In 2006, human papillomavirus (HPV) vaccine was first recommended in the United States to prevent cancers and other diseases caused by HPV; vaccination coverage increased steadily through 2021, and increasing numbers of young women had received HPV vaccine as children or adolescents. Since 2008, CDC has monitored incidence of precancerous lesions (cervical intraepithelial neoplasia [CIN] grades 2-3 and adenocarcinoma in situ [AIS], collectively CIN2+), which are detected through cervical cancer screening and can be used as an intermediate outcome for monitoring vaccination impact, via the five-site Human Papillomavirus Vaccine Impact Monitoring Project. This analysis describes trends in incidence of CIN2+ and CIN3+ (i.e., CIN grade 3 and AIS) lesions during 2008-2022. Among women aged 20-24 years who were screened for cervical cancer, rates during 2008-2022 decreased for CIN2+ by 79%, and for CIN3+ by 80%. In the same period, CIN3+ rates among screened women aged 25-29 years decreased by 37%. These data are consistent with considerable impact of HPV vaccination for preventing cervical precancers among women in the age groups most likely to have been vaccinated, and support existing recommendations to vaccinate children at the routinely recommended ages as a cancer prevention measure.

Objectives: Although invasive cervical cancer (ICC) rates have declined since the advent of screening, the annual age-adjusted ICC rate in the United States remains 7.5 per 100,000 women. Failure of recommended screening and management often precedes ICC diagnoses. The study aimed to evaluate characteristics of women with incident ICC, including potential barriers to accessing preventive care. Materials and Methods: We abstracted medical records for patients with ICC identified during 2008-2020 in five U.S. population-based surveillance sites covering 1.5 million women. We identified evidence of adverse social and medical conditions, including uninsured/underinsured, language barrier, substance use disorder, incarceration, serious mental illness, severe obesity, or pregnancy at diagnosis. We calculated descriptive frequencies and compared potential barriers by race/ethnicity, and among women with and without symptoms at diagnosis using chi-square tests. Results: Among 1,606 women with ICC (median age: 49 years; non-White: 47.4%; stage I: 54.7%), the majority (68.8%) presented with symptoms. Forty-six percent of women had at least one identified potential barrier; 15% had multiple barriers. The most common potential barriers among all women were being underinsured/uninsured (17.3%), and language (17.1%). Presence of any potential barrier was more frequent among non-White women and women with than without symptoms (p < 0.05). Conclusions: In this population-based descriptive study of women with ICC, we identified adverse circumstances that might have prevented women from seeking screening and treatment to prevent cancer. Interventions to increase appropriate cervical cancer screening and management are critical for reducing cervical cancer rates.

The four common human coronaviruses (HCoVs), including two alpha (HCoV-NL63 and HCoV-229E) and two beta (HCoV-HKU1 and HCoV-OC43) types, generally cause mild, upper respiratory illness. HCoVs are known to have seasonal patterns and variation in predominant types each year, but defined measures of seasonality are needed. We defined seasonality of HCoVs during July 2014 to November 2021 in the United States using a retrospective method applied to National Respiratory and Enteric Virus Surveillance System (NREVSS) data. In the six HCoV seasons prior to 2020-2021, onsets ranged from October to November, peaks from January to February, and offsets from April to June; most (>93%) HCoV detections occurred within the defined seasonal onsets and offsets. The 2020-2021 HCoV season onset was delayed by 11 weeks compared to prior seasons, likely due to COVID-19 mitigation efforts. Better defining HCoV seasonality can inform clinical preparedness and the expected patterns of emerging HCoVs. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

The 4 common types of human coronaviruses (HCoVs)-2 alpha (HCoV-NL63 and HCoV-229E) and 2 beta (HCoV-HKU1 and HCoV-OC43)-generally cause mild upper respiratory illness. Seasonal patterns and annual variation in predominant types of HCoVs are known, but parameters of expected seasonality have not been defined. We defined seasonality of HCoVs during July 2014-November 2021 in the United States by using a retrospective method applied to National Respiratory and Enteric Virus Surveillance System data. In the 6 HCoV seasons before 2020-21, season onsets occurred October 21-November 12, peaks January 6-February 13, and offsets April 18-June 27; most (>93%) HCoV detection was within the defined seasonal onsets and offsets. The 2020-21 HCoV season onset was 11 weeks later than in prior seasons, probably associated with COVID-19 mitigation efforts. Better definitions of HCoV seasonality can be used for clinical preparedness and for determining expected patterns of emerging coronaviruses.

BACKGROUND: We quantified the risk of respiratory syncytial virus (RSV) hospitalizations and severe outcomes among children with neurological disorders. METHODS: We estimated RSV-specific and RSV-associated hospitalization rates using International Classification of Diseases, Ninth Revision (ICD-9) codes from 2 insurance claims IBM MarketScan Research Databases (Commercial and Multi-State Medicaid) from July 2006 through June 2015. For comparison, a simple random sample of 10% of all eligible children was selected to represent the general population. Relative rates (RRs) of RSV hospitalization were calculated by dividing rates for children with neurological disorders by rates for children in the general population by age group and season. RESULTS: The RSV-specific hospitalization rate for children with any neurological condition was 4.2 (95% confidence interval [CI]: 4.1, 4.4) per 1000 person-years, and the RSV-associated hospitalization rate was 7.0 (95% CI: 6.9, 7.2) per 1000 person-years among children <19 years of age. Among privately insured children, the overall RR of RSV hospitalization in children with neurological disorders compared with the general population was 10.7 (95% CI: 10.0, 11.4) for RSV-specific hospitalization and 11.1 (95% CI: 10.5, 11.7) for RSV-associated hospitalizations. Among children in Medicaid, the RSV-specific hospitalization RR was 6.1 (95% CI: 5.8, 6.5) and the RSV-associated hospitalization RR was 6.4 (95% CI: 6.2, 6.7) compared with the general population. CONCLUSIONS: Our population-based study of children with neurological disorders found that the risk of RSV hospitalization was 6 to 12 times higher among children with neurological disorders than among the general pediatric population. These findings should be considered when determining who should be targeted for current and future RSV interventions.

The mRNA COVID-19 vaccines (Moderna and Pfizer-BioNTech) provide strong protection against severe COVID-19, including hospitalization, for at least several months after receipt of the second dose (1,2). However, studies examining immune responses and differences in protection against COVID-19-associated hospitalization in real-world settings, including by vaccine product, are limited. To understand how vaccine effectiveness (VE) might change with time, CDC and collaborators assessed the comparative effectiveness of Moderna and Pfizer-BioNTech vaccines in preventing COVID-19-associated hospitalization at two periods (14-119 days and ≥120 days) after receipt of the second vaccine dose among 1,896 U.S. veterans at five Veterans Affairs medical centers (VAMCs) during February 1-September 30, 2021. Among 234 U.S. veterans fully vaccinated with an mRNA COVID-19 vaccine and without evidence of current or prior SARS-CoV-2 infection, serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2 were also compared. Adjusted VE 14-119 days following second Moderna vaccine dose was 89.6% (95% CI = 80.1%-94.5%) and after the second Pfizer-BioNTech dose was 86.0% (95% CI = 77.6%-91.3%); at ≥120 days VE was 86.1% (95% CI = 77.7%-91.3%) for Moderna and 75.1% (95% CI = 64.6%-82.4%) for Pfizer-BioNTech. Antibody levels were significantly higher among Moderna recipients than Pfizer-BioNTech recipients across all age groups and periods since vaccination; however, antibody levels among recipients of both products declined between 14-119 days and ≥120 days. These findings from a cohort of older, hospitalized veterans with high prevalences of underlying conditions suggest the importance of booster doses to help maintain long-term protection against severe COVID-19.(†).

COVID-19 mRNA vaccines (Pfizer-BioNTech and Moderna) have been shown to be highly protective against COVID-19-associated hospitalizations (1-3). Data are limited on the level of protection against hospitalization among disproportionately affected populations in the United States, particularly during periods in which the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, predominates (2). U.S. veterans are older, more racially diverse, and have higher prevalences of underlying medical conditions than persons in the general U.S. population (2,4). CDC assessed the effectiveness of mRNA vaccines against COVID-19-associated hospitalization among 1,175 U.S. veterans aged ≥18 years hospitalized at five Veterans Affairs Medical Centers (VAMCs) during February 1-August 6, 2021. Among these hospitalized persons, 1,093 (93.0%) were men, the median age was 68 years, 574 (48.9%) were non-Hispanic Black (Black), 475 were non-Hispanic White (White), and 522 (44.4%) had a Charlson comorbidity index score of ≥3 (5). Overall adjusted vaccine effectiveness against COVID-19-associated hospitalization was 86.8% (95% confidence interval [CI] = 80.4%-91.1%) and was similar before (February 1-June 30) and during (July 1-August 6) SARS-CoV-2 Delta variant predominance (84.1% versus 89.3%, respectively). Vaccine effectiveness was 79.8% (95% CI = 67.7%-87.4%) among adults aged ≥65 years and 95.1% (95% CI = 89.1%-97.8%) among those aged 18-64 years. COVID-19 mRNA vaccines are highly effective in preventing COVID-19-associated hospitalization in this older, racially diverse population of predominately male U.S. veterans. Additional evaluations of vaccine effectiveness among various age groups are warranted. To prevent COVID-19-related hospitalizations, all eligible persons should receive COVID-19 vaccination.

Coronavirus disease 2019 (COVID-19) is primarily a respiratory illness, although increasing evidence indicates that infection with SARS-CoV-2, the virus that causes COVID-19, can affect multiple organ systems (1). Data that examine all in-hospital complications of COVID-19 and that compare these complications with those associated with other viral respiratory pathogens, such as influenza, are lacking. To assess complications of COVID-19 and influenza, electronic health records (EHRs) from 3,948 hospitalized patients with COVID-19 (March 1-May 31, 2020) and 5,453 hospitalized patients with influenza (October 1, 2018-February 1, 2020) from the national Veterans Health Administration (VHA), the largest integrated health care system in the United States,* were analyzed. Using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes, complications in patients with laboratory-confirmed COVID-19 were compared with those in patients with influenza. Risk ratios were calculated and adjusted for age, sex, race/ethnicity, and underlying medical conditions; proportions of complications were stratified among patients with COVID-19 by race/ethnicity. Patients with COVID-19 had almost 19 times the risk for acute respiratory distress syndrome (ARDS) than did patients with influenza, (adjusted risk ratio [aRR] = 18.60; 95% confidence interval [CI] = 12.40-28.00), and more than twice the risk for myocarditis (2.56; 1.17-5.59), deep vein thrombosis (2.81; 2.04-3.87), pulmonary embolism (2.10; 1.53-2.89), intracranial hemorrhage (2.85; 1.35-6.03), acute hepatitis/liver failure (3.13; 1.92-5.10), bacteremia (2.46; 1.91-3.18), and pressure ulcers (2.65; 2.14-3.27). The risks for exacerbations of asthma (0.27; 0.16-0.44) and chronic obstructive pulmonary disease (COPD) (0.37; 0.32-0.42) were lower among patients with COVID-19 than among those with influenza. The percentage of COVID-19 patients who died while hospitalized (21.0%) was more than five times that of influenza patients (3.8%), and the duration of hospitalization was almost three times longer for COVID-19 patients. Among patients with COVID-19, the risk for respiratory, neurologic, and renal complications, and sepsis was higher among non-Hispanic Black or African American (Black) patients, patients of other races, and Hispanic or Latino (Hispanic) patients compared with those in non-Hispanic White (White) patients, even after adjusting for age and underlying medical conditions. These findings highlight the higher risk for most complications associated with COVID-19 compared with influenza and might aid clinicians and researchers in recognizing, monitoring, and managing the spectrum of COVID-19 manifestations. The higher risk for certain complications among racial and ethnic minority patients provides further evidence that certain racial and ethnic minority groups are disproportionally affected by COVID-19 and that this disparity is not solely accounted for by age and underlying medical conditions.

BACKGROUND: Acute gastroenteritis (AGE) burden, etiology, and severity in adults is not well-characterized. We implemented a multisite AGE surveillance platform in 4 Veterans Affairs Medical Centers (Atlanta, Bronx, Houston and Los Angeles), collectively serving >320,000 patients annually. METHODS: From July 1, 2016-June 30, 2018, we actively identified AGE inpatient cases and non-AGE inpatient controls through prospective screening of admitted patients and passively identified outpatient cases through stool samples submitted for clinical diagnostics. We abstracted medical charts and tested stool samples for 22 pathogens via multiplex gastrointestinal PCR panel followed by genotyping of norovirus- and rotavirus-positive samples. We determined pathogen-specific prevalence, incidence, and modified Vesikari severity scores. RESULTS: We enrolled 724 inpatient cases, 394 controls, and 506 outpatient cases. Clostridioides difficile and norovirus were most frequently detected among inpatients (cases vs controls: C. difficile, 18.8% vs 8.4%; norovirus, 5.1% vs 1.5%; p<0.01 for both) and outpatients (norovirus: 10.7%; C. difficile: 10.5%). Incidence per 100,000 population was highest among outpatients (AGE: 2715; C. difficile: 285; norovirus: 291) and inpatients >/=65 years old (AGE: 459; C. difficile: 91; norovirus: 26). Clinical severity scores were highest for inpatient norovirus, rotavirus, and Shigella/EIEC cases. Overall, 12% of AGE inpatient cases had ICU stays and 2% died; 3 deaths were associated with C. difficile and 1 with norovirus. C. difficile and norovirus were detected year-round with a fall/winter predominance. CONCLUSIONS: C. difficile and norovirus were leading AGE pathogens in outpatient and hospitalized US Veterans, resulting in severe disease. Clinicians should remain vigilant for bacterial and viral causes of AGE year-round.

BACKGROUND: Up-to-date estimates of the burden of norovirus, a leading cause of acute gastroenteritis (AGE) in the United States, are needed to assess the potential value of norovirus vaccines in development. We aimed to estimate the rates, annual counts, and healthcare charges of norovirus-associated ambulatory clinic encounters, Emergency Department (ED) visits, hospitalizations, and deaths in the United States. METHODS: We analyzed administrative data on AGE outcomes from July 1, 2001 through June 30, 2015. Data were sourced from IBM(R) MarketScan(R) Commercial and Medicare Supplemental Databases (ambulatory clinic and ED visits), the Healthcare Utilization Project National Inpatient Sample (NIS; hospitalizations), and the National Center for Health Statistics multiple-cause-of-mortality (MCM) data (deaths). Outcome data (ambulatory clinic and ED visits, hospitalizations, or deaths) were summarized by month, age group, and setting. Healthcare charges were estimated based on insurance claims. Monthly counts of cause-unspecified gastroenteritis-associated outcomes were modeled as functions of cause-specified outcomes, and model residuals were analyzed to estimate norovirus-associated outcomes. Healthcare charges were estimated by applying average charges per cause-unspecified gastroenteritis encounter to the estimated number of norovirus encounters. RESULTS: We estimate 900 deaths (95% Confidence Interval [CI]: 650 - 1100), 110,000 hospitalizations (95%CI: 80,000 - 145,000), 470,000 ED visits (95% CI: 348,000 - 610,000), and 2.3 million ambulatory clinic encounters (95% CI: 1.7 - 2.9 million) annually due to norovirus, with an associated $430 - 740 million in healthcare charges. CONCLUSIONS: Norovirus causes a substantial health burden in the United States each year, and an effective vaccine could have important public health impact.

This cohort study uses commercial insurance data to examine the association between rotavirus vaccination and type 1 diabetes incidence.

BACKGROUND: Human parainfluenza viruses (HPIVs) cause upper and lower respiratory tract illnesses, most frequently among infants and young children, but also in the elderly. While seasonal patterns of HPIV types 1-3 have been described, less is known about national patterns of HPIV-4 circulation. OBJECTIVES: To describe patterns of HPIVs circulation in the United States (US). STUDY DESIGN: We used data from the National Respiratory and Enteric Virus Surveillance System (NREVSS), a voluntary passive laboratory-based surveillance system, to characterize the epidemiology and circulation patterns of HPIVs in the US during 2011-2019. We summarized the number of weekly aggregated HPIV detections nationally and by US census region, and used a subset of data submitted to NREVSS from public health laboratories and several clinical laboratories during 2015-2019 to analyze differences in patient demographics. RESULTS: During July 2011 - June 2019, 2,700,135 HPIV tests were reported; 122,852 (5 %) were positive for any HPIV including 22,446 for HPIV-1 (18 %), 17,474 for HPIV-2 (14 %), 67,649 for HPIV-3 (55 %), and 15,283 for HPIV-4 (13 %). HPIV testing increased substantially each year. The majority of detections occurred in children aged </= 2 years (36 %) with fluctuations in the distribution of age by type. CONCLUSIONS: HPIVs were detected year-round during 2011-2019, with type-specific year-to-year variations in circulation patterns. Among HPIV detections where age was known, the majority were aged </= 2 years. HPIV-4 exhibited an annual fall-winter seasonality, both nationally and regionally. Continued surveillance is needed to better understand national patterns of HPIV circulation.

BACKGROUND: We describe changes in rates of cervical intraepithelial neoplasia grades 2, 3 and adenocarcinoma in situ (CIN2+) during a period of human papillomavirus (HPV) vaccine uptake and changing cervical cancer screening recommendations. METHODS: We conducted population-based laboratory surveillance for CIN2+ in catchment areas in 5 states, 2008-2015. We calculated age-specific CIN2+ rates per 100000 women by age groups. We estimated incidence rate ratios (IRR) of CIN2+ for 2-year periods among all women and among screened women to evaluate changes over time. RESULTS: A total of 16572 CIN2+ cases were reported. Among women aged 18-20 and 21-24 years, CIN2+ rates declined in all sites, whereas in women aged 25-29, 30-34, and 35-39 years, trends differed across sites. The percent of women screened annually declined in all sites and age groups. Compared to 2008-2009, rates among screened women were significantly lower for all 3 periods in women aged 18-20 years (2010-2011: IRR 0.82, 95% confidence interval [CI] 0.67-0.99; 2012-2013: IRR 0.63, 95% CI 0.47-0.85; 2014-2015: IRR 0.44, 95% CI 0.28-0.68) and lower for the latter 2 time periods in women aged 21-24 years (2012-2013: IRR 0.86, 95% CI 0.79-0.94; 2014-2015: IRR 0.61, 95% CI 0.55-0.67). CONCLUSIONS: From 2008-2015, both CIN2+ rates and cervical cancer screening declined in women aged 18-24 years. The significant decreases in CIN2+ rates among screened women aged 18-24 years are consistent with a population-level impact of HPV vaccination.

Rotavirus vaccination has been associated with a short-term increased risk of intussusception. Our analysis of insurance claims for 1 858 827 US children with 544 recorded cases of intussusception found a nonsignificant decrease in intussusception (hazard ratio, 0.79 [95% confidence interval, 0.57-1.09]) in fully rotavirus-vaccinated children followed up to the age of 2 years.

Middle East respiratory syndrome coronavirus (MERS-CoV) shedding and antibody responses are not fully understood, particularly in relation to underlying medical conditions, clinical manifestations, and mortality. We enrolled MERS-CoV-positive patients at a hospital in Saudi Arabia and periodically collected specimens from multiple sites for real-time reverse transcription PCR and serologic testing. We conducted interviews and chart abstractions to collect clinical, epidemiologic, and laboratory information. We found that diabetes mellitus among survivors was associated with prolonged MERS-CoV RNA detection in the respiratory tract. Among case-patients who died, development of robust neutralizing serum antibody responses during the second and third week of illness was not sufficient for patient recovery or virus clearance. Fever and cough among mildly ill patients typically aligned with RNA detection in the upper respiratory tract; RNA levels peaked during the first week of illness. These findings should be considered in the development of infection control policies, vaccines, and antibody therapeutics.

BACKGROUND: The direct effectiveness of infant rotavirus vaccination implemented in 2006 in the United States has been evaluated extensively, however, understanding of population-level vaccine effectiveness (VE) is still incomplete. METHODS: We analyzed time series data on rotavirus gastroenteritis (RVGE) and all-cause acute gastroenteritis (AGE) hospitalization rates in the United States from the MarketScan(R) Research Databases for July 2001-June 2016. Individuals were grouped into ages 0-4, 5-9, 10-14, 15-24, 25-44, and 45-64 years. Negative binomial regression models were fitted to monthly RVGE and AGE data to estimate the direct, indirect, overall, and total VE. RESULTS: A total of 9211 RVGE and 726,528 AGE hospitalizations were analyzed. Children 0-4 years of age had the largest declines in RVGE hospitalizations with direct VE of 87% (95% CI: 83, 90%). Substantial indirect effects were observed across age groups and generally declined in each older group. Overall VE against RVGE hospitalizations for all ages combined was 69% (95% CI: 62, 76%). Total VE was highest among young children; a vaccinated child in the post-vaccine era has a 95% reduced risk of RVGE hospitalization compared to a child in the pre-vaccine era. We observed higher direct VE in odd post-vaccine years and an opposite pattern for indirect VE. CONCLUSIONS: Vaccine benefits extended to unvaccinated individuals in all age groups, suggesting infants are important drivers of disease transmission across the population. Imperfect disease classification and changing disease incidence may lead to bias in observed direct VE. TRIAL REGISTRATION: Not applicable.

BACKGROUND: The effectiveness of rotavirus vaccines in low and very low birth weight infants (LBW and VLBW) weighing <2500 and <1500 g at birth, respectively, a high-risk population for severe rotavirus gastroenteritis, has not been well examined. METHODS: We analyzed inpatient commercial claims data for US children <5 years of age from July 2001 to June 2015. Claims for acute gastroenteritis (AGE) and rotavirus-coded hospitalizations and LBW, VLBW and normal birth weight (NBW) infants were identified. Receipt of rotavirus vaccine was defined using Current Procedural Terminology. Rate reductions were calculated using prevaccine (2001-2006) and postvaccine (2007-2015) annual AGE and rotavirus hospitalization rates. RESULTS: As of December 2014, rotavirus vaccine coverage was 87%, 82% and 64%, for NBW, LBW and VLBW infants, respectively. For 2014-2015, among NBW, LBW and VLBW children <5 years of age, AGE hospitalization rate reductions relative to the prevaccine introduction period were 60% [95% confidence interval (CI): 58%-61%], 64% (95% CI: 57%-70%) and 55% (95% CI: 39%-67%), respectively. Rotavirus hospitalization rate reductions were 91% (95% CI: 90%-92%), 98% (95% CI: 93%-100%) and 93% (95% CI: 70%-98%). Rotavirus vaccines resulted in a 62% (95% CI: 51%-71%), 72% (95% CI: 44%-86%) and 71% (95% CI: 7%-91%) reduction in AGE hospitalization rates comparing vaccinated versus unvaccinated NBW, LBW and VLBW children 3-23 months of age, respectively. CONCLUSIONS: Rotavirus vaccines have substantially reduced AGE hospitalizations and are highly effective in LBW and VLBW infants, similar to NBW infants. Efforts to improve vaccination coverage, particularly in LBW and VLBW infants, should continue.

Background: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection (ALRTI) in young children, but data on surveillance case definition performance in estimating burdens have been limited. Methods: We enrolled children aged <5 years hospitalized for ALRTI (or neonatal sepsis in young infants) through active prospective surveillance at 5 sentinel hospitals in South Africa and collected nasopharyngeal aspirates from them for RSV molecular diagnostic testing between 2009 and 2014. Clinical data were used to characterize RSV disease and retrospectively evaluate the performance of respiratory illness case definitions (including the World Health Organization definition for severe acute respiratory infection [SARI]) in identifying hospitalized children with laboratory-confirmed RSV according to age group (<3, 3-5, 6-11, 12-23, and 24-59 months). Results: Of 9969 hospitalized children, 2723 (27%) tested positive for RSV. Signs and symptoms in RSV-positive children varied according to age; fever was less likely to occur in children aged <3 months (57%; odds ratio [OR], 0.8 [95% CI, 0.7-0.9]) but more likely in those aged >/=12 months (82%; OR, 1.7-1.9) than RSV-negative children. The sensitivity (range, 55%-81%) and specificity (range, 27%-54%) of the SARI case definition to identify hospitalized RSV-positive children varied according to age; the lowest sensitivity was for infants aged <6 months. Using SARI as the case definition would have missed 36% of RSV-positive children aged <5 years and 49% of those aged <3 months; removing the fever requirement from the definition recovered most missed cases. Conclusion: Including fever in the SARI case definition lowers the sensitivity for RSV case detection among young children hospitalized with an ALRTI and likely underestimates its burden.

Rotavirus commonly causes diarrhea but can also cause seizures. Analysis of insurance claims for 1,773,295 US children with 2950 recorded seizures found that, compared to rotavirus-unvaccinated children, seizure hospitalization risk was reduced by 24% (95% confidence interval [CI], 13% - 33%) and 14% (95%CI, 0% - 26%) among fully and partially rotavirus-vaccinated children, respectively.

We used administrative data to study the impact of family history on the risk of herpes zoster (HZ). Our HZ cases and our HZ family history were both ascertained on the basis of medically attended diagnoses, without reliance on self-report or recall bias. Family history was associated with HZ risk among both siblings and parents. The strength of the association differed when the index child was latently infected with vaccine-strain vs wild-type varicella zoster virus.

BACKGROUND: Rotavirus vaccination was introduced in the United States in 2006. Our objectives were to examine reductions in diarrhea-associated health care utilization after rotavirus vaccine implementation and to assess direct vaccine effectiveness (VE) in US children. METHODS: Retrospective cohort study using claims data of US children under 5 years of age. We compared rates of diarrhea-associated health care utilization in prevaccine versus post-vaccine introduction years. We also examined vaccine effectiveness (VE) and duration of protection. RESULTS: Compared with the average rate of rotavirus-coded hospitalizations in the prevaccine years, overall vaccine rates were reduced by 75% in 2007-2008, 60% in 2008-2009, 94% in 2009-2010, 80% in 2010-2011, 97% in 2011-2012, 88% in 2012-2013, 98% in 2013-2014 and 92% in 2014-2015. RV5 adjusted VE was 88% against rotavirus-coded hospitalization among 3 to 11 months of age, 88% in 12 to 23 months of age, 87% in 24 to 35 months of age, 87% in 36 to 47 months of age, and 87% in 48 to 59 months of age. RV1 adjusted VE was 87% against rotavirus-coded hospitalization among 3 to 11 months of age, 86% in 12 to 23 months of age and 86% in 24 to 35 months of age. CONCLUSION: Implementation of rotavirus vaccines has substantially reduced diarrhea-associated health care utilization in US children under 5 years of age. Both vaccines provided good and enduring protection through the fourth year of life against rotavirus hospitalizations.

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.

BACKGROUND: Human coronaviruses (HCoVs) -OC43, -229E, -NL63 and -HKU1 cause upper and lower respiratory tract infections. HCoVs are globally distributed and the predominant species may vary by region or year. Prior studies have shown seasonal patterns of HCoV species and annual variation in species prevalence but national circulation patterns in the US have not yet been described. OBJECTIVES: To describe circulation patterns of HCoVs -OC43, -229E, -NL63 and -HKU1 in the US. STUDY DESIGN: We reviewed real-time reverse transcription polymerase chain reaction (rRT-PCR) test results for HCoV-OC43, -229E, -NL63 and -HKU1 reported to The National Respiratory and Enteric Virus Surveillance System (NREVSS) by U.S. laboratories from July 2014-June 2017. We calculated the total number of tests and percent positive by week. For a subset of HCoV positive submissions with age and sex of the patient available, we tested for differences in age and sex across the four HCoV species using Chi Square and Kruskal Wallace tests. RESULTS: 117 laboratories reported 854,575 HCoV tests; 2.2% were positive for HCoV-OC43, 1.0% for HCoV-NL63, 0.8% for HCoV-229E, and 0.6% for HCoV-HKU1. The percentage of positive tests peaked during December - March each year. No significant differences in sex were seen across species, although a significant difference in age distribution was noted. CONCLUSIONS: Common HCoVs may have annual peaks of circulation in winter months in the US, and individual HCoVs may show variable circulation from year to year. Different HCoV species may be detected more frequently in different age groups. Further years of data are needed to better understand patterns of activity for HCoVs.

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 Fisher's 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.).

BACKGROUND: The emergence of Middle East Respiratory Syndrome coronavirus (MERS-CoV) has prompted enhanced surveillance for respiratory infections among pilgrims returning from the Hajj, one of the largest annual mass gatherings in the world. OBJECTIVES: To describe the epidemiology and etiologies of respiratory illnesses among pilgrims returning to Jordan after the 2014 Hajj. STUDY DESIGN: Surveillance for respiratory illness among pilgrims returning to Jordan after the 2014 Hajj was conducted at sentinel health care facilities using epidemiologic surveys and molecular diagnostic testing of upper respiratory specimens for multiple respiratory pathogens, including MERS-CoV. RESULTS: Among the 125 subjects, 58% tested positive for at least one virus; 47% tested positive for rhino/enterovirus. No cases of MERS-CoV were detected. CONCLUSIONS: The majority of pilgrims returning to Jordan from the 2014 Hajj with respiratory illness were determined to have a viral etiology, but none were due to MERS-CoV. A greater understanding of the epidemiology of acute respiratory infections among returning travelers to other countries after Hajj should help optimize surveillance systems and inform public health response practices.

The number of immunosuppressed adults in the United States is unknown but thought to be increasing because of both greater life expectancy among immunosuppressed adults due to improvements in medical management, as well as new indications for immunosuppressive treatments.1-4 Immunosuppression increases the risks and severity of primary or reactivation infections; its prevalence has implications for food and water safety, tuberculosis control, vaccine programs, infection control strategies, outbreak preparedness, travel medicine, and other facets of public health.1 We present data on the prevalence of self-reported immunosuppressed adults in the United States.

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 (2008/09), and males 30-39 years (2009/10). 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.