Postlicensure evaluations have identified an association between rotavirus vaccination and intussusception in several high- and middle-income countries. We assessed the association between monovalent ...human rotavirus vaccine and intussusception in lower-income sub-Saharan African countries.
Using active surveillance, we enrolled patients from seven countries (Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia, and Zimbabwe) who had intussusception that met international (Brighton Collaboration level 1) criteria. Rotavirus vaccination status was confirmed by review of the vaccine card or clinic records. The risk of intussusception within 1 to 7 days and 8 to 21 days after vaccination among infants 28 to 245 days of age was assessed by means of the self-controlled case-series method.
Data on 717 infants who had intussusception and confirmed vaccination status were analyzed. One case occurred in the 1 to 7 days after dose 1, and 6 cases occurred in the 8 to 21 days after dose 1. Five cases and 16 cases occurred in the 1 to 7 days and 8 to 21 days, respectively, after dose 2. The risk of intussusception in the 1 to 7 days after dose 1 was not higher than the background risk of intussusception (relative incidence i.e., the incidence during the risk window vs. all other times, 0.25; 95% confidence interval CI, <0.001 to 1.16); findings were similar for the 1 to 7 days after dose 2 (relative incidence, 0.76; 95% CI, 0.16 to 1.87). In addition, the risk of intussusception in the 8 to 21 days or 1 to 21 days after either dose was not found to be higher than the background risk.
The risk of intussusception after administration of monovalent human rotavirus vaccine was not higher than the background risk of intussusception in seven lower-income sub-Saharan African countries. (Funded by the GAVI Alliance through the CDC Foundation.).
There is a continuing risk for COVID-19 transmission in school settings while transmission is ongoing in the community, particularly among unvaccinated populations. To ensure that schools continue to ...operate safely and to inform implementation of prevention strategies, it is imperative to gain better understanding of the risk behaviors of staff and students. This secondary analysis describes the prevalence of COVID-19 risk behaviors in an exposed population of students and school staff in the pre-vaccine era and identifies associations between these behaviors and testing positive for SARS-CoV-2.
From December 2020-January 2021, school staff and students exposed to confirmed COVID-19 cases in a Georgia school district were tested for SARS-CoV-2 and surveyed regarding risk behaviors in and out of school. Prevalence of risk behaviors was described by age group and school level, and associations with SARS-CoV-2 positivity were identified using chi squared tests.
Overall, 717 students and 79 school staff participated in the investigation; SARS-CoV-2 positivity was 9.2%. In the 2 weeks prior to COVID-19 exposure, 24% of participants reported unmasked indoor time at school, 40% attended social gatherings with non-household members, and 71% visited out-of-school indoor locations, including 19% who ate indoors in restaurants. Frequencies of risk behaviors increased by age. Among students, 17% participated in school sports, of whom 86% participated without a mask. SARS-CoV-2 positivity was significantly associated with school sports and unmasked time in sports. Among K-5 students, positivity was associated with exposure to a teacher index case.
This analysis highlights the high prevalence of risk behaviors in an unvaccinated population exposed to COVID-19 in school and identifies an association between student sports participation and SARS-CoV-2 positivity. These findings illustrate the importance of school-level prevention measures to reduce SARS-CoV-2 transmission, including limiting close-contact indoor sports and promoting consistent mask use in unvaccinated individuals. Future research could explore the role of community vaccination programs as a strategy to reduce COVID-19 transmission and introductions into school settings.
Rotavirus vaccine performance appears worse in countries with high rotavirus genotype diversity. Evidence suggests diminished vaccine efficacy (VE) against G2P4, which is heterotypic with existing ...monovalent rotavirus vaccine formulations. Most studies assessing genotype-specific VE have been underpowered and inconclusive.
We pooled individual-level data from 10 Phase II and III clinical trials of rotavirus vaccine containing G1 and P8 antigens (RV1) conducted between 2000 and 2012. We estimated VE against both any-severity and severe (Vesikari score ≥11) rotavirus gastroenteritis (RVGE) using binomial and multinomial logistic regression models for non-specific VE against any RVGE, genotype-specific VE, and RV1-typic VE against genotypes homotypic, partially heterotypic, or fully heterotypic with RV1 antigens. We adjusted models for concomitant oral poliovirus and RV1 vaccination and the country's designated child mortality stratum.
Analysis included 87 644 infants from 22 countries in the Americas, Europe, Africa, and Asia. For VE against severe RVGE, non-specific VE was 91% (95% confidence interval CI: 87-94%). Genotype-specific VE ranged from 96% (95% CI: 89-98%) against G1P8 to 71% (43-85%) against G2P4. RV1-typic VE was 92% (95% CI: 84-96%) against partially heterotypic genotypes but 83% (67-91%) against fully heterotypic genotypes. For VE against any-severity RVGE, non-specific VE was 82% (95% CI: 75-87%). Genotype-specific VE ranged from 94% (95% CI: 86-97%) against G1P8 to 63% (41-77%) against G2P4. RV1-typic VE was 83% (95% CI: 72-90%) against partially heterotypic genotypes but 63% (40-77%) against fully heterotypic genotypes.
RV1 VE is comparatively diminished against fully heterotypic genotypes including G2P4.
Rapid antigen tests, such as the Abbott BinaxNOW COVID-19 Ag Card (BinaxNOW), offer results more rapidly (approximately 15-30 minutes) and at a lower cost than do highly sensitive nucleic acid ...amplification tests (NAATs) (1). Rapid antigen tests have received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in symptomatic persons (2), but data are lacking on test performance in asymptomatic persons to inform expanded screening testing to rapidly identify and isolate infected persons (3). To evaluate the performance of the BinaxNOW rapid antigen test, it was used along with real-time reverse transcription-polymerase chain reaction (RT-PCR) testing to analyze 3,419 paired specimens collected from persons aged ≥10 years at two community testing sites in Pima County, Arizona, during November 3-17, 2020. Viral culture was performed on 274 of 303 residual real-time RT-PCR specimens with positive results by either test (29 were not available for culture). Compared with real-time RT-PCR testing, the BinaxNOW antigen test had a sensitivity of 64.2% for specimens from symptomatic persons and 35.8% for specimens from asymptomatic persons, with near 100% specificity in specimens from both groups. Virus was cultured from 96 of 274 (35.0%) specimens, including 85 (57.8%) of 147 with concordant antigen and real-time RT-PCR positive results, 11 (8.9%) of 124 with false-negative antigen test results, and none of three with false-positive antigen test results. Among specimens positive for viral culture, sensitivity was 92.6% for symptomatic and 78.6% for asymptomatic individuals. When the pretest probability for receiving positive test results for SARS-CoV-2 is elevated (e.g., in symptomatic persons or in persons with a known COVID-19 exposure), a negative antigen test result should be confirmed by NAAT (1). Despite a lower sensitivity to detect infection, rapid antigen tests can be an important tool for screening because of their quick turnaround time, lower costs and resource needs, high specificity, and high positive predictive value (PPV) in settings of high pretest probability. The faster turnaround time of the antigen test can help limit transmission by more rapidly identifying infectious persons for isolation, particularly when used as a component of serial testing strategies.
Abstract
Background
A correlate of protection for rotavirus gastroenteritis would facilitate rapid assessment of vaccination strategies and the next generation of rotavirus vaccines. We aimed to ...quantify a threshold of postvaccine serum antirotavirus immunoglobulin A (IgA) as an individual-level immune correlate of protection against rotavirus gastroenteritis.
Methods
Individual-level data on 5074 infants in 9 GlaxoSmithKline Rotarix Phase 2/3 clinical trials from 16 countries were pooled. Cox proportional hazard models were fit to estimate hazard ratios (HRs) describing the relationship between IgA thresholds and occurrence of rotavirus gastroenteritis.
Results
Seroconversion (IgA ≥ 20 U/mL) conferred substantial protection against any and severe rotavirus gastroenteritis to age 1 year. In low child mortality settings, seroconversion provided near perfect protection against severe rotavirus gastroenteritis (HR, 0.04; 95% confidence interval CI, .01–.31). In high child mortality settings, seroconversion dramatically reduced the risk of severe rotavirus gastroenteritis (HR, 0.46; 95% CI, .25–.86). As IgA threshold increased, risk of rotavirus gastroenteritis generally decreased. A given IgA threshold provided better protection in low compared to high child mortality settings.
Discussion
Postvaccination antirotavirus IgA is a valuable correlate of protection against rotavirus gastroenteritis to age 1 year. Seroconversion provides an informative threshold for assessing rotavirus vaccine performance.
Individual-level data on infants enrolled in 9 rotavirus vaccine clinical trials from 16 countries were pooled. We found that postvaccination serum antirotavirus immunoglobulin A is an imperfect but informative measure of an infant’s risk of rotavirus gastroenteritis following vaccination.
By the end of 2017, 32 (68%) of 47 countries in the World Health Organization’s African Region had introduced rotavirus vaccine into their national immunization programs, including 27 countries that ...received financial support from the Gavi, the Vaccine Alliance. Several early introducing African countries previously evaluated the impact, vaccine effectiveness, and/or cost effectiveness of their routine rotavirus vaccination programs and found that rotavirus vaccine was effective and resulted in substantial declines in hospitalizations due to rotavirus. This Special Issue of Vaccine provides additional rotavirus vaccine effectiveness and impact data from a broader range of African countries, describes the longer term impact and potential indirect benefits of rotavirus vaccination programs, describes trends in circulating genotypes in the pre- and post-vaccine introduction eras, and evaluates the cost-effectiveness of a rotavirus vaccination program in a post-introduction setting. As countries begin transitioning from Gavi support, the findings of these studies provide evidence of the impact and effectiveness of rotavirus vaccination programs under conditions of routine use.
Abstract
Background
Improved understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spectrum of disease is essential for clinical and public health interventions. There are ...limited data on mild or asymptomatic infections, but recognition of these individuals is key as they contribute to viral transmission. We describe the symptom profiles from individuals with mild or asymptomatic SARS-CoV-2 infection.
Methods
From 22 March to 22 April 2020 in Wisconsin and Utah, we enrolled and prospectively observed 198 household contacts exposed to SARS-CoV-2. We collected and tested nasopharyngeal specimens by real-time reverse-transcription polymerase chain reaction (rRT-PCR) 2 or more times during a 14-day period. Contacts completed daily symptom diaries. We characterized symptom profiles on the date of first positive rRT-PCR test and described progression of symptoms over time.
Results
We identified 47 contacts, median age 24 (3–75) years, with detectable SARS-CoV-2 by rRT-PCR. The most commonly reported symptoms on the day of first positive rRT-PCR test were upper respiratory (n = 32 68%) and neurologic (n = 30 64%); fever was not commonly reported (n = 9 19%). Eight (17%) individuals were asymptomatic at the date of first positive rRT-PCR collection; 2 (4%) had preceding symptoms that resolved and 6 (13%) subsequently developed symptoms. Children less frequently reported lower respiratory symptoms (21%, 60%, and 69% for <18, 18–49, and ≥50 years of age, respectively; P = .03).
Conclusions
Household contacts with laboratory-confirmed SARS-CoV-2 infection reported mild symptoms. When assessed at a single timepoint, several contacts appeared to have asymptomatic infection; however, over time all developed symptoms. These findings are important to inform infection control, contact tracing, and community mitigation strategies.
In January 2018, Afghanistan introduced the monovalent oral rotavirus vaccine (Rotarix) nationwide, administered as a 2-dose series at six and ten weeks of age. We describe characteristics of ...intussusception cases and assess potential intussusception risk associated with Rotarix vaccination in Afghan infants.
Multi-center prospective active hospital-based surveillance for intussusception was conducted from May 2018 to March 2022 in four sentinel sites in Afghanistan. We applied the Brighton Level 1 criteria for intussusception and verified vaccination status by reviewing vaccine cards. We used the self-controlled case series (SCCS) methodology to compare intussusception incidence in the 1 to 21 days after each dose of Rotarix vaccination against non-risk periods.
A total of 468 intussusception cases were identified in infants under 12 months, with 264 cases aged between 28 and 245 days having confirmed vaccination status contributing to the SCCS analysis. Most case-patients (98 %) required surgery for treatment, and over half (59 %) of those who underwent surgery required intestinal resection. Nineteen (7 %) case-patients died. Eighty-six percent of case-patients received the first dose of Rotarix, and 69 % received the second dose before intussusception symptom onset. There was no increased risk of intussusception in the 1–7 days (relative incidence: 0.9, 95 % CI: 0.1, 7.5), 8–21 days (1.3, 95 % CI: 0.4, 4.2), or 1–21 days (1.1, 95 % CI: 0.4, 3.4) following receipt of the first dose or in the 1–7 days (0.2, 95 % CI: 0.3, 1.8), 8–21 days (0.7, 95 % CI: 0.3, 1.5), or 1–21 days (0.6, 95 % CI: 0.3, 1.2) following the second dose.
Rotarix vaccination was not associated with an increased intussusception risk, supporting its continued use in Afghanistan's immunization program. However, there was a high level of death and resection due to intussusception among Afghan infants.
Abstract
During July–August 2021, a coronavirus disease 2019 (COVID-19) outbreak involving 21 residents (all fully vaccinated) and 10 staff (9 fully vaccinated) occurred in a Connecticut nursing ...home. The outbreak was likely initiated by a fully vaccinated staff member and propagated by fully vaccinated persons. Prior COVID-19 was protective among vaccinated residents.
Diarrhea is a leading cause of childhood morbidity and mortality in sub-Saharan Africa. Data on risk factors for mortality are limited. We conducted hospital-based surveillance to characterize the ...etiology of diarrhea and identify risk factors for death among children hospitalized with diarrhea in rural western Kenya.
We enrolled all children <5 years old, hospitalized with diarrhea (≥3 loose stools in 24 hours) at two district hospitals in Nyanza Province, western Kenya. Clinical and demographic information was collected. Stool specimens were tested for bacterial and viral pathogens. Bivariate and multivariable logistic regression analyses were carried out to identify risk factors for death. From May 23, 2005 to May 22, 2007, 1,146 children <5 years old were enrolled; 107 (9%) children died during hospitalization. Nontyphoidal Salmonella were identified in 10% (118), Campylobacter in 5% (57), and Shigella in 4% (42) of 1,137 stool samples; rotavirus was detected in 19% (196) of 1,021 stool samples. Among stools from children who died, nontyphoidal Salmonella were detected in 22%, Shigella in 11%, rotavirus in 9%, Campylobacter in 5%, and S. Typhi in <1%. In multivariable analysis, infants who died were more likely to have nontyphoidal Salmonella (adjusted odds ratio aOR = 6·8; 95% CI 3·1-14·9), and children <5 years to have Shigella (aOR = 5·5; 95% CI 2·2-14·0) identified than children who survived. Children who died were less likely to be infected with rotavirus (OR = 0·4; 95% CI 0·2-0·8). Further risk factors for death included being malnourished (aOR = 4·2; 95% CI 2·1-8·7); having oral thrush on physical exam (aOR = 2·3; 95% CI 1·4-3·8); having previously sought care at a hospital for the illness (aOR = 2·2; 95% CI 1·2-3·8); and being dehydrated as diagnosed at discharge/death (aOR = 2·5; 95% CI 1·5-4·1). A clinical diagnosis of malaria, and malaria parasites seen on blood smear, were not associated with increased risk of death. This study only captured in-hospital childhood deaths, and likely missed a substantial number of additional deaths that occurred at home.
Nontyphoidal Salmonella and Shigella are associated with mortality among rural Kenyan children with diarrhea who access a hospital. Improved prevention and treatment of diarrheal disease is necessary. Enhanced surveillance and simplified laboratory diagnostics in Africa may assist clinicians in appropriately treating potentially fatal diarrheal illness.
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