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Phylogeography of Influenza A(H3N2) Virus in Peru, 2010–2012 - Volume 21, Number 8—August 2015 - Emerging Infectious Disease journal - CDC

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Phylogeography of Influenza A(H3N2) Virus in Peru, 2010–2012 - Volume 21, Number 8—August 2015 - Emerging Infectious Disease journal - CDC

Volume 21, Number 8—August 2015


Phylogeography of Influenza A(H3N2) Virus in Peru, 2010–2012

Simon PollettComments to Author , Martha I. Nelson, Matthew Kasper, Yeny Tinoco, Mark Simons, Candice Romero, Marita Silva, Xudong Lin, Rebecca A. Halpin, Nadia Fedorova, Timothy B. Stockwell, David Wentworth, Edward C. Holmes, and Daniel G. Bausch
Author affiliations: University of California San Francisco, California, USA (S. Pollett)United States Naval Medical Research Unit No. 6, Lima, Peru (S. Pollett, M. Kasper, Y. Tinoco, M. Simons, C. Romero, M. Silva, D.G. Bausch)University of Sydney, Sydney, New South Wales, Australia (S. Pollett, E.C. Holmes)National Institutes of Health, Bethesda, Maryland, USA (M.I. Nelson)Arizona State University, Tempe, Arizona, USA (M.I. Nelson)J. Craig Venter Institute, Rockville, Maryland, USA (X. Lin, R.A. Halpin, N. Fedorova, T.B. Stockwell, D. Wentworth);Tulane School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA (D.G. Bausch)


It remains unclear whether lineages of influenza A(H3N2) virus can persist in the tropics and seed temperate areas. We used viral gene sequence data sampled from Peru to test this source–sink model for a Latin American country. Viruses were obtained during 2010–2012 from influenza surveillance cohorts in Cusco, Tumbes, Puerto Maldonado, and Lima. Specimens positive for influenza A(H3N2) virus were randomly selected and underwent hemagglutinin sequencing and phylogeographic analyses. Analysis of 389 hemagglutinin sequences from Peru and 2,192 global sequences demonstrated interseasonal extinction of Peruvian lineages. Extensive mixing occurred with global clades, but some spatial structure was observed at all sites; this structure was weakest in Lima and Puerto Maldonado, indicating that these locations may experience greater viral traffic. The broad diversity and co-circulation of many simultaneous lineages of H3N2 virus in Peru suggests that this country should not be overlooked as a potential source for novel pandemic strains.
Worldwide, influenza virus causes substantial illness and death and considerable public health costs (1). Like other countries, Peru experiences a significant number of influenza cases (2,3). The epidemiology of influenza virus in tropical and low- to middle-income countries and the role they play in global influenza ecology remains unclear (4). One outstanding question is whether a global source–sink dynamic exists. In the source–sink model, countries have putative tropical sources of influenza characterized by year-round (or multiannual) transmission, local persistence of influenza lineages, and relatively high genetic diversity. Then, it is postulated, that influenza lineages migrate and seed seasonal epidemics in cooler temperate regions, where they experience interseasonal extinction (5). Determining if and where this source–sink dynamic exists is of major importance because the results could guide targeted influenza surveillance for vaccine recommendations, pandemic planning, and prediction of novel strains (4,6).
Most analyses of whether a global source population exists have focused on East and Southeast Asia, in part because several pandemic and seasonal epidemics appear to have originated in those areas (711). Because of the lower availability of local influenza sequence data from tropical Latin America, relatively little is known about the possible role that region plays in global influenza dynamics (12). Nonmolecular epidemiologic studies have hinted at climate-driven patterns of influenza virus spread in South America; for example, diffusion of influenza activity from tropical to temperate areas has been noted in Brazil (13). Peru’s diverse climates make it an ideal location to test aspects of the source–sink model in Latin America, particularly because some tropical areas in Peru are known to experience year-round influenza activity (14). In recent years, prospective community-based influenza-like illness (ILI) surveillance cohorts were established in multiple regions of Peru, providing a unique opportunity to examine the epidemiology of human influenza virus (15).
Our study objectives were to determine whether 1) a source–sink influenza dynamic exists within Peru, including the existence of genetically diverse hubs and virus lineage persistence between seasons; 2) Peru could act as a global source for influenza virus lineages that could seed temperate regions; and 3) influenza virus is circulating within Peru in a closed system. We also sought to compare the spatial dynamics of influenza A(H3N2) virus across the 4 climatically and demographically diverse Peruvian sites.
We based our analysis on human influenza A(H3N2) virus because, over a long-term scale, it is the best represented lineage in sequence databases, and it has caused regular seasonal influenza epidemics in both hemispheres, including in Latin America (16,17). Although much attention has been paid to the study of pandemic influenza A(H1N1)pdm09 virus (18), H3N2 virus remains a significant cause of influenza in Peru, is a dominant seasonal influenza A virus subtype in other regions of the world, and causes substantial illness and death in Peru and beyond. A key aspect of this study is that we obtained samples from diverse ecologies and populations, including viruses from large urban and semirural locations and diverse altitudes and climates, and the distance between study sites was sufficient to allow spatial analysis. In addition, the prospective cohort studies involved continuous, active, year-round surveillance that enabled capture of any interseasonal strains.
Dr. Pollett is an infectious disease physician and research scientist affiliated with the University of California San Francisco, the Marie Bashir Institute at the University of Sydney, and NAMRU-6. His main focus of research is in the molecular and digital epidemiology of communicable diseases, particularly in tropical regions.


We thank all participants and households who enrolled in this study, and we thank Sebastian Loli for his assistance. We gratefully acknowledge the authors and originating and submitting laboratories of the sequences from the Global Initiative on Sharing Avian Influenza Data EpiFlu Database that were used as comparator sequences for this research; accession numbers are listed in online Technical Appendix Table 4.
The study was funded by the CDC; the National Institutes of Health, Fogarty International Center; and the US Department of Defense Global Emerging Infections Surveillance (grant no. I0082_09_LI). Sequencing was performed by the J. Craig Venter Institute as a partner to the National Institute of Allergy and Infectious Disease’s Influenza Genome Sequencing Project. E.C.H. is supported by a National Health and Medical Research Council fellowship from the Australian government (AF30).


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Technical Appendix

Suggested citation for this article: Pollett S, Nelson MI, Kasper M, Tinoco Y, Simons M, Romero C, et al. Phylogeography of influenza A(H3N2) virus in Peru, 2010–2012. Emerg Infect Dis. 2015 Aug [date cited].
DOI: 10.3201/eid2108.150084

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