BACKGROUND: Outbreaks of rotavirus gastroenteritis in elderly adults are reported infrequently but are often caused by G2P[4] strains. In 2011, outbreaks were reported in 2 Illinois retirement facilities. OBJECTIVE: To implement control measures, determine the extent and severity of illness, and assess risk factors for disease among residents and employees. DESIGN: Cohort studies using surveys and medical chart abstraction. SETTING: Two large retirement facilities in Cook County, Illinois. PATIENTS: Residents and employees at both facilities and community residents with rotavirus disease. MEASUREMENTS: Attack rates, hospitalization rates, and rotavirus genotype. RESULTS: At facility A, 84 of 324 residents (26%) were identified with clinical or laboratory-confirmed rotavirus gastroenteritis (median age, 84 years) and 11 (13%) were hospitalized. The outbreak lasted 7 weeks. At facility B, 90 case patients among 855 residents (11%) were identified (median age, 88 years) and 19 (21%) were hospitalized. The facility B outbreak lasted 9.3 weeks. Ill employees were identified at both locations. In each facility, attack rates seemed to differ by residential setting, with the lowest rates among those in more separated settings or with high baseline level of infection control measures. The causative genotype for both outbreaks was G2P[4]. Some individuals shed virus detected by enzyme immunoassay or genotyping reverse transcription polymerase chain reaction for at least 35 days. G2P[4] was also identified in 17 of 19 (89%) samples from the older adult community but only 15 of 40 (38%) pediatric samples. LIMITATION: Medical or cognitive impairment among residents limited the success of some interviews. CONCLUSION: Rotavirus outbreaks can occur among elderly adults in residential facilities and can result in considerable morbidity. Among older adults, G2P[4] may be of unique importance. Health professionals should consider rotavirus as a cause of acute gastroenteritis in adults. PRIMARY FUNDING SOURCE: None.

This article summarizes what is currently known about the 2019 novel coronavirus and offers interim guidance.

BACKGROUND: Rotavirus vaccines are effective in preventing severe rotavirus. Haiti introduced 2-dose monovalent (G1P[8]) rotavirus vaccine recommended for infants at 6 and 10 weeks of age in 2014. We calculated the effectiveness of rotavirus vaccine against hospitalization for acute gastroenteritis in Haiti. METHODS: We enrolled children 6-59 months old admitted May 2014-September 2019 for acute watery diarrhea at any sentinel surveillance hospital. Stool was tested for rotavirus using enzyme immunoassay (EIA) and genotyped with multiplex one-step RT-PCR assay and Sanger sequencing for stratification by genotype. We used a case-negative design where cases were children positive for rotavirus and controls were negative for rotavirus. Only children eligible for vaccination were included and a child was considered vaccinated if vaccine was given ≥ 14 days before enrollment. We used unconditional logistic regression to calculate odds ratios and calculated 2-dose and 1-dose vaccine effectiveness (VE) as (1 - odds ratio) * 100. RESULTS: We included 129 (19%) positive cases and 543 (81%) negative controls. Among cases, 77 (60%) were positive for equine-like G3P[8]. Two doses of rotavirus vaccine were 66% (95% CI: 44, 80) effective against hospitalizations due to any strain of rotavirus and 64% (95% CI: 33, 81) effective against hospitalizations due to the equine-like G3P[8] genotype. CONCLUSIONS: These findings are comparable to other countries in the Americas region. To the best of our knowledge, this is the first VE estimate both against the equine-like G3P[8] genotype and from a Caribbean country. Overall, these results support rotavirus vaccine use and demonstrate the importance of complete vaccination.

In April 2016, an indigenous monovalent rotavirus vaccine (Rotavac) was introduced to the National Immunization Program in India. Hospital-based surveillance for acute gastroenteritis was conducted in five sentinel sites from 2012 to 2020 to monitor the vaccine impact on various genotypes and the reduction in rotavirus positivity at each site. Stool samples collected from children under 5 years of age hospitalized with diarrhea were tested for group A rotavirus using a commercial enzyme immunoassay, and rotavirus strains were characterized by RT-PCR. The proportion of diarrhea hospitalizations attributable to rotavirus at the five sites declined from a range of 56-29.4% in pre-vaccine years to 34-12% in post-vaccine years. G1P[8] was the predominant strain in the pre-vaccination period, and G3P[8] was the most common in the post-vaccination period. Circulating patterns varied throughout the study period, and increased proportions of mixed genotypes were detected in the post-vaccination phase. Continuous long-term surveillance is essential to understand the diversity and immuno-epidemiological effects of rotavirus vaccination.

BACKGROUND: Following the implementation of rotavirus vaccination in 2006, severe acute gastroenteritis (AGE) due to group A rotavirus (RVA) has substantially declined in USA (US) children. We report the RVA genotype prevalence as well as co-infection data from seven US New Vaccine Surveillance Network (NVSN) sites during three consecutive RVA seasons, 2014-2016. METHODS: A total of 1041 stool samples that tested positive for RVA by Rotaclone enzyme immunoassay (EIA) were submitted to the Centers for Disease Control and Prevention (CDC) for RVA genotyping and multipathogen testing. RESULTS: A total of 795 (76%) contained detectable RVA at CDC. Rotavirus disease was highest in children < 3 years of age. Four G types (G1, G2, G9, and G12) accounted for 94.6% of strains while two P types (P[4] and P[8]) accounted 94.7% of the strains. Overall, G12P[8] was the most common genotype detected in all three seasons. Stepwise conditional logistic analysis found year and study site were significant predictors of genotype. Twenty four percent (24%) of RVA-positive specimens contained other AGE pathogens. CONCLUSIONS: G12P[8] predominated over three seasons, but strain predominance varied by year and study site. Ongoing surveillance provides continuous tracking and monitoring of US genotypes during the post vaccine era.

BACKGROUND: Acute gastroenteritis (AGE) and acute respiratory infections (ARIs) cause significant pediatric morbidity and mortality. Developing childhood vaccines against major enteric and respiratory pathogens should be guided by the natural history of infection and acquired immunity. The United States currently lacks contemporary birth cohort data to guide vaccine development. OBJECTIVE: The PREVAIL (Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal) Cohort study was undertaken to define the natural history of infection and immune response to major pathogens causing AGE and ARI in US children. METHODS: Mothers in Cincinnati, Ohio, were enrolled in their third trimester of pregnancy, with intensive child follow-up to 2 years. Blood samples were obtained from children at birth (cord), 6 weeks, and 6, 12, 18, and 24 months. Whole stool specimens and midturbinate nasal swabs were collected weekly and tested by multipathogen molecular assays. Saliva, meconium, maternal blood, and milk samples were also collected. AGE (≥3 loose or watery stools or ≥1 vomiting episode within 24 hours) and ARI (cough or fever) cases were documented by weekly cell phone surveys to mothers via automated SMS text messaging and review of medical records. Immunization records were obtained from registries and providers. follow-up ended in October 2020. Pathogen-specific infections are defined by a PCR-positive sample or rise in serum antibody. RESULTS: Of the 245 enrolled mother-child pairs, 51.8% (n=127) were White, 43.3% (n=106) Black, 55.9% (n=137) publicly insured, and 86.5% (n=212) initiated breastfeeding. Blood collection was 100.0% for mothers (n=245) and 85.7% for umbilical cord (n=210). A total of 194/245 (79.2%) mother-child pairs were compliant based on participation in at least 70% (≥71/102 study weeks) of child-weeks and providing 70% or more of weekly samples during that time, or blood samples at 18 or 24 months. Compliant participants (n=194) had 71.0% median nasal swab collection (IQR 30.0%-90.5%), with 98.5% (191/194) providing either an 18- or 24-month blood sample; median response to weekly SMS text message surveys was 95.1% (IQR 76.5%-100%). Compliant mothers reported 2.0 AGE and 4.5 ARI cases per child-year, of which 25.5% (160/627) and 38.06% (486/1277) of cases, respectively, were medically attended; 0.5% of AGE (3/627) and 0.55% of ARI (7/1277) cases were hospitalized. CONCLUSIONS: The PREVAIL Cohort demonstrates intensive follow-up to document the natural history of enteric and respiratory infections and immunity in children 0-2 years of age in the United States and will contribute unique data to guide vaccine recommendations. Testing for pathogens and antibodies is ongoing. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/22222.

Globally, rotavirus group A (RVA) remains a major cause of severe childhood diarrhea, despite the use of vaccines in more than 100 countries. RVA sequencing for local outbreaks facilitates investigation into strain composition, origins, spread, and vaccine failure. In 2018, we collected 248 stool samples from children aged less than 13 years admitted with diarrheal illness to Kilifi County Hospital, coastal Kenya. Antigen screening detected RVA in 55 samples (22.2%). Of these, VP7 (G) and VP4 (P) segments were successfully sequenced in 48 (87.3%) and phylogenetic analysis based on the VP7 sequences identified seven genetic clusters with six different GP combinations: G3P[8], G1P[8], G2P[4], G2P[8], G9P[8] and G12P[8]. The G3P[8] strains predominated the season (n = 37, 67.2%) and comprised three distinct G3 genetic clusters that fell within Lineage I and IX (the latter also known as equine-like G3 Lineage). Both the two G3 lineages have been recently detected in several countries. Our study is the first to document African children infected with G3 Lineage IX. These data highlight the global nature of RVA transmission and the importance of increasing global rotavirus vaccine coverage.

BACKGROUND: Globally, noroviruses are recognized as an important cause of acute gastroenteritis (AGE), but data from low and middle-income countries are limited. AIMS: To examine the epidemiology and strain diversity of norovirus infections among children hospitalized for AGE in Bangladesh. METHODS: We implemented active surveillance of children <5 years of age hospitalized with AGE at 8 geographically dispersed tertiary care hospitals in Bangladesh from July 2012 to June 2016. We tested random samples of AGE cases stratified by site and age group for norovirus by real-time RT-PCR. Noro-positive specimens were genotyped. Coinfection with rotavirus was assessed based on prior EIA testing. RESULTS: We enrolled 5622 total AGE cases, of which 1008 were tested for norovirus. Total of 137 (14%) AGE cases tested positive for norovirus (range, 11%-17% by site). Most (94%) norovirus-associated hospitalizations were among children less than 2 years of age. Norovirus was detected year-round, with higher detection from March to June (20%-38%) and November to January (9%-18%). Genogroup II (GII) noroviruses were detected in 96% of cases, and the most frequent genotypes were GII.4 Sydney [P4 New Orleans] (33%), GII.3 [P16] (20%), and GII.4 Sydney [P16] (11%). The proportion of norovirus-positive specimens was significantly greater among rotavirus-negative AGE patients compared with rotavirus-positive AGE patients (27% vs. 5%, P < 0.001). As measured by the Vesikari severity score, a similar proportion of norovirus and rotavirus positive AGE patients were considered severe (68% vs. 70%, P = 0.86). CONCLUSIONS: Norovirus is an important cause of AGE hospitalization in Bangladeshi children with most infections caused by GII viruses.

INTRODUCTION: Rotavirus vaccine (Rotarix®, RV1) has reduced diarrhea-associated hospitalizations and deaths in Malawi. We examined the trends in circulating rotavirus genotypes in Malawi over a 22-year period to assess the impact of RV1 introduction on strain distribution. METHODS: Data on rotavirus-positive stool specimens among children age <5 years hospitalized with diarrhea in Blantyre, Malawi before (July 1997 - October 2012, n=1765) and after (November 2012 - October 2019, n=934) RV1 introduction were analyzed. Rotavirus G and P genotypes were assigned using reverse transcription polymerase chain reaction. RESULTS: A rich rotavirus strain diversity circulated throughout the 22-year period; Shannon (H) and Simpson diversity (D) indices did not differ between the pre- and post-vaccine periods (H' p < 0.149: D' p < 0.287). Overall, G1 (n=268/924; 28.7%), G2 (n=308/924; 33.0%), G3 (n=72/924; 7.7%) and G12 (n=109/924; 11.8%) were the most prevalent genotypes identified following RV1 introduction. The prevalence of G1P[8] and G2P[4] genotypes declined each successive year following RV1 introduction, and were not detected after 2018. Genotype G3 re-emerged and became the predominant genotype from 2017. No evidence of genotype selection was observed seven years post-RV1 introduction. CONCLUSION: Rotavirus strain diversity and genotype variation in Malawi is likely driven by natural mechanisms rather than vaccine pressure.

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 <5 y admitted with acute diarrhea had stool specimens collected and tested for rotavirus by enzyme immunoassay. Proportions testing rotavirus-positive in post-vaccine years were compared with the pre-vaccine period. Vaccine records were obtained and effectiveness of 2 RV1 doses vs 0 doses was estimated using rotavirus-case and test-negative design among children enrolled from Bukhara city. In 2015 and 2016, 8%-15% of infants and 10%-16% of children aged<5 y hospitalized with acute diarrhea at the sites tested rotavirus-positive, compared with 26% of infants and 27% of children aged<5 y in pre-vaccine period (reductions in proportion positive of 42%-68%, p <.001). Vaccine effectiveness of 2 RV1 doses vs 0 doses in protecting against hospitalization for rotavirus disease among those aged ≥6 months was 51% (95% CI 2-75) and is based on cases predominantly of genotype G2P[4]. Vaccine effectiveness point estimates tended to be higher against cases with higher illness severity (e.g., clinical severity based on modified Vesikari score ≥11). Our data demonstrate that the monovalent rotavirus vaccine is effective in reducing the likelihood of hospitalization for rotavirus disease in young children in Uzbekistan.

BACKGROUND: Kenya introduced the monovalent G1P [8] Rotarix(R) vaccine into the infant immunization schedule in July 2014. We examined trends in rotavirus group A (RVA) genotype distribution pre- (January 2010-June 2014) and post- (July 2014-December 2018) RVA vaccine introduction. METHODS: Stool samples were collected from children aged < 13 years from four surveillance sites across Kenya: Kilifi County Hospital, Tabitha Clinic Nairobi, Lwak Mission Hospital, and Siaya County Referral Hospital (children aged < 5 years only). Samples were screened for RVA using enzyme linked immunosorbent assay (ELISA) and VP7 and VP4 genes sequenced to infer genotypes. RESULTS: We genotyped 614 samples in pre-vaccine and 261 in post-vaccine introduction periods. During the pre-vaccine introduction period, the most frequent RVA genotypes were G1P [8] (45.8%), G8P [4] (15.8%), G9P [8] (13.2%), G2P [4] (7.0%) and G3P [6] (3.1%). In the post-vaccine introduction period, the most frequent genotypes were G1P [8] (52.1%), G2P [4] (20.7%) and G3P [8] (16.1%). Predominant genotypes varied by year and site in both pre and post-vaccine periods. Temporal genotype patterns showed an increase in prevalence of vaccine heterotypic genotypes, such as the commonly DS-1-like G2P [4] (7.0 to 20.7%, P < .001) and G3P [8] (1.3 to 16.1%, P < .001) genotypes in the post-vaccine introduction period. Additionally, we observed a decline in prevalence of genotypes G8P [4] (15.8 to 0.4%, P < .001) and G9P [8] (13.2 to 5.4%, P < .001) in the post-vaccine introduction period. Phylogenetic analysis of genotype G1P [8], revealed circulation of strains of lineages G1-I, G1-II and P [8]-1, P [8]-III and P [8]-IV. Considerable genetic diversity was observed between the pre and post-vaccine strains, evidenced by distinct clusters. CONCLUSION: Genotype prevalence varied from before to after vaccine introduction. Such observations emphasize the need for long-term surveillance to monitor vaccine impact. These changes may represent natural secular variation or possible immuno-epidemiological changes arising from the introduction of the vaccine. Full genome sequencing could provide insights into post-vaccine evolutionary pressures and antigenic diversity.

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.

INTRODUCTION: Noroviruses are a leading cause of acute gastroenteritis worldwide. An estimated 21 million illnesses in the United States and upwards of 684 million illnesses worldwide are attributed to norovirus infection. There are no licensed vaccines to prevent norovirus, but several candidates are in development. Areas covered: We review recent advances in molecular epidemiology of noroviruses, immunology, and in-vitro cultivation of noroviruses using human intestinal enteroids. We also provide an update on the status of norovirus vaccine candidates. Expert opinion: Molecular epidemiological studies confirm the tremendous genetic diversity of noroviruses, the continuous emergence of new recombinant strains, and the predominance of GII.4 viruses worldwide. Duration of immunity, extent of cross protection between different genotypes, and differences in strain distribution for young children compared with adults remain key knowledge gaps. Recent discoveries regarding which epitopes are targeted by neutralizing antibodies using the novel in vitro culture of human noroviruses in human intestinal enteroids are enhancing our understanding of mechanisms of protection and providing guidance for vaccine development. A future norovirus vaccine has the potential to substantially reduce the burden of illnesses due to this ubiquitous virus.

Group A rotavirus (RVA) associated diarrhea in piglets represents one of the major causes of morbidity and mortality in pig farms worldwide. A diarrhea outbreak occurred among nomadic piglets in north-western district of Bangladesh in February 2014. Outbreak investigation was performed to identify the cause, epidemiologic and clinical features of the outbreak. Rectal swabs and clinical information were collected from diarrheic piglets (n=36). Rectal swabs were tested for RVA RNA by real time reverse transcription polymerase chain reaction (rRT-PCR) using NSP3-specific primers. The G (VP7) and P (VP4) genes were typed by conventional RT-PCR and sanger sequencing and full genome sequences were determined using next generation sequencing. We found the attack rate was 61% (50/82) among piglets in the nomadic pig herd and the case fatality rate was 20% (10/50) among piglets with diarrhea. All study piglets cases had watery diarrhea, lack of appetite or reluctance to move. A novel RVA strain with a new P[49] genotype combined with G4 was identified among all piglets with diarrhea. The genome constellation of the novel RVA strains was determined to be G4-P [49]-I1-R1-C1-M1-A8-N1-T7-E1-H1. Genetic analysis shows that the novel G4P[49] strain is similar to Indian and Chinese porcine or porcine-like G4 human strains and is genetically distant from Bangladeshi human G4 strains. Identification of this novel RVA strain warrants further exploration for disease severity and zoonotic potential. This article is protected by copyright. All rights reserved.

Background: Norovirus is a leading cause of acute gastroenteritis (AGE); however, few data exist on endemic norovirus disease burden among adults. Candidate norovirus vaccines are currently in development for all ages, and robust estimates of norovirus incidence among adults are needed to provide baseline data. Methods: We conducted active surveillance for AGE among inpatients at a Veterans Affairs (VA) hospital in Houston, Texas. Patients with AGE (>/=3 loose stools, >/=2 vomiting episodes, or >/=1 episode of both loose stool and vomiting, within 24 hours) within 10 days of enrollment and non-AGE control patients were enrolled. Demographic data and clinical characteristics were collected. Stool samples were tested using the FilmArray gastrointestinal panel; virus-positives were confirmed by real-time reverse transcription polymerase chain reaction and genotyped by sequencing. Results: From November 2, 2015 through November 30, 2016, 147 case patients and 19 control patients were enrolled and provided a stool specimen. Among case patients, 139 (95%) were male and 70 (48%) were aged >/=65 years. Norovirus was the leading viral pathogen detected (in 16 of 20 virus-positive case patients) and accounted for 11% of all AGE cases. No viral pathogens were detected among control patients. Incidence of norovirus-associated hospitalization was 20.3 cases/100 000 person-years and was similar among those aged <65 and >/=65 years. Conclusions: This active surveillance platform employed screening and enrollment of hospitalized VA patients meeting a standardized AGE case definition, as well as non-AGE control patients. Data from this study highlight the burden of norovirus in a VA inpatient population and will be useful in policy considerations of a norovirus vaccine.

BACKGROUND: Sentinel surveillance for diarrhoea is important to monitor changes in rotavirus epidemiological trends and circulating genotypes among children under 5years before and after vaccine introduction. The Zimbabwe Ministry of Health and Child Care introduced rotavirus vaccine in national immunization program in May 2014. METHODS: Active hospital-based surveillance for diarrhoea was conducted at 3 sentinel sites from 2008 to 2016. Children aged less than 5years, who presented with acute gastroenteritis as a primary illness and who were admitted to a hospital ward or treated at the emergency unit, were enrolled and had a stool specimen collected and tested for rotavirus by enzyme immunoassay (EIA). Genotyping of positive stools was performed using reverse-transcription polymerase chain reaction and genotyping assays. Pre-vaccine introduction, 10% of all positive stool specimens were genotyped and all adequate positive stools were genotyped post-vaccine introduction. RESULTS: During the pre-vaccine period, a total of 6491 acute gastroenteritis stools were collected, of which 3016 (46%) tested positive for rotavirus and 312 (10%) of the rotavirus positive stools were genotyped. During the post-vaccine period, a total of 3750 acute gastroenteritis stools were collected, of which 937 (25%) tested positive for rotavirus and 784 (84%) were genotyped. During the pre-vaccine introduction the most frequent genotype was G9P[8] (21%) followed by G2P[4] (12%), G1P[8] (6%), G2P[6] (5%), G12P[6] (4%), G9P[6] (3%) and G8P[4] (3%). G1P[8] (30%) was most dominant two years after vaccine introduction followed by G9P[6] (20%), G2P[4] (15%), G9P[8] (11%) and G1P[6] (4%). CONCLUSION: The decline in positivity rate is an indication of early vaccine impact. Diversity of circulating strains underscores the importance of continued monitoring and strain surveillance after vaccine introduction.

BACKGROUND: Ghana introduced the monovalent rotavirus vaccine (Rotarix) into its national paediatric vaccination programme in May2012. Vaccine introduction was initiated nationwide and achieved >85% coverage within a few months. Rotavirus strain distribution pre- and post-RV vaccine introduction is reported. METHODS: Stool samples were collected from diarrhoeic children <5years of age hospitalized between 2009 and 2016 at sentinel sites across Ghana and analyzed for the presence of group A rotavirus by enzyme immunoassay. Rotavirus strains were characterized by RT-PCR and sequencing. RESULTS: A total of 1363 rotavirus EIA-positive samples were subjected to molecular characterization. These were made up of 823 (60.4%) and 540 (39.6%) samples from the pre- and post-vaccine periods respectively. Rotavirus VP7 genotypes G1, G2 and G3, and VP4 genotypes P[6] and P[8] constituted more than 65% of circulating G and P types in the pre-vaccine period. The common strains detected were G1P[8] (20%), G3P[6] (9.2%) and G2P[6] (4.9%). During the post-vaccine period, G12, G1 and G10 genotypes, constituted more than 65% of the VP7 genotypes whilst P[6] and P[8] made up more than 75% of the VP4 genotypes. The predominant circulating strains were G12P[8] (26%), G10P[6] (10%) G3P[6] (8.1%) and G1P[8] (8.0%). We also observed the emergence of the unusual rotavirus strain G9P[4] during this period. CONCLUSION: Rotavirus G1P[8], the major strain in circulation during the pre-vaccination era, was replaced by G12P[8] as the most predominant strain after vaccine introduction. This strain replacement could be temporary and unrelated to vaccine introduction since an increase in G12 was observed in countries yet to introduce the rotavirus vaccine in West Africa. A continuous surveillance programme in the post-vaccine era is necessary for the monitoring of circulating rotavirus strains and the detection of unusual/emerging genotypes.

To combat the high burden of rotavirus gastroenteritis, multiple African countries have introduced rotavirus vaccines into their childhood immunisation programmes. Malawi incorporated a G1P[8] rotavirus vaccine (Rotarix) into its immunisation schedule in 2012. Utilising a surveillance platform of hospitalised rotavirus gastroenteritis cases, we examined the phylodynamics of G1P[8] rotavirus strains that circulated in Malawi before (1998 - 2012) and after (2013 - 2014) vaccine introduction. Analysis of whole genomes obtained through next generation sequencing revealed that all randomly-selected pre-vaccine G1P[8] strains sequenced (n=32) possessed a Wa-like genetic constellation, whereas post-vaccine G1P[8] strains (n=18) had a DS-1-like constellation. Phylodynamic analyses indicated that post-vaccine G1P[8] strains emerged through reassortment events between human Wa- and DS-1-like rotaviruses that circulated in Malawi from the 1990's, hence classified as atypical DS-1-like reassortants. The time to the most recent common ancestor for G1P[8] strains was from 1981-1994; their evolutionary rates ranged from 9.7 x 10-4-4.1 x 10-3 nucleotide/substitutions/site/year. Three distinct G1P[8] lineages chronologically replaced each other between 1998 and 2014. Genetic drift was the likely driver for lineage turnover in 2005, whereas replacement in 2013 was due to reassortment. Amino acid substitution within the outer glycoprotein VP7 of G1P[8] strains had no impact on the structural conformation of the antigenic regions, suggesting that it is unlikely that they would affect recognition by vaccine-induced neutralizing antibodies. While the emergence of DS-1-like G1P[8] rotavirus reassortants in Malawi was therefore likely due to natural genotype variation, vaccine effectiveness against such strains needs careful evaluation.ImportanceThe error-prone RNA-dependent RNA polymerase and the segmented RNA genome predispose rotaviruses to genetic mutation and genome reassortment, respectively. These evolutionary mechanisms generate novel strains and have the potential to lead to the emergence of vaccine-escape mutants. While multiple African countries have introduced rotavirus vaccine, there are few data describing the evolution of rotaviruses that circulated before and after vaccine introduction. We report the emergence of atypical DS-1-like G1P[8] strains during the post-vaccine era in Malawi. Three distinct G1P[8] lineages circulated chronologically from 1998-2014; mutation and reassortment drove lineage turnover in 2005 and 2013, respectively. Amino acid substitutions within the outer capsid VP7 glycoprotein did not affect the structural conformation of mapped antigenic sites, suggesting limited effect in recognition of G1 specific vaccine-derived antibodies. The genes that constitute the remaining genetic backbone may play important roles in immune evasion, and vaccine effectiveness against such atypical strains needs careful evaluation.

Norovirus is the leading cause of endemic and epidemic acute gastroenteritis in the United States. New variant strains of norovirus GII.4 emerge every 2-4 years and are often associated with increased disease and health care visits. Since 2009, CDC has obtained epidemiologic data on norovirus outbreaks from state health departments through the National Outbreak Reporting System (NORS) and laboratory data through CaliciNet. 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.

Norovirus and sapovirus are important causes of acute gastroenteritis (AGE) among American Indian infants. We investigated the prevalence and molecular epidemiology of norovirus and sapovirus in American Indian infants who have historically experienced a high burden of AGE compared to other US populations. Stool samples were collected from 241 children with AGE (cases) and from 343 infants without AGE (controls) ≤9 months of age from 2002-2004. Cases experienced forceful vomiting and/or 3 or more watery or looser-than-normal stools in 24 hours. Stools were tested by real-time RT-PCR for norovirus GI, GII and GIV and sapovirus GI, GII, GIV and GV. Positive samples were genotyped after sequencing conventional RT-PCR products. Norovirus was identified in 76 (31.5%) of the cases and 70 (20.4%) of the controls (p<0.001). GII.3 and GII.4 Farmington Hills were the most frequently identified genotypes in 14.5% and 30.3% of cases and 17.1% and 27.1% of controls, respectively. Sapovirus GI and GII genotypes were identified in 8 (3.3%) of cases and 8 (2.3%) of controls and a single GIV virus was detected in a control. The same norovirus and sapovirus genotypes were circulating in the general U.S. population in the same time period. The high detection rate of norovirus in healthy controls suggests significant asymptomatic transmission in young infants in these communities.

Thirty-three infants aged approximately 2 months had serial stool samples collected after receipt of Rotarix(R) vaccine dose 1, and 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(R) 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 numbers in any infant supports transient passage and there are inherent limitations to the results. We found that 21% of infants did not shed Rotarix(R) 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 approximately 40%, and after day 5 in approximately 60%, and shedding can be prolonged (≥45 days).

BACKGROUND: Group A rotaviruses (RVA) are a significant cause of pediatric gastroenteritis worldwide. The New Vaccine Surveillance Network (NVSN) has conducted active surveillance for RVA at pediatric hospitals and emergency departments at three to seven geographically diverse sites in the U.S. since 2006. METHODS: Over six consecutive years, from 2008 to 2013, 1,523 samples from NVSN sites that were test-positive by Rotaclone(R) enzyme immunoassay were submitted to the CDC for genotyping. RESULTS: In the 2009, 2010, and 2011 seasons, genotype G3P[8] was the predominant genotype throughout the network with 46-84% prevalence. In the 2012 season, G12P[8] replaced G3P[8] as the most common genotype with 70% prevalence and this trend persisted in 2013 (68.0% prevalence). Vaccine (RotaTeq(R), Rotarix(R)) strains were detected in 0.6-3.4% of genotyped samples each season. Uncommon and unusual strains (e.g., G8P[4], G3P[24], G2P[8], G3P[4], G3P[6], G24P[14], G4P[6], G9P[4]) were detected sporadically over the study period. Year, study site, and race were found to be significant predictors of genotype. CONCLUSION: Continued active surveillance is needed to monitor RVA genotypes in the U.S. and to detect potential changes since vaccine licensure.

Here we report the genome of a novel rotavirus A (RVA) strain detected in a stool sample collected during routine surveillance by the Centers for Disease Control and Prevention's New Vaccine Surveillance Network. The strain, RVA/human-wt/USA/2012741499/2012/G24P[14], has a genomic constellation of G24-P[14]-I2-R2-C2-M2-A3-N2-T9-E2-H3. The VP2, VP3, VP7 and NSP3 genes cluster phylogenetically with bovine strains. The other genes occupy mixed clades containing animal and human strains. Strain RVA/human-wt/USA/2012741499/2012/G24P[14] most likely is the product of interspecies transmission and reassortment events. This is the second report of the G24 genotype and the first report of the G24P[14] genotype combination in humans.

Background. Botswana introduced monovalent G1P[8] rotavirus vaccine (RV1) in July 2012, providing one of the first opportunities to assess the effectiveness of routine RV1 vaccination in a high-burden setting in Africa. We sought to determine the effectiveness of RV1 against rotavirus diarrhea hospitalization using a case-control evaluation. Methods. Vaccine age-eligible children <5 years of age admitted with diarrhea at 4 hospitals in Botswana were enrolled from June 2013 to April 2015. Card-confirmed vaccine history was compared between case patients (children with laboratory-confirmed rotavirus diarrhea) and nonrotavirus "test-negative" diarrhea controls. Vaccine effectiveness (VE) was computed using unconditional logistic regression models adjusting for age, birth month/year, and hospital. Sequence-based genotyping was performed on antigen-positive samples. Results. Among 242 case patients and 368 controls, 82% (199/242) and 92% (339/368), respectively, had received >=1 doses of RV1. Effectiveness of a full series (2 doses) of RV1 against rotavirus diarrhea requiring hospitalization was 54% (95% confidence interval [CI], 23%-73%); 1 dose of RV1 was 48% (95% CI, 1%-72%) effective. Effectiveness was 59% (95% CI, 4%-83%) against rotavirus caused by G2P[4], the most common (37%) circulating genotype. However, the effectiveness of 2 RV1 doses was significantly higher in children with no undernutrition (VE, 75% [95% CI, 41%-89%]), compared to those with moderate or severe undernutrition (VE, -28% [95% CI, -309% to 60%]) (P=.02). Conclusions. Routine RV1 vaccination in Botswana showed effectiveness similar to that in clinical trials in Africa, including against a serotype fully heterotypic to the vaccine. Undernutrition may in part explain the lower rotavirus VE in low-income settings.

Background. In Bolivia, monovalent rotavirus vaccine was introduced in 2008 and a previous evaluation reported a vaccine effectiveness (VE) of 77% with 2 doses of vaccine in children aged <3 years. This evaluation sought to determine if rotavirus vaccine provided protection through the second year of life against circulating genotypes. Methods. A case-control study was performed in 5 hospitals from April 2013 to March 2014. Among enrolled participants who met study criteria and had rotavirus stool testing performed and vaccine status confirmed, we calculated VE using a logistic regression model. Subgroup analyses were performed among children aged <1 year and those aged >=1 year, among children with severe diarrhea (Vesikari score >=11) and very severe diarrhea (Vesikari score >=15), and among G and P strains with at least 40 specimens. Results. A total of 776 children were enrolled. For children <1 year and >=1 year of age with severe diarrhea, VE for 2 doses was 75% (95% confidence interval [CI], 46%-88%) and 53% (95% CI, 9%-76%), respectively. For children <1 year and >=1 year of age with very severe diarrhea, VE for 2 doses was 80% (95% CI, 44%-93%) and 74% (95% CI, 35%-90%), respectively. Genotype-specific analysis demonstrated similar VE for the 4 most common G and P types (G3, G9, P[6] and P[8]). Conclusions. A monovalent rotavirus vaccine remains effective against a broad range of circulating strains as part of a routine immunization program >5 years after its introduction in Bolivia. Although VE appears to wane in children aged >=1 year, it still provides significant protection, and does not wane against severe disease.

During the 2008-2009 rotavirus season of the Centers for Disease Control and Prevention New Vaccine Surveillance Network, one case of paediatric acute gastroenteritis associated with a rotavirus G14P[24] strain was identified. This was the first detection of the genotype G14 and P[24] in humans, and the first detection of the G14P[24] combination. To gain an insight into the origins and the evolution of this strain, we determined the complete ORF sequences of all 11 genes. A majority of the genes identified were similar to the simian strain TUCH, except for the VP1 and VP7 genes that clustered only distantly with the bovine and equine strains, respectively. In addition, this strain carried AU-1-like NSP2 and NSP4 genes. Using codon-partitioning and protein-based phylogenetic approaches, we determined that the VP7 genotype of strain 2009727118 was actually G3; therefore, the proposed full genomic classification of the 2009727118 strain is G3-P[24]-I9-R2-C3-M3-A9-N3-T3-E3-H6. These findings indicate the possibility that the 2009727118 strain originated by interspecies transmission and multiple reassortment events involving human, bovine and equine rotaviruses, resulting in the introduction of some genes into the genome of simian rotaviruses. Additionally, we found evidence of mutational saturation in the third codon position of the VP7 ORF which presented an issue with homoplasy in phylogenetic analyses.

Group A rotaviruses (RVAs) are a leading cause of acute gastroenteritis-associated deaths among children <5 years of age in developing countries (1). The genome of RVA consists of 11 double-stranded RNA segments that code for 11 or 12 viral proteins (VP1–VP4, VP6, VP7, nonstructural protein 1 [NSP1]–NSP5/6) (2). In 2008, the Rotavirus Classification Working Group established a system of extended classification that was based on the sequences of all 11 gene segments and used the notations Gx-P[x]-Ix-Rx-Cx-Mx-Ax-Nx-Tx-Ex-Hx for the genes VP7, VP4, VP6, VP1–VP3, NSP1–NSP5, respectively (3). Similar to other RNA viruses, RVAs show high genomic diversity, which is generated primarily through point mutations, reassortment, rearrangement, and recombination events. | In 2006 and 2008, two live-attenuated vaccines, RotaTeq (Merck, Whitehouse Station, NJ, USA) and Rotarix (GlaxoSmithKline, Rixensart, Belgium), respectively, were introduced in the United States (4). RotaTeq is a pentavalent human bovine reassortant vaccine that contains 4 G types (G1, G2, G3, and G4; VP7 gene) plus the P[8] VP4 type on a bovine WC3 (G6P[5]) backbone (5). In 2012, Bucardo et al. reported finding a vaccine-derived nonstructural protein 2 (NSP2) gene in 2 wild-type RVA strains with a G1P[8] genogroup 1 backbone (6). Each of these strains had been found during routine surveillance in Nicaragua, where RotaTeq was introduced in 2006, suggesting reassortment of the vaccine strain with circulating wild-type strains. The authors also examined alignments of the NSP2 gene and found no differences at functional domains between the vaccine-derived NSP2 and the circulating wild-type NSP2 (6). This finding could explain why a vaccine-derived NSP2 reassortant was viable.

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

BACKGROUND: Norovirus is a leading cause of acute gastroenteritis (AGE). Noroviruses bind to gut histo-blood group antigens (HBGAs), but only 70-80% of individuals have a functional copy of the FUT2 ("secretor") gene required for gut HBGA expression; these individuals are known as "secretors." Susceptibility to some noroviruses depends on FUT2 secretor status, but the population impact of this association is not established. METHODS: From 12/2011 to 11/2012, active AGE surveillance was performed at six geographically diverse US pediatric sites. Cases under five years were recruited from emergency departments and inpatient units; age-matched healthy controls were recruited at well-child visits. Salivary DNA was collected to determine secretor status and genetic ancestry. Stool was tested for norovirus by realtime RT-PCR. Norovirus genotype was then determined by sequencing. RESULTS: Norovirus was detected in 302 (21%) of 1465 AGE cases and 52 (6%) of 826 healthy controls. Norovirus AGE cases were 2.8-fold more likely than norovirus-negative controls to be secretors (p<0.001) in a logistic regression model adjusted for ancestry, age, site, and health insurance. Secretors comprised all 155 cases and 21 asymptomatic infections with the most prevalent norovirus, GII.4. Control children of Meso-American ancestry were more likely than children of European or African ancestry to be secretors (96% versus 74%, p<0.001). CONCLUSIONS: FUT2 status is associated with norovirus infection and varies by ancestry. GII.4 norovirus exclusively infected secretors. These findings are important to norovirus vaccine trials and design of agents that may block norovirus-HBGA binding.