Fogarty's RAPIDD program has catalyzed the field of infectious disease modeling

May / June 2016 | Volume 15, Issue 3

Researcher wearing protective face mask and gloves holds small brown rodent up to the camera
Photo by Dr. Angie Luis/
University of Montana

RAPIDD's small mammals working group
is studying how diseases might jump the
species barrier and travel from animals to
humans.

By Karin Zeitvogel

In just seven years, Fogarty's Research and Policy for Infectious Disease Dynamics (RAPIDD) group catalyzed major advances in infectious disease modeling, and helped to grow the discipline from one with little impact on public health policy decisions to one that government agencies and major international groups have incorporated into their operations, veterans of the group said.

"Things have come a long way," said Fogarty senior scientist Dr. Ellis McKenzie, who co-founded RAPIDD in 2008.

The group has punched above its weight class in the modeling world, with RAPIDD researchers publishing more than 900 peer-reviewed papers, which have been cited more than 23,500 times, and organizing 114 workshops that have drawn more than 800 scientists from 39 countries.

Supported over its 7-year existence with $17.3 million from the Department of Homeland Security, RAPIDD has achieved its main objective of improving the modeling of infectious diseases. Since it began, RAPIDD has been credited with enhancing the understanding of pathogens ranging from measles, Ebola and rabies to the less well known Nipah virus and the Leptospirosa interrogans bacterium.

RAPIDD's work has helped to establish infectious diseases modeling as an essential weapon in the arsenals of both policymakers and scientists, said the group's co-founder, Dr. Bryan Grenfell of Princeton University.

"Modeling is a very cost-effective way of thinking about how to control an outbreak. It helps us to summarize our biological understanding, and suggests what key data we need to collect next," Grenfell said. "Ellis McKenzie and his colleagues are world-leading scientists in infectious disease dynamics. In RAPIDD, they were able to bring together pre-eminent researchers whose modeling work will impact policymaking long into the future."

The 85 core faculty and junior researchers, and 13 postdoctoral fellows who were involved in RAPIDD often pivoted quickly and applied information gathered in earlier modeling exercises to new outbreaks. Modelers who worked on how dengue is transmitted, for instance, "almost instantly" produced a map showing the projected spread of Zika throughout the Americas after Brazilian officials reported a surge in infections and microcephalic births, McKenzie said. Dengue and Zika are carried by the same mosquito, the Aedes aegypti.

Global Distribution of Dengue

Reprinted by permission Macmillan Publishers Ltd Nature 2013, map of global dengue distribution, described #denguemapdescription
Reprinted by permission from Macmillan Publishers Ltd: Nature, 2013

RAPIDD modelers mapped the global burden of dengue, which was found to be higher than policymakers thought. For full details see long description below.

Source: The global distribution and burden of dengue, Nature, April 7, 2013

"RAPIDD's small structure and lack of bureaucracy also allowed it to quickly convene workshops, often in the middle of an outbreak," Grenfell noted. In March 2015, for example, as the WHO reported more than 10,000 Ebola deaths in Guinea, Liberia and Sierra Leone, a RAPIDD working group held a model comparison workshop, which gave rise to a months-long competition in which modelers from the U.S., U.K. and Canada tried to predict Ebola would peak in Liberia and how it would progress between September and December 2015. Most accurately forecast the time of peak infection, and even the weakest model held useful information, showing that transmission is not exponential at the beginning of an outbreak.

RAPIDD modelers often thought creatively to find ways to produce the information that policymakers need to resolve a health problem. For example, given the reluctance of ranchers to grant scientists access to their land so that they could gather data on the movement of livestock, which would help to prepare for a potential outbreak of foot and mouth disease in the U.S., a RAPIDD postdoctoral fellow devised a way to use veterinary records and licenses that ranchers are obliged to file, and arrived at "some pretty good guesses as to what was going on," McKenzie said.

The scientists also undertook large-scale reviews of previous modeling exercises to identifying gaps in the field. One such review looked at nearly 400 models of mosquito-borne pathogen transmission, conducted between 1970 and 2010. The analyses of previous modeling exercises, in addition to primary research done by RAPIDD, together formed a substantial body of work that McKenzie and Grenfell call "case law." When there is a new outbreak, modelers can refer to the case law and advise decision makers that "if it is like this other pathogen, then here's what we should do while we're learning more," McKenzie said.

RAPIDD helped to narrow the gap between what researchers want from modeling - information that allows them to compare strategies for tackling an outbreak and identifying knowledge gaps - and the actionable data that policymakers seek.

For instance, RAPIDD modelers estimated that around one million children in Liberia, Sierra Leone and Guinea were vulnerable to measles following the suspension of vaccination campaigns during the 2014 Ebola outbreak.

"The message was that you have to mount an aggressive vaccination campaign when Ebola subsides," McKenzie said. That message plea appears to have been heeded by public health authorities, as measles vaccination campaigns targeting several million children were launched in Sierra Leone and Guinea in October 2015 and in Liberia a few months earlier.

Another sign of RAPIDD's success is that most of the group's postdoctoral fellows have gone on to tenure-track faculty positions at top U.S. universities, where they are "educating future generations of modelers to further strengthen the field," McKenzie said. Among them, Dr. Virginia Pitzer is an assistant professor at Yale University, where her research includes an NIH-funded project to develop statistical and mathematical models that can be used to improve understanding of rotavirus immunity and transmission in developing countries. Dr. Angela Luis, who led many of the projects in RAPIDD's small mammals working group - affectionately known as the bats and rats group - uses mathematical models in her lab at the University of Montana to predict what leads to an outbreak, when one might occur and how a disease jumps the species barrier from animal to human.

Two bats with wings spread soar, mathematical equations display in background
Image courtesy of Plowright Lab

At Notre Dame University, former RAPIDD fellow, Dr. Alex Perkins, applies mathematical, computational and statistical approaches to better understand the dynamics of infectious disease transmission and control. And Dr. Juliet Pulliam, who was part of a research team that used simulations to help inform study design decisions for vaccine trials during the West African Ebola epidemic, and whose research has included work that identified what was driving Nipah virus emergence in Bangladesh, has been named director of the South African Centre for Epidemiological Modelling and Analysis (SACEMA).

Pulliam credited RAPIDD with "changing the landscape of infectious disease modeling" by pushing researchers to do comprehensive reviews of previous studies and undertake their own research.

RAPIDD's directors hope to procure funding to allow several working groups to continue their research, covering everything from the selection of a vaccine strain for seasonal flu to drug resistance and emerging human and animal infections in small mammal reservoirs. Keeping the working groups up and running is essential to allow scientists to act quickly when "something even more unknown than Zika comes to whack us," McKenzie said.

Grenfell agreed.

"Zika underlines to us that we never know what will emerge as the next threat," he said. "RAPIDD has taught us that by modeling a wide and diverse range of diseases - not just immediate threats - we're better prepared to react to the next threat."

More Information


Long description of Global Distribution of Dengue heat map: A map of the world showing the countries in which modelers predicted dengue was present or absent in 2010, based on scientific evidence. Dark green indicates a complete absence of dengue, while red indicates a complete presence. Countries where there was a complete presence of dengue include Brazil and all other South American countries other than Argentina, Chile and Uruguay; Mexico, all of Central America, the Caribbean; most of West Africa, except for Equatorial Guinea, Liberia, Mauritania, the Republic of Congo and Togo (indeterminable or poor evidence); East Africa, Madagascar, Yemen; and South and Southeast Asia.

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