Solnick receives Gates Foundation grant to explore latent tuberculosis
Jay Solnick, UC Davis professor of medicine and medical microbiology at the Center for Comparative Medicine, was selected to receive a grant from the Bill and Melinda Gates Foundation to explore the basis for latency in tuberculosis.
Solnick’s grant is among 104 chosen from nearly 4,000 applications that the foundation announced recently “to explore bold and largely unproven ways to improve global health.” The grants, each for $100,000, were made to scientists from 22 countries and five continents. They mark the first round of funding from Grand Challenges Explorations, an initiative to help lower the barriers for testing innovative ideas in global health.
The initial set of grants is intended to inject fresh perspective into research for preventing or curing infectious diseases such as HIV/AIDS and tuberculosis, and limiting the emergence of drug resistance. Successful applicants showed how their project falls outside current scientific paradigms and could lead to significant advances if successful — in just two pages.
“We were hoping this program would level the playing field so anyone with a transformational idea could more quickly assess its potential for the benefit of global health,” said Dr. Tachi Yamada, president of global health at the Gates Foundation. “The quality of the applications exceeded all of our expectations. It was so hard for reviewers to champion just one great idea that we selected almost twice as many projects for funding as we had initially planned.”
One-third of the world’s population is estimated to be infected with Mycobacterium tuberculosis. However, most individuals do not show clinical symptoms of disease, a form of infection commonly known as latency. Latent TB represents a vast reservoir from which active disease and subsequent transmission propagates. Interventions that identify and eliminate latent infection might break the cycle of disease transmission and reverse the TB epidemic.
Current approaches to detection, prevention and treatment of latent infection are inadequate, and rational development of new tools has been limited by a poor understanding of the fundamental biology of latent TB infection.
Solnick, along with Julie Parsonnet, a professor of medicine at Stanford School of Medicine, and other researchers at Stanford, proposed that one unexplored explanation for why TB remains latent in some people may be enhanced non-specific immunity caused by chronic infection with Helicobacter pylori, which is better known as an important cause of peptic ulcers and gastric cancer. Solnick and colleagues propose that in some people H. pylori may actually have beneficial effects, one of which may be protection against TB.
Center for Comparative Medicine
The University of California Davis Center for Comparative Medicine (CCM) is a cooperative, interdisciplinary research and teaching center that is co-sponsored by the School of Medicine and the School of Veterinary Medicine. CCM Faculty members have academic appointments in one or both Schools.
The CCM Research Mission is to investigate the pathogenesis of human and animal disease, using animal models or naturally occurring animal diseases. Areas of emphasis include host-agent interactions during infectious disease, intervention and prevention strategies for infectious diseases, cancer, and mouse biology.
In preliminary experiments conducted in The Gambia, patients with latent TB were more than nine times more likely to be infected with H. pylori than were patients with active tuberculosis. This difference could not be explained by general loss of humoral immunity because cases and contacts were equally likely to be seropositive for measles. Solnick hypothesizes that H. pylori may non-specifically boost the host immune response and help maintain TB in a latent state.
To address this hypothesis, Solnick and colleagues will take two approaches. First, they will conduct a prospective study of households in Pakistan and The Gambia with an index TB case, and ask if the outcome of TB exposure in other family members living in the household is affected by whether they are seropositive for H. pylori. To control for enteric disease exposure and normal antibody responses, they will also measure antibodies to hepatitis A virus and measles, to which nearly all participants will likely have been exposed.
Second, Solnick will take advantage of ongoing studies in non-human primates by JoAnne Flynn, a professor immunology at the University of Pittsburgh School of Medicine, to determine whether the outcome of experimental challenge with TB is altered by the presence of H. pylori, which sometimes infects monkeys as well.
Because TB would be eliminated if all infections could be maintained in latency, Solnick’s studies raise the possibility that a recombinant H. pylori could be engineered that does not cause ulcers or gastric cancer, but promotes non-specific innate immunity and protects against TB. Future studies will explore this idea with Dr. Barry Marshal, who won the Nobel Prize in Physiology or Medicine in 2005 for his discovery of H. pylori, and who recently formed a commercial venture devoted to the use of H. pylori as an antigen delivery system.
Such an approach is a novel strategy that may not only prevent disease from TB, or maintain it in latency, but may also produce collateral benefits by prevention of diarrhea, pneumococcal disease, and other childhood infections.