High school students acted as health officials, responding to a simulated infectious disease outbreak public health crisis at the UofL Health Sciences Center on April 15. Event organizers from UofL’s School of Medicine and School of Public Health and Information Sciences and the Kentucky Department for Public Health guided approximately 20 Central High School students through a series of activities to identify the source of a disease outbreak and plan a response.

Presented with a health crisis scenario, the students researched three potential diagnoses, interviewed standardized patients and participated in a “tick drag” to gather insects they suspected to be the source of infections. After determining the outbreak was caused by Rocky Mountain Spotted Fever, the students designed a public health plan to curb the spread.��

The project was a pilot for a larger event to take place June 5 at Morehead State University for 32 students in the Rogers Scholars Program. It is designed to interest the students in health careers.

Microbiologists at the University of Louisville study Yersinia pestis, the bacteria that causes bubonic plague, however, because it has the potential to be used as a bioweapon and it provides knowledge that may help defeat other bacteria. Through this work, they have made an important discovery about a molecule secreted by Y. pestis and other bacteria that helps defeat the host’s immune defenses, allowing the bacteria to infect its hosts.

Sarah Price, a doctoral student researcher, and her mentor, Matthew Lawrenz, associate professor of microbiology and immunology, have found that yersiniabactin, a small molecule secreted by Y. pestis, gathers zinc, a necessary element for bacterial replication. This discovery may have implications in other infections as well since bacteria causing pneumonia, sepsis and other illnesses also are known to release yersiniabactin.

“While yersiniabactin’s role in iron acquisition has been well known for over 30 years, we were surprised to see its significant impact on zinc acquisition during Y. pestis infection,” Price said��“This is very exciting because it helps us understand how Y. pestis and other bacteria acquire nutrients that allow them to cause disease.”

Invading bacteria as well as the hosts they infect all require iron, zinc and other metals in order to grow. The host’s immune system employs a strategy called nutritional immunity to protect against these bacterial infections, sealing the metals away from the bacteria.

It has been known for many years that yersiniabactin defeats this defense by stealing away iron and delivering it into the bacterial cells. Price and Lawrenz have discovered that the molecule also is involved in securing zinc and perhaps even other metals to assist Y. pestis infection.

Yersiniabactin also is used by Escherichia coli, which causes a multitude of infections such as intestinal illness and kidney infections, and Klebsiella pneumoniae, which causes pneumonia and sepsis. These more common diseases can be life-threatening and multidrug-resistant infections. The new understanding may lead to additional strategies for controlling infection by all of these bacteria.

An article describing the research published Oct. 29 in ��provides details about how the researchers determined that yersiniabactin was responsible for the collection of not only iron, but zinc. Price is first author on the publication, “.” Lawrenz is senior author and researchers from the University of Kentucky, Washington State University and the University of Illinois also contributed to these studies.

“With this understanding of the broader role of yersiniabactin in plague infection, we can explore further to understand its role in enabling other bacteria to infect a human or other host,” Lawrenz said. “If this mechanism holds true across these bacteria, it may be possible to develop a drug or vaccine that could inhibit yersiniabactin’s effectiveness, thus preventing all of these infections.”

Bubonic plague most often is transmitted to humans through the bite of an infected flea, usually carried by a rodent. By not handling animal carcasses, preventing flea bites and avoiding contact with bodily fluids of those infected, the spread of bubonic plague is largely controlled. However, since human-to-human transmission is possible, mortality from an infection ranges from 30-to-90% and no vaccine is available to prevent the infection, it remains an important pathogen for research. In addition, Y. pestis, has the potential for weaponization and is considered a bioterrorism threat.

Lawrenz, Price and their colleagues conduct research within the , which focuses on the development of prevention and treatment strategies for infectious diseases and other harmful pathogens. Its researchers utilize the Regional Biocontainment Laboratory, a member of the National Institute of Allergy and Infectious Diseases network of 12 regional and 2 national biocontainment laboratories for studying infectious agents. The lab includes Biosafety Level 3 facilities built to the most exacting federal safety and security standards to protect researchers and the public from exposure to the pathogens being investigated.��

The center’s researchers were called upon in early 2020 to develop tests and prevention and treatment strategies against SARS-CoV-2, the virus that causes COVID-19. This work continues.

Bacteria called Group B Streptococcus or Streptococcus agalactiae (Group B strep, GBS) commonly live in people’s gastrointestinal and genital tracts. Most of the time, the bacteria are not harmful and do not make people feel sick or have any symptoms. Sometimes, however, the bacteria invade the body and cause certain infections, which are known as GBS disease. GBS bacteria can cause bacteremia (bloodstream infection) and sepsis (the body’s extreme response to an infection), meningitis, pneumonia, bone and joint and skin and soft-tissue infections. An invasive GBS infection is one that involves blood or internal organs, whereas a noninvasive infection could involve skin or other soft tissue, the urinary tract or bones and joints.

Previous studies describing the burden of GBS infection in adults have primarily focused on invasive disease because existing surveillance systems rely on blood culture collection. In the new study, however, non-invasive disease was three to four times more common than invasive disease, suggesting that adult GBS burden is considerably greater than previously recognized. Of the infections reviewed, 79% were non-invasive. In 60% of the infections, GBS was identified as the only pathogen.

“These new data suggest that the burden of GBS infection is considerably greater than previously recognized in earlier surveillance studies that only focused on invasive disease, ” said Julio Ramirez, MD, chief of the Division of Infectious Diseases at UofL. “Importantly, we found that the rates of GBS infection in this study are comparable to that of other adult infections for which vaccines are routinely recommended, which underscores the need for developing approaches for preventing this infectious disease among an aging adult population.”

In conducting the study, the researchers reviewed laboratory and medical records from six hospitals in Louisville between Jan. 1, 2014 and Dec. 31, 2016. Louisville’s population is generally similar to the United States in terms of demographics and prevalence of underlying chronic medical conditions.

Rates of GBS-associated hospitalization were significantly higher in adults 65 years and older, African Americans and people with underlying chronic medical conditions such as obesity, diabetes, chronic renal disease and coronary artery disease. The finding that obesity and diabetes put patients at increased risk for GBS-associated hospitalization is especially noteworthy given that recent Centers for Disease Control and Prevention reports have highlighted that 42% of U.S. adults are obese and that as many as 34 million American adults (roughly 13% of all U.S. adults) have diabetes, with another 88 million having pre-diabetes.

Additional findings from the study included the following:

• Annual rates of GBS infection in African American adults were 2.6 times higher than in white adults, or 157 per 100,000 in African American vs. 60 per 100,000 in white adults.
• Compared with the general population, annual GBS infection rates were 2 to 6 times higher among adults with underlying chronic medical conditions, such as chronic kidney disease, diabetes, obesity or heart disease.

“This type of study, evaluating both invasive and non-invasive GBS infections, is essential for understanding the full spectrum of GBS disease burden among adults,” said John M. McLaughlin, PhD, Global Epidemiology and Scientific Affairs Lead, Pipeline Vaccines, Pfizer Inc., and the lead study author. “These data should aid health care providers with clinical decision-making. Our population-based study gives the first estimates of total annual GBS burden in the United States, emphasizing the importance of preventive efforts in the growing population of adults who are older or have chronic medical conditions, and will inform future vaccination strategies.

In January, Pfizer launched its , a global program of collaborations with academic institutions to conduct real-world epidemiologic research to accurately identify and measure the burden of specific vaccine-preventable diseases and potentially evaluate vaccine effectiveness in adults. At that time, the UofL Division of Infectious Diseases was designated as the first . This collaboration is aimed at determining the human health burden of important infectious diseases and potential vaccine effectiveness

The GBS collaborative study between UofL and Pfizer was completed prior to the university being named as Pfizer Vaccine’s first Center of Excellence site.