Minesh P. Shah

Effectiveness of a Third Dose of MMR Vaccine for Mumps Outbreak Control

BACKGROUND The effect of a third dose of the measles–mumps–rubella (MMR) vaccine in stemming a mumps outbreak is unknown. During an outbreak among vaccinated students at the University of Iowa, health officials implemented a widespread MMR vaccine campaign. We evaluated the effectiveness of a third dose for outbreak control and assessed for waning immunity. METHODS Of 20,496 university students who were enrolled during the 2015–2016 academic year, mumps was diagnosed in 259 students. We used Fishers exact test to compare unadjusted attack rates according to dose status and years since receipt of the second MMR vaccine dose. We used multivariable time‐dependent Cox regression models to evaluate vaccine effectiveness, according to dose status (three vs. two doses and two vs. no doses) after adjustment for the number of years since the second dose. RESULTS Before the outbreak, 98.1% of the students had received at least two doses of MMR vaccine. During the outbreak, 4783 received a third dose. The attack rate was lower among the students who had received three doses than among those who had received two doses (6.7 vs. 14.5 cases per 1000 population, P<0.001). Students had more than nine times the risk of mumps if they had received the second MMR dose 13 years or more before the outbreak. At 28 days after vaccination, receipt of the third vaccine dose was associated with a 78.1% lower risk of mumps than receipt of a second dose (adjusted hazard ratio, 0.22; 95% confidence interval, 0.12 to 0.39). The vaccine effectiveness of two doses versus no doses was lower among students with more distant receipt of the second vaccine dose. CONCLUSIONS Students who had received a third dose of MMR vaccine had a lower risk of mumps than did those who had received two doses, after adjustment for the number of years since the second dose. Students who had received a second dose of MMR vaccine 13 years or more before the outbreak had an increased risk of mumps. These findings suggest that the campaign to administer a third dose of MMR vaccine improved mumps outbreak control and that waning immunity probably contributed to propagation of the outbreak. (Funded by the Centers for Disease Control and Prevention.)

Decline in Emergency Department Visits for Acute Gastroenteritis Among Children in 10 US States After Implementation of Rotavirus Vaccination, 2003 to 2013.

Background: Rotavirus vaccination of all infants began in the United States in 2006. Although the effect of vaccination on childhood hospitalizations for rotavirus has been well described, the effects of rotavirus vaccine on emergency department (ED) visits are less well documented. Methods: Using the State Emergency Department Databases for 10 US states, we compared the rates of gastroenteritis- and rotavirus-coded ED visits among children <5 years of age in prevaccine (2003 to 2006) with those in postvaccine (2008–2013) years; 2007 was excluded as a transition year. We analyzed ED visit rates by age group, sex, race and rotavirus season. Results: The prevaccine annual gastroenteritis-coded ED visit rate among children <5 years of age of 426 per 10,000 (annual range, 396–477 per 10,000) declined to 382 per 10,000 in postvaccine years, a 10.3% (±0.3%, P < 0.0001) rate reduction overall. Compared with prevaccine years, annual ED visit rates for gastroenteritis decreased by 6.5% (±0.6%) in 2008, 12.3% (±0.6%) in 2010, 14.8% (±0.5%) in 2011, 20.4% (±0.5%) in 2012 and 10.1% (±0.6%) in 2013; a small increase of 1.8% (±0.6%) was seen in 2009 (P < 0.0001 for all individual comparisons). Declines were similar by sex and race and were greater in children <2 years of age (range 14.1%–20.6%, P < 0.0001) than in older children (increase of 3.3% ±0.6%, P < 0.0001). A decline of 21.2% (±0.4%, P < 0.0001) in ED visits was seen during the rotavirus season months from January through June versus an increase of 9.5% (±0.6%, P < 0.0001) during July to December. ED visits specifically coded for rotavirus showed more prominent declines than for all gastroenteritis. Conclusions: ED visits for gastroenteritis in US children have declined since the introduction of rotavirus vaccine.

Mumps Outbreak in a Highly Vaccinated University-Affiliated Setting Before and After a Measles-Mumps-Rubella Vaccination Campaign—Iowa, July 2015–May 2016

Background In response to a mumps outbreak at the University of Iowa and surrounding community, university, state, and local health officials implemented a vaccination campaign targeting students <25 years of age with an additional dose of measles-mumps-rubella (MMR) vaccine. More than 4700 vaccine campaign doses were administered; 97% were documented third doses. We describe the epidemiology of the outbreak before and after the campaign, focusing on cases in university students. Methods Mumps cases were identified from reportable disease databases and university health system records. Detailed information on student cases was obtained from interviews, medical chart abstractions, university and state vaccination records, and state public health laboratory results. Pre- and postcampaign incidence among students, university faculty/staff, and community members <25 vs ≥25 years old were compared using Fisher exact test. Multivariable regression modeling was performed to identify variables associated with a positive mumps polymerase chain reaction test. Results Of 453 cases in the county, 301 (66%) occurred in university students. Student cases were primarily undergraduates (90%) and highly vaccinated (86% had 2 MMR doses, and 12% had 3 MMR doses). Fewer cases occurred in students after the campaign (75 [25%]) than before (226 [75%]). Cases in the target group (students <25 years of age) declined 9% postcampaign (P=.01). A positive mumps polymerase chain reaction test was associated with the presence of parotitis and early sample collection, and inversely associated with recent receipt of MMR vaccine. Conclusions Following a large additional dose MMR vaccination campaign, fewer mumps cases occurred overall and in the target population.

Estimated reductions in hospitalizations and deaths from childhood diarrhea following implementation of rotavirus vaccination in Africa

ABSTRACT Introduction: Rotavirus is the leading cause of hospitalizations and deaths from diarrhea. 33 African countries had introduced rotavirus vaccines by 2016. We estimate reductions in rotavirus hospitalizations and deaths for countries using rotavirus vaccination in national immunization programs and the potential of vaccine introduction across the continent. Areas covered: Regional rotavirus burden data were reviewed to calculate hospitalization rates, and applied to under-5 population to estimate baseline hospitalizations. Rotavirus mortality was based on 2013 WHO estimates. Regional pre-licensure vaccine efficacy and post-introduction vaccine effectiveness studies were used to estimate summary effectiveness, and vaccine coverage was applied to calculate prevented hospitalizations and deaths. Uncertainties around input parameters were propagated using boot-strapping simulations. In 29 African countries that introduced rotavirus vaccination prior to end 2014, 134,714 (IQR 112,321–154,654) hospitalizations and 20,986 (IQR 18,924–22,822) deaths were prevented in 2016. If all African countries had introduced rotavirus vaccines at benchmark immunization coverage, 273,619 (47%) (IQR 227,260–318,102) hospitalizations and 47,741 (39%) (IQR 42,822–52,462) deaths would have been prevented. Expert commentary: Rotavirus vaccination has substantially reduced hospitalizations and deaths in Africa; further reductions are anticipated as additional countries implement vaccination. These estimates bolster wider introduction and continued support of rotavirus vaccination programs.

Near Real-Time Surveillance of U.S. Norovirus Outbreaks by the Norovirus Sentinel Testing and Tracking Network — United States, August 2009–July 2015

Norovirus is the leading cause of endemic and epidemic acute gastroenteritis in the United States (1). New variant strains of norovirus GII.4 emerge every 2-4 years (2-4) and are often associated with increased disease and health care visits (5-7). Since 2009, CDC has obtained epidemiologic data on norovirus outbreaks from state health departments through the National Outbreak Reporting System (NORS) (8) and laboratory data through CaliciNet (9). NORS is a web-based platform for reporting waterborne, foodborne, and enteric disease outbreaks of all etiologies, including norovirus, to CDC. CaliciNet, a nationwide electronic surveillance system of local and state public health and regulatory agency laboratories, collects genetic sequences of norovirus strains associated with gastroenteritis outbreaks. Because these two independent reporting systems contain complementary data, integration of NORS and CaliciNet records could provide valuable public health information about norovirus outbreaks. However, reporting lags and inconsistent identification codes in NORS and CaliciNet records have been an obstacle to developing an integrated surveillance system.

Impact of pentavalent rotavirus vaccine against severe rotavirus diarrhoea in The Gambia

INTRODUCTION Rotavirus vaccines protect against the leading cause of severe childhood diarrhoea, and have been introduced in many low-income African countries. The Gambia introducedRotateq® (RV5) into their national immunization program in 2013. We revieweddata from an active rotavirus sentinel surveillancesitefor early evidence of vaccine impact. METHODS We compared rotavirus prevalence in diarrhoeal stool in children< 5 years of age admittedat the Edward Francis Small Teaching Hospital sentinel surveillance site before (2013) andafterRV5 introduction (2015-2016) in the Gambia. The rotavirus-percent positive was separately compared for all diarrhoealhospitalizations and for hospitalizations with severe symptoms. Rotavirus prevalence was compared annually for the pre-vaccine year of 2013 with post-vaccine years of 2015 and 2016 using chi-square or Fishers exact tests and the p-value to establish significant relationship was set at p < 0.05. All analyses were completed in SAS 9.3 (SAS Analytics, North Carolina). RESULTS Rotavirus prevalence among all diarrhoeahospitalizations decreased from 22% in 2013 to 11% in 2015 (p = 0.04), while remaining unchanged in 2016 (18%, p = 0.56). For hospitalizations that were clinically severe and/or treated with intravenous fluids (mean of 46 per year), the rotavirus prevalence decreased from 33% in 2013 to 8% in 2015 (p = 0.04), and to 15% in 2016 (p = 0.08). The children with age <1 year accounted for 45% the population infected with rotavirus in both pre and post rotavirus vaccination periods. CONCLUSIONS Rotavirus vaccine introduction in the Gambia could be among factors resulting in decreased diarrhea hospitalizations among children at the Edward Francis Small Teaching Hospital, particularly those with severe disease. These results support the continuation of rotavirus vaccine and additional monitoring of rotavirus hospitalization trends in the country.

Annual changes in rotavirus hospitalization rates before and after rotavirus vaccine implementation in the United States

Background Hospitalizations for rotavirus and acute gastroenteritis (AGE) have declined in the US with rotavirus vaccination, though biennial peaks in incidence in children aged less than 5 years occur. This pattern may be explained by lower rotavirus vaccination coverage in US children (59% to 73% from 2010–2015), resulting in accumulation of susceptible children over two successive birth cohorts. Methods Retrospective cohort analysis of claims data of commercially insured US children aged <5 years. Age-stratified hospitalization rates for rotavirus and for AGE from the 2002–2015 rotavirus seasons were examined. Median age and rotavirus vaccination coverage for biennial rotavirus seasons during pre-vaccine (2002–2005), early post-vaccine (2008–2011) and late post-vaccine (2012–2015) years. Results Age-stratified hospitalization rates decreased from pre-vaccine to early post-vaccine and then to late post-vaccine years. The clearest biennial pattern in hospitalization rates is the early post-vaccine period, with higher rates in 2009 and 2011 than in 2008 and 2010. The pattern diminishes in the late post-vaccine period. For rotavirus hospitalizations, the median age and the difference in age between biennial seasons was highest during the early post-vaccine period; these differences were not observed for AGE hospitalizations. There was no significant difference in vaccination coverage between biennial seasons. Conclusions These observations provide conflicting evidence that incomplete vaccine coverage drove the biennial pattern in rotavirus hospitalizations that has emerged with rotavirus vaccination in the US. As this pattern is diminishing with higher vaccine coverage in recent years, further increases in vaccine coverage may reach a threshold that eliminates peak seasons in hospitalizations.

Norovirus Illnesses in Children and Adolescents

Norovirus is a leading cause of childhood vomiting and diarrhea in the United States and globally. Although most illnesses caused by norovirus are self-resolving, severe outcomes may occur from dehydration, including hospitalization and death. A vast majority of deaths from norovirus occur in developing countries. Immunocompromised children are at risk for more severe outcomes. Treatment of norovirus illness is focused on early correction of dehydration and maintenance of fluid status and nutrition. Hand hygiene, exclusion of ill individuals, and environmental cleaning are important for norovirus outbreak prevention and control, and vaccines to prevent norovirus illness are currently under development.

Timing of Birth as an Emergent Risk Factor for Rotavirus Hospitalization and Vaccine Performance in the Postvaccination Era in the United States

Rotavirus vaccines were introduced in the United States in 2006, and in the years since they have fundamentally altered the seasonality of rotavirus infection and have shifted disease outbreaks from annual epidemics to biennial epidemics. We investigated whether season and year of birth have emerged as risk factors for rotavirus or have affected vaccine performance. We constructed a retrospective birth cohort of US children under age 5 years using the 2001-2014 MarketScan database (Truven Health Analytics, Chicago, Illinois). We evaluated the associations of season of birth, even/odd year of birth, and interactions with vaccination. We fitted Cox proportional hazards models to estimate the hazard of rotavirus hospitalization according to calendar year of birth and season of birth assessed for interaction with vaccination. After the introduction of rotavirus vaccine, we observed monotonically decreasing rates of rotavirus hospitalization for each subsequent birth cohort but a biennial incidence pattern by calendar year. In the postvaccine period, children born in odd calendar years had a higher hazard of rotavirus hospitalization than those born in even years. Children born in winter had the highest hazard of hospitalization but also had greater vaccine effectiveness than children born in spring, summer, or fall. With the emergence of a strong biennial pattern of disease following vaccine introduction, the timing of a childs birth has become a risk factor for rotavirus infection.

Global Disease Burden of Foodborne Illnesses Associated With Norovirus

Noroviruses are the most common etiology of acute gastroenteritis worldwide, causing an estimated 685 million illnesses, 210,000 deaths, and 15 million disability-adjusted life years annually. Approximately 14–23% of all norovirus illnesses are attributed to foodborne transmission, making norovirus the leading cause of foodborne illnesses and fourth-leading cause of death from foodborne illness. Although the number of illnesses and the severity of outcomes vary by geographic region and mortality strata, norovirus is a major cause of foodborne illness in all countries. Young children and older adults are at higher risk for severe outcomes from norovirus disease. Challenges to estimating norovirus disease burden include the lack of widely available rapid diagnostic testing for norovirus, variation in health-seeking behavior and stool specimen testing, and inconsistent diagnostic coding for norovirus disease, particularly in lower- and middle-income countries.