Leila C. Sahni

Effectiveness of Pentavalent Rotavirus Vaccine in a Large Urban Population in the United States

OBJECTIVE: The goal was to assess the effectiveness of complete (3-dose) or partial (1- or 2-dose) immunization with pentavalent rotavirus vaccine (RV5) against rotavirus acute gastroenteritis (AGE) in US clinical practice. METHODS: A case-control evaluation was conducted in February through June 2008 at an emergency department in Houston, Texas. Case patients with rotavirus AGE (N = 90) were identified through testing for rotavirus in fecal specimens obtained from 205 children 15 days through 23 months of age presenting with AGE. Control groups included rotavirus-negative AGE patients (N = 115), concurrently enrolled patients with acute respiratory infection (ARI) (N = 228), and up to 10 age- and zip code-matched children sampled from the Houston-Harris County Immunization Registry (HHCIR) for each case patient >8 months of age. Immunization data were obtained from parent records, health care providers, and/or the HHCIR. Vaccine effectiveness was calculated as 1 minus odds of RV5 vaccination for case patients versus control patients, after adjustment for age at presentation and birth date. RESULTS: The vaccine effectiveness of a complete RV5 series was 89% (95% confidence interval [CI]: 70%–96%) and 85% (95% CI: 55%–95%) with rotavirus-negative AGE and ARI control patients, respectively. Immunization data were available for 44% of case patients (n = 40) from the HHCIR; the estimated 3-dose vaccine effectiveness with these HHCIR control patients was 82% (95% CI: 19%–96%). A complete RV5 series conferred 100% protection (95% CI: 71%–100%) against severe rotavirus disease requiring hospitalization and 96% protection (95% CI: 72%–99%) against disease requiring intravenous hydration. Vaccine effectiveness of 1 and 2 doses against hospitalization and emergency department visits was 69% (95% CI: 13%–89%) and 81% (95% CI: 13%–96%), respectively, using rotavirus-negative AGE and ARI control groups combined. CONCLUSIONS: In this setting, a complete series of RV5 was highly effective against severe rotavirus AGE. Partial immunization also conferred substantial protection.

Effectiveness of Pentavalent and Monovalent Rotavirus Vaccines in Concurrent Use Among US Children <5 Years of Age, 2009–2011

BACKGROUND We assessed vaccine effectiveness (VE) for RotaTeq (RV5; 3 doses) and Rotarix (RV1; 2 doses) at reducing rotavirus acute gastroenteritis (AGE) inpatient and emergency department (ED) visits in US children. METHODS We enrolled children <5 years of age hospitalized or visiting the ED with AGE symptoms from November 2009-June 2010 and from November 2010-June 2011 at 7 medical institutions. Fecal specimens were tested for rotavirus by enzyme immunoassay and genotyped. Vaccination among laboratory-confirmed rotavirus cases was compared with rotavirus-negative AGE controls. Regression models calculated VE estimates for each vaccine, age, ethnicity, genotype, and clinical setting. RESULTS RV5-specific analyses included 359 rotavirus cases and 1811 rotavirus-negative AGE controls. RV1-specific analyses included 60 rotavirus cases and 155 rotavirus-negative AGE controls. RV5 and RV1 were 84% (95% confidence interval [CI], 78%-88%) and 70% (95% CI, 39%-86%) effective, respectively, against rotavirus-associated ED visits and hospitalizations combined. By clinical setting, RV5 VE against ED and inpatient rotavirus-associated visits was 81% (95% CI, 70%-84%) and 86% (95% CI, 74%-91%), respectively. RV1 was 78% (95% CI, 46%-91%) effective against ED rotavirus disease; study power was insufficient to evaluate inpatient RV1 VE. No waning of immunity was evident during the first 4 years of life for RV5, nor during the first 2 years of life for RV1. RV5 provided genotype-specific protection against each of the predominant strains (G1P[8], G2P[4], G3P[8], G12P[8]), while RV1 VE was statistically significant for the most common genotype, G3P[8]. CONCLUSIONS Both RV5 and RV1 significantly protected against medically attended rotavirus gastroenteritis in this real-world assessment.

Sustained protection from pentavalent rotavirus vaccination during the second year of life at a large, urban United States pediatric hospital.

Fecal specimens from children presenting to Texas Childrens Hospital with acute gastroenteritis were tested for the presence of rotavirus. Children were grouped according to vaccination status, and pentavalent rotavirus vaccine effectiveness was calculated. Pentavalent rotavirus vaccine effectiveness against severe rotavirus gastroenteritis was sustained during the first 2 years of the vaccination program. Overall 3-dose effectiveness was 83% to 86%; it was 92% to 93% among children 6 to 11 months of age and 78% to 84% among children ≥12 months of age.

Epidemiologic Association Between FUT2 Secretor Status and Severe Rotavirus Gastroenteritis in Children in the United States

IMPORTANCE A genetic polymorphism affecting FUT2 secretor status in approximately one-quarter of humans of European descent affects the expression of histo-blood group antigens on the mucosal epithelia of human respiratory, genitourinary, and digestive tracts. These histo-blood group antigens serve as host receptor sites necessary for attachment and infection of some pathogens, including norovirus. OBJECTIVE We investigated whether an association exists between FUT2 secretor status and laboratory-confirmed rotavirus infections in US children. DESIGN, SETTING, AND PARTICIPANTS Multicenter case-control observational study involving active surveillance at 6 US pediatric medical institutions in the inpatient and emergency department clinical settings. We enrolled 1564 children younger than 5 years with acute gastroenteritis (diarrhea and/or vomiting) and 818 healthy controls frequency matched by age and month, from December 1, 2011, through March 31, 2013. MAIN OUTCOMES AND MEASURES Paired fecal-saliva specimens were tested for rotavirus and for secretor status. Comparisons were made between rotavirus test-positive cases and healthy controls stratified by ethnicity and vaccination status. Adjusted multivariable analyses assessed the preventive association of secretor status against severe rotavirus gastroenteritis. RESULTS One (0.5%) of 189 rotavirus test-positive cases was a nonsecretor, compared with 188 (23%) of 818 healthy control participants (P < .001). Healthy control participants of Hispanic ethnicity were significantly less likely to be nonsecretors (13%) compared with healthy children who were not of Hispanic ethnicity (25%) (P < .001). After controlling for vaccination and other factors, children with the nonsecretor FUT2 polymorphism appeared statistically protected (98% [95% CI, 84%-100%]) against severe rotavirus gastroenteritis. CONCLUSIONS AND RELEVANCE Severe rotavirus gastroenteritis was virtually absent among US children who had a genetic polymorphism that inactivates FUT2 expression on the intestinal epithelium. We observed a strong epidemiologic association among children with rotavirus gastroenteritis compared with healthy control participants. The exact cellular mechanism behind this epidemiologic association remains unclear, but evidence suggests that it may be rotavirus genotype specific. The lower prevalence of nonsecretors among Hispanic children may translate to an enhanced burden of rotavirus gastroenteritis among this group. Our findings may have bearing on our full understanding of rotavirus infections and the effects of vaccination in diverse populations.

Long-term Consistency in Rotavirus Vaccine Protection: RV5 and RV1 Vaccine Effectiveness in US Children, 2012–2013

BACKGROUND Using a multicenter, active surveillance network from 2 rotavirus seasons (2012 and 2013), we assessed the vaccine effectiveness of RV5 (RotaTeq) and RV1 (Rotarix) rotavirus vaccines in preventing rotavirus gastroenteritis hospitalizations and emergency department (ED) visits for numerous demographic and secular strata. METHODS We enrolled children hospitalized or visiting the ED with acute gastroenteritis (AGE) for the 2012 and 2013 seasons at 7 medical institutions. Stool specimens were tested for rotavirus by enzyme immunoassay and genotyped, and rotavirus vaccination histories were compared for rotavirus-positive cases and rotavirus-negative AGE controls. We calculated the vaccine effectiveness (VE) for preventing rotavirus associated hospitalizations and ED visits for each vaccine, stratified by vaccine dose, season, clinical setting, age, predominant genotype, and ethnicity. RESULTS RV5-specific VE analyses included 2961 subjects, 402 rotavirus cases (14%) and 2559 rotavirus-negative AGE controls. RV1-specific VE analyses included 904 subjects, 100 rotavirus cases (11%), and 804 rotavirus-negative AGE controls. Over the 2 rotavirus seasons, the VE for a complete 3-dose vaccination with RV5 was 80% (confidence interval [CI], 74%-84%), and VE for a complete 2-dose vaccination with RV1 was 80% (CI, 68%-88%).Statistically significant VE was observed for each year of life for which sufficient data allowed analysis (7 years for RV5 and 3 years for RV1). Both vaccines provided statistically significant genotype-specific protection against predominant circulating rotavirus strains. CONCLUSIONS In this large, geographically and demographically diverse sample of US children, we observed that RV5 and RV1 rotavirus vaccines each provided a lasting and broadly heterologous protection against rotavirus gastroenteritis.

Use of an immunization information system to assess the effectiveness of pentavalent rotavirus vaccine in US children

Immunization information systems (IISs) are accessible sources of immunization data. We validated immunization information from a local IIS against provider records and assessed the systems utility in evaluating vaccine effectiveness against rotavirus disease using a case-control study. Among the 91% of case and control patients with immunization records, 49% were in the IIS, and 97% had a provider record. Good agreement was observed across record sources (k=0.65). Vaccine effectiveness (VE) was 82% using IIS data compared to 82-88% using provider data. Controls identified through the IIS provided VE estimates similar to hospital control patients. IISs could represent a valuable source of data for effectiveness evaluations.

Rotavirus Strain Trends During the Postlicensure Vaccine Era: United States, 2008–2013

BACKGROUND Group A rotaviruses (RVA) are a significant cause of pediatric gastroenteritis worldwide. The New Vaccine Surveillance Network (NVSN) has conducted active surveillance for RVA at pediatric hospitals and emergency departments at 3-7 geographically diverse sites in the United States since 2006. METHODS Over 6 consecutive years, from 2008 to 2013, 1523 samples from NVSN sites that were tested positive by a Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention for genotyping. RESULTS In the 2009, 2010, and 2011 seasons, genotype G3P[8] was the predominant genotype throughout the network, with a 46%-84% prevalence. In the 2012 season, G12P[8] replaced G3P[8] as the most common genotype, with a 70% prevalence, and this trend persisted in 2013 (68.0% prevalence). Vaccine (RotaTeq; Rotarix) strains were detected in 0.6%-3.4% of genotyped samples each season. Uncommon and unusual strains (eg, G8P[4], G3P[24], G2P[8], G3P[4], G3P[6], G24P[14], G4P[6], and G9P[4]) were detected sporadically over the study period. Year, study site, and race were found to be significant predictors of genotype. CONCLUSIONS Continued active surveillance is needed to monitor RVA genotypes in the United States and to detect potential changes since vaccine licensure.

Detection of rotavirus antigenemia in routinely obtained serum specimens to augment surveillance and vaccine effectiveness evaluations.

Background: Antigenemia is common among children with rotavirus disease. Because obtaining stool specimens is cumbersome, we evaluated whether detection of antigenemia in sera obtained during routine clinical practice could augment rotavirus surveillance to assess the effect of vaccination. Methods: We determined the sensitivity, specificity, and positive and negative predictive values of serum/plasma rotavirus antigen detection using fecal antigen positivity as the gold standard. Fecal specimens obtained by active surveillance and residual serum/plasma specimens obtained during routine clinical testing from children 15 days to 23 months of age presenting with acute gastroenteritis (AGE) to a childrens hospital in Houston were tested for rotavirus using a commercially available enzyme immunoassay. Using case-control methods, we compared vaccine effectiveness (VE) using cases identified through serum/plasma testing versus stool testing. Results: Of the 205 AGE patients with fecal specimens, 71 (35%) had a serum/plasma sample available. Among these 71 children, antigenemia was detected in 22 of 29 with rotavirus-positive fecal specimens (sensitivity = 75%; 95% confidence interval [CI] = 60%–91%) versus 2 of 42 children with rotavirus-negative fecal specimens (specificity = 95%; 95% CI = 89%–100%). The positive and negative predictive values of rotavirus antigenemia were 92% (95% CI = 81%–100%) and 85% (95% CI = 75%–95%), respectively. Thirty-four of 195 children with AGE without fecal specimens had serum/plasma available; 10 (29%) had rotavirus antigenemia. Three-dose VE using cases identified through serum/plasma testing was similar (VE = 84%; 95% CI = 25%–96%) to that using cases identified though fecal testing (VE = 85%; 95% CI = 55%–95%). Conclusions: Detection of antigenemia in routinely collected serum/plasma could augment identification of rotavirus disease for postlicensure evaluation of impact and effectiveness of rotavirus vaccination.

Variation in Rotavirus Vaccine Coverage by Provider Location and Subsequent Disease Burden

BACKGROUND: Rotavirus vaccines were introduced in the United States in 2006. Full-series coverage is lower than for other vaccines, and disease continues to occur. We examined variation in vaccine coverage among provider locations and correlated coverage with the detection of rotavirus in children who sought treatment of severe acute gastroenteritis (AGE). METHODS: Vaccine records of children enrolled in an AGE surveillance program were obtained and children were grouped by the location that administered each child’s 2-month vaccines. Cases were children with laboratory-confirmed rotavirus AGE; controls were children with rotavirus-negative AGE or acute respiratory infection. Location-level coverage was calculated using ≥1 dose rotavirus vaccine coverage among controls and classified as low (<40%), medium (≥40% to <80%), or high (≥80%). Rotavirus detection rates among patients with AGE were calculated by vaccine coverage category. RESULTS: Of controls, 80.4% (n = 1123 of 1396) received ≥1 dose of rotavirus vaccine from 68 locations. Four (5.9%) locations, including a NICU, were low coverage, 22 (32.3%) were medium coverage, and 42 (61.8%) were high coverage. In low-coverage locations, 31.4% of patients with AGE were rotavirus-positive compared with 13.1% and 9.6% in medium- and high-coverage locations, respectively. Patients with AGE from low-coverage locations had 3.3 (95% confidence interval 2.4–4.4) times the detection rate of rotavirus than patients with AGE from high vaccine coverage locations. CONCLUSIONS: We observed the highest detection of rotavirus disease among locations with low rotavirus vaccine coverage, suggesting that ongoing disease transmission is related to failure to vaccinate. Educational efforts focusing on timely rotavirus vaccine administration to age-eligible infants are needed.

Parental report of vaccine receipt in children with autism spectrum disorder: Do rates differ by pattern of ASD onset?

A contentious theory espoused by some parents is that regressive-onset of autism spectrum disorder (ASD) is triggered by vaccines. If this were true, then vaccine receipt should be higher in children with regressive-onset ASD compared with other patterns of onset. Parental report of rate of receipt for six vaccines (DPT/DTaP, HepB, Hib, polio, MMR, varicella) was examined in children with ASD (N=2755) who were categorized by pattern of ASD onset (early onset, plateau, delay-plus-regression, regression). All pairwise comparisons were significantly equivalent within a 10% margin for all vaccines except varicella, for which the delay-plus-regression group had lower rates of receipt (81%) than the early-onset (87%) and regression (87%) groups. Findings do not support a connection between regressive-onset ASD and vaccines in this cohort.