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The causes of diarrhea after 10 years of rotavirus vaccination in Rwanda were investigated with real-time polymerase chain reaction in 496 children with diarrhea and 298 without. Rotavirus was detected in 11% of children with diarrhea (odds ratio, 2.48; P =.002). Comparison of population attributable fractions (PAFs) shows that Shigella (PAF, 11%) and enterotoxigenic Escherichia coli producing labile toxin (PAF, 12%) have replaced rotavirus as the main causative agents. The PAF for rotavirus had declined from 41% prevaccination to 6.5% postvaccination, indicating that rotavirus has become one among several similarly important causes of childhood diarrhea in Rwanda. A rotavirus genotype shift to G3P[8] points at the importance of continued genotype surveillance. [ABSTRACT FROM AUTHOR]

Background Quantitative molecular assays are increasingly used for detection of enteric viruses. Methods We compared the clinical severity using the modified Vesikari score (mVS) of enteric viruses detected by conventional assays (enzyme immunoassays [EIAs] for rotavirus and adenovirus 40/41 and conventional polymerase chain reaction for astrovirus, sapovirus, and norovirus) and a quantitative molecular assay (TaqMan Array Card [TAC]) among children aged 0–59 months in the Global Enteric Multicenter Study. For rotavirus and adenovirus 40/41, we compared severity between EIA-positive and TAC-positive cases assigned etiologies using different cycle threshold (Ct) cutoffs. Results Using conventional assays, the median mVS (interquartile range) was 10 (8–11) for rotavirus, 9 (7–11) for adenovirus 40/41, 8 (6–10) for astrovirus, sapovirus, and norovirus GII, and 7 (6–9) for norovirus GI. Compared with rotavirus EIA-positive cases, the median mVS was 2 and 3 points lower for EIA-negative/TAC-positive cases with Ct <32.6 or Ct ≥32.6 and <35, respectively (P <.001). Adenovirus 40/41 EIA-positive and EIA-negative/TAC-positive cases were similar, regardless of Ct cutoff. Conclusions Quantitative molecular assays compared with conventional assays, such as EIA, may influence the severity of identified cases, especially for rotavirus. Cutoffs to assign etiology for quantitative assays should be considered in the design and interpretation of enteric virus studies. [ABSTRACT FROM AUTHOR]

Background Globally, rotavirus infections are the most common cause of diarrhea-related deaths, especially among children under 5 years of age. This virus can be transmitted through the fecal-oral route, although zoonotic and environmental contributions to transmission are poorly defined. The purpose of this study is to determine the epidemiology of rotavirus in humans, animals, and the environment in Africa, as well as the impact of vaccination. Methods We searched PubMed, Web of Science, Africa Index Medicus, and African Journal Online, identifying 240 prevalence data points from 224 articles between 2009 and 2022. Results Human rotavirus prevalence among patients with gastroenteritis was 29.8% (95% confidence interval [CI], 28.1%–31.5%; 238 710 participants), with similar estimates in children under 5 years of age, and an estimated case fatality rate of 1.2% (95% CI,.7%–2.0%; 10 440 participants). Prevalence was estimated to be 15.4% and 6.1% in patients with nongastroenteritis illnesses and apparently healthy individuals, respectively. Among animals, prevalence was 9.3% (95% CI, 5.7%–13.7%; 6115 animals), and in the environmental water sources, prevalence was 31.4% (95% CI, 17.7%–46.9%; 2530 samples). Discussion Our findings highlight the significant burden of rotavirus infection in Africa, and underscore the need for a One Health approach to limiting the spread of this disease. [ABSTRACT FROM AUTHOR]

Background Even moderate differences in rotavirus vaccine effectiveness against nonvaccine genotypes may exert selective pressures on circulating rotaviruses. Whether this vaccine effect or natural temporal fluctuations underlie observed changes in genotype distributions is unclear. Methods We systematically reviewed studies reporting rotavirus genotypes from children <5 years of age globally between 2005 and 2023. We compared rotavirus genotypes between vaccine-introducing and nonintroducing settings globally and by World Health Organization (WHO) region, calendar time, and time since vaccine introduction. Results Crude pooling of genotype data from 361 studies indicated higher G2P[4], a nonvaccine genotype, prevalence in vaccine-introducing settings, both globally and by WHO region. This difference did not emerge when examining genotypes over time in the Americas, the only region with robust longitudinal data. Relative to nonintroducing settings, G2P[4] detections were more likely in settings with recent introduction (eg, 1–2 years postintroduction adjusted odds ratio [aOR], 4.39; 95% confidence interval [CI], 2.87–6.72) but were similarly likely in settings with more time elapsed since introduction, (eg, 7 or more years aOR, 1.62; 95% CI,.49–5.37). Conclusions When accounting for both regional and temporal trends, there was no substantial evidence of long-term vaccine-related selective pressures on circulating genotypes. Increased prevalence of G2P[4] may be transient after rotavirus vaccine introduction. [ABSTRACT FROM AUTHOR]

To examine the potential for respiratory transmission of rotavirus, we systematically assessed if rotavirus RNA is detectable by real-time quantitative reverse transcription-polymerase chain reaction from nasal and oropharyngeal swab specimens of Bangladeshi children with acute rotavirus gastroenteritis. Forehead swabs were collected to assess skin contamination. Among 399 children aged <2 years hospitalized for gastroenteritis during peak rotavirus season, rotavirus RNA was detected in stool, oral, nasal and forehead swab specimens of 354 (89%). A subset was genotyped; genotype was concordant within a child's specimen set and several different genotypes were detected across children. These findings support possible respiratory transmission of rotavirus and warrant further investigation. [ABSTRACT FROM AUTHOR]

Background: Since rotavirus vaccines became available in the United States in 2006, there have been reductions in rotavirus hospitalizations, changes in seasonality, and the emergence of a biennial trend of rotavirus activity. Reductions in other pathogens have been associated with coronavirus disease 2019 (COVID-19) mitigation measures. We assessed ongoing rotavirus disease trends during the COVID-19 pandemic.Methods: We report a 3-week moving average of the number of rotavirus tests, positive tests, and the percent positivity from laboratories reporting to the National Respiratory and Enteric Virus Surveillance System (NREVSS) from July 2000 through June 2021. To complement NREVSS data, we analyzed Google internet search interest in "rotavirus" from July 2004 to June 2021.Results: Declines in rotavirus activity following vaccine introduction and the biennial trend are evident through the 2018-2019 surveillance year. In 2019-2021, rotavirus test positivity was below the historic ranges during the months of typically high rotavirus activity, and precipitous declines were noted in March 2020.Conclusions: In the 15 years since rotavirus vaccine was introduced, the number of laboratory-detected rotavirus infections has been consistently lower than during the prevaccine era. During the COVID-19 pandemic, rotavirus activity was suppressed. There may be many rotavirus-susceptible children during the 2021-2022 rotavirus season. [ABSTRACT FROM AUTHOR]

Background: Rotavirus is a leading cause of pediatric diarrheal mortality. The rotavirus outer capsid consists of VP7 and VP4 proteins, which, respectively, determine viral G and P type and are primary targets of neutralizing antibodies.Methods: To elucidate VP7-specific neutralizing antibody responses, we engineered monoreassortant rotaviruses each containing a human VP7 segment from a sequenced clinical specimen or a vaccine strain in an identical genetic background. We quantified replication and neutralization of engineered viruses using sera from infants vaccinated with monovalent ROTARIX or multivalent RotaTeq vaccines.Results: Immunization with RotaTeq induced broader neutralizing antibody responses than ROTARIX. Inclusion of a single dose of RotaTeq in the schedule enhanced G-type neutralization breadth of vaccinated infant sera. Cell type-specific differences in infectivity, replication, and neutralization were detected for some monoreassortant viruses.Conclusions: These findings suggest that rotavirus VP7, independent of VP4, can contribute to cell tropism and the breadth of vaccine-elicited neutralizing antibody responses. [ABSTRACT FROM AUTHOR]

Background: Following the implementation of rotavirus vaccination in 2006, severe acute gastroenteritis (AGE) due to group A rotavirus (RVA) has substantially declined in US children. We report the RVA genotype prevalence as well as coinfection data from 7 US New Vaccine Surveillance Network sites during 3 consecutive RVA seasons, 2014-2016.Methods: A total of 1041 stool samples that tested positive for RVA by Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention (CDC) for RVA genotyping and multipathogen testing.Results: A total of 795 (76%) samples contained detectable RVA when tested at the 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 2 P types (P[4] and P[8]) accounted for 94.7% of the strains. Overall, G12P[8] was the most common genotype detected in all 3 seasons. Stepwise conditional logistic analysis found year and study site were significant predictors of genotype. Twenty-four percent of RVA-positive specimens contained other AGE pathogens.Conclusions: G12P[8] predominated over 3 seasons, but strain predominance varied by year and study site. Ongoing surveillance provides continuous tracking and monitoring of US genotypes during the postvaccine era. [ABSTRACT FROM AUTHOR]

Secretor status controls mucosal histo-blood group antigen expression and is associated with susceptibility to rotavirus (RV) diarrhea, with nonsecretors less susceptible to symptomatic infection. The role of breast milk secretor status on oral live-attenuated RV vaccine response in breastfed infants has not been explored. In a monovalent G1P[8] RV vaccine (Rotarix) trial in Bangladesh, RV-specific plasma immunoglobulin A antibody seroconversion rates were higher among infants of maternal nonsecretors (39%) than infants of maternal secretors (23%; P = .001). Maternal status remained a significant predictor when correcting for infant status (P = .002). Maternal secretor status should be considered when interpreting oral RV vaccine responses in low- and middle-income settings. Clinical Trials Registration. NCT01375647. [ABSTRACT FROM AUTHOR]

Background: To inform the introduction of pneumococcal conjugate vaccine (PCV) and rotavirus vaccine, the World Health Organization (WHO) established the Global Invasive Bacterial Vaccine-Preventable Disease Surveillance Network (GISN) and the Global Rotavirus Surveillance Network (GRSN) in 2008. We investigated whether participation in these networks or other surveillance was associated with vaccine introduction.Methods: Between 2006 and 2018, among all WHO member states, we used multivariable models adjusting for economic status to assess (1) the association between surveillance for pneumococcal disease or rotavirus disease, including participation in GISN or GRSN and the introduction of the PCV or the rotavirus vaccine, respectively, and (2) the association between the rotavirus disease burden and the rotavirus vaccine introduction among 56 countries participating in GRSN from 2008 to 2018.Results: Countries that participated in or conducted surveillance for invasive pneumococcal disease or rotavirus disease were 3.5 (95% confidence interval [CI], 1.7-7.1) and 4.2 (95% CI, 2.1-8.6) times more likely to introduce PCV or rotavirus respectively, compared to those without surveillance. Among countries participating in GRSN, there was insufficient evidence to demonstrate an association between countries with higher rotavirus positivity and vaccine introduction.Conclusions: Surveillance should be incorporated into advocacy strategies to encourage the introduction of vaccines, with countries benefiting from data from, support for, and coordination of international disease surveillance networks. [ABSTRACT FROM AUTHOR]

To assess whether titers of anti-rotavirus immunoglobulin G persist during the post-rotavirus vaccine era, the Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal (PREVAIL) Cohort analyzed serum samples collected from Cincinnati-area mothers and young infants in 2017-2018. Rotavirus-specific antibodies continue to be transferred from US mothers to their offspring in the post-rotavirus vaccine era, despite dramatic decreases in childhood rotavirus gastroenteritis. [ABSTRACT FROM AUTHOR]

Quantifying rotavirus shedding among vaccinated individuals will aid understanding of vaccine indirect effects. Serial stool samples were collected from 196 children who presented with rotavirus gastroenteritis to health facilities in Blantyre, Malawi, and were tested for rotavirus using a VP6 semi-quantitative, real-time polymerase chain reaction. The median duration of fecal shedding was 28 days (95% CI, 19-28). The median copy numbers for peak shedding were 1.99 × 107 (interquartile range, 3.39 × 106 to 6.37 × 107). The fecal viral load was positively associated with disease severity and negatively associated with serum anti-rotavirus immunoglobin A. High and persistent rotavirus shedding among vaccinated children with breakthrough disease may contribute to ongoing transmission in this setting. [ABSTRACT FROM AUTHOR]

Background: The degree of protection conferred by natural immunity is unknown for many enteropathogens, but it is important to support the development of enteric vaccines.Methods: We used the Andersen-Gill extension of the Cox model to estimate the effects of previous infections on the incidence of subsequent subclinical infections and diarrhea in children under 2 using quantitative molecular diagnostics in the MAL-ED cohort. We used cross-pathogen negative control associations to correct bias due to confounding by unmeasured heterogeneity of exposure and susceptibility.Results: Prior rotavirus infection was associated with a 50% lower hazard (calibrated hazard ratio [cHR], 0.50; 95% confidence interval [CI], 0.41-0.62) of subsequent rotavirus diarrhea. Strong protection was evident against Cryptosporidium diarrhea (cHR, 0.32; 95% CI, 0.20-0.51). There was also protection due to prior infections for norovirus GII (cHR against diarrhea, 0.67; 95% CI, 0.49-0.91), astrovirus (cHR, 0.62; 95% CI, 0.48-0.81), and Shigella (cHR, 0.79; 95% CI, 0.65-0.95). Minimal protection was observed for other bacteria, adenovirus 40/41, and sapovirus.Conclusions: Natural immunity was generally stronger for the enteric viruses than bacteria, potentially due to less antigenic diversity. Vaccines against major causes of diarrhea may be feasible but likely need to be more immunogenic than natural infection. [ABSTRACT FROM AUTHOR]

Background: Since 2006, more than 100 countries have introduced rotavirus vaccine into their immunization programs. We reviewed published data on relative reductions of rotavirus hospitalizations, acute gastroenteritis (AGE) hospitalizations, and AGE deaths among children <5 years old.Methods: Articles published from January 1, 2006 to December 31, 2019 with at least 12 months of data before and after rotavirus vaccine introduction were included. Relative reductions were abstracted into a standardized form. Descriptive statistics are presented as medians and interquartile ranges (IQRs).Results: We reviewed 1827 total records and included 105 articles from 49 countries. Among children <5 years old, there was a median reduction of 59% (IQR, 46-74) in rotavirus hospitalizations, 36% (IQR, 23-47) in AGE hospitalizations, and 36% (IQR, 28-46) AGE mortality. Reductions were larger in countries with low child mortality, among younger age groups, and in countries with higher coverage. The median percentage of specimens that tested positive for rotavirus among children <5 years old hospitalized for diarrhea was 40% (IQR, 28-45) before rotavirus vaccine introduction and 20% (IQR, 20-20) 4 years after introduction.Conclusions: Overall, we found sustained impact on rotavirus and AGE hospitalizations and deaths. These results should encourage countries still considering rotavirus vaccine implementation. [ABSTRACT FROM AUTHOR]

Although the etiology of type 1 diabetes (T1D) is not well understood, it is believed to comprise both genetic and environmental factors. Viruses are the most well studied environmental trigger, and there is a small but growing body of research on the potential influence of rotavirus on T1D. Rotavirus infections were initially identified as possible triggers of T1D given similarities between viral peptide sequences and T1D autoantigen peptide sequences. Furthermore, rotavirus infection has been shown to modify T1D risk in T1D-prone mice. However, research into associations of rotavirus infections with T1D development in humans have yielded mixed findings and suggested interactions with age and diet. As global availability of rotavirus vaccines increases, recent studies have assessed whether rotavirus vaccination modifies T1D development, finding null or protective associations. Overall, evidence to date suggests a possible triggering relationship between some wild-type rotavirus infections and T1D, but the potential effect of rotavirus vaccination remains unclear. [ABSTRACT FROM AUTHOR]

In Tunisia, we observed that rotavirus P[8]-3 and P[4] strains in young children with gastroenteritis associate with secretor histo-blood group phenotype. In contrast, the emerging P[8]-4 strain, representing 10% of cases, was exclusively found in nonsecretor patients. Unlike VP8* from P[8]-3 and P[4] strains, the P[8]-4 VP8* protein attached to glycans from saliva samples regardless of the donor's secretor status. Interestingly, a high frequency of FUT2 enzyme deficiency (nonsecretor phenotype) was observed in the population. This may allow cocirculation of P[8]-3 and P[8]-4 strains in secretor and nonsecretor children, respectively. [ABSTRACT FROM AUTHOR]

Despite rotavirus vaccination, diarrhea remains a leading cause of child mortality. We collected stool specimens from 684 children <5 years of age hospitalized with diarrhea (cases) and 527 asymptomatic community controls for 4 years after rotavirus vaccine introduction in Malawi. Specimens were tested for 29 pathogens, using polymerase chain reaction analysis. Three or more pathogens were detected in 71% of cases and 48% of controls. Pathogens significantly associated with diarrhea included rotavirus (in 34.7% of cases and 1.5% of controls), enteric adenovirus (in 29.1% and 2.7%, respectively), Cryptosporidium (in 27.8% and 8.2%, respectively), heat-stable enterotoxin-producing Escherichia coli (in 21.2% and 8.5%, respectively), typical enteropathogenic E. coli (in 18.0% and 8.3%, respectively), and Shigella/enteroinvasive E. coli (in 15.8% and 5.7%, respectively). Additional interventions are required to prevent diarrhea due to rotavirus and other common causal pathogens. [ABSTRACT FROM AUTHOR]

Horizontal transmission of rotavirus vaccine virus may contribute to indirect effects of rotavirus vaccine, but data are lacking from low-income countries. Serial stool samples were obtained from Malawian infants who received 2 doses of monovalent human rotavirus vaccine (RV1) (days 4, 6, 8, and 10 after vaccination) and from their household contacts (8-10 days after vaccine). RV1 vaccine virus in stool was detected using semiquantitative real-time reverse-transcription polymerase chain reaction. RV1 fecal shedding was detected in 41 of 60 vaccinated infants (68%) and in 2 of 147 household contacts (1.4%). Horizontal transmission of vaccine virus within households is unlikely to make a major contribution to RV1 indirect effects in Malawi. [ABSTRACT FROM AUTHOR]

Rotaviruses bind to enterocytes in a genotype-specific manner via histo-blood group antigens (HBGAs), which are also detectable in saliva. We evaluated antirotavirus immunoglobulin A seroconversion ('vaccine take") among 166 Ghanaian infants after 2–3 doses of G1P[8] rotavirus vaccine during a vaccine trial, by HBGA status from saliva collected at age 4.1 years. Only secretor status was associated with seroconversion: 41% seroconversion for secretors vs 13% for nonsecretors; relative risk, 3.2 (95% confidence interval, 1.2–8.1; P =.016). Neither Lewis antigen nor salivary antigen blood type was associated with seroconversion. Likelihood of "take" for any particular rotavirus vaccine may differ across populations based on HBGAs. [ABSTRACT FROM AUTHOR]

A safe and highly efficient antiviral is needed for the prophylaxis and/or treatment of viral diarrhea. We here demonstrate the in vitro antiviral activity of four 2'-C-methyl nucleoside analogues against noro-, rota-, and sapoviruses. The most potent nucleoside analogue, 7-deaza-2'-C-methyladenosine, inhibits replication of these viruses with a 50% effective concentration < 5 µM. Mechanistically, we demonstrate that the 2'-C-methyl nucleoside analogues act by inhibiting transcription of the rotavirus genome. This provides the first evidence that a single viral-diarrhea-targeted treatment can be developed through a viral-polymerase-targeting small molecule. [ABSTRACT FROM AUTHOR]

Background: Introduction of rotavirus vaccines into national immunization programs (NIPs) could result in strain selection due to vaccine-induced selective pressure. This study describes the distribution and diversity of rotavirus genotypes before and after rotavirus vaccine introduction into the Australian NIP. State-based vaccine selection facilitated a unique comparison of diversity in RotaTeq and Rotarix vaccine states.Methods: From 1995 to 2015, the Australian Rotavirus Surveillance Program conducted genotypic analysis on 13051 rotavirus-positive samples from children <5 years of age, hospitalized with acute gastroenteritis. Rotavirus G and P genotypes were determined using serological and heminested multiplex reverse-transcription polymerase chain reaction assays.Results: G1P[8] was the dominant genotype nationally in the prevaccine era (1995-2006). Following vaccine introduction (2007-2015), greater genotype diversity was observed with fluctuating genotype dominance. Genotype distribution varied based on the vaccine implemented, with G12P[8] dominant in states using RotaTeq, and equine-like G3P[8] and G2P[4] dominant in states and territories using Rotarix.Conclusions: The increased diversity and differences in genotype dominance observed in states using RotaTeq (G12P[8]), and in states and territories using Rotarix (equine-like G3P[8] and G2P[4]), suggest that these vaccines exert different immunological pressures that influence the diversity of rotavirus strains circulating in Australia. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to assess the transmissibility of rotavirus vaccine strains after rotavirus vaccination in a neonatal intensive care unit (NICU).Methods: Pentavalent (RV5) or monovalent (RV1) rotavirus vaccine was administered to infants admitted to the NICU. Nineteen vaccinated infants and 49 unvaccinated infants whose beds were located in close proximity to the vaccinated infants were enrolled in this study. Dissemination and fecal shedding of vaccine viruses within the NICU were examined using real-time reverse transcription-polymerase chain reaction.Results: Shedding of the vaccine strain was detected in all 19 vaccinated infants. RV5 virus shedding started 1 day after the first vaccination and persisted for 8 days after the first vaccination, and viral shedding terminated by day 5 after administration of the second RV5 dose. The kinetics of RV1 virus shedding differed among vaccinated infants. The duration of RV1 virus shedding was longer after the first vaccination than after the second vaccination. In contrast to the vaccinated infants, no vaccine virus genomes were detected in any of the stool samples collected from the 49 unvaccinated infants.Conclusions: This study is direct evidence of no transmission of rotavirus vaccine strains between vaccinated infants and unvaccinated infants in close proximity within a NICU. [ABSTRACT FROM AUTHOR]

Background: Observational studies in socioeconomically distinct populations have yielded conflicting conclusions about the strength of naturally acquired immunity against rotavirus gastroenteritis (RVGE), mirroring vaccine underperformance in low-income countries. We revisited birth cohort studies to understand naturally acquired protection against rotavirus infection and RVGE.Methods: We reanalyzed data from 200 Mexican and 373 Indian children followed from birth to 2 and 3 years of age, respectively. We reassessed protection against RVGE, decomposing the incidence rate into the rate of rotavirus infection and the risk of RVGE given infection, and tested for serum antibody correlates of protection using regression models.Results: Risk for primary, secondary, and subsequent infections to cause RVGE decreased per log-month of age by 28% (95% confidence interval [CI], 12%-41%), 69% (95% CI, 30%-86%), and 64% (95% CI, -186% to 95%), respectively, in Mexico City, and by 10% (95% CI, -1% to 19%), 51% (95% CI, 41%-59%) and 67% (95% CI, 57%-75%), respectively, in Vellore. Elevated serum immunoglobulin A and immunoglobulin G titers were associated with partial protection against rotavirus infection. Associations between older age and reduced risk for RVGE or moderate-to-severe RVGE given infection persisted after controlling for antibody levels.Conclusions: Dissimilar estimates of protection against RVGE may be due in part to age-related, antibody-independent risk for rotavirus infections to cause RVGE. [ABSTRACT FROM AUTHOR]

Background: The etiology of acute watery diarrhea remains poorly characterized, particularly after rotavirus vaccine introduction.Methods: We performed quantitative polymerase chain reaction for multiple enteropathogens on 878 acute watery diarrheal stools sampled from 14643 episodes captured by surveillance of children <5 years of age during 2013-2014 from 16 countries. We used previously developed models of the association between pathogen quantity and diarrhea to calculate pathogen-specific weighted attributable fractions (AFs).Results: Rotavirus remained the leading etiology (overall weighted AF, 40.3% [95% confidence interval {CI}, 37.6%-44.3%]), though the AF was substantially lower in the Americas (AF, 12.2 [95% CI, 8.9-15.6]), based on samples from a country with universal rotavirus vaccination. Norovirus GII (AF, 6.2 [95% CI, 2.8-9.2]), Cryptosporidium (AF, 5.8 [95% CI, 4.0-7.6]), Shigella (AF, 4.7 [95% CI, 2.8-6.9]), heat-stable enterotoxin-producing Escherichia coli (ST-ETEC) (AF, 4.2 [95% CI, 2.0-6.1]), and adenovirus 40/41 (AF, 4.2 [95% CI, 2.9-5.5]) were also important. In the Africa Region, the rotavirus AF declined from 54.8% (95% CI, 48.3%-61.5%) in rotavirus vaccine age-ineligible children to 20.0% (95% CI, 12.4%-30.4%) in age-eligible children.Conclusions: Rotavirus remained the leading etiology of acute watery diarrhea despite a clear impact of rotavirus vaccine introduction. Norovirus GII, Cryptosporidium, Shigella, ST-ETEC, and adenovirus 40/41 were also important. Prospective surveillance can help identify priorities for further reducing the burden of diarrhea. [ABSTRACT FROM AUTHOR]

In 2006, 2 rotavirus vaccines were licensed. We summarize the impact of rotavirus vaccination on hospitalizations and deaths from rotavirus and all-cause acute gastroenteritis (AGE) during the first 10 years since vaccine licensure, including recent evidence from countries with high child mortality. We used standardized guidelines (PRISMA) to identify observational evaluations of rotavirus vaccine impact among children <5 years of age that presented at least 12 months of pre- and post-vaccine introduction surveillance data. We identified 57 articles from 27 countries. Among children <5 years of age, the median percentage reduction in AGE hospitalizations was 38% overall and 41%, 30%, and 46% in countries with low, medium, and high child mortality, respectively. Hospitalizations and emergency department visits due to rotavirus AGE were reduced by a median of 67% overall and 71%, 59%, and 60% in countries with low, medium, and high child mortality, respectively. Implementation of rotavirus vaccines has substantially decreased hospitalizations from rotavirus and all-cause AGE. [ABSTRACT FROM AUTHOR]

Histo-blood group antigens (HBGAs) expressed on enterocytes are proposed receptors for rotaviruses and can be measured in saliva. Among 181 Pakistani infants in a G1P[8] rotavirus vaccine trial who were seronegative at baseline, anti-rotavirus immunoglobulin A seroconversion rates after 3 vaccine doses differed significantly by salivary HBGA phenotype, with the lowest rate (19%) among infants who were nonsecretors (ie, who did not express the carbohydrate synthesized by FUT2), an intermediate rate (30%) among secretors with non-blood group O, and the highest rate (51%) among secretors with O blood group. Differences in HBGA expression may be responsible for some of the discrepancy in the level of protection detected for the current rotavirus vaccines in low-income versus high-income settings. [ABSTRACT FROM AUTHOR]

Background:  Rotavirus (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.Methods:  We 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.Results:  We 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).Conclusions:  The intestinal microbiome composition correlates significantly with RVV immunogenicity and may contribute to the diminished RVV immunogenicity observed in developing countries. [ABSTRACT FROM AUTHOR]

Background: P[6] rotaviruses have been circulating with a high prevalence in African and, to a more limited extent, Asian countries, but they have not been highly prevalent in other parts of the world.Methods: To investigate the genomic relationship between African and Asian human P[6] rotaviruses and P[4] and P[8] rotaviruses circulating worldwide, we sequenced 39 P[6] strains, collected in Ghana, Mali, Kenya and Bangladesh, providing the largest data set of P[6] rotavirus genomes isolated in low-income countries or anywhere else in the world that has been published thus far.Results: Overall, the data indicate that the genetic backbone of human P[6] strains from the low-income countries are similar to those of P[4] or P[8] strains circulating worldwide.Conclusions: The observation that gene segment 4 is the main differentiator between human P[6] and non-P[6] strains suggests that the VP4 spike protein is most likely one of the main reasons preventing the rapid spread of P[6] strains to the rest of the world despite multiple introductions. These observations reinforce previous findings about the receptor specificity of P[6] rotavirus strains. [ABSTRACT FROM AUTHOR]

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 3-7 geographically diverse sites in the United States since 2006.Methods: Over 6 consecutive years, from 2008 to 2013, 1523 samples from NVSN sites that were tested positive by a Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention for genotyping.Results: In the 2009, 2010, and 2011 seasons, genotype G3P[8] was the predominant genotype throughout the network, with a 46%-84% prevalence. In the 2012 season, G12P[8] replaced G3P[8] as the most common genotype, with a 70% prevalence, and this trend persisted in 2013 (68.0% prevalence). Vaccine (RotaTeq; Rotarix) strains were detected in 0.6%-3.4% of genotyped samples each season. Uncommon and unusual strains (eg, G8P[4], G3P[24], G2P[8], G3P[4], G3P[6], G24P[14], G4P[6], and G9P[4]) were detected sporadically over the study period. Year, study site, and race were found to be significant predictors of genotype.Conclusions: Continued active surveillance is needed to monitor RVA genotypes in the United States and to detect potential changes since vaccine licensure. [ABSTRACT FROM AUTHOR]

The article offers information about studies on rotavirus vaccine and rotavirus strains, which are often classified according to the two surface capsid proteins, such as G (VP7) and P (VP4), that induce neutralizing antibodies. Other information related to surveillance systems in medicine and the development of a vaccine is presented.

Background. A recombinant canarypox vector expressing human immunodeficiency virus type 1 (HIV-1) Gag, Pro, and membrane-linked gp120 (vCP1521), combined with a bivalent gp120 protein boost (AIDSVAX B/E), provided modest protection against HIV-1 infection in a community-based population in Thailand (RV144 trial). No protection was observed in Thai injection drug users who received AIDSVAX B/E alone (Vax003 trial). We compared the neutralizing antibody response in these 2 trials.Methods. Neutralization was assessed with tier 1 and tier 2 strains of virus in TZM-bl and A3R5 cells.Results. Neutralization of several tier 1 viruses was detected in both RV144 and Vax003. Peak titers were higher in Vax003 and waned rapidly in both trials. The response in RV144 was targeted in part to V3 of gp120.vCP1521 priming plus 2 boosts with gp120 protein was superior to 2 gp120 protein inoculations alone, confirming a priming effect for vCP1521. Sporadic weak neutralization of tier 2 viruses was detected only in Vax003 and A3R5 cells.Conclusion. The results suggest either that weak neutralizing antibody responses can be partially protective against HIV-1 in low-risk heterosexual populations or that the modest efficacy seen in RV144 was mediated by other immune responses, either alone or in combination with neutralizing antibodies. [ABSTRACT FROM PUBLISHER]

Background. RotaTeq vaccine was introduced into the Australian National Immunisation Program in 2007. This study identified and characterised rotavirus strains excreted by infants who presented with symptoms of gastroenteritis following recent RotaTeq vaccination.Methods. Fecal samples (N = 61) from children who developed gastroenteritis following recent RotaTeq vaccination were forwarded to the Australian Rotavirus Surveillance Program (ARSP). RotaTeq-positive samples were genotyped and regions of the VP3, VP4, VP6, and VP7 genes were sequenced. Also, 460 rotavirus-positive ARSP routine surveillance samples were analyzed by dot-blot Northern hybridization to detect RotaTeq vaccine–derived strains circulating in the community.Results. Thirteen of the 61 samples collected from infants developing gastroenteritis after RotaTeq vaccination contained vaccine-derived (vd) rotavirus strains. Of these, 4 contained a vdG1P[8] strain derived by reassortment between the G1P[5] and G6P[8] parental vaccine strains. Northern hybridization analysis of 460 surveillance samples identified 3 samples that contained RotaTeq vaccine–derived strains, including 2 vdG1P[8] reassortant vaccine strains.Conclusions. During replication and excretion of RotaTeq vaccine, reassortment of parental strains can occur. Shedding of RotaTeq vaccine strains in 7 of 13 infants was associated with underlying medical conditions that may have altered their immune function. The benefits of vaccination outweigh any small risk of vaccine-associated gastroenteritis. [ABSTRACT FROM PUBLISHER]

The article presents the immune responses to natural rotavirus (RV) vaccination and RV infection in both experimental humans and animals. It states that RV-specific IgA antibodies in the gut lumen are related with protection from the immune responses to natural RV infection in humans and animals. It mentions that RV-specific maternal antibody may intervene with the efficacy of RV vaccination in young animals and infants.

Background. Prophylactic vitamin A supplementation (VAS) reduces mortality and may reduce morbidity associated with diarrhea in children >6 months of age. Rotavirus is the most common cause of acute dehydrating diarrhea among children worldwide. Methods. In a randomized placebo-controlled study of 50,000 IU of vitamin A versus placebo given with bacille Calmette-Guérin vaccine at birth, 287 infants were followed up with weekly interviews and stool sample obtainment to test the hypothesis that VAS reduced the risk of rotavirus infection. Results. VAS was associated with increased risk of rotavirus infection and diarrhea (incidence rate ratio [IRR] of infection, 1.72 [95% confidence interval (CI), 1.04-2.85]; IRR of diarrhea, 3.74 [95% CI, 1.40-9.98]) among children <6 months of age. There was no effect in older children. VAS had a beneficial effect on nonrotavirus diarrhea in boys <6 months of age (IRR, 0.51; 95% CI, 0.27-0.95) and a detrimental effect in girls >6 months of age (IRR, 1.84; 95% CI, 0.96-3.55). Conclusion. VAS at birth did not reduce rotavirus morbidity. The effect of VAS on nonrotavirus diarrhea may differ by sex, being more beneficial in boys. [ABSTRACT FROM AUTHOR]

Limited genotyping data are available for rotavirus strains in the Middle East. In this study, we investigated the molecular epidemiology of human rotavirus strains circulating in the Sultanate of Oman during 2005. Rotavirus was detected in 178 (57.4%) of 310 of the diarrheal stools of young children <5 years admitted to hospitals and outpatients clinics. Polyacrylamide gel electrophoresis demonstrated the cocirculation of 8 strains, although 2 strains predominated across the Sultanate. Genotyping revealed the presence of human rotavirus strains of types G1P[8], G2P[4], and G3P[8]. Several strains exhibited unusual combinations of G and P genotypes and RNA electropherotypes, indicating the likelihood of natural reassortment events occurring with a high frequency. In addition, the unusual P[10] genotype was identified among the rotavirus strains, in combination with the G1 type. [ABSTRACT FROM AUTHOR]

An epidemiological survey investigating rotavirus infection in children was undertaken in the coastal region of Tunisia from January 2000 through September 2003. A total of 309 fecal specimens were screened by enzyme-linked immunosorbent assay and latex agglutination assay for the presence of group A rotavirus antigen. The detection rate was 26.2%. Rotavirus outbreaks showed a temperature-dependant pattern (P = .026) but no significant association with rainfall. Rotavirus strains isolated were analyzed by RNA polyacrylamide gel electrophoresis and were characterized antigenically by monoclonal antibodies to the VP6 subgroup. Eight RNA electropherotypes were identified, with 3 long and 5 short different RNA profiles. Among VP6 typeable strains, all isolates with a long electrophoretic pattern carried the subgroup II specificity, whereas those with a short profile belonged to subgroup I. In total, 48 rotavirus-positive samples were analyzed for G and P typing by reverse-transcription polymerase chain reaction. A total of 8 different G and P combinations were found: G1P[8] (35.7%), G1P[6] (21.4%), G2P[4] (4.8%), G3P[4] (4.8%), G4P[6] (4.8%), G8P[8] (4.8%), G3P[8] (2.3%), and G4P[8] (2.3%). Mixed infections were detected in 19.1% of stool samples. The emergence in Tunisia of unconventional types, such as G8VP7 specificity, highlights the need for a continual survey of the uncommon strains in North Africa. [ABSTRACT FROM AUTHOR]

Rotavirus is one of the most common causes of childhood diarrhea! disease and deaths in sub-Saharan Africa. This article reviews community- and hospital-based surveillance of rotavirus disease in Bissau, Guinea-Bissau, West Africa. Here, rotavirus infections exhibit a seasonal pattern, with annual epidemics occurring during the relatively dry and cooler months, from January to April, and few cases registered from May to December. Most children (74%) experience their first infection before the age of 2 years, and rotavirus has been identified as the most pathogenic of all diarrheal agents during 2 large prospective studies involving several hundred children <5 years of age. In the hospital setting, rotavirus accounts for a high case-fatality ratio (8%) and a high rate of nosocomial transmission; during the rotavirus season, 23% of all children admitted for nonrotavirus diarrheal disease acquired rotavirus infection during hospitalization (>48 h after admission). [ABSTRACT FROM AUTHOR]

From October 2003 through September 2004, a total of 289 stool samples were collected from children <5 years of age who had severe diarrhea at admission to or when visiting the emergency department at the Navrongo War Memorial Hospital in rural Ghana during a study on rotavirus disease burden. Rotavirus antigen was detected in 115 stool samples (39.8%) tested for rotavirus. Four rotavirus-positive samples were found to bear G10P[6] specificity by reverse-transcription polymerase chain reaction, polymerase chain reaction-enzyme-linked immunosorbent assay, and oligonucleotide microarray hybridization. Two of these strains further exhibited serotype G10 specificity by neutralization and subgroup II specificity by enzyme immunoassay and possessed long electropheretic patterns by polyacrylamide gel electrophoresis. Their VP7 genes shared a much closer nucleotide identity with other African human Gb strains (>97%) than with human Gb strain from Asia or South America (<86%) or animal strains (<85%). The VP8* genes of the Ghanaian G10 strains exhibited >94% identity to that of human P[6] virus strains and belonged to the P[6] lineage la. The deduced VP7 amino acid sequence showed that the Ghanaian strains were more closely related to human G10 strains than to animal Gb strains. The possession of the typical human subgroup II specificity and the P[6] specificity (frequently found in Ghana and the rest of Africa) and the marked similarity in the VP7 antigenic sites suggest that these G10 strains may have evolved through genetic reassortment between bovine and human strains. [ABSTRACT FROM AUTHOR]

Thirty-six of 37 rotavirus strains recovered from the diarrheal stools of 166 children <3 years of age in Burkina Faso were characterized at both the antigenic and molecular levels. The rotavirus strains were confirmed by polyacrylamide gel electrophoresis; 30 displayed predominantly short electropherotype patterns, and 6 had a long RNA pattern. The strains were subgrouped by monoclonal antibody enzyme immunoassay for VP6 and were typed as subgroup I (29 of 30 short rotavirus strains) and subgroup II (5 of 6 long strains). The VP7 serotyping and genotyping showed that all 6 viruses with long electropherotype patterns were G1. The short strains were determined: to be VP7 serotype G2 by reverse-transcription polymerase chain reaction (PCR) in 27 strains and nucleic acid sequencing of selected strains, although only 1 reacted with the G2-specific monoclonal antibodies. Finally, the short patterns were shown by the PCR genotyping method to be VP4 genotype P[6], and the long patterns were shown to be P[8]. The predominant strain found in Burkina Faso in this small study was an unusual G2P[6] strain that showed a short RNA electropherotype and VP6 subgroup I specificity and failed to react with a panel of G2-specific monoclonal antibodies. [ABSTRACT FROM AUTHOR]

In this study, we characterized human rotavirus strains recovered from infants and young children with acute diarrhea in Abidjan, Cote d'Ivoire, during 2000-2004. In total, 719 fecal specimens were collected from children aged 1-60 months with acute infantile gastroenteritis. Examination with a commercial enzyme-linked immunosorbent assay showed the presence of group A rotavirus antigen in 208 diarrheal specimens (28.9%). Polyacrylamide gel electrophoresis of the RNA extracted from rotavirus-positive stools yielded a variety of "long" and "short" RNA electropherotypes, which were used to help select strains for VP4 and VP7 genotyping. VP7 genotype G1 strains were circulating most commonly during the study period (53%), followed by G2 (22%) and G3 (5%) strains. Strains with multiple VP7 genotype reactivity were observed in 7.6% of specimens, and a similar number (8%) could not be typed at all. VP4 P[6] and P[8] strains circulated at similar levels (33%). Strains demonstrating multiple VP4 types were quite common (9%); however, 20% of the strains were untypeable by the methods used. Rotavirus strain diversity in Cote d'Ivoire was similar to that observed in other West African countries. [ABSTRACT FROM AUTHOR]

During routine rotavirus surveillance projects in Cameroon and Cote d'Ivoire, 2 fecal samples collected from 2 children <5 years of age who presented with symptoms of gastroenteritis were found to give anomalous G typing results. These specimens were strongly rotavirus positive by enzyme immunoassay, displayed VP6 subgroup II specificity and long RNA electropherotypes, and were typed as rotavirus serotype G2 with monoclonal antibodies. In addition, the strains were typed as rotavirus VP7 genotype G3 and VP4 genotype P[8] by reverse-transcription polymerase chain reaction. Further investigation of the polymerase chain reaction G-typing results with a second set of primers revealed that the specimens were not genotype G3, and both samples were sequenced to elucidate the problem. Both strains were found to be genotype Gb by nucleotide sequence. Comparison of nucleotide and amino acid sequences and phylogenetic analysis of the African G10 strains revealed that these strains are closely related to the human G10 strains that were detected during the 2001-2003 rotavirus season in Ghana. The detection of G10 rotavirus in Africa adds to the global distribution of this strain and strengthens the need to continue strain surveillance in developing countries to understand the extent of strain distribution and diversity. [ABSTRACT FROM AUTHOR]

Rotavirus remains a priority candidate for vaccine development, because it is the major cause of viral diarrhea in children worldwide. This study characterized rotavirus strains in 195 stool specimens collected from children <5 years of age with diarrhea, in the Southwest Province and Western Province of Cameroon during 1999- 2000. The predominant G type was G1 (detected in 44.9% of specimens) and the most predominant P type was P[8] (in 82.7%). The most common G-P combination detected was G1P[8] (in 37.1% of specimens), followed by G9P[8] (in 14%). Rotavirus strains with unusual G-P combinations, such as G1P[4], G2P[8], G8P[8], G9P[4], G5P[8], and G10P[8], were also observed in significant numbers. Analysis of the age distribution showed that G1P[8] was found circulating in all age groups except in infants <6 months old. Strains G2P[4] and G3P[8] were identified in children >37 months and 19-24 months of age, respectively. Strain G9P[8] was found circulating among children >25 months of age. Unusual strains and mixed infections were found circulating in the different age groups, albeit at lower levels. The high prevalence of mixed infections and diversity of rotavirus strains detected in this first study based on genotyping of Cameroonian strains reinforce the need to continue with surveillance programs in Africa, where a high diversity of strains has been reported. [ABSTRACT FROM AUTHOR]

Background. Nigeria has recently been ranked third among the 10 countries with the greatest number of rotavirus disease-associated deaths per year. Estimates attribute up to 33,000 deaths annually to rotavirus disease in Nigerian children <5 years old. Although the introduction of the new oral, live attenuated rotavirus vaccines may not occur for another 4-6 years in developing countries, background data on burden of disease, cost of rotavirus disease, and characterization of circulating strains is required to hasten this introduction to children who would clearly benefit from the intervention. Methods. Between July 2002 and July 2004, fecal specimens were collected from 869 infants and young children <5 years of age presenting with diarrhea in Kaduna, Kebbi, Sokoto, and Zamfara states in northwestern Nigeria. In addition, 194 control specimens were also collected from children matched for age. Specimens were screened for the presence of rotavirus antigens. Rotavirus-positive specimens were further analyzed to determine electro- pherotype, subgroup specificity, and G and P genotypes. Results. Rotavirus was detected in 18% of children with diarrhea and 7.2% of the age-matched case control subjects. The highest rotavirus burden was detected in children aged <6 months. The majority of the rotavirus-positive specimens revealed viruses of long electropherotypes, subgroup II specificity, and G1P[8] genotypes. Furthermore, more than a quarter of specimens (37%) displayed mixed G and P genotypes, and almost a third could not be genotyped. Conclusions. The high numbers of mixed rotavirus infections highlight the multitude of enteric pathogens to which children in African countries are exposed. Data on circulating rotavirus strains serve to inform African government officials to the serious health threat posed by rotavirus in their respective countries and to document the diversity of strains before vaccine introduction. [ABSTRACT FROM AUTHOR]

Between July and October of 2003, 2004, and 2005, outbreaks of acute gastroenteritis occurred among children <5 years of age in Kinshasa, Democratic Republic of the Congo. Stool specimens (67 in 2003, 108 in 2004, and 116 in 2005) were collected and screened for rotaviruses using either latex agglutination (Diarlex LAA; Orion Diagnostics) or enzyme immunoassay (IDELA; DakoCytomation). The molecular characteristics of the rotavirus strains were then determined. Group A rotavirus was detected in 195 (76%) of 258 stool specimens. Polyacrylamide gel electrophoresis was used to observe the 11 rotavirus double-stranded RNA segments in 83% of the 195 rotavirus-positive specimens. Six rotavirus group A electropherotypic patterns were noted, predominantly within the short classic pattern (111 [69%]) and the long pattern (37 [23%]). Mixed patterns were noted in the 14 remaining specimens (9%). Of the 29 samples subjected to subgrouping VP6 enzyme immunoassay, subgroup I predominated. Some of the specimens collected in 2003 (n = 26), 2004 (n = 38), and 2005 (n = 52) were analyzed by reverse-transcription polymerase chain reaction, which showed that t G8P[6] and G8P[8] strains predominated in 2003, and GIP[6] strains with short electropherotypic patterns predominated in 2004 and 2005. The emergence in Kinshasa of G8 serotypes, unusually associated with the P[6] genotype, as well as uncommon G1 rotavirus strains showing a short RNA pattern, is significant in relation to the introduction of a rotavirus vaccine and underscores the need for continued rotavirus serotype surveillance in the Democratic Republic of the Congo. [ABSTRACT FROM AUTHOR]

Rotavirus infection is a major cause of diarrhea! illness and hospitalization in children <5 years old in Kenya and has been described in various settings and locations across the country and for different time points. In this study, we expand on the molecular characterization of rotavirus strains collected in Nairobi and Kisumu, Kenya, between 2000 and 2002. Rotavirus strains were typed by reverse-transcription polymerase chain reaction and characterized using VP6 monoclonal antibodies and RNA electrophoresis of the viral genome. A large proportion of specimen~ could not be genotyped; 41% did not produce a G type result, and 43% did not produce a P type result. Of the strains that could be genotyped, G1P[8] strains were predominant, followed by G2P[4] strains. In addition, G8 and G9 strains were seen in similar proportions Interestingly, the G and P combinations were more diverse among G8 and G9 rotavirus strains, suggesting the recent introduction of these strains into the human population. These observations are a link between the occasional observation of G8 and G9 strains at the turn of the century and the high predominance of G9P[8] strains observed in Kenya in 2005. [ABSTRACT FROM AUTHOR]

Background. The effectiveness of rotavirus vaccines will be dependent on the immunity conferred against prevalent and emergent variants causing severe diarrhea! disease. Longitudinal surveillance of disease-causing strains is a prerequisite to intervention. Methods. Molecular characterization was conducted on rotavirus-positive stool samples from children admitted with diarrhea to a rural district hospital during 2002-2004. Extracted viral RNA was separated by polyacrylamide gel electrophoresis, and rotavirus VP4 (P types) and VP7 (G types) specificities were determined. Results. Among 558 investigated cases, the predominant genotype was P[8]G1 (42%), followed by P[8]G9 (15%), P[4]G8 (7%), P[6]G8 (6%), and P[8]G8 (4%), with 10% mixed strains. Overall, there were 6 different P types and 7 G types. No association was identified between genotype and child age, sex, or severity of diarrhea. The P and G genotypes and polyacrylamide gel electropherotypes showed significant temporal variation in frequency: P[8]G1 decreased from 51% (95% confidence interval [CI], 43%-58%) in 2002 to 30% (95% CI, 24%- 37%) in 2004, and P[4]G8 increased from 2% (95% CI, 0%-5%) in 2002 to 13% (95% CI, 9%-19%). Quarterly data revealed seasonally endemic and emergence and/or decay patterns. Conclusions. Our study of rotavirus strains causing severe diarrhea in rural Kenyan children showed a predominance of P[8]G1 and confirms the importance of G8 and G9 strains in sub-Saharan Africa. Considerable genetic diversity of rotavirus strains was observed, including substantial mixed and unusual types, coupled with significant temporal strain variation and emergence. These results warn of variable vaccine efficacy and the need for long-term surveillance of circulating rotavirus genotypes. [ABSTRACT FROM AUTHOR]

Rotavirus infection is the most common cause of severe dehydrating gastroenteritis in infants and young children and remains a significant clinical problem worldwide. The severity and the burden of rotavirus disease could be reduced through the implementation of an effective vaccine. The aim of this study was to characterize rotavirus strains circulating in the local community as part of an ongoing hospital burden of disease study when a G1P[8] rotavirus vaccine candidate was being evaluated in the same community. From 2003 through 2006, 729 rotavirus-positive stool specimens were collected from children <5 years of age who were treated for diarrhea at Dr George Mukhari Hospital, Ga-Rankuwa, South Africa. Molecular characterization of the strains was performed by polyacrylamide gel electrophoresis and genotyping of the VP4 and VP7 alleles using well-established seminested multiplex reverse-transcription polymerase chain reaction methods. In 2003, 62% of strains exhibited the short rotavirus electropherotype, and the most common rotavirus strain was G2P[4]. In subsequent years, predominant rotavirus strains included G1P[8] and G1P[6] in 2004, G3P[8] and G3P[6] in 2005, and G1P[8] in 2006. For the 4 years of the study, rotavirus strains with P[6] genotype were detected in 25% of all rotavirus-positive specimens. In addition, unusual G12P[6] and G8 strains were detected at a low frequency. These results reflect the diversity of rotavirus strains circulating in South African communities. [ABSTRACT FROM AUTHOR]

Acute gastroenteritis caused by rotavirus infection is an important cause of morbidity and mortality among infants and young children in Africa. From 1997 through 2007, we enrolled 3740 children <5 years of age with acute gastroenteritis who received hospital care at the Queen Elizabeth Central Hospital in Blantyre, Malawi. Group A rotavirus was detected in fecal specimens by enzyme immunoassay. Rotavirus strains were characterized for VP7 (G) and VP4 (P) types with use of reverse-transcription polymerase chain reaction. Overall, rotavirus was detected in one-third of children. The median age of children with rotavirus gastroenteritis was 7.8 months, compared with 10.9 months for those without rotavirus in stool specimens (P< .001). Rotavirus circulated throughout the year, with the detection proportion greatest during the dry season (from May through October). A total of 15 single rotavirus strain types were detected during the study period, with genotypes P[8]G1, P[6]G8, P[4]G8, P[6]G1, P[8]G3, and P[6]G9 comprising 83% of all strains characterized. Serotype G12 was detected for the first time in Blantyre during the final 2 years of study. Zoonotic transmission and viral reassortment contributed to the rich diversity of strains identified. Current rotavirus vaccines have the potential to greatly reduce the rotavirus disease burden in Malawi, but they will be required to protect against a broad range of rotavirus serotypes in a young population with year-round rotavirus exposure. [ABSTRACT FROM AUTHOR]

Background. Namibia, located on the southwestern coast of southern Africa, is characterized by vast deserts, limited fresh water, and low population density. Mortality estimates among children <5 of age are 63 deaths per 1000 live-births, with diarrheal diseases contributing to 3% of these deaths. Data on the burden of rotavirus disease and circulating serotypes in Namibia are currently not available. Materials and methods. From May 1998 through December 1999, 815 stool specimens were collected from children <5 years of age who attended the Windhoek State Hospital, Windhoek, Namibia, for diarrhea. Specimens were screened for the presence of rotavirus antigens. Rotavirus-positive specimens were further analyzed to determine electropherotype, subgroup (SG) specificity, and G and P genotypes. Results. Rotavirus was detected in 113 (13.8%) of 815 specimens, with the majority of infections occurring in children <18 months of age. Strains bearing 1 long electropherotype, SGII, and G1P[8] or G1P[6] specificity predominated during the 20-month study period. In addition to the typical winter rotavirus season, a peak in rotavirus infection was also observed during the summer. Conclusions. Serotypes G1P[8], G1P[6], G1P[4], and G2P[4] were found throughout the study period, predominantly in children <18 months of age. The observed summer rotavirus peak coincided with increased rainfall in Namibia and an increase in the diversity of detected serotypes. During the October to December 1999 peak, 2 G9P[6] strains and 1 G8P[4] strain were identified. Expanded and updated information on prevalence of rotavirus infection, circulating serotypes, and burden of disease will be required to enable local government to make decisions on the implementation of rotavirus vaccination in Namibia. [ABSTRACT FROM AUTHOR]

Background. Data regarding the prevalence and molecular epidemiology of rotavirus infection in rural areas of Africa are limited. In this study the prevalence and genetic diversity of rotaviruses in a rural South African setting were investigated. Methods. During June 1998 to June 2000, 420 stool specimens were collected from children with acute diarrhea who visited primary health care clinics in the rural Vhembe region, Limpopo Province, South Africa. Group A rotaviruses were detected by enzyme-linked immunosorbent assay, and the G and P types were determined by reverse-transcription polymerase chain reaction. Results. Of the 420 specimens, 111 (26.4%) were positive for group A rotavirus; P[6]G1 strains predominated (32.4%), followed by P[8]G1 (13.5%), P[6]G9 (4.5%), P[4]G8 (3.6%), P[4]G1 (3.6%), P[6]G8 (3.6%), and P[6]G2 (2.7%). Dual infections, with >1 P type, were seen in 33 (37.1%) of the positive specimens. Conclusion. The unusual serotype and genotype combinations of rotavirus circulating in the rural communities of the Limpopo Province highlight the need for more studies to monitor the geographic distribution of rotavirus strains in rural African settings. [ABSTRACT FROM AUTHOR]