Currently Funded Projects:

Surveillance Platform for Acute Illness: Respiratory and Enteric Pathogens (inSPIRE)
inSPIRE recruits Marshfield Clinic Health System patients when they present for clinical care of acute illnesses. The goals of this project are to estimate the incidence of medically-attended acute respiratory illness and acute gastroenteritis associated with a variety of common respiratory and gastrointestinal pathogens, to describe pathogen-specific outcomes and spectrum of clinical disease, assess immune responses to infection, and characterize the genetic diversity of infecting pathogens.   

Funding source: Industry
PI: Joshua Petrie, PhD, MPH and Huong Nguyen, PhD, MPH 


Prospective Assessment in a Community Cohort: Enteric and Respiratory Pathogens (PACC-ER)
PACC-ER is a community cohort study that will follow approximately 1,500 participants in the local area for up to 2 years. The goals of this project are to estimate the community incidence of acute respiratory illness and acute gastroenteritis associated with a variety of common respiratory and gastrointestinal pathogens, to describe pathogen-specific outcomes and spectrum of clinical disease, assess immune responses to infection and vaccination, and characterize the genetic diversity of infecting pathogens.   

Funding source: Industry
PI: Huong Nguyen, PhD, MPH and Joshua Petrie, PhD, MPH


SERVE – Optimal Strategies to Estimate the Relative Effectiveness of Influenza Vaccines 
There are many different influenza vaccine products available for use in the United States, but most have not been directly compared to determine if one product might work better than another. This information is needed to inform policymakers, healthcare providers, and the public on how influenza vaccines should be best used. In addition, new influenza vaccine products are expected in the coming years given rapid technology advancements during the COVID-19 pandemic, and ongoing efforts to develop a universal influenza vaccine. Therefore, the goal of this project is to develop strategies for comparing the effectiveness of current and novel influenza vaccines. 

Funding Source: Centers for Disease Control and Prevention 
PI: Joshua Petrie, PhD, MPH and Huong Nguyen, PhD, MPH 


First Influenza Infection and Immunization (FI3) 
A person’s first exposures to influenza during their life by infection or vaccination can affect how their immune system responds to future exposures. In this study we are studying how the immune response to influenza differs among children who are vaccinated against or infected with influenza for the first or second time in their lives. The information learned in this study could help improve how well future influenza vaccines work.  

Funding Source: National Institute of Allergy and Infectious Diseases 
PI: Joshua Petrie, PhD, MPH and Huong Nguyen, PhD, MPH 


Monitoring for Vaccine-Associated Enhanced Disease following COVID-19 Vaccines in the Vaccine Safety Datalink
The Marshfield Clinic Research Institute (MCRI) has received a 3 year award from the Centers for Disease Control and Prevention (CDC) to lead a study to assess vaccine-mediated enhanced disease (VMED) in the Vaccine Safety Datalink network. There is a theoretical risk that a COVID-19 vaccine could trigger an immune system response that increases the severity of a subsequent infection with SARS-CoV-2. Multiple studies of COVID-19 vaccines have found no evidence for VMED, but this study will monitor risk over time to ensure vaccine safety. It will also provide an estimate of COVID-19 vaccine effectiveness for preventing hospital admission.

Funding Source: Centers for Disease Control and Prevention
PI: Edward Belongia, MD


Vaccine Safety Datalink
Vaccines are rigorously evaluated for safety and efficacy during development, but post-licensure monitoring is essential to identify safety signals and maintain public confidence. MCRI is one of 13 organizations participating in the Vaccine Safety Datalink (VSD) project in collaboration with the Centers for Disease Control and Prevention (CDC). The VSD utilizes linked electronic health records to conduct observational studies of vaccine safety in different settings and populations, including near-real time safety monitoring for selected vaccines after licensure. Over 13 million individuals are represented in the VSD population each year, and more than 200 safety studies have been published by VSD investigators. MCRI has participated in VSD for more than two decades, and MCRI researchers are  currently leading near-real time safety assessment for RSV vaccine in older adults, a study of pneumococcal vaccine safety, and a study of epilepsy risk after early childhood vaccination.  More information about VSD is available at https://www.cdc.gov/vaccine-safety-systems/vsd/

Funding Source: Centers for Disease Control and Prevention
PI: Edward Belongia, MD and Maria Sundaram, PhD


SubLyme

CDC has established a multi-site collaboration to use electronic health records (EHRs) to strengthen Lyme disease (LD) surveillance by estimating the incidence of LD and monitoring epidemiologic trends in three endemic regions: Pennsylvania, Wisconsin/Michigan and Massachusetts/Maine. This network is called SubLyme (Surveillance Based Lyme Disease Network). Work done by the SubLyme network will inform future assessments of the effectiveness and impact of upcoming LD vaccines, and will be able to measure changes in LD incidence over time. Individual-level data will be extracted from medical records from each site, with manual medical chart reviews of a subset of individuals identified by LD diagnoses, tests, or medication orders. Information from chart reviews will serve to evaluate the performance of possible EHR algorithms, or computable phenotypes (CPs).

Funding Source: Centers for Disease Control and Prevention
PI: Anna Schotthoefer, PhD and Maria Sundaram, PhD

Recently Completed Projects:

Rapid Cycle Analysis (RCA) to Monitor the Safety of COVID-19 Vaccines in Near Real-Time
Multiple COVID-19 vaccines have been authorized or approved by the Food and Drug Administration and recommended by the Centers for Disease Control and Prevention (CDC); all have been subject to intensive safety evaluation. The Vaccine Safety Datalink (VSD) is a collaborative project between the CDC and thirteen integrated healthcare organizations; it is one of several systems monitoring the safety of COVID-19 vaccines in the U.S. As one of the VSD sites, Marshfield Clinic Research Institute (MCRI) received three years of funding from the CDC to co-lead a project that evaluated the safety of COVID-19 vaccines using near real-time surveillance of adverse events potentially associated with COVID-19 vaccines in the VSD population. This surveillance system provided an opportunity to identify potential vaccine safety issues in weeks or months rather than years. The Marshfield team worked closely with investigators at all VSD sites, and in particular with those at the CDC and Kaiser Permanente Northern California. The results of this surveillance were reassuring. The VSD surveillance confirmed results reported by others that two adverse events, myocarditis/pericarditis and Guillain-Barré Syndrome, were associated with specific vaccines in certain subgroups, although their occurrence was very rare.

The project was begun in late 2020 and ended in September 2024; results have been published in several journals:

Funding Source: Centers for Disease Control and Prevention
PI: James Donahue, PhD, DVM


Prospective Assessment of COVID-19 in a Community (PACC) 
This was a prospective cohort study of 1520 participants with weekly illness surveillance for up to 26 months conducted in collaboration with CDC and University of Wisconsin-Madison. Participant collected respiratory specimens with qualifying illness and serum specimens periodically to identify SARS-CoV-2 and influenza infections. Assessed incidence, seroprevalence, and vaccine effectiveness and immune response. Results have been published in several journals. 

Funding Source: Centers for Disease Control and Prevention 
PI: Huong Nguyen, PhD, MPH


Assessment of the Effectiveness of COVID-19 and Influenza Vaccines for Preventing Transmission in Households 
Transmission of respiratory viruses in households play a large role in the spread of epidemics. This was a case-ascertained household study that followed participants who have COVID-19 or influenza and their household contacts to describe how the SARS-CoV-2 and influenza virus spreads among household members and whether vaccination can help reduce the risk of transmission. Marshfield Clinic Research Institute (MCRI) is one of 7 enrollment sites in this respiratory virus transmission network led by investigators at Vanderbilt University Medical Center. Results have been published in several journals. 

Funding Source: Centers for Disease Control and Prevention 
PI: Huong Nguyen, PhD, MPH


Persistence of Measles, Mumps, and Rubella Antibodies following Receipt of a Third Dose of Measles-Mumps-Rubella (MMR) Vaccine 
In the United States, third doses of MMR vaccine have been administered in recent mumps outbreaks among highly vaccinated populations. Third doses are also routinely administered to military recruits, healthcare personnel, women of child-bearing age before becoming pregnant or after delivery, college students, and international travelers. However, data on the long term immune response to a third dose of MMR vaccine are limited. In 2009-10, young adults were vaccinated with a third dose of MMR vaccine and were followed through 11 years after receipt of the third dose to assess the long term immune response.  

Funding Source: Centers for Disease Control and Prevention 
PI: Huong Nguyen, PhD, MPH 


Understanding and Addressing the Disparity in Vaccination Coverage Among U.S. Adolescents Living in Rural Versus Urban Areas 
This was a multi-year, multi-component collaboration with the Minnesota Department of Health (MDH), Wisconsin Department of Health Services (WDHS), and Centers for Disease Control and Prevention (CDC) to better understand the determinants of rural-urban differences in vaccine uptake among adolescents in the upper Midwest. Surveys and qualitative interviews were used to inform interventions. Several reminder / recall interventions targeting adolescents in the Health System were developed, implemented, and evaluated to improve adolescent vaccination coverage and inform strategies to increase vaccination rates. Results have been published in several journals. 

Funding Source: Centers for Disease Control and Prevention  
PI: Huong Nguyen, PhD, MPH


Hospital-Associated Respiratory Virus Infections: Molecular Epidemiology, Clinical Outcomes, and Cost-Effectiveness of Interventions 
The major goals of this project were to determine the overall impact of hospital-associated respiratory virus infections, improve case-definitions for their identification, and determine the cost-effectiveness of interventions for their prevention. Results have been published in several journals.

Funding Source: National Institute of Allergy and Infectious Diseases 
PI: Joshua Petrie, PhD, MPH