Search

Background: Group B Streptococcus (GBS) is a major cause of mortality and morbidity in infants and is associated with transmission from a colonized mother at birth and via infected breastmilk. Although maternal/infant colonization with GBS is common, the majority of infants exposed to GBS remain unaffected. The association between breastmilk immune factors and infant colonization and disease prevention has not been elucidated.\ud \ud Objectives: We have investigated the association between SIgA and cytokines in breastmilk and infant GBS colonization and clearance.\ud \ud Methods: Mother/infant GBS colonization was determined in a prospective cohort of 750 Gambian mother/infant pairs followed to day 89 of life. Anti-GBS secretory IgA bound to the surface of whole bacteria was assessed by flow cytometry and a panel of 12 cytokines quantified by mesoscale discovery in colostrum, breastmilk and serum.\ud \ud Results: Compared with infants receiving low anti-GBS SIgA in colostrum, infants receiving high anti-GBS SIgA were at decreased risk of GBS colonization for serotypes III and V. Infants colonized at day 6 were twice as likely to receive colostrum with high TGF-β1, TNFα, IL10, and IL-6 compared to uncolonized infants. Infants receiving high colostral TGF-β1, TNFα, and IL-6 had two-fold enhanced GBS clearance between birth and day 89.\ud \ud Conclusion: Our results suggest that the infant GBS colonization risk diminishes with increasing anti-GBS SIgA antibody in breastmilk and that key maternally derived cytokines might contribute to protection against infant colonization. These findings might be leveraged to develop interventions including maternal vaccination that may reduce infant GBS colonization.

Background: Group B Streptococcus is a major cause of mortality and morbidity in infants and is associated with transmission from a colonised mother at birth and via infected breastmilk. Although maternal/infant colonisation with Group B Streptococcus (GBS) is common, the majority of infants exposed to GBS remain unaffected. The association between breastmilk immune factors and infant colonisation and disease prevention has not been elucidated. Objectives: We have investigated the association between SIgA and cytokines in breastmilk and infant GBS colonisation and clearance. Methods: Mother/infant GBS colonisation was determined in a prospective cohort of 750 Gambian mother/infant pairs followed to day 90 of life. Anti-GBS secretory IgA bound to the surface of whole bacteria was assessed by flow cytometry and a panel of 12 cytokines quantified by mesoscale discovery in colostrum, breastmilk and serum. Results: Compared with infants receiving low anti-GBS SIgA in colostrum, infants receiving high anti-GBS SIgA were at decreased risk of GBS colonisation for serotypes III and V. Infants colonised at day 6 were twice as likely to receive colostrum with high TGF- β1, TNFα, IL10 and IL-6 compared to uncolonised infants. Infants receiving high colostral TGF- β1, TNFα and IL-6 had two-fold enhanced GBS clearance between birth and day 90. Conclusion: Our results suggest that the infant GBS colonisation risk diminishes with increasing anti-GBS SIgA antibody in breastmilk and that key maternally-derived cytokines might contribute to protection against infant colonisation. These findings might be leveraged to develop interventions including maternal vaccination that may reduce infant GBS colonisation.

Highlights • As maternally-derived anti-GBS antibody increases infant colonization risk decreases. • There is a serotype-specific threshold above which an infant is uncolonised with GBS. • Higher anti-GBS antibody is associated with infant clearance of GBS between birth and 3 months., Background Vertical transmission of Group B Streptococcus (GBS) is a prerequisite for early-onset disease and a consequence of maternal GBS colonization. Disease protection is associated with maternally-derived anti-GBS antibody. Using a novel antibody-mediated C3b/iC3b deposition flow cytometry assay which correlates with opsonic killing we developed a model to assess the impact of maternally-derived functional anti-GBS antibody on infant GBS colonization from birth to day 60–89 of life. Methods Rectovaginal swabs and cord blood (birth) and infant nasopharyngeal/rectal swabs (birth, day 6 and day 60–89) were obtained from 750 mother/infant pairs. Antibody-mediated C3b/iC3b deposition with cord and infant sera was measured by flow cytometry. Results We established that as maternally-derived anti-GBS functional antibody increases, infant colonization decreases at birth and up to three months of life, the critical time window for the development of GBS disease. Further, we observed a serotype (ST)-dependent threshold above which no infant was colonized at birth. Functional antibody above the upper 95th confidence interval for the geometric mean concentration was associated with absence of infant GBS colonization at birth for STII (p

OBJECTIVES: The aim of this study was to evaluate the HIV-1 RNA pooled nucleic acid amplification testing (NAAT) strategy to screen pregnant women in the 'window period' of acute HIV infection (AHI) in rural South Africa. METHODS: In 2007 and 2008, 750 consecutive pregnant women on their first antenatal care visit to a primary health care clinic were tested anonymously for HIV infection. HIV-1 RNA pooled NAAT was performed on HIV antibody-negative samples. All positive pools were tested individually and positive samples were classified as incident cases to calculate HIV incidence. RESULTS: The overall HIV prevalence was 37.3% [95% confidence interval (CI) 34.3-41.3]. Of the 467 HIV antibody-negative samples, four (0.9%) were HIV-1 RNA-positive. The mean viral load in the four samples was 386 260 HIV-1 RNA copies/mL (range 64 200-1 228130). The HIV incidence was 11.2%per year (95% CI 0.3-22.1) and all women with AHI were 21 years of age. CONCLUSIONS: Identifying AHI in pregnancy is important for health interventions to reduce perinatal and heterosexual transmission of HIV, and to estimate HIV incidence for epidemiological surveillance.