Multinational Influenza Seasonal Mortality Study (MISMS)

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?

Vaccine

• 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?