Introduction of effective and available rotavirus vaccines could substantially affect worldwide deaths attributable to diarrhoea. Our new estimates can be used to advocate for rotavirus vaccine introduction and to monitor the effect of vaccination on mortality once introduced.
While rotavirus vaccine had been introduced in >60 countries worldwide by the end of 2013, the majority of countries using rotavirus vaccine during the review period were low-mortality countries and the impact of rotavirus vaccine on global estimates of rotavirus mortality has been limited. Continued monitoring of rotavirus mortality rates and deaths through rotavirus surveillance will aid in monitoring the impact of vaccination.
Rotavirus infections are a leading cause of severe, dehydrating gastroenteritis in children <5 years of age. Despite the global introduction of vaccinations for rotavirus over a decade ago, rotavirus infections still result in >200,000 deaths annually, mostly in low-income countries. Rotavirus primarily infects enterocytes and induces diarrhoea through the destruction of absorptive enterocytes (leading to malabsorption), intestinal secretion stimulated by rotavirus non-structural protein 4 and activation of the enteric nervous system. In addition, rotavirus infections can lead to antigenaemia (which is associated with more severe manifestations of acute gastroenteritis) and viraemia, and rotavirus can replicate in systemic sites, although this is limited. Reinfections with rotavirus are common throughout life, although the disease severity is reduced with repeat infections. The immune correlates of protection against rotavirus reinfection and recovery from infection are poorly understood, although rotavirus-specific immunoglobulin A has a role in both aspects. The management of rotavirus infection focuses on the prevention and treatment of dehydration, although the use of antiviral and anti-emetic drugs can be indicated in some cases.
BackgroundRotavirus (RV) is the leading cause of diarrhea-related death in children
worldwide and 95% of RV-associated deaths occur in Africa and Asia
where RV vaccines (RVVs) have lower efficacy. We hypothesize that
differences in intestinal microbiome composition correlate with the
decreased RVV efficacy observed in poor settings.MethodsWe conducted a nested, case-control study comparing prevaccination, fecal
microbiome compositions between 6-week old, matched RVV responders and
nonresponders in rural Ghana. These infants' microbiomes were then
compared with 154 age-matched, healthy Dutch infants' microbiomes,
assumed to be RVV responders. Fecal microbiome analysis was performed in all
groups using the Human Intestinal Tract Chip.ResultsWe analyzed findings in 78 Ghanaian infants, including 39 RVV responder and
nonresponder pairs. The overall microbiome composition was significantly
different between RVV responders and nonresponders (FDR, 0.12), and Ghanaian
responders were more similar to Dutch infants than nonresponders
(P = .002). RVV response correlated with an
increased abundance of Streptococcus bovis and a decreased
abundance of the Bacteroidetes phylum in comparisons between both Ghanaian
RVV responders and nonresponders (FDR, 0.008 vs 0.003) and Dutch infants and
Ghanaian nonresponders (FDR, 0.002 vs 0.009).ConclusionsThe intestinal microbiome composition correlates significantly with RVV
immunogenicity and may contribute to the diminished RVV immunogenicity
observed in developing countries.
Antigen-based tests for SARS-CoV-2, the virus that causes coronavirus disease 2019 , are inexpensive and can return results within 15 minutes (1). Antigen tests have received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in asymptomatic and symptomatic persons within the first 5-12 days after symptom onset (2). These tests have been used at U.S. colleges and universities and other congregate settings (e.g., nursing homes and correctional and detention facilities), where serial testing of asymptomatic persons might facilitate early case identification (3-5). However, test performance data from symptomatic and asymptomatic persons are limited. This investigation evaluated performance of the Sofia SARS Antigen Fluorescent Immunoassay (FIA) (Quidel Corporation) compared with real-time reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 detection among asymptomatic and symptomatic persons at two universities in Wisconsin. During September 28-October 9, a total of 1,098 paired nasal swabs were tested using the Sofia SARS Antigen FIA and real-time RT-PCR. Virus culture was attempted on all antigenpositive or real-time RT-PCR-positive specimens. Among 871 (79%) paired swabs from asymptomatic participants, the antigen test sensitivity was 41.2%, specificity was 98.4%, and in this population the estimated positive predictive value (PPV) was 33.3%, and negative predictive value (NPV) was 98.8%. Antigen test performance was improved among 227 (21%) paired swabs from participants who reported one or more symptoms at specimen collection (sensitivity = 80.0%; specificity = 98.9%; PPV = 94.1%; NPV = 95.9%). Virus was isolated from 34 (46.6%) of 73 antigen-positive or real-time RT-PCR-positive nasal swab specimens, including two of 18 that were antigen-negative and real-time RT-PCR-positive (false-negatives). The advantages of antigen tests such as low cost and rapid turnaround might allow for rapid identification of infectious persons. However, these advantages need to be
RV1 was associated with a short-term risk of intussusception in approximately 1 of every 51,000 to 68,000 vaccinated infants. The absolute number of deaths and hospitalizations averted because of vaccination far exceeded the number of intussusception cases that may have been associated with vaccination. (Funded in part by the GAVI Alliance and the U.S. Department of Health and Human Services.).
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 * Specimens were used to perform a limiting-dilution inoculation of Vero CCL-81 cells, and cultures showing evidence of cytopathic effect were tested by real-time RT-PCR for the presence of SARS-CoV-2 RNA. Viral recovery was defined as any culture in which the first passage had an N1 Ct value at least two Ct values lower than the corresponding clinical specimen. † https://www.biorxiv
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