The Division of Infectious Disease at Children’s Hospital of Montefiore (CHAM) is active in a wide array of clinical, basic and translational research. A sample of these projects is described below.
1. Maternal Immunization with a Single Cycle Candidate Vaccine, HSV-2 ΔgD-2, Protects Neonatal Mice from Lethal Viral Challenge (Betsy Herold, MD and Carol Kao, MD)
Perinatal HSV is associated with high mortality and morbidity. The Herold and Jacobs’ labs at Einstein engineered a single-cycle virus deleted in glycoprotein-D (∆gD-2) that induces high titer antibodies that are weakly neutralizing, but potently activate Fc receptors to elicit antibody-dependent cell-mediated killing (ADCK).
Carol Kao, MD, a pediatric infectious disease fellow, optimized a model of neonatal disease and showed that maternal immunization with ∆gD-2 protects newborn pups from lethal HSV-1 or HSV-2 challenge following intranasal challenge on Day 7 of life; Day 7 pups are immunologically similar to term human newborns. The antibodies are transferred to pups across the placenta and from breast milk. However, protection is reduced when pups are challenged on day 1 of life and ongoing work indicates that this reflects immaturity of immune cell cytolytic activity. Studies are under development to study the quantity and quality of antibodies that cross the placenta in humans at different gestational ages and ADCK activity of neonatal immune cells.
2. The Role of Pneumocystis Airway Colonization in Asthma (David L. Goldman, MD)
Asthma is the most common chronic health condition in children, disproportionately affecting children from urban areas like the Bronx. Despite advances in therapy, the morbidity and costs associated with this disease remain exceedingly high. Changes in the microbiome have been associated with a number of disease states; however, the role of the airway microbiome in promoting asthma is poorly understood.
Recently, Goldman et al conducted a biome study of the bronchoalveolar lavage of children with severe asthma and discovered that children with sever asthma are commonly colonized with Pneumocystis. Interestingly, colonization with this fungal pathogen has also been recently implicated in the pathogenesis of COPD. Studies are underway to confirm these initial findings and understand the immune mechanisms by which Pneumocystis colonization enhances asthma symptoms. We are hopeful that these studies will ultimately lead to new avenues of treatment for severe asthma.
3. Urinary Tract Infectious in Pediatrics (UTIP) (Vijaya Soma, MD and Philip Lee, PharmD)
Local antibiotic susceptibility patterns should be important determinants of antibiotic selection. Inattention to this data can lead to poor antibiotic selection and foster the emergence of resistant bacteria. We are conducting a three-part Quality Improvement Study to assess and improve antibiotic prescribing patterns by community pediatricians in the treatment of UTIs.
The first portion of this study was a retrospective review of diagnosis and management of pediatric UTIs in the ambulatory setting; this included review of clinicians’ use of diagnostic studies and empiric antibiotic choices as well as a review of local gram negative isolates and susceptibility profiles. We have found that trimethoprim-sulfamethoxazole is commonly used in the community, despite high rates of resistance. The second portion of the study, which is ongoing, consists of a stewardship intervention, where we provide each participating site with a local antibiogram for their clinic/school and compare the data with their prescribing habits- with a focus on encouraging the most narrow spectrum treatment possible. We will provide monthly “report cards” and then re-assess their prescribing habits and also rate of return, to hopefully demonstrate that use of narrower agents did not increase the return rate.