mammals inhabiting Kirindy Mitea National Park in western Madagascar. This research was conducted as part of The Sifaka Research Project, a long-term research study led by Dr. Rebecca Lewis (UT-Austin).

Key findings include:

  • The gut microbiomes of wild Verreaux’s sifaka (Propithecus verreauxi) clearly reflect their social group membership, and both grooming and scent-marking behaviors promote microbial exchange and within-host diversity.
  • Sifaka social groups harbor distinct gut microbial communities over the course of several years, and compositional changes in the microbiota of individual animals are influenced by the gain or loss of unique social partners and male dispersal between groups.
  • The ecological relationships among mammalian gut microbiomes mirror their hosts’ phylogeny.
  • The predicted functionality of lemur microbiomes differentiate according to diet, and distantly-related terrestrial mammals have overlapping microbial communities, suggesting that ground dwelling facilitates the indirect horizontal transmission of gut bacteria among sympatric wild mammals.

Together, these findings demonstrate that patterns of gut microbiome composition in wild mammals are scale-dependent: host phylogeny, diet, and substrate use shape microbial variation among sympatric mammal taxa, while social groupings and social contacts constrain the horizontal transmission of gut bacteria within a single host population.

Publications

  • Perofsky, A.C., L.A. Meyers, L.A. Abondano, A. Di Fiore, R.J. Lewis. Social groups constrain the spatiotemporal dynamics of wild sifaka gut microbiomes. 2021. Molecular Ecology 30: 6759–6775. DOI
  • Perofsky, A.C., R.J. Lewis, L.A. Meyers. Terrestriality and bacterial transfer: A comparative study of gut microbiomes in sympatric Malagasy mammals. 2018. The ISME Journal 13:50–63. DOI
  • Perofsky, A.C., R.J. Lewis, L. Abondano, A. Di Fiore, L.A. Meyers. Hierarchical social networks shape gut microbial composition in wild Verreaux’s sifaka. 2017. Proceedings of the Royal Society B: Biological Sciences 284:20172274. DOI
captured sifaka grooming
Left: Amanda Perofsky holding a sedated sifaka during the Sifaka Research Project’s annual capture in 2016. Right: Sifaka grooming at Ankoatsifaka Research Station in Kirindy Mitea National Park.

Predoctoral Research

I graduated from the University of Georgia in 2009 with degrees in Biology and Ecology. My undergraduate research focused on salamander ecology and population modeling (Maerz Lab, University of Georgia). After graduating, I worked as a research assistant in Andrew Park’s Lab (University of Georgia) investigating the environmental drivers of hemorrhagic disease outbreaks in white-tailed deer. As a National Institutes of Health post-baccalaureate fellow, I characterized viral profiles unique to Sjögren’s Syndrome (AAV Biology Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research).