Incidence, Risk Factors and Outcome of Pre-engraftment Gram-Negative Bacteremia after Allogeneic and Autologous Hematopoietic Stem Cell Transplantation: An Italian Prospective Multicenter Survey

Pneumococcal progression from carriage to otitis media declined following rollout of PCV7/13 in Israel. Vaccine-targeted and non-vaccine serotypes showed lower progression rates. Early-life otitis media episodes, historically often caused by PCV7/13-targeted serotypes, may exacerbate children's future susceptibility to otitis media.Reductions in otitis media (OM) burden following rollout of pneumococcal conjugate vaccines (PCVs) have exceeded predictions of vaccine impact. In settings with active surveillance, reductions in OM caused by vaccine-targeted pneumococcal serotypes have co-occurred with reductions in OM caused by other pathogens carried in the upper-respiratory tract of children. To understand these changes, we investigated the progression of vaccine-targeted and non-vaccine pneumococcal serotypes from carriage to OM before and after vaccine rollout.Nasopharyngeal carriage prevalence of pneumococcus was monitored in prospective studies of Bedouin and Jewish children < 3 years old in southern Israel between 2004 and 2016. Incidence of OM necessitating middle-ear fluid culture (predominantly complex OM including recurrent, spontaneously-draining, non-responsive, and chronic cases) was monitored via prospective, population-based active surveillance. We estimated rates of pneumococcal serotype-specific progression from carriage to disease before and after rollout of PCV7/13, measured as OM incidence per carrier. We pooled serotype-specific estimates using Bayesian random-effects models.On average, rates of progression declined 92% (95% credible interval: 79-97%) and 80% (46-93%) for PCV7/13 serotypes among Bedouin and Jewish children < 12 months old, respectively, and 32% (-58-71%) and 61% (-5-86%) among children aged 12-35m. For non-vaccine serotypes, rates of progression among Bedouin and Jewish children aged < 12m declined 74% (55-85%) and 43% (4-68%), respectively.Vaccine-targeted and non-vaccine pneumococcal serotypes showed lower rates of progression to complex OM after rollout of PCV7/13. Early-life OM episodes historically associated with vaccine-serotype pneumococci may impact the susceptibility of children to OM progression.