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In this study, we report the detection of a G6P[14] rotavirus strain from a human stool sample within the United States. The full genotype constellation of the G6P[14] strain was identified as G6-P[14]-I2-R2-C2-M2-A11-N2-T6-E2-H3.

BACKGROUND AND OBJECTIVES Limited postauthorization safety data for the Pfizer-BioNTech coronavirus disease 2019 vaccination among children ages 5 to 11 years are available, particularly for the adverse event myocarditis, which has been detected in adolescents and young adults. We describe adverse events observed during the first 4 months of the United States coronavirus disease 2019 vaccination program in this age group. METHODS We analyzed data from 3 United States safety monitoring systems: v-safe, a voluntary smartphone-based system that monitors reactions and health effects; the Vaccine Adverse Events Reporting System (VAERS), the national spontaneous reporting system comanaged by the Centers for Disease Control and Prevention and Food and Drug Administration; and the Vaccine Safety Datalink, an active surveillance system that monitors electronic health records for prespecified events, including myocarditis. RESULTS Among 48 795 children ages 5 to 11 years enrolled in v-safe, most reported reactions were mild-to-moderate, most frequently reported the day after vaccination, and were more common after dose 2. VAERS received 7578 adverse event reports; 97% were nonserious. On review of 194 serious VAERS reports, 15 myocarditis cases were verified; 8 occurred in boys after dose 2 (reporting rate 2.2 per million doses). In the Vaccine Safety Datalink, no safety signals were detected in weekly sequential monitoring after administration of 726 820 doses. CONCLUSIONS Safety findings for Pfizer-BioNTech vaccine from 3 United States monitoring systems in children ages 5 to 11 years show that most reported adverse events were mild and no safety signals were observed in active surveillance. VAERS reporting rates of myocarditis after dose 2 in this age group were substantially lower than those observed among adolescents ages 12 to 15 years.

Uzbekistan, the most populous country in central Asia, was the first in the region to introduce rotavirus vaccine into its national immunization program. Rotarix (GlaxoSmithKline Biologicals, RV1) was introduced in June 2014, with doses recommended at age 2 and 3 months. To evaluate vaccine impact, active surveillance for rotavirus diarrhea was reestablished in 2014 at 2 hospitals in Tashkent and Bukhara which had also performed surveillance during the pre-vaccine period 2005−2009. Children aged

Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the USA, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorisations. We aimed to investigate reports of individuals aged 12-20 years with MIS-C after COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to the US Centers for Disease Control and Prevention (CDC).In this surveillance activity, we investigated potential cases of MIS-C after COVID-19 vaccination reported to CDC's MIS-C national surveillance system, the Vaccine Adverse Event Reporting System (co-administered by CDC and the US Food and Drug Administration), and CDC's Clinical Immunization Safety Assessment Project. A multidisciplinary team adjudicated cases by use of the CDC MIS-C definition. Any positive SARS-CoV-2 serology test satisfied case criteria; although anti-nucleocapsid antibodies indicate previous SARS-CoV-2 infection, anti-spike protein antibodies indicate either past or recent infection or COVID-19 vaccination. We describe the demographic and clinical features of cases, stratified by laboratory evidence of SARS-CoV-2 infection. To calculate the reporting rate of MIS-C, we divided the count of all individuals meeting the MIS-C case definition, and of those without evidence of SARS-CoV-2 infection, by the number of individuals aged 12-20 years in the USA who received one or more COVID-19 vaccine doses up to Aug 31, 2021, obtained from CDC national vaccine surveillance data.Using surveillance results from Dec 14, 2020, to Aug 31, 2021, we identified 21 individuals with MIS-C after COVID-19 vaccination. Of these 21 individuals, median age was 16 years (range 12-20); 13 (62%) were male and eight (38%) were female. All 21 were hospitalised: 12 (57%) were admitted to an intensive care unit and all were discharged home. 15 (71%) of 21 individuals had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. As of Aug 31, 2021, 21 335 331 individuals aged 12-20 years had received one or more doses of a COVID-19 vaccine, making the overall reporting rate for MIS-C after vaccination 1·0 case per million individuals receiving one or more doses in this age group. The reporting rate in only those without evidence of SARS-CoV-2 infection was 0·3 cases per million vaccinated individuals.Here, we describe a small number of individuals with MIS-C who had received one or more doses of a COVID-19 vaccine before illness onset; the contribution of vaccination to these illnesses is unknown. Our findings suggest that MIS-C after COVID-19 vaccination is rare. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted.US Centers for Disease Control and Prevention.

Objectives: The number of SARS-CoV-2 infections is underestimated in surveillance data. Various approaches to assess the seroprevalence of antibodies to SARS-CoV-2 have different resource requirements and generalizability. We estimated the seroprevalence of antibodies to SARS-CoV-2 in Denver County, Colorado, via a cluster-sampled community survey. Methods: We estimated the overall seroprevalence of antibodies to SARS-CoV-2 via a community seroprevalence survey in Denver County in July 2020, described patterns associated with seroprevalence, and compared results with cumulative COVID-19 incidence as reported to the health department during the same period. In addition, we compared seroprevalence as assessed with a temporally and geographically concordant convenience sample of residual clinical specimens from a commercial laboratory. Results: Based on 404 specimens collected through the community survey, 8.0% (95% CI, 3.9%-15.7%) of Denver County residents had antibodies to SARS-CoV-2, an infection rate of about 7 times that of the 1.1% cumulative reported COVID-19 incidence during this period. The estimated infection-to-reported case ratio was highest among children (34.7; 95% CI, 11.1-91.2) and males (10.8; 95% CI, 5.7-19.3). Seroprevalence was highest among males of Black race or Hispanic ethnicity and was associated with previous COVID-19–compatible illness, a previous positive SARS-CoV-2 test result, and close contact with someone who had confirmed SARS-CoV-2 infection. Testing of 1598 residual clinical specimens yielded a seroprevalence of 6.8% (95% CI, 5.0%-9.2%); the difference between the 2 estimates was 1.2 percentage points (95% CI, −3.6 to 12.2 percentage points). Conclusions: Testing residual clinical specimens provided a similar seroprevalence estimate yet yielded limited insight into the local epidemiology of COVID-19 and might be less representative of the source population than a cluster-sampled community survey. Awareness of the limitations of various sampling strategies is necessary when interpreting findings from seroprevalence assessments.

Background Rotavirus vaccine (RV) coverage levels for US infants are Methods We surveyed nationally representative networks of pediatricians by internet/mail from April to June, 2019. Multivariable regression assessed factors associated with difficulty administering the first RV dose (RV#1) by the maximum age. Results Response rate was 68% (303/448). Ninety-nine percent of providers reported strongly recommending RV. The most common barriers to RV delivery overall (definite/somewhat of a barrier) were: parental concerns about vaccine safety overall (27%), parents wanting to defer (25%), parents not thinking RV was necessary (12%), and parent concerns about RV safety (6%). The most commonly reported reasons for nonreceipt of RV#1 by 4 to 5 months (often/always) were parental vaccine refusal (9%), hospitals not giving RV at discharge from nursery (7%), infants past the maximum age when discharged from neonatal intensive care unit/nursery (6%), and infant not seen before maximum age for well care visit (3%) or seen but no vaccine given (4%). Among respondents 4% strongly agreed and 25% somewhat agreed that they sometimes have difficulty giving RV#1 before the maximum age. Higher percentage of State Child Health Insurance Program/Medicaid-insured children in the practice and reporting that recommendations for timing of RV doses are too complicated were associated with reporting difficulty delivering the RV#1 by the maximum age. Conclusions US pediatricians identified multiple, actionable issues that may contribute to suboptimal RV immunization rates including lack of vaccination prior to leaving nurseries after prolonged stays, infants not being seen for well care visits by the maximum age, missed opportunities at visits and parents refusing/deferring.

Introduction intussusception surveillance was initiated in Tanzania in 2013 after monovalent rotavirus vaccine was introduced, as part of the 7-country African evaluation to assess whether the vaccine was associated with an increased risk of intussusception. An increased risk from vaccine was not identified. Published data on intussusception in Tanzanian infants are limited. Methods prospective intussusception surveillance was conducted at 7 referral hospitals during 2013-2016 to identify all infants with intussusception meeting Brighton Level 1 criteria. Demographic, household and clinical data were collected by hospital clinicians and analyzed. Results a total of 207 intussusception cases were identified. The median age of cases was 5.8 months and nearly three-quarters were aged 4-7 months. Median number of days from symptom onset to admission at treatment hospital was 3 (IQR 2-5). Seventy-eight percent (152/195) of cases had been admitted at another hospital before transfer to the treating hospital. Enema reduction was not available; all infants were treated surgically and 55% (114/207) had intestinal resection. The overall case-fatality rate was 30% (62/206). Compared with infants who survived, those who died had longer duration of symptoms before admission to treatment hospital (median 4 vs 3 days; p < 0.01), higher rate of intestinal resection (81% [60/82] vs 44% [64/144], p < 0.001), and from families with lower incomes (i.e., less likely to own a television [p < 0.01] and refrigerator [p < 0.05). Conclusion Tanzanian infants who develop intussusception have a high case-fatality rate. Raising the index of suspicion among healthcare providers, allocating resources to allow wider availability of abdominal ultrasound for earlier diagnosis, and training teams in ultrasound-guided enema reduction techniques used in other African countries could reduce the fatality rate.

In 2016, Zika virus disease developed in a man (patient A) who had no known risk factors beyond caring for a relative who died of this disease (index patient). We investigated the source of infection for patient A by surveying other family contacts, healthcare personnel, and community members, and testing samples for Zika virus. We identified 19 family contacts who had similar exposures to the index patient; 86 healthcare personnel had contact with the index patient, including 57 (66%) who had contact with body fluids. Of 218 community members interviewed, 28 (13%) reported signs/symptoms and 132 (61%) provided a sample. Except for patient A, no other persons tested had laboratory evidence of recent Zika virus infection. Of 5,875 mosquitoes collected, none were known vectors of Zika virus and all were negative for Zika virus. The mechanism of transmission to patient A remains unknown but was likely person-to-person contact with the index patient.

Histo-blood group antigens (HBGAs) expressed on enterocytes are proposed receptors for rotaviruses and can be measured in saliva. Among 181 Pakistani infants in a G1P[8] rotavirus vaccine trial who were seronegative at baseline, anti-rotavirus immunoglobulin A seroconversion rates after 3 vaccine doses differed significantly by salivary HBGA phenotype, with the lowest rate (19%) among infants who were nonsecretors (ie, who did not express the carbohydrate synthesized by FUT2), an intermediate rate (30%) among secretors with non-blood group O, and the highest rate (51%) among secretors with O blood group. Differences in HBGA expression may be responsible for some of the discrepancy in the level of protection detected for the current rotavirus vaccines in low-income versus high-income settings.

BACKGROUND: Rotavirus vaccines (RVVs) were included in the US immunization program in 2006 and are coadministered with the diphtheria-tetanus-acellular pertussis (DTaP) vaccine, yet their coverage lags behind DTaP. We assessed timing, initiation, and completion of the RVV series among children enrolled in active gastroenteritis surveillance at 7 US medical institutions during 2014–2016. METHODS: We compared coverage and timing of each vaccine series and analyzed characteristics associated with RVV initiation and completion. We report odds ratios (ORs) and 95% confidence intervals (CIs) from multivariable logistic regression models. RESULTS: We enrolled 10 603 children. In 2015, ≥1 dose coverage was 91% for RVV and 97% for DTaP. Seven percent of children received their first DTaP vaccine at age ≥15 weeks versus 4% for RVV (P ≤ .001). Recent birth years (2013–2016) were associated with higher odds of RVV initiation (OR = 5.72; 95% CI 4.43–7.39), whereas preterm birth (OR = 0.32; 95% CI 0.24–0.41), older age at DTaP initiation (OR 0.85; 95% CI 0.80–0.91), income between $50 000 and $100 000 (OR = 0.56; 95% CI 0.40–0.78), and higher maternal education (OR = 0.52; 95% CI 0.36–0.74) were associated with lower odds. Once RVV was initiated, recent birth years (2013–2016; OR = 1.57 [95% CI 1.32–1.88]) and higher maternal education (OR = 1.31; 95% CI 1.07–1.60) were associated with higher odds of RVV completion, whereas preterm birth (OR = 0.76; 95% CI 0.62–0.94), African American race (OR = 0.82; 95% CI 0.70–0.97) and public or no insurance (OR = 0.75; 95% CI 0.60–0.93) were associated with lower odds. Regional differences existed. CONCLUSIONS: RVV coverage remains lower than that for the DTaP vaccine. Timely DTaP administration may help improve RVV coverage.

BACKGROUND The Republic of Armenia was 1 of the 2 earliest countries in the Newly Independent States to introduce rotavirus vaccine into its national immunization program to reduce the burden of rotavirus disease (documented to cause 38% of acute gastroenteritis hospitalizations [AGE] among children aged

We report here the full coding region sequences for all 11 segments of the first equine-like G3P[8] rotavirus strain detected in the United States, strain RVA/Human-wt/USA/3000390639/2015/G3P[8]. The full genotype constellation of this strain is G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2.

We used Truven Health Marketscan claims database (2008-2011) to compare gastroenteritis rates during January-June among households whose child had received rotavirus vaccine with those whose child did not receive vaccine. Statistically significantly lower rates of hospitalization with a rotavirus gastroenteritis or unspecified-gastroenteritis discharge code occurred in vaccinated households among persons 20-29 years and females 20-29 years (2008/2009), and males 30-39 years (2009/2010). Lower emergency department gastroenteritis rates occurred in vaccinated households among females 20-29 years (2009/2010) and individuals 5-19 years (2010/2011). These data suggest rotavirus vaccination of infants provides indirect protection against moderate-to-severe rotavirus disease in young parents and older siblings.

Background Current oral rotavirus vaccines perform suboptimally in resource-poor settings. We investigated the effect of an additional dose and later schedule on the immunogenicity of monovalent rotavirus vaccine (RV1) in a developing country. Methods Infants received RV1 at 6 and 10, 10 and 14, or 6, 10, and 14 weeks of age. The primary objective was to compare antirotavirus immunoglobulin A (IgA) seroconversion at 18 weeks in the 6/10/14 arm to the cumulative seroconversion (highest result at 14 or 18 weeks) in the 6/10 arm. Results Overall, 480 (76.2%) of 630 randomized infants completed the trial per protocol. Seroconversion in the 6/10/14 arm was 36.7% (95% CI, 29.8, 44.2) compared to 36.1% (CI, 29.0, 43.9) in the 6/10 arm, (P=1.0); the result from the 10/14 arm was 38.5% (CI, 31.2, 46.3). Seroconversion in the 6/10 arm at 14 weeks (post hoc) was lower at 29.7% (CI, 23.1, 37.3). Conclusions In Pakistani infants, the immunogenicity of RV1 did not increase significantly with 3 doses at 6, 10, and 14 weeks compared to 2 doses at 6 and 10 weeks. Additional strategies should be evaluated for improving rotavirus vaccine immunogenicity in high burden countries.

Thirty-three infants aged ∼2 months had serial stool samples collected after receipt of Rotarix® vaccine dose 1, and were assessed for shedding of porcine circovirus type 1 DNA and Rotavirus group A RNA by molecular methods. We did not find strong evidence that porcine circovirus type 1 replication occurred. Porcine circovirus type 1 genome with the same sequence as that in Rotarix® was detected in a few infants as late as day ≥ 13; while this timing could suggest there may have been replication and not just transient passage through the gastrointestinal tract, the lack of increase in copy number in any infant supports transient passage and there are inherent limitations to the results. We found that 21% of infants did not shed Rotarix® RVA RNA beyond the day 3 sample, which may suggest lack of vaccine virus replication. Of the infants in whom Rotarix RVA RNA shedding continued, peak copy numbers were reached on days 3–5 for ∼40%, and after day 5 in ∼60%, and shedding can be prolonged (≥ 45 days).

Background During late summer/fall 2014, pediatric cases of acute flaccid myelitis (AFM) occurred in the United States, coincident with a national outbreak of enterovirus D68 (EV-D68)-associated severe respiratory illness. Methods Clinicians and health departments reported standardized clinical, epidemiologic, and radiologic information on AFM cases to the Centers for Disease Control and Prevention (CDC), and submitted biological samples for testing. Cases were ≤21 years old, with acute onset of limb weakness 1 August-31 December 2014 and spinal magnetic resonance imaging (MRI) showing lesions predominantly restricted to gray matter. Results From August through December 2014, 120 AFM cases were reported from 34 states. Median age was 7.1 years (interquartile range, 4.8-12.1 years); 59% were male. Most experienced respiratory (81%) or febrile (64%) illness before limb weakness onset. MRI abnormalities were predominantly in the cervical spinal cord (103/118). All but 1 case was hospitalized; none died. Cerebrospinal fluid (CSF) pleocytosis (>5 white blood cells/µL) was common (81%). At CDC, 1 CSF specimen was positive for EV-D68 and Epstein-Barr virus by real-time polymerase chain reaction, although the specimen had >3000 red blood cells/µL. The most common virus detected in upper respiratory tract specimens was EV-D68 (from 20%, and 47% with specimen collected ≤7 days from respiratory illness/fever onset). Continued surveillance in 2015 identified 16 AFM cases reported from 13 states. Conclusions Epidemiologic data suggest this AFM cluster was likely associated with the large outbreak of EV-D68-associated respiratory illness, although direct laboratory evidence linking AFM with EV-D68 remains inconclusive. Continued surveillance will help define the incidence, epidemiology, and etiology of AFM.

BACKGROUND. The Republic of Moldova was the first low- to middle-income country in the World Health Organization European Region to introduce rotavirus vaccine (July 2012). We aimed to assess the impact of the rotavirus vaccine program and estimate vaccine effectiveness (VE). METHODS. Surveillance for rotavirus gastroenteritis was conducted in 2 hospitals in the capital city of Chisinau starting in September 2009. Monthly rotavirus admissions by age were examined before and after introduction of rotavirus vaccination using interrupted time-series analyses. We performed a case-control study of VE by comparing rotavirus case patients with test-negative controls. RESULTS. Coverage with at least 1 dose of vaccine increased from 35% in year 1 to 55% in year 2 for children

Background Case-control studies are often performed to estimate postlicensure vaccine effectiveness (VE), but the enrollment of controls can be challenging, time-consuming, and costly. We evaluated whether children enrolled in the same hospital-based diarrheal surveillance used to identify rotavirus cases but who test negative for rotavirus (test-negative controls) can be considered a suitable alternative to nondiarrheal hospital or community-based control groups (traditional controls). Methods We compared calculated VE estimates as a function of varying values of true VE, attack rates of rotavirus and nonrotavirus diarrhea in the population, and sensitivity and specificity of the rotavirus enzyme immunoasssay. We also searched the literature to identify rotavirus VE studies that used traditional and test-negative control groups and compared VE estimates obtained using the different control groups. Results Assuming a 1% attack rate for severe rotavirus diarrhea, a 3% attack rate for severe nonrotavirus diarrhea in the population, a test sensitivity of 96%, and a specificity of 100%, the calculated VE estimates using both the traditional and test-negative control groups closely approximated the true VE for all values from 30% to 100%. As true VE decreased, the traditional case-control approach slightly overestimated the true VE and the test-negative case-control approach slightly underestimated this estimate, but the absolute difference was only ±0.2 percentage points. Field VE estimates from 10 evaluations that used both traditional and test-negative control groups were similar regardless of control group used. Conclusions The use of rotavirus test-negative controls offers an efficient and cost-effective approach to estimating rotavirus VE through case-control studies.

OBJECTIVE: Electronic immunization information systems (IISs) are now established in almost all US states. We used the IIS in Minnesota, Georgia, and Connecticut for immunization data and as the source of 1 of 2 control groups to measure pentavalent rotavirus vaccine (RV5) effectiveness (VE) using case-control methodology. PATIENTS AND METHODS: Case-subjects were vaccine-eligible children who presented to 1 of 5 hospitals or emergency departments with gastroenteritis and had rotavirus antigen detected in stool during any of 3 rotavirus seasons (2007–2009). Two control groups were used: children with gastroenteritis who tested negative for rotavirus and children from the IIS matched by zip code and birth date. In Minnesota and Georgia, immunization records for rotavirus-positive and -negative children were also obtained from providers. RESULTS: Overall, 402 (96%) rotavirus case-subjects and 825 (97%) rotavirus-negative controls who met eligibility criteria were found in the IISs. Ten IIS controls were identified for each case. VE estimates for RV5 were similar across control groups, immunization data sources, and states. VE point estimates for 3 vs 0 doses were 89% to 94% among children aged 8 months or older and 86% to 92% among those aged 24 months or older. VE for 2 doses was ≥90% among children aged 8 months or older, and VE for 1 dose was 66% among those aged 6 weeks through 5 months. CONCLUSIONS: Three RV5 doses confer sustained protection against rotavirus disease during the first 3 years of life in US children. Two RV5 doses also seem to provide good protection. IISs can be valuable tools for assessing the effectiveness of vaccines administered to young children.

Background. In 2006, a mumps outbreak occurred on a university campus despite $ 95% coverage of students with 2 doses of measles-mumps-rubella (MMR) vaccine. Using plasma samples from a blood drive held on campus before identification of mumps cases, we compared vaccine-induced preoutbreak mumps antibody levels between individuals who developed mumps (case patients) and those who did not develop mumps (nonpatients). Methods. Preoutbreak samples were available from 11 case patients, 22 nonpatients who reported mumps exposure but no mumps symptoms, and 103 nonpatients who reported no known exposure and no symptoms. Antibody titers were measured by plaque reduction neutralization assay using Jeryl Lynn vaccine virus and the outbreak virus Iowa-G/USA-06 and by enzyme immunoassay (EIA). Results. Preoutbreak Jeryl Lynn virus neutralization titers were significantly lower among case patients than unexposed nonpatients (P 5 .023), and EIA results were significantly lower among case patients than exposed nonpatients (P 5 .007) and unexposed nonpatients (P 5 .009). Proportionately more case patients than exposed nonpatients had a preoutbreak anti‐Jeryl Lynn titer , 31 (64% vs 27%, respectively; P 5 .065), an anti‐Iowa-G/ USA-06 titer , 8 (55% vs 14%; P 5 .033), and EIA index standard ratio , 1.40 (64% vs 9%; P 5 .002) and , 1.71 (73% vs 14%, P 5 .001). Discussion. Case patients generally had lower preoutbreak mumps antibody levels than nonpatients. However, titers overlapped and no cutoff points separated all mumps case patients from all nonpatients.

BACKGROUND Data on rotavirus burden among children in the 15 newly independent states of the former Union of Soviet Socialist Republics, particularly contemporary data from poorer countries, are not widely available. These data are desired by policy makers to assess the value of rotavirus vaccination, especially since the GAVI Alliance approved financial support for the region's eligible countries. The Rotavirus Surveillance Network was established to provide these data. METHODS We reviewed the region's literature on rotavirus burden. We established an active surveillance network for rotavirus and analyzed data from 2007 from 4 sentinel hospitals in 3 countries (Georgia, Tajikistan, and Ukraine) that were collected using standardized enrollment and stool sample testing methods. RESULTS Specimens for rotavirus testing were collected before 1997 in most studies, and the majority of studies were from 1 country, the Russian Federation. Overall, the studies indicated that approximately 33% of hospitalizations for gastroenteritis among children were attributable to rotavirus. The Rotavirus Surveillance Network documented that 1425 (42%) of 3374 hospitalizations for acute gastroenteritis among children aged

Background. Because a previous rotavirus vaccine was associated with intussusception, new rotavirus vaccines are monitored postlicensure for any such association. Accurate background intussusception rates are needed to determine whether the number of cases observed after vaccination exceeds that expected by chance. Previously, intussusception rates were obtained from inpatient discharge databases. We sought to determine the rate of intussusception among infants managed only with short-stay or emergency department care. Methods. Intussusception cases occurring in infants were identified retrospectively at 3 children's hospitals from January 2001 through March 2006, a period without rotavirus vaccine use, by a search of discharge, billing, and radiology databases for International Classification of Diseases, Ninth Revision, Clinical Modification code 560.0 (intussusception) and procedure codes and by review of medical records. Results. Of 156 infants with intussusception fulfilling Brighton level 1 criteria, 81 (52%) were billed as inpatients, 68 (44%) as short-stay patients, and 7 (4%) as emergency department patients only. The use of only inpatients assigned code 560.0 underestimated the total number of level 1 cases at the hospitals by 44%. The mean annual intussusception rate for the hospitals' catchment counties was 49.3 cases per 100,000 live births (inpatient cases: 27.1 cases per 100,000 live births; short-stay or emergency department cases: 22.3 cases per 100,000 live births). Conclusions. Intussusception rates based solely on inpatient discharge databases could underestimate the true incidence of level 1 intussusception by >40%. Background rates used for assessment of risk after vaccination should account for cases managed only with short-stay or emergency department care.

Objectives.Routine measles-mumps-rubella (MMR) vaccine use has greatly decreased the incidence of mumps in the U.S. However, a resurgence of mumps occurred in 2006. We investigated the large outbreak at a university and assessed risk factors for disease.Methods.We described the outbreak and conducted a case-control study. We interviewed case students (identified from student health service and health department records) and control students (selected from a randomly ordered administrative list) and assessed their vaccination status. We compared case students with ≥2 MMR doses and control students with ≥2 MMR doses in univariate and multivariate analyses.Results.The mean age of the 174 case students was 20.9 years; 65% were women. Ninety-seven case students and 147 control students were enrolled in the study. Two-dose MMR coverage was 99% among case and control students with complete records. Only 33% of case students reported exposure to someone with mumps. Case students were more likely than control students to be aged 18 to 19 years (vs. aged 22 years, adjusted odds ratio [AOR] = 5.55; 95% confidence interval [CI] 2.09, 14.74), to report exposure to mumps (AOR=2.31, 95% CI 1.13, 4.73), and to have worked/volunteered on campus (AOR=2.91, 95% CI 1.33, 6.33). Also, women in dormitories had increased odds of mumps compared with men in dormitories.Conclusion.High two-dose MMR coverage was not sufficient to prevent the outbreak. Further study is needed to better understand the effects of dormitory residency and gender on mumps transmission. Clinicians should be vigilant for mumps in young adults presenting with parotitis regardless of immunization history.

Numerous evaluations of the clinical sensitivity and specificity of PCR and serologic assays for Bordetella pertussis have been hampered by the low sensitivity of culture, the gold standard test, which leads to biased accuracy estimates. The bias can be reduced by using statistical approaches such as the composite reference standard (CRS) (e.g., positive if culture or serology positive; negative otherwise) or latent class analysis (LCA), an internal reference standard based on a statistical model. We illustrated the benefits of the CRS and LCA approaches by reanalyzing data from a 1995 to 1996 study of cough illness among 212 patients. The accuracy of PCR in this study was evaluated using three reference standards: culture, CRS, and LCA. Using specimens obtained 0 to 34 days after cough onset, estimates of the sensitivity of PCR obtained using CRS (47%) and LCA (34%) were lower than the culture-based estimate (62%). The CRS and LCA approaches, which utilized more than one diagnostic marker of pertussis, likely produced more accurate reference standards than culture alone. In general, the CRS approach is simple, with a well-defined disease status. LCA requires statistical modeling but incorporates more indicators of disease than CRS. When three or more indicators of pertussis are available, these approaches should be used in evaluations of pertussis diagnostic tests.

Background. The burden of rotavirus morbidity and mortality is high in children aged

(See the editorial commentary by Cunliffe and Kang on pages 1673–5, and major article by Zaman et al on pages 1686–93.) Rotavirus is a leading cause of diarrhea-associated mortality among children

Objective Using case-control methodology, we measured the vaccine effectiveness (VE) of the 2-dose monovalent rotavirus vaccine (RV1) and 3-dose pentavalent rotavirus vaccine (RV5) series given in infancy against rotavirus disease resulting in hospital emergency department or inpatient care. Study design Children were eligible for enrollment if they presented to any 1 of 3 hospitals in Atlanta, Georgia with diarrhea ≤10 days duration during January-June 2013 and were born after RV1 introduction. Stool samples were tested for rotavirus by enzyme immunoassay and immunization records were obtained from providers and the state electronic immunization information system. Case-subjects (children testing rotavirus antigen-positive) were compared with children testing rotavirus antigen-negative. Results Overall, 98 rotavirus-case subjects and 175 rotavirus-negative controls were enrolled. Genotype G12P[8] predominated (n = 87, 89%). The VE of 2 RV1 doses was 84% (95% CI 38, 96) among children aged 8-23 months and 82% (95% CI 41, 95) among children aged ≥24 months. For the same age groups, the VE of 3 RV5 doses was 80% (95% CI 27, 95) and 87% (95% CI 22, 98), respectively. Conclusions Under routine use, the RV1 and RV5 series were both effective against moderate-to-severe rotavirus disease during a G12P[8] season, and both vaccines demonstrated sustained protection beyond the first 2 years of life.

This is a report of the complete genomic sequence of a rare rotavirus group A G8-P[14]-I2-R3-C2-M2-A3-N2-T6-E2-H3 strain detected in a stool sample from a 57-year-old subject.

Background Rotavirus infection in adults is poorly understood and few rotavirus outbreaks among US adults have been reported in the literature. We describe an outbreak due to genotype G12P[8] rotavirus among medical students, faculty, and guests who attended a formal dinner event in April 2013. Methods A web-based questionnaire was distributed to event attendees to collect symptom and exposure data. A clinical case was defined as a person who developed diarrhea after attending the formal event. A laboratory-confirmed case was defined as a clinical case who attended the formal event, with rotavirus detected in stool by enzyme immunoassay or reverse transcription-polymerase chain reaction (RT-PCR) assay. Results Among 334 dinner attendees, 136 (41%) completed the web-based questionnaire; 58 (43%) respondents reported illness. Symptom onset ranged from 1 to 8 days, with peak onset 3 days after the event. In addition to diarrhea, predominant symptoms included fever (91%), abdominal pain (84%), and vomiting (49%). The median duration of illness was 2.5 days. Thirteen (22%) of 58 cases sought medical attention; none were hospitalized. Analysis of food exposures among questionnaire respondents did not identify significant associations between any specific food or drink item and illness. Stool specimens were negative for bacterial pathogens by culture and negative for norovirus by RT-PCR assay; 4 specimens were positive for rotavirus by enzyme immunoassay or PCR. G12P[8]-R1-C1-M1-A1-N1-T1-E1-H1 was identified as the causative full-genome genotype. Conclusions Rotavirus outbreaks can occur among adults, including young adults. Health professionals should consider rotavirus as a cause of acute gastroenteritis in adults.

This is a report of the complete genomic sequence of a reassortant rotavirus group A G9-P[4]-I2-R2-C2-M2-A2-N2-T2-E6-H2 strain designated RVA/Human-wt/USA/ LB1562/2010/G9P[4].

Group A Rotaviruses (RVA) are double stranded RNA viruses that are a significant cause of acute pediatric gastroenteritis. Beginning in 2006 and 2008, respectively, two vaccines, Rotarix™ and RotaTeq®, have been approved for use in the USA for prevention of RVA disease. The effects of possible vaccine pressure on currently circulating strains in the USA and their genome constellations are still under investigation. In this study we report 33 complete RVA genomes (ORF regions) collected in multiple cities across USA during 2006 – 2009, including 8 collected from children with verified receipt of 3 doses of rotavirus vaccine. The strains included 16 G1P[8], 10 G3P[8], and 7 G9P[8]. All 33 strains had a Wa like backbone with the consensus genotype constellation of G(1/3/9)-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. From maximum likelihood based phylogenetic analyses, we identified 3 to7 allelic constellations grouped mostly by respective G types, suggesting a possible allelic segregation based on the VP7 gene of RVA primarily for the G3 and G9 strains. The vaccine failure strains showed similar grouping for all genes in G9 strains and most genes of G3 strains suggesting that these constellations were necessary to evade vaccine-derived immune protection. Substitutions in the antigenic region of VP7 and VP4 genes were also observed for the vaccine failure strains which could possibly explain how these strains escape vaccine induced immune response. This study helps elucidate how RVA strains are currently evolving in the population post vaccine introduction and supports the need for continued RVA surveillance.

Rotavirus is the leading cause of severe diarrhea among children

This is a report of the complete genomic sequence of a rare rotavirus group A G3-P[9]-I2-R2-C2-M2-A3-N2-T1-E2-H3 strain designated RVA/Human-wt/USA/12US1134/2012/G3P[9].

The duration of mumps virus RNA detection was studied during a mumps outbreak in a highly vaccinated university population. Seven of the eight reverse transcription-PCR-positive specimens were collected during the first 3 days of parotitis, suggesting that viral shedding is minimal after the first 3 days of symptoms.

OBJECTIVE: Previous US evaluations have not assessed monovalent rotavirus vaccine (RV1, a G1P[8] human rotavirus strain) effectiveness, because of its later introduction (2008). Using case-control methodology, we measured the vaccine effectiveness (VE) of the 2-dose RV1 and 3-dose pentavalent vaccine (RV5) series against rotavirus disease resulting in hospital emergency department or inpatient care. METHODS: Children were eligible for enrollment if they presented to 1 of 5 hospitals (3 in Georgia, 2 in Connecticut) with diarrhea of ≤10 days’ duration during January through June 2010 or 2011, and were born after RV1 introduction. Stools were collected; immunization records were obtained from providers and state electronic immunization information system (IIS). Case-subjects (children testing rotavirus antigen-positive) were compared with 2 control groups: children testing rotavirus negative and children selected from IIS. RESULTS: Overall, 165 rotavirus-case subjects and 428 rotavirus-negative controls were enrolled. Using the rotavirus-negative controls, RV1 VE was 91% (95% confidence interval [CI] 80 to 95) and RV5 VE was 92% (CI 75 to 97) among children aged ≥8 months. The RV1 VE against G2P[4] disease was high (94%, CI 78 to 98), as was that against G1P[8] disease (89%, CI 70 to 96). RV1 effectiveness was sustained among children aged 12 through 23 months (VE 91%; CI 75 to 96). VE point estimates using IIS controls were similar to those using rotavirus-negative controls. CONCLUSIONS: RV1 and RV5 were both highly effective against severe rotavirus disease. RV1 conferred sustained protection during the first 2 years of life and demonstrated high effectiveness against G2P[4] (heterotypic) disease.

Background International data show a low-level increased risk of intussusception associated with rotavirus vaccination. Although US data have not documented a risk, we assumed a risk similar to international settings and compared potential vaccine-associated intussusception cases with benefits of prevention of rotavirus gastroenteritis by a fully implemented US rotavirus vaccine program. Methods To calculate excess intussusception cases, we used national data on vaccine coverage and baseline intussusception rates, and assumed a vaccine-associated intussusception relative risk of 5.3 (95% confidence interval [CI]: 3.0-9.3) in the first week after the first vaccine dose, the risk seen in international settings. We used postlicensure vaccine effectiveness data to calculate rotavirus disease burden averted. Results For a US birth cohort of 4.3 million infants, vaccine-associated intussusception could cause an excess 0.2 (range: 0.1-0.3) deaths, 45 (range: 21-86) hospitalizations and 13 (range: 6-25) cases managed in short-stay or emergency department settings. Vaccination would avert 14 (95% CI: 10-19) rotavirus-associated deaths, 53,444 (95% CI: 37,622-72,882) hospitalizations and 169,949 (95% CI: 118,161-238,630) emergency department visits. Summary benefit-risk ratios for death and hospitalization are 71:1 and 1093:1, respectively. Conclusions The burden of severe rotavirus disease averted due to vaccination compared with the vaccine-associated intussusception events offers a side-by-side analysis of the benefits and potential risks. If an intussusception risk similar to that seen internationally exists in the United States, it is substantially exceeded by the benefits of rotavirus disease burden averted by vaccination.

BACKGROUND Although US data have not documented an intussusception risk with current rotavirus vaccines, international data indicate a possible low risk, primarily after the first dose. METHODS Among infants in 26 US states comprising 75% of the birth cohort, we examined age-specific trends in population-level intussusception hospitalization rates before (2000-2005) and after (2007-2009) rotavirus vaccine introduction. RESULTS Compared with 2000-2005 (35.3 per 100,000), the rate was greater in 2007 (39.0 per 100,000; rate ratio [RR], 1.10; 95% confidence interval [CI], 1.04-1.18), similar in 2008 (33.4 per 100,000; RR, 0.95; 95% CI, .89-1.01), and lower in 2009 (32.9 per 100,000; RR, 0.93; 95% CI, .87-.99). Among infants aged 8-11 weeks, compared with 2000-2005 (6.9 per 100,000), a small, significant increase was observed in each of 2007 (11.4 per 100,000; RR, 1.64; 95% CI, 1.08-2.50), 2008 (12.2 per 100,000; RR, 1.76; 95% CI, 1.17-2.65), and 2009 (11.0 per 100,000; RR, 1.59; 95% CI, 1.04-2.44). CONCLUSIONS Following rotavirus vaccine introduction, a small increase in intussusception rates was seen among US infants aged 8-11 weeks, to whom most first doses of vaccine are given; no sustained population-level change in overall rates was observed.

Rotavirus causes one-third to one-half of severe diarrheal disease in children under the age of five years worldwide. In 2006 two rotavirus vaccines became available and, in the intervening years, approximately thirty countries have introduced them into their immunization programs, primarily in high-income and middle-income settings. Major reductions in rotavirus hospitalizations have been observed in a number of these locations, and in select countries, there have been impacts on gastroenteritis mortality associated with rotavirus vaccine introduction. In addition to these direct health benefits, reduced gastroenteritis risk has been documented in unvaccinated groups, including older children and adults, suggesting indirect benefits (i.e. herd immunity). In this paper, we summarize what has been learned from programs studying post-licensure vaccine effectiveness, impact on health-care utilization and death, safety issues (namely, intussception and the detection of adventitious viruses) and the potential selective pressure of vaccination on the diversity of rotavirus genotypes.

Early rotavirus vaccine adopter countries in the Americas, Europe, and in Australia have documented substantial declines in rotavirus disease burden following the introduction of vaccination. However, the full public health impact of rotavirus vaccines has not been realized as they have not been introduced into routine immunization programs in countries of Africa and Asia with the highest rotavirus disease morbidity and mortality burden. In this article, we review the epidemiology of rotavirus disease, the development and current status of rotavirus vaccines including newly available vaccine impact data from early-introducer countries, and future priorities for implementation and monitoring of rotavirus vaccination programs in developing countries.

Background. Rotavirus vaccine was recommended for routine use among US infants in 2006. To provide prevaccine data, we conducted strain surveillance for 9 consecutive seasons during 1996-2005. Methods. Using reverse-transcriptase polymerase chain reaction genotyping and nucleotide sequencing, we determined P/G genotypes of >3100 rotavirus strains collected in up to 12 cities each year from different US regions. Results. The most prevalent strain globally, P[8] G1, was the most prevalent each year in the United States (overall, 78.5% of strains; range, 60.0%-93.9%), and 9.2% of the samples were P[4] G2, 3.6% were P[8] G9, 1.7% were P[8] G3, and 0.8% were P[8] G4. Genotype P[6] G9, which emerged in 1995, was detected continuously for several seasons (from 1996-1997 to 2000-2001, 0.2%-5.4%) but was not identified in the subsequent 4 seasons. Single or a few detections of rare genotypes (eg, P[6] G12, P[9] G6, and P[9] G3) were observed during several rotavirus seasons at frequencies of 0.5%-1.7% and, overall, comprised 0.6% of all the samples from the entire surveillance period. Several globally common strains in addition to G1, especially G2 and G9, circulated at high prevalence (33%-62%) in some cities during certain years. Conclusions. Almost 85% of strains during 1996-2005 had either a G or P antigen that is present in both RotaTeq (Merck) and Rotarix (GlaxoSmithKline). Monitoring of strains after introduction of rotavirus vaccines is important.