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Multinational Influenza Seasonal Mortality Study (MISMS)

The Multinational Influenza Seasonal Mortality Study (MISMS), an international collaborative effort to analyze the epidemiology and evolution of influenza viruses globally, is led by Fogarty's Division of International Epidemiology and Population Studies (DIEPS). Since 2005, MISMS has worked to advance evidence-based policies for influenza control in the U.S. and globally.In recent years, the program has been expanded to study program into other respiratory pathogens, including RSV and SARS-CoV-2. The program, based at NIH and led by a core team of Fogarty scientists, focuses on research and training activities, with a concentration on low- and middle-income countries (LMICs).

Illustration of a virus - MISMSMISMS aims to advance the understanding of influenza virus epidemiology and evolution through scientific research; and to build analytical capacity in influenza research (e.g., time-series analyses, mathematical models, phylogenetic analysis). The program:

  • Holds hands-on training workshops
    with global partners at the NIH, abroad, or virtually, to learn methods of influenza data analysis, including time-series, modeling and phylogenetic analysis
  • Hosts visiting guest researchers at the NIH (including the Short-Term Visiting Fellows program)
  • Establishes long-term collaborations with influenza researchers globally to facilitate data-sharing and large-scale studies of disease dynamics
  • Participates in global initiatives to advance influenza research with partners, including the Centers for Excellence in Influenza Research (CEIRS), led by the National Institute of Allergy and Infectious Disease (NIAID); the U.S. Centers for Diseases Control and Prevention (CDC); and the World Health Organization (WHO)

Interested in co-hosting a workshop, visiting Fogarty as a guest researcher or requesting assistance with data analysis? Please email the MISMS team at ficmisms@mail.nih.gov.

MISMS Scientists

MISMS Staff at the National Institutes of Health

  • Amanda Perofsky, PhD, Post-doctoral Researcher
    Research Interests: Influenza epidemiology and transmission dynamics; evolution;primate microbial ecology; networks; human-animal interface

  • David Spiro, PhD, Division Director
    Research Interests: Influenza and other respiratory viruses

  • James R. Otieno, PhD, Post-doctoral Researcher
    Research Interests: Evolution of influenza, coronaviruses and other respiratory viruses; phylodynamics; phylogeography
  • Kaiyun (Sunky) Sun, PhD, Post-doctoral Researcher
    Research Interests: RSV seasonality; COVID-19 transmission and immunity, influenza transmission; vector-borne diseases; mathematical and network models

  • Nídia S. Trovão, PhD, Post-doctoral Researcher
    Research Interests: Evolutionary and spatio-temporal dynamics, Bayesian methods; phylogeography; phylodynamics; RNA viruses

  • Cécile Viboud, PhD, Staff Scientist
    Research Interests: Mortality burden of infectious disease, spatial and temporal transmission dynamics; mathematical modeling; seasonality

MISMS Affiliates

  • Gerardo Chowell, PhD
  • Bryan Grenfell, PhD
  • Jamie Lloyd-Smith, PhD
  • Andrew Rambaut, PhD

MISMS Alumni

  • Wladimir Alonso, PhD
  • Kimberly Bloom-Feshbach
  • Vivek Charu
  • Bob Gaffey
  • Aubree Gordon, PhD
  • Edward Holmes, PhD
  • Mark Miller, MD
  • Martha Nelson, PhD
  • Colin Russell, PhD
  • Lone Simonsen, PhD
  • Derek Smith, PhD
  • Katherine Sturm-Ramirez, PhD
  • Yi Tan, PhD
  • Daniel Weinberger, PhD

Past MISMS Guest Researchers

  • Cheryl Cohen
  • Alice Fusaro
  • Magnus Gottfredsson
  • Jong-Won Kang
  • Aba Mahamat
  • Anthony Newall
  • Baltazar Nunes
  • Nesli Saglanmak

MISMS Policy Implications

MISMS research has impacted policy decision-making in a number of ways, including:

  • Improving influenza vaccination strategies during pandemics based on the age-shift from elderly to younger adults
  • Seasonal influenza vaccine campaigns in children, who are key vectors of transmission in communities, can provide indirect protection to vulnerable seniors with low immune responses to vaccination and high mortality
  • Advising countries in tropical and sub-tropical regions on whether to use the Northern hemisphere or Southern hemisphere vaccine formulation, based on the seasonal timing of their influenza epidemics, which tends to be more variable than the winter epidemics seen in temperate regions
  • Recognizing role of humans in transmitting influenza viruses to animals (reverse zoonosis), including transmission of pandemic H1N1 viruses from humans to swine and to zoo animals

Addressing pandemic threats

As we have seen with COVID-19, pandemics can have devastating and long-lasting impacts. A future pandemic could have a severe impact on the global economy, reducing global GDP by an estimated 5-12%. Much of the economic cost is driven by the disruptive impact of avoiding infection (estimated 60%). These costs could be reduced substantially by a robust response, including strategic use of vaccine, antivirals, and potentially school closings or other public health measures. In addition, by studying how influenza viruses evolve in animal reservoirs (particularly birds and pigs), and periodically infect humans, we might be able to avert a future pandemic before it becomes transmissible in humans. By working collaboratively with researchers across the world, in both human and veterinary health, the MISMS network strives to build analytical capacity globally and understand fundamental dynamics of pandemics - whom they infect, how they spread between locations, and how human-adapted viruses disseminate between countries - so that global pandemic responses around the world will be informed by the best science available, based on data collected by as many global partners as possible.

MISMS Influenza Research

  • Used vital statistics data from over 15 countries on six continents to elucidate the direct and indirect impact of seasonal and pandemic influenza viruses on pneumonia and chronic comorbid conditions in temperate and tropical environments.
  • Assessed the low effectiveness of vaccines among elderly populations, leading to new strategies to optimize direct and indirect protection for vulnerable populations. MISMS also increased interest in vaccine dosages, multiple doses, and the use of vaccine adjuvants in certain populations.
  • Evaluated the global patterns of transmission and evolution for A(H3) and A(H1) influenza across time and space, accounting for shift and drift patterns of influenza in tropical and temperate areas. Findings demonstrate the sink-source ecological role of temperate and tropical regions in virus evolution and transmission.
  • Antiviral resistance to adamantane drugs evolved not due to antiviral overuse but rather due to ‘genetic hitch-hiking’ via the reassortment of resistant gene segments with those coding for more fit hemagglutinin proteins.
    Simonsen et al., 2007, Nelson et al., 2009
  • Analyzed age-specific patterns of past pandemics to underscore the importance of virus subtype reemergence and the phenomenon of relative immunity in older populations. These findings have helped establish priorities for control towards younger populations in resource-constrained pandemic settings.
  • Ascertained the transmission patterns of influenza viruses associated with climate in Brazil and globally; established a prospective cohort influenza study in Central America.
    Alonso et al., 2007, Gordon et al., 2009, Tamerius et al 2013

Pandemic H1N1

  • MISMS scientists were at the forefront of influenza research that drives policy, including during the early stages of the 2009 H1N1 influenza pandemic.
  • Where did the 2009 H1N1 virus originally evolve in pigs? (Smith et al., 2009 Nature; Mena et al., 2016 eLife;Trovão NS, Nelson MI. 2020. PLoS Pathogens)
  • How did the virus spread globally in humans? Where did the first outbreak occur? (Lemey et al., 2009 PLoS Currents).
  • Which human populations were at risk for severe disease and should be given priority for limited vaccine stocks?
  • Why did some countries experience higher morbidity and mortality during the pandemic than others?


  • Should large countries like Brazil and China that span temperate and tropical areas use different influenza vaccines (Northern versus Southern hemisphere) in different regions?
  • Can we better predict which influenza virus strains should be included in next year’s vaccine?
  • Would using different age groups for vaccine prioritization prevent more disease at a community level?

Disease Burden

  • Does influenza cause a greater burden of disease in tropical countries than recognized
  • Are tropical countries central to the evolution and persistence of influenza viruses globally?

Animal-human interface

  • What is the frequency of human-to-swine transmission?
  • How does international trade of live swine spread influenza viruses around the world, creating opportunities for novel pandemic viruses to emerge from pigs?
  • How can we break transmission of influenza viruses in US exhibition swine?

Updated November 16, 2022