OBJECTIVE: To determine the vaccine effectiveness (VE) of complete and partial vaccination with the pentavalent rotavirus vaccine (RV5) in the prevention of rotavirus acute gastroenteritis (AGE) hospitalizations and emergency department visits during the first 3 rotavirus seasons after vaccine introduction. METHODS: Active, prospective population-based surveillance for AGE and acute respiratory infection (ARIs) in inpatient and emergency department settings provided subjects for a case-control evaluation of VE in 3 US counties from January 2006 through June 2009. Children with laboratory-confirmed rotavirus AGE (cases) were matched according to date of birth and onset of illness to 2 sets of controls: children with rotavirus-negative AGE and children with ARI. The main outcome measure was VE with complete (3 doses) or partial (1 or 2 doses) RV5 vaccination. RESULTS: Of age-eligible children enrolled, 18% of cases, 54% of AGE controls, and 54% of ARI controls received ≥1 dose of RV5. The VE of RV5 for 1, 2, and 3 doses against all rotavirus genotypes with the use of rotavirus-negative AGE controls was 74% (95% confidence interval [CI]: 37%–90%), 88% (95% CI: 66%–96%), and 87% (95% CI: 71%–94%), respectively, and with the use of ARI controls was 73% (95% CI: 43%–88%), 88% (95% CI: 68%–95%), and 85% (95% CI: 72%–91%), respectively. The overall VE estimates were comparable during the first and second years of life and against AGE caused by different rotavirus strains. CONCLUSION: RV5 was highly effective in preventing severe rotavirus disease, even after a partial series, with protection persisting throughout the second year of life.

Respiratory viral infections are a major cause of morbidity and hospitalization in young children. Nevertheless, the population burden of respiratory viral infections, especially asymptomatic cases, is not known due to the lack of prospective community-based cohort studies with intensive monitoring. To address this gap, we enacted the PREVAIL cohort, a CDC-sponsored birth cohort in Cincinnati, Ohio where children were followed from birth to 2 years of age. Weekly text surveys were administered to mothers to record acute respiratory illnesses (ARIs), which were defined as the presence of cough or fever (≥38^oC). Weekly mid-turbinate nasal swabs were collected and tested using the Luminex Respiratory Pathogen Panel, which detected 16 viral pathogens. Viral infection was defined as one or more positive tests from the same virus or viral subtype within 30 days of previous positive. Maternal report and medical chart abstractions identified health care utilization. From 4/2017 to 7/2020, 245 mother-infant pairs were recruited and followed. From the 13,781 nasal swabs tested, a total of 2,211 viral infections were detected, of which, 821 (37%) were symptomatic. Children experienced 9.4 respiratory viral infections/child-year; half were rhinovirus/enterovirus. Viral ARI incidence was 3.3 episodes/child-year. Emergency department visits or hospitalization occurred with only 15% of respiratory syncytial virus infections, 10% of influenza infections, and only 4% of all viral infections. Regardless of pathogen, most infections were asymptomatic or mild. Respiratory viral infections are common in children 0-2 years. Most viral infections are asymptomatic or non-medically attended, underscoring the importance of community-based cohort studies. This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/burden-of-respiratory-viruses-in-children-less-than-two-years-in-a-community-based-longitudinal-birth-cohort

A major polymorphism in the fucosyltransferase2 (FUT2) gene influences risk of multiple gut diseases, but its impact on the microbiome of breastfed infants was unknown. In individuals with an active FUT2 enzyme (“secretors”), the intestinal mucosa is abundantly fucosylated, providing mutualist bacteria with a rich endogenous source of fucose. Non-secretors comprise approximately one-fifth of the population, and they lack the ability to create this enzyme. Similarly, maternal secretor status influences the abundance of a breastfeeding mother’s fucosylated milk oligosaccharides. We compared the impact of maternal secretor status, measured by FUT2 genotype, and infant secretor status, measured by FUT2 genotype and phenotype, on early infant fecal microbiome samples collected from 2-month-old exclusively breastfed infants (n = 59). Infant secretor status (19% non-secretor, 25% low-secretor, and 56% full-secretor) was more strongly associated with the infant microbiome than it was with the maternal FUT2 genotype. Alpha diversity was greater in the full-secretors than in the low- or non-secretor infants (p = 0.049). Three distinct microbial enterotypes corresponded to infant secretor phenotype (p = 0.022) and to the dominance of Bifidobacterium breve, B. longum, or neither (p < 0.001). Infant secretor status was also associated with microbial metabolic capacity, specifically, bioenergetics pathways. We concluded that in exclusively breastfed infants, infant—but not maternal—secretor status is associated with infant microbial colonization and metabolic capacity.

OBJECTIVES: To evaluate risk factors for postdischarge sequelae in children and adolescents hospitalized for acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome in children (MIS-C). METHODS: Multicenter prospective cohort study conducted in 25 United States pediatric hospitals. Patients <21-years-old, hospitalized May 2020 to May 2021 for acute COVID-19 or MIS-C with follow-up 2 to 4 months after admission. We assessed readmissions, persistent symptoms or activity impairment, and new morbidities. Multivariable regression was used to calculate adjusted risk ratios (aRR) and 95% confidence intervals (CI). RESULTS: Of 358 eligible patients, 2 to 4 month survey data were available for 119 of 155 (76.8%) with acute COVID-19 and 160 of 203 (78.8%) with MIS-C. Thirteen (11%) patients with acute COVID-19 and 12 (8%) with MIS-C had a readmission. Thirty-two (26.9%) patients with acute COVID-19 had persistent symptoms (22.7%) or activity impairment (14.3%) and 48 (30.0%) with MIS-C had persistent symptoms (20.0%) or activity impairment (21.3%). For patients with acute COVID-19, persistent symptoms (aRR, 1.29 [95% CI, 1.04–1.59]) and activity impairment (aRR, 1.37 [95% CI, 1.06–1.78]) were associated with more organ systems involved. Patients with MIS-C and pre-existing respiratory conditions more frequently had persistent symptoms (aRR, 3.09 [95% CI, 1.55–6.14]) and those with obesity more frequently had activity impairment (aRR, 2.52 [95% CI, 1.35–4.69]). New morbidities were infrequent (9% COVID-19, 1% MIS-C). CONCLUSIONS: Over 1 in 4 children hospitalized with acute COVID-19 or MIS-C experienced persistent symptoms or activity impairment for at least 2 months. Patients with MIS-C and respiratory conditions or obesity are at higher risk of prolonged recovery.

OBJECTIVE: Our goal was to determine the prevalence of intestinal parasites in internationally adopted children, to examine factors associated with infection, and to determine if evaluating multiple stool specimens increases the yield of parasite identification. METHODS: We evaluated internationally adopted children with at least 1 stool specimen submitted for ova and parasite testing within 120 days after arrival to the United States. In children submitting 3 stool specimens, in which at least 1 specimen was positive for the pathogen studied, we examined whether multiple stool specimens increased the likelihood of pathogen identification. RESULTS: Of the 1042 children studied, 27% had at least 1 pathogen identified; with pathogen-specific prevalence of Giardia intestinalis (19%), Blastocystis hominis (10%), Dientamoeba fragilis (5%), Entamoeba histolytica (1%), Ascaris lumbricoides (1%), and Hymenolepsis species (1%). The lowest prevalence occurred in South Korean (0%), Guatemalan (9%), and Chinese (13%) children, and the highest prevalence occurred in Ethiopian (55%) and Ukrainian (74%) children. Increasing age was significantly associated with parasite identification, whereas malnutrition and gastrointestinal symptoms were not. Overall, the yield of 1 stool specimen was 79% with pathogen recovery significantly increasing for 2 (92%) and 3 (100%) specimens, respectively (P < .0001). Pathogen identification also significantly increased with evaluation of additional stool specimens for children with and without gastrointestinal symptoms. CONCLUSIONS: We provide data for evidence-based guidelines for intestinal parasite screening in internationally adopted children. Gastrointestinal symptoms were not predictive of pathogen recovery, and multiple stool specimens increased pathogen identification in this high-risk group of children.

The seasonal influenza vaccine contains strains of viruses from distinct subtypes that are grown independently and then combined. However, most individuals exhibit a more robust response to one of these strains and thus are vulnerable to infection by others. By studying a monozygotic twin cohort, we found that although prior exposure is a factor, host genetics are a stronger driver of subtype bias to influenza viral strains. We found that covalent coupling of heterologous hemagglutinin (HA) from different viral strains could largely eliminate subtype bias in an animal model and in a human tonsil organoid system. We proposed that coupling of heterologous antigens improves antibody responses across influenza strains by broadening T cell help, and we found that using this approach substantially improved the antibody response to avian influenza HA.