Research

Prior to the introduction of routine vaccination in 2006, epidemics of rotavirus-associated gastroenteritis (RVGE) occurred each winter in the US, beginning in the southwestern states and “spreading” to the northeast. We were able to link this pattern of epidemics to underlying variation in birth rates across states. Vaccination has had a profound impact on rotavirus in the US and other high-income countries, both decreasing the incidence of RVGE and altering the pattern and timing of epidemics. The mathematical models we developed have been instrumental in helping to understand and anticipate these changes, and in predicting the “herd immunity” effects of vaccination.

Despite the introduction of live oral rotavirus vaccines into more than 90 countries worldwide, rotavirus remains a leading cause of severe diarrhea in children and a major source of morbidity and mortality in low- and middle-income countries (LMICs). The response, efficacy, and impact of current live oral rotavirus vaccines is lower in LMICs for reasons that are still not fully understood. New vaccines and approaches may be needed to overcome the poor immune response to current live oral rotavirus vaccines in LMICs. We are working with collaborators in Bangladesh, Malawi, and Ghana to use mathematical models to better understand pre-vaccination rotavirus dynamics and to predict the potential impact of different rotavirus vaccination strategies, accounting for both the direct and indirect effects of vaccination. We are also conducting economic evaluations to determine the most cost-effective approach to reducing the burden of diarrhea due to rotavirus in these countries and other LMICs. Our analyses will help to better define the vaccine response, duration of immunity, and price at which next-generation rotavirus vaccines are likely to be cost-effective, and will provide a validated platform that decision-makers in LMICs can use to weigh the costs and benefits of different rotavirus vaccination strategies.

Salmonella Typhi and Paratyphi A are another major source of morbidity and mortality in many LMICs, but the burden of typhoid and dynamics of transmission are poorly understood. Typhoid conjugate vaccines (TCVs) have recently been recommended by WHO, and Gavi, the Vaccine Alliance, has pledged financial support for TCV introduction in LMICs, but models are needed to evaluate the potential impact and cost-effectiveness of different vaccination strategies. We are working with collaborators to analyze data from field studies and clinical trials conducted in Bangladesh, Nepal, and Malawi. We are using these data to inform models to better understand the burden of typhoid fever and predict the impact and cost-effectiveness of different methods of typhoid control, including vaccination and investment in clean water and sanitation. We are also part of the Vaccine Impact Modeling Consortium (VIMC), which coordinates the work of several research groups modelling the impact of vaccination programs worldwide. We are one of two teams modeling the impact of vaccination on typhoid fever in 93 countries.

Respiratory syncytial virus (RSV) is the most common cause of childhood respiratory tract infections and hospitalizations worldwide. In addition to its long-term sequelae in children, such as increased risk of developing asthma, there is also mounting evidence suggesting RSV causes substantial burden among older adults and persons with underlying health conditions. There are currently no approved RSV vaccines; however, several promising candidates recently completed (or are currently in) clinical trials, and it is widely anticipated that one may be approved in the coming years. Unlike other common respiratory infections, such as influenza, much remains unknown about the factors driving variations in local seasonal RSV transmission dynamics. Our research focuses on 1) environmental factors driving large-scale variations in the peak timing of RSV across the US; 2) geographic and socio-demographic drivers of local RSV transmission dynamics; and 3) the implications of COVID-19 mitigation policies on disrupting the typical seasonal RSV season. We also collaborate with colleagues from the RSV Network (ReSViNet), located at the University Medical Center Utrecht in the Netherlands, on a number of RSV-related research projects.

Our group is currently contributing to a number of COVID-19-related projects, including: 1) Collaborating with researchers from KSM-Maccabi Healthcare Services in Israel to estimate the effectiveness of current COVID-19 vaccines in reducing household transmission of SARS-CoV-2. 2) Estimating the incidence of the COVID-19 infections and understanding patterns of transmission and disease across the US (https://covidestim.org/). 3) Examining the impact that COVID-19 mitigation policies have had on other respiratory infections, such as RSV.