Influence of Pneumococcal Vaccines and Respiratory Syncytial Virus on Alveolar Pneumonia, Israel

Daniel M. Weinberger

, Noga Givon-Lavi, Yonat Shemer-Avni, Jacob Bar-Ziv, Wladimir J. Alonso, David Greenberg, and Ron Dagan

Author affiliations: Yale School of Public Health, New Haven, Connecticut, USA (D.M. Weinberger); National Institutes of Health, Bethesda, Maryland, USA (D.M. Weinberger, W.J. Alonso); Soroka University Medical Center, Beer-Sheva, Israel (N. Givon-Lavi, Y. Shemer-Avni, D. Greenberg); Ben-Gurion University of the Negev, Beer-Sheva (N. Givon-Lavi, Y. Shemer-Avni, D. Greenberg, R. Dagan); Hadassah University Medical Center, Jerusalem, Israel (J. Bar-Ziv)

Abstract

Postlicensure surveillance of pneumonia incidence can be used to estimate whether pneumococcal conjugate vaccines (PCVs) affect incidence. We used Poisson regression models that control for baseline seasonality to determine the impact of PCVs and the possible effects of variations in virus activity in Israel on these surveillance estimates. PCV was associated with significant declines in radiologically confirmed alveolar pneumonia (RCAP) among patients <6 18="" 2="" 44="" 6="" 7-valent="" activity="" after="" age="" among="" and="" associated="" attributable="" but="" cases="" children.="" children="" ci="" especially="" first="" for="" impact="" impacts="" in="" incidence="" increases="" infants="" introduction.="" lower="" masked="" months="" of="" older="" p="" particularly="" pcvs="" rcap="" respectively="" respiratory="" rsv="" seasonal="" significant="" strong="" syncytial="" the="" to="" up="" vaccine="" variations="" virus="" was="" with="" years="" young="">

Streptococcus pneumoniae is a major cause of pneumonia worldwide, but in only a small fraction of severe cases are bacteria detectable in blood or cerebrospinal fluid (1). Because of the limitations of the diagnostic tools, identifying pneumococcal pneumonia is difficult and insensitive. Thus, using an endpoint of radiologically confirmed alveolar pneumonia (RCAP) can provide a more sensitive, but less specific, diagnosis of bacterial pneumonia that can be used to monitor the impact of pneumococcal conjugate vaccines (PCVs) on disease incidence (2,3).
The effect of vaccination on nonbacteremic pneumonia can be determined in the context of randomized control trials (4), in case–control studies (5,6), or by monitoring changes in the incidence of disease through routine surveillance (7). Of these options, surveillance data are the most readily available and give the most realistic estimate of vaccine effect, but they also are subject to biases, including secular trends and changes in detection or reporting (8,9). In the monitoring of nonbacteremic pneumonia incidence in children, a major source of variation might be year-to-year fluctuations in virus activity, which could influence the baseline and the post-PCV estimates of incidence (7,10).
Southern Israel provides a unique setting for evaluating the influence of PCVs on the incidence of pneumonia in children and the contributing role of respiratory viruses toward these estimates. The Jewish and Bedouin populations in this region inhabit the same geographic area but have limited social contact and generally differ in terms of socioeconomic status and illness patterns (11,12). Reflecting this diversity, there was little uptake of 7-valent PCV (PVC7) by the Bedouin population before the vaccine was introduced into the national immunization program in 2009 but moderate use among Jewish children on the private market. Since 2009, vaccine coverage has increased rapidly in both populations.
We sought to quantify the effect of PCV vaccination on RCAP incidence in southern Isreal. We took advantage of ongoing prospective studies of pediatric RCAP incidence and virus prevalence in children (13,14) that were conducted in the only hospital in southern Israel, which covers 95% of the population. We used Poisson regression models to estimate and control for the effects of seasonality and respiratory syncytial virus (RSV) and influenza activity on RCAP incidence and to determine the decline in incidence associated with increased uptake of PCVs.