Monday, August 24 12:30 PM–1:45 PM Grand Hall
Board 70. Global Age Distribution of Pediatric Norovirus Cases
Background: Norovirus has been increasingly recognized for its predominant role as a cause of acute gastroenteritis (AGE); however, there remains a need for detailed data on the burden of norovirus in specific populations. We describe the global age distribution of pediatric norovirus AGE to investigate differences by income level or disease severity. Methods: We performed a systematic review of the Embase, Medline, and Global Health databases for studies published from Jan. 2001 to Aug. 2014 that included age distribution among patients <5 years of age with laboratory-confirmed norovirus AGE. Studies were included if they used PCR to detect norovirus in stool specimens collected from AGE cases, if the study period was at least one year, and if a specific catchment area was defined. We extracted data on the total number of norovirus AGE cases. Data were used to calculate the age distribution of norovirus cases for each study and to construct a weighted and pooled cumulative proportion. We fit linear
regression models to assess bivariate associations between the cumulative proportion of pediatric norovirus cases by the age of 12 months with per capita GDP of each country and study settings (e.g. outpatient vs inpatient). Results: We identified 35 studies that included the age distribution of norovirus AGE cases. Twenty of them were conducted in the inpatient setting. Overall, of norovirus AGE cases aged <5 years, 13% were in children <6 months, 33% were aged 6-11 months, 36% were aged 12-23 months, and 19% were aged 24-59 months after weighting by study population size. The cumulative proportion of norovirus AGE cases <12 months of age was inversely associated with per capita GDP (- 5.9% for every 10,000 USD increase, p<.0001, R2=0.42). The said cumulative proportion in the inpatient
setting (51%) was higher than the outpatient (38%, p=0.02) and community setting (25%, p=0.004). Conclusions: Across various settings, the majority of pediatric norovirus cases occurred within the 6-23 month age range. Cases in lower income settings and inpatient cases were generally younger in age. These findings suggest that a norovirus immunization schedule completed by 6 months could potentially prevent ~85% of cases in children <5 years, while a vaccine delivered at one year of age could potentially prevent about 50% of cases in the same age group.
Board 71. Estimating the Impact of Pediatric Non-typhoidal Salmonella Vaccination on the Number of Invasive Illnesses Prevented Among Children < 5 Years of Age in the United States
M. C. Judd1, K. K. Wong1, B. E. Mahon1, P. M. Griffin1, M. M. Levine2, R. K. Mody1; 1Enteric Diseases
Epidemiology Branch, CDC, Atlanta, GA, USA, 2Univ. of Maryland Sch. of Med., Ctr. for Vaccine Dev.,
Baltimore, MD, USA
Background: Invasive non-Typhoidal Salmonella (NTS) infections are often severe and can be fatal; young children are at highest risk. Glycoconjugate NTS vaccines provide protection in animal models. We estimated the number of invasive NTS infections that would be averted annually in the United States in children <5 years of age by adding NTS vaccination to the routine immunization schedule of infants aged 2, 4, and 6 months. Methods: We defined invasive infections as isolation of NTS from blood. Using mean annual frequency of invasive NTS infections reported to the Laboratory-based Enteric Disease
Surveillance (LEDS) system and mean US census data from 1996-2012, we estimated incidence rates among children in the following age groups (months): <2, 2-3, 4-5, 6-11, 12-23, 24-35, 36-47, 48-59. We
then simulated the effect of a three-dose vaccine protective against NTS serogroups B, C, and D on mean annual incidence of reported NTS infections. Based on data for the Vi conjugate typhoid vaccine (Vi-rEPA) in children, we assumed a NTS vaccine effectiveness range of 75-90% following 3 doses. We specified the following age group-specific parameters: 1) proportion of invasive NTS infections
attributable to serogroup B, C, or D based on LEDS data, 2) population at risk, 3) vaccine coverage, and 4) average time until dose. Real-world coverage and dose timing (accounting for catch-up doses in children up to 3 years of age) were estimated using the 2012 National Immunization Survey. Results: Without vaccination, an annual mean of 303 invasive NTS infections per 19,777,485 US children <5 years of age was reported to LEDS. Incidence rates were highest in infants aged <2 months (4.8/100,000 children), 2-3 months (3.0), and 4-5 months (2.6), and lowest in children aged 24-59 months (0.9). With a NTS vaccination program, we estimate 153-193 (51-64%) fewer infections would be reported to LEDS. Conclusions: A NTS vaccination program may prevent more than half of the annual invasive NTS infections in US children <5 years, but would not protect infants <2 months of age, the group at highest risk. However, our analysis underestimates the absolute number of invasive NTS infections averted due to underdetection and underreporting. Maternal NTS vaccination may be able to prevent additional pediatric infections.
Board 72. Modeling Norovirus Transmission and Strategies for Vaccination in the United States M. K. Steele1,2, J. V. Remais1, A. Handel3, B. A. Lopman1,2; 1Emory Univ., Atlanta, GA, USA, 2CDC,
Atlanta, GA, USA, 3Univ. of Georgia, Athens, GA, USA
Background: Noroviruses are the leading cause of acute gastroenteritis in the United States. Norovirus vaccine development has progressed rapidly in recent years, but critical questions, including which age groups should be vaccinated to maximize population health impact remain to be addressed. Methods: We developed a deterministic, age-structured compartmental model that tracks norovirus transmission and immunity in the U.S. population. We estimated three age specific transmission parameters using maximum likelihood by fitting the model to age-specific monthly US hospitalizations (1996 and 2007). Assuming that vaccination provides the same duration of protection as natural infection, we simulated two vaccine strategies: routine immunization at birth and individuals turning 65 years old. We assumed vaccine efficacy was 50% and coverage was 50%. Results: The model provided a good fit to the U.S. hospitalization data, with the best fit model suggesting that 0-4 year olds were much more important in transmission (R0=3.38), than 5-64 year olds (R0=1.86), and ≥65 years (R0=0.33). The routine infant
immunization program at equilibrium, is predicted to avert 17,258 (a 19% reduction) hospitalizations in 0- 4 year olds and 12,784 (9%) hospitalizations in the 65 years and older age group over a five year time period. A routine immunization program of individuals turning 65 is predicted to avert 5,341 (4%) hospitalizations in the 65 year and older age group over a five year time period. In considering total population effects, vaccinating 0-4 and 65 years and older is predicted to avert 39 and 6 hospitalizations, respectively, per 10,000 doses administered, with much greater indirect benefits in the infant
of norovirus vaccination are maximized by vaccinating infants, due to their importance in transmission and that immunization of infants provides the elderly with better protection from disease than vaccinating 65 year olds. Simulations of other levels of coverage, efficacy and duration of vaccine protection will also be considered along with other outcomes, including illnesses and deaths.
Board 73. Indirect Cohort Analysis of 10-valent Pneumococcal Conjugate Vaccine Effectiveness Against Vaccine-type and Vaccine-related Invasive Pneumococcal Disease
J. R. Verani1, C. M. Domingues2, J. C. de Moraes3, Brazilian Pneumococcal Conjugate Vaccine
Effectiveness Study Group; 1CDC, Atlanta, GA, USA, 2Ministry of Hlth., Brasilia, Brazil, 3Sch. of Med. Sci.
of Santa Casa, São Paulo, Brazil
Background: Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis and sepsis worldwide. In March 2010, Brazil introduced a newly available 10-valent pneumococcal conjugate vaccine (PCV10); PCV10 effectiveness against invasive pneumococcal disease (IPD) was demonstrated in a multi-state case-control study. However, case-control studies of vaccine effectiveness can be costly and challenging to carry out. A secondary analysis of case-only data was conducted to evaluate use of IPD surveillance data to measure vaccine effectiveness. Methods: We applied the indirect cohort method to estimate effectiveness of 10-valent pneumococcal conjugate vaccine (PCV10) in Brazil. Cases of invasive pneumococcal disease (i.e. S. pnuemoniae detected in a normally sterile fluid) were identified through national laboratory-based surveillance, and classified as vaccine-type (serotypes in PCV10), vaccine-related (same serogroup as a vaccine-type), or non-vaccine types. We estimated vaccine effectiveness using multivariable logistic regression comparing PCV10 vaccination among children with vaccine-type or vaccine-related invasive disease versus children with non-vaccine type disease. Results: The adjusted effectiveness of ≥1 doses against vaccine-type IPD was 72.8% (95% confidence interval [CI] 44.1 to 86.7) and against vaccine-related IPD 61.3% (95%CI 14.5 to 82.5).These estimates were similar to those of the case-control study (83.8% [95%CI 65.9 to 92.3] and 77.9% [95%CI 41.0 to 91.7] respectively). One or more doses were significantly protective against vaccine serotypes 14 (75.4%, 95%CI 14.5 to 82.5), 6B (69.7%, 95%CI 16.5 to 89.0), 23F (76.6%, 95%CI 14.6 to 93.6), and 18C (86.6%, 95%CI 30.6 to 97.4), as well as vaccine-related serotype 19A (71.3%, 95%CI 16.6 to 90.1). Conclusions: PCV10 protects against invasive pneumococcal disease due to vaccine- and vaccine- related serotype in young children in Brazil. An analysis of case-only data yielded very similar results to more resource-intensive case-control study, and provided additional insight on serotype-specific protection. The indirect cohort is a methodologically sound approach for evaluating pneumococcal conjugate vaccines that leverages existing surveillance and is feasible even in resource-limited settings.