ID Epi News & Events

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ID-Epi Doctoral Candidate Awarded Prestigious Harvard Catalyst Pilot Grant

Congratulations to ID-Epi doctoral candidate Meghan Baker, MD on her receipt of a $50,000 Harvard Catalyst Pilot grant. Funding is for one year, and began on November 1.

Harvard Catalyst is a pan-University collaborative effort committed to harnessing the human, technological, and fiscal resources of Harvard and its Academic Healthcare Centers to reduce the burden of human illness. To foster cross-institutional and cross-disciplinary collaboration, Harvard Catalyst offers seed funds in the form of Pilot Grants. The main impetus behind the grants is to support pilot studies that will lead to sustainable, innovative, and collaborative projects that will impact human health.

Dr. Baker's project, entitled “A novel diagnostic test for tuberculosis utilizing antibodies specific for siderocalin-carboxymycobactin complexes” is summarized below in the abstract.

To accomplish aims of the study, she put together a collaborative team that includes expertise in clinical infectious diseases, tuberculosis epidemiology, immunology and the role of iron metabolism, and MTB lipid isolation: Bobby Cherayil, MD, Associate Professior of Pediatrics at Harvard Medical School and a mucosal immunologist at MGH; Dr. Branch Moody, Associate Professor of Medicine at HMS and and immunologist at BWH; and finally, Megan Murray, MD, Professor of Epidemiology at Harvard School of Public Health.

ABSTRACT: One-third of the world's population is estimated to be infected with Mycobacterium tuberculosis (MTB), 9 million people develop the disease each year, and almost 2 million die annually from the disease. There is an urgent need for rapid diagnostic methods to identify patients with tuberculosis. The ideal test would be a point-of-care urine dipstick that would identify individuals with MTB, especially those co-infected with HIV in whom conventional testing has a low yield.

We propose a novel diagnostic approach based on the detection of carboxymycobactin, a secreted MTB siderophore, complexed to the soluble mammalian protein siderocalin. Siderocalin, which is secreted in response to bacterial infection, binds carboxymycobactin with high affinity. This complex is freely filtered in the urine. We propose to generate a complex of purified MTB carboxymycobactin bound to a recombinant glutathione S-transferase-siderocalin fusion protein. Mice immunized with the complex will be used to create B cell hybridomas, which will then be screened for monoclonal antibodies specific for the siderocalin-carboxymycobactin complex as opposed to siderocalin alone. Such antibodies will be tested in an ELISA to determine if they are able to detect carboxymycobactin bound to siderocalin in tissue culture models of MTB infected cells.

In future studies, we will examine the ability of this assay to distinguish individuals with MTB infection from those who are healthy or are infected with other bacteria. A urine ELISA that could identify a patient with smear negative tuberculosis could be used in resource limited settings and would improve individual outcomes and decrease transmission.

ID-Epi Professor Shares Expertise on H1N1

During the last week of April, ID-Epi's Professor Marc Lipsitch joined an international team at the Centers for Disease Control in Atlanta, lending his statistical modelling expertise to efforts to estimate the severity and transmission of the emerging H1N1 virus.

Before the epidemic emerged, Lipsitch had co-authored a draft paper on the challenges of managing an emerging influenza pandemic and delaying drug resistance to flu medications. Understanding the importance of the paper, PLoS Medicine fast-tracked its publication, making it available online on April 30. It has since been published in NEJM.

Click here for more on this topic and to link to the NEJM article.

Other H1N1 Contributions of ID-Epi Researchers

Members of Marc Lipsitch's group -- including Christina Astley, Leon Danon, Ted Cohen, Justin O'Hagan, and Joel Miller -- worked with HSPH doctoral student Martin Lajous on an inventive public health response effort using text messaging in Mexico....

And, research scientist Edward Goldstein, in collaboration with other members of the Lipsitch group, drafted a memo that was influential in policy decisions of Mexican health officials about the H1N1 virus.