7 research outputs found
Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children: Why, What, and How to Undertake Estimates?
Improving maternal, newborn, and child health is central to Sustainable Development Goal targets for 2030, requiring acceleration especially to prevent 5.6 million deaths around the time of birth. Infections contribute to this burden, but etiological data are limited. Group B Streptococcus (GBS) is an important perinatal pathogen, although previously focus has been primarily on liveborn children, especially early-onset disease. In this first of an 11-article supplement, we discuss the following: (1) Why estimate the worldwide burden of GBS disease? (2) What outcomes of GBS in pregnancy should be included? (3) What data and epidemiological parameters are required? (4) What methods and models can be used to transparently estimate this burden of GBS? (5) What are the challenges with available data? and (6) How can estimates address data gaps to better inform GBS interventions including maternal immunization? We review all available GBS data worldwide, including maternal GBS colonization, risk of neonatal disease (with/without intrapartum antibiotic prophylaxis), maternal GBS disease, neonatal/infant GBS disease, and subsequent impairment, plus GBS-associated stillbirth, preterm birth, and neonatal encephalopathy. We summarize our methods for searches, meta-analyses, and modeling including a compartmental model. Our approach is consistent with the World Health Organization (WHO) Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER), published in The Lancet and the Public Library of Science (PLoS). We aim to address priority epidemiological gaps highlighted by WHO to inform potential maternal vaccination
Lipid analogs reveal features critical for hemolysis and diminish granadaene mediated Group B Streptococcus infection
Although certain microbial lipids are toxins, the structural features important for cytotoxicity
remain unknown. Increased functional understanding is essential for developing therapeutics
against toxic microbial lipids. Group B Streptococci (GBS) are bacteria associated with preterm
births, stillbirths, and severe infections in neonates and adults. GBS produce a pigmented,
cytotoxic lipid, known as granadaene. Despite its importance to all manifestations of
GBS disease, studies towards understanding granadaene’s toxic activity are hindered by its
instability and insolubility in purified form. Here, we report the synthesis and screening of
lipid derivatives inspired by granadaene, which reveal features central to toxin function,
namely the polyene chain length. Furthermore, we show that vaccination with a non-toxic
synthetic analog confers the production of antibodies that inhibit granadaene-mediated
hemolysis ex vivo and diminish GBS infection in vivo. This work provides unique structural
and functional insight into granadaene and a strategy to mitigate GBS infection, which will be
relevant to other toxic lipids encoded by human pathogens.This work was supported by funding from the National Institutes of Health
Grants R01AI112619, R01AI133976, R01AI100989, and R21AI125907 and seed funds
from Seattle Childrens Research Institute to L.