MAC-Epid: Doing Battle with Bugs

Although epidemiologist Betsy Foxman doesn’t think of herself as a children’s health researcher, “it works out that that’s where the action is,” she says. Foxman and her colleagues in the UM Center for Molecular and Clinical Epidemiology of Infectious Diseases (MAC-EPID), which Foxman directs, study the transmission, pathogenesis, evolution, and ecology of infectious disease—and as anyone with a preschooler knows, children are prodigious carriers of bugs. So it’s hardly surprising that Foxman’s center is currently engaged in four studies focused on kids’ health:

  • Ear Infections: Although otitis media, or ear infection, is “not a killer, thank goodness,” says SPH epidemiologist Janet Gilsdorf, it’s nevertheless a “huge problem.” By the time they turn three years old, more than 80 percent of U.S. children have had at least one episode of acute otitis media, and 40 percent have had three or more infections. Not only do ear infections keep parents awake at night, but nationwide the annual cost of preventing, diagnosing, and treating otitis media ranges from three to five billion dollars. Gilsdorf and her colleagues in MAC-EPID are trying to identify otitis media–related genetic components of Haemophilus influenzae, a bacterium that commonly causes ear infections. Because these germs normally live in the throat, where they cause no disease, the researchers are working to distinguish between the throat and ear strains of the bacterium and ultimately to identify potential vaccine components that can target the strains that cause ear infections.
  • Preterm Births: Preterm birth—defined as a birth before 37 weeks’ gestation—and its complications are the single greatest cause of infant death in the U.S. Researchers at MAC-EPID are trying to find out whether the presence of microbial “communities” in the vaginal cavity and mouth can predict a woman’s risk of giving birth to a preterm baby. Independently, both bacterial vaginosis and periodontal disease have been linked to a twofold increased risk of preterm birth, but it’s not clear, says Betsy Foxman, whether the cause is direct or indirect. “It may be indirectly due to systemic inflammation, or because bacteria end up in the bloodstream and then in the uterus,” she says. “It’s unclear what the mechanism is, but systemic inflammation is a pretty com-mon hypothesis.” In a collaborative study with colleagues at Wayne State University, researchers at MAC-EPID are working to identify the genetic sequences of both oral and vaginal microbial communities. By sequencing all the microbes in these communities, the scientists hope to deepen their understanding of the existing functional pathways and how they may contribute to the risk of pre-term birth.
  • Dental Caries: By the time they enter kindergarten, nearly half of all American kids have dental caries. For a variety of reasons—including diet, behavior, and genetics as well as access to dental care—Native American, African-American, and Hispanic children in the U.S. suffer disproportionately higher rates of tooth decay than white children. In the worst cases, dental caries can lead to life-threatening infections. Even mild cases of tooth decay can lead to sleep deprivation, eating difficulties, tooth loss, hearing problems, and other chronic conditions. In a collaborative study with the University of Pittsburgh and West Virginia University, Lixin Zhang, Carl Marrs, Usha Srinivasan, and Betsy Foxman are studying both the transmission of cariogenic bacteria in the mouth—with a focus on transmission within families—and the genetics of Strep mutans, a significant cause of dental caries. Working with migrant populations in Appalachia, a region with extremely high rates of dental caries among kids, Zhang and his colleagues are attempting to untangle the complex interactions between microbes and the environment—including food—that cause tooth enamel to erode and bacteria to take root and grow.
  • Group B Streptococcus: A bacterial infection that can be passed to babies during delivery, Group B Streptococcus (GBS) can cause life-threatening injuries in newborns and debilitating disease in pregnant women, the elderly, and adults with other illnesses. Infants who get GBS at birth can contract neonatal sepsis or meningitis and die. Prior to delivery, GBS can cause miscarriages. Although physicians are able to screen for GBS during labor, and commonly use antibiotics to protect infants whose mothers have the infection, GBS remains a source of fear to women worldwide. At MAC-EPID, researchers Carl Marrs, Lixin Zhang, and Usha Srinivasan are working to understand how new subtypes of GBS emerge and spread. They’re also looking to identify genes in GBS that may be resistant to antibiotics. While GBS is susceptible to penicillin, it is developing resistance to second-line antibiotics, and this poses a challenge to physicians because ten to 15 percent of women are allergic to penicillin. The MAC-EPID team is using new molecular genetic tools to find out what makes GBS such a successful pathogen and how it’s being transmitted. They hope their work may someday contribute to a vaccine against GBS.

Each Pound at Birth Lowers TB Risk

Just one more pound may help a newborn avoid tuberculosis later in life. In a new study, Eduardo Villamor, associate professor of environmental health sciences and epidemiology at SPH, looked at how much protection additional birth weight added against developing the disease years later and found that every 1.1 pounds of birth weight decreases the risk of developing TB later by 46 percent among identical twins.

The association between birth weight and developing tuberculosis is much stronger for males than females, says Villamor, who collaborated on the study with colleagues at the Karolinska Institute in Sweden and began the research while at Harvard.

The findings are important because TB infects about one-third of the planet’s population and is second only to HIV in deaths caused by a single infection. Low birth weight of babies is a larger problem in developing countries, but it occurs everywhere, he says.

It’s too early to say if insufficient prenatal growth causes clinical tuberculosis, but the findings suggest that may be the case. “Prenatal exposure to environmental insults, including maternal malnutrition, could program what happens later on in terms of our immune responses to infection, possibly through programming of the immune system,” Villamor says. “This study is an example of that.”
by Laura Bailey