ABSTRACT
Globally, Group A rotavirus (RVA) is the leading cause of acute gastroenteritis in children under 5 years old, with Pakistan having the highest rates of RVA-related morbidity and mortality. The current study aims to determine the genetic diversity of rotavirus and evaluate the impact of Rotarix-vaccine introduction on disease epidemiology in Pakistan. A total of 4749 children, hospitalized with acute gastroenteritis between 2018 and 2020, were tested at four hospitals in Lahore and Karachi. Of the total, 19.3% (918/4749) cases were tested positive for RVA antigen, with the positivity rate varying annually (2018 = 22.7%, 2019 = 14.4%, 2020 = 20.9%). Among RVA-positive children, 66.3% were under 1 year of age. Genotyping of 662 enzyme-linked immuno sorbent assay-positive samples revealed the predominant genotype as G9P[4] (21.4%), followed by G1P[8] (18.9%), G3P[8] (11.4%), G12P[6] (8.7%), G2P[4] (5.7%), G2P[6] (4.8%), and 10.8% had mixed genotypes. Among vaccinated children, genotypes G9P[4] and G12P[6] were more frequently detected, whereas a decline in G2P[4] was observed. Phylogenetic analysis confirmed the continued circulation of indigenous genotypes detected earlier in the country except G9 and P[6] strains. Our findings highlight the predominance of G9P[4] genotype after the vaccine introduction thus emphasizing continual surveillance to monitor the disease burden, viral diversity, and their impact on control of rotavirus gastroenteritis in children.
Subject(s)
Gastroenteritis , Genotype , Phylogeny , Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Vaccines, Attenuated , Humans , Rotavirus/genetics , Rotavirus/isolation & purification , Rotavirus/classification , Gastroenteritis/virology , Gastroenteritis/epidemiology , Rotavirus Infections/virology , Rotavirus Infections/epidemiology , Rotavirus Infections/prevention & control , Rotavirus Vaccines/administration & dosage , Rotavirus Vaccines/immunology , Infant , Child, Preschool , Pakistan/epidemiology , Female , Male , Vaccines, Attenuated/immunology , Genetic Variation , Feces/virology , Acute Disease/epidemiologyABSTRACT
INTRODUCTION: Rotavirus is a leading cause of severe diarrheal disease and death in children under five years of age worldwide. Vaccination is one of the most important public health interventions to reduce this significant burden. AREAS COVERED: This literature review examined vaccination coverage, hospitalization rate, mortality, genotypic distribution, immunogenicity, cost-effectiveness, and risk versus benefit of rotavirus vaccination in children in South America. Nine out of twelve countries in South America currently include a rotavirus vaccine in their national immunization program with coverage rates in 2022 above 90%. EXPERT OPINION: Introduction of the rotavirus vaccination has led to a marked reduction in hospitalizations and deaths from diarrheal diseases in children under 5 years, particularly infants under 1 year, in several South American countries. In Brazil, hospitalizations decreased by 59% and deaths by 21% (30-38% in infants). In Peru, hospitalizations in infants fell by 46% and deaths by 37% (56% in infants). Overall, data suggest that rotavirus vaccination has reduced rotavirus deaths by 15-50% in various South American countries. There is some evidence that immunity wanes after the age of 1-year old. Ongoing surveillance of vaccine coverage and changes in morbidity and mortality is important to maximize protection against this disease.
Subject(s)
Diarrhea , Hospitalization , Immunization Programs , Rotavirus Infections , Rotavirus Vaccines , Humans , Rotavirus Vaccines/administration & dosage , Rotavirus Vaccines/immunology , Rotavirus Infections/prevention & control , Rotavirus Infections/epidemiology , Diarrhea/prevention & control , Diarrhea/epidemiology , Diarrhea/virology , Infant , Hospitalization/statistics & numerical data , South America/epidemiology , Child, Preschool , Vaccination/statistics & numerical data , Cost-Benefit Analysis , Rotavirus/immunology , Vaccination Coverage/statistics & numerical data , Cost of IllnessABSTRACT
G3 rotaviruses rank among the most common rotavirus strains worldwide in humans and animals. However, despite a robust long-term rotavirus surveillance system from 1997 at Queen Elizabeth Central Hospital in Blantyre, Malawi, these strains were only detected from 1997 to 1999 and then disappeared and re-emerged in 2017, 5 years after the introduction of the Rotarix rotavirus vaccine. Here, we analysed representative twenty-seven whole genome sequences (G3P[4], n = 20; G3P[6], n = 1; and G3P[8], n = 6) randomly selected each month between November 2017 and August 2019 to understand how G3 strains re-emerged in Malawi. We found four genotype constellations that were associated with the emergent G3 strains and co-circulated in Malawi post-Rotarix vaccine introduction: G3P[4] and G3P[6] strains with the DS-1-like genetic backbone genes (G3-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2 and G3-P[6]-I2-R2-C2-M2-A2-N2-T2-E2-H2), G3P[8] strains with the Wa-like genetic backbone genes (G3-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1), and reassortant G3P[4] strains consisting of the DS-1-like genetic backbone genes and a Wa-like NSP2 (N1) gene (G3-P[4]-I2-R2-C2-M2-A2-N1-T2-E2-H2). Time-resolved phylogenetic trees demonstrated that the most recent common ancestor for each ribonucleic acid (RNA) segment of the emergent G3 strains was between 1996 and 2012, possibly through introductions from outside the country due to the limited genetic similarity with G3 strains which circulated before their disappearance in the late 1990s. Further genomic analysis revealed that the reassortant DS-1-like G3P[4] strains acquired a Wa-like NSP2 genome segment (N1 genotype) through intergenogroup reassortment; an artiodactyl-like VP3 through intergenogroup interspecies reassortment; and VP6, NSP1, and NSP4 segments through intragenogroup reassortment likely before importation into Malawi. Additionally, the emergent G3 strains contain amino acid substitutions within the antigenic regions of the VP4 proteins which could potentially impact the binding of rotavirus vaccine-induced antibodies. Altogether, our findings show that multiple strains with either Wa-like or DS-1-like genotype constellations have driven the re-emergence of G3 strains. The findings also highlight the role of human mobility and genome reassortment events in the cross-border dissemination and evolution of rotavirus strains in Malawi necessitating the need for long-term genomic surveillance of rotavirus in high disease-burden settings to inform disease prevention and control.
ABSTRACT
Oral rotavirus vaccines show diminished immunogenicity in low-resource settings where rotavirus burden is highest. This study assessed the safety and immune boosting effect of a third dose of oral ROTARIX® (GlaxoSmithKline) vaccine administered at 9 months of age. A total of 214 infants aged 6 to 12 weeks were randomised to receive two doses of ROTARIX® as per standard schedule with other routine vaccinations or an additional third dose of ROTARIX® administered at 9 months old concomitantly with measles/rubella vaccination. Plasma collected pre-vaccination, 1 month after first- and second-dose vaccination, at 9 months old before receipt of third ROTARIX® dose and/or measles/rubella vaccination, and at 12 months old were assayed for rotavirus-specific IgA (RV-IgA). Geometric mean RV-IgA at 12 months of age and the incidence of clinical adverse events 1 month following administration of the third dose of ROTARIX® among infants in the intervention arm were compared between infants in the two arms. We found no significant difference in RV-IgA titres at 12 months between the two arms. Our findings showed that rotavirus vaccines are immunogenic in Zambian infants but with modest vaccine seroconversion rates in low-income settings. Importantly, however, a third dose of oral ROTARIX® vaccine was shown to be safe when administered concomitantly with measles/rubella vaccine at 9 months of age in Zambia. This speaks to opportunities for enhancing rotavirus vaccine immunity within feasible schedules in the national immunization program.
ABSTRACT
Rotavirus vaccination has been shown to reduce rotavirus burden in many countries, but the long-term magnitude of vaccine impacts is unclear, particularly in low-income countries. We use a transmission model to estimate the long-term impact of rotavirus vaccination on deaths and disability adjusted life years (DALYs) from 2006 to 2034 for 112 low- and middle-income countries. We also explore the predicted effectiveness of a one- vs two- dose series and the relative contribution of direct vs indirect effects to overall impacts. To validate the model, we compare predicted percent reductions in severe rotavirus cases with the percent reduction in rotavirus positivity among gastroenteritis hospital admissions for 10 countries with pre- and post-vaccine introduction data. We estimate that vaccination would reduce deaths from rotavirus by 49.1 % (95 % UI: 46.6-54.3 %) by 2034 under realistic coverage scenarios, compared to a scenario without vaccination. Most of this benefit is due to direct benefit to vaccinated individuals (explaining 69-97 % of the overall impact), but indirect protection also appears to enhance impacts. We find that a one-dose schedule would only be about 57 % as effective as a two-dose schedule 12 years after vaccine introduction. Our model closely reproduced observed reductions in rotavirus positivity in the first few years after vaccine introduction in select countries. Rotavirus vaccination is likely to have a substantial impact on rotavirus gastroenteritis and its mortality burden. To sustain this benefit, the complete series of doses is needed.
Subject(s)
Gastroenteritis , Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Humans , Infant , Rotavirus Infections/prevention & control , Gastroenteritis/prevention & control , Vaccination , Cost-Benefit AnalysisABSTRACT
Sicily was the first Italian region to introduce rotavirus (RV) vaccination with the monovalent G1P[8] vaccine Rotarix® in May 2012. In this study, the seasonal distribution and molecular characterization of RV strains detected over 19 years were compared to understand the effect of Rotarix® on the evolutionary dynamics of human RVs. A total of 7846 stool samples collected from children < 5 years of age, hospitalized with acute gastroenteritis, were tested for RV detection and genotyping. Since 2013, vaccine coverage has progressively increased, while the RV prevalence decreased from 36.1% to 13.3% with a loss of seasonality. The local distribution of RV genotypes changed over the time possibly due to vaccine introduction, with a drastic reduction in G1P[8] strains replaced by common and novel emerging RV strains, such as equine-like G3P[8] in the 2018−2019 season. Comparison of VP7 and VP4 amino acid (aa) sequences with the cognate genes of Rotarix® and RotaTeq® vaccine strains showed specific aa changes in the antigenic epitopes of VP7 and of the VP8* portion of VP4 of the Italian RV strains. Molecular epidemiological surveillance data are required to monitor the emergence of novel RV strains and ascertain if these strains may affect the efficacy of RV vaccines.
ABSTRACT
BACKGROUND: Rotarix (GlaxoSmithKline) oral rotavirus vaccine is licensed as 2 doses in the first 6 months of life. In settings with high child mortality rates, clinical protection conferred by 2 doses of Rotarix is reduced. We assessed vaccine immune response when an additional dose of Rotarix was given to Australian Aboriginal children 6 toâ <12 months old. METHODS: ORVAC is a 2-stage, double-blind, randomized, placebo-controlled trial. Australian Aboriginal children 6 toâ <12 months old who had received 1 or 2 prior doses of Rotarix rotavirus vaccine were randomized 1:1 to receive an additional dose of Rotarix or matched placebo. The primary immunological end point was seroresponse defined as an anti-rotavirus immunoglobulin A levelâ ≥20 AU/mL, 28-56 days after the additional dose of Rotarix or placebo. RESULTS: Between March 2018 and August 2020, a total of 253 infants were enrolled. Of these, 178 infants (70%) had analyzable serological results after follow-up; 89 were randomized to receive Rotarix, and 89 to receive placebo. The proportion with seroresponse was 85% after Rotarix compared with 72% after placebo. There were no occurrences of intussusception or any serious adverse events. CONCLUSIONS: An additional dose of Rotarix administered to Australian Aboriginal infants 6 toâ <12 months old increased the proportion with a vaccine seroresponse. CLINICAL TRIALS REGISTRATION: NCT02941107.
Subject(s)
Rotavirus Infections , Rotavirus Vaccines , Infant , Child , Humans , Rotavirus Infections/prevention & control , Australia , Vaccines, Attenuated , Antibodies, Viral , Double-Blind Method , Immunogenicity, VaccineABSTRACT
Globally, rotavirus (RV) is the leading cause of acute gastroenteritis (AGE) in young children under 5 years of age. Implementation of RV vaccination is expected to result in fewer cases of RV in the target population, but it is unknown if this also results in vaccine-induced virus strain replacement. Rotarix, a monovalent vaccine based on G1P[8] RV, was introduced in Norway in the children's immunization program in September 2014. The main aim of this study was to describe the diversity of RV circulating pre and post introduction of the RV vaccine in Norway and investigate changes in genotype distribution during the first 4 years after implementation. A total of 1108 samples were collected from children under 5 years enrolled with AGE from five large hospitals in Norway and were analyzed for RV by enzyme immunoassay (EIA). All positive results were genotyped by multiplex semi-nested reverse transcription PCR for identification of G and P types. In total, 487 of the 1108 (44%) samples, collected from the enrolled children, were positive for RV by EIA method which were further genotyped. G1P[8] was found to be the most common type of RV pre and post RV vaccine implementation followed by G9P[8]. There were neither geographical nor temporal differences in genotype dominance. Also, no apparent changes were shown in the genotype distribution in the postvaccine era for years from 2015 to 2018. In 21.4% of the cases, vaccine strains were detected. Continuous RV genotype surveillance is vital for assessing the effectiveness of a vaccine program and monitoring for any emergence of vaccine-escape strains. Genotyping is also necessary to detect vaccine strains to avoid reporting false-positive cases of active RV infection in newly vaccinated cases.
Subject(s)
Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Antigens, Viral/genetics , Child , Child, Preschool , Feces , Genetic Variation , Genotype , Humans , Infant , Rotavirus/genetics , Rotavirus Infections/epidemiology , Rotavirus Infections/prevention & control , VaccinationABSTRACT
Rotaviruses by virtue of its segmented genome generate numerous genotypes. G1P[8] is the most common genotype reported globally. We intend to identify the evolutionary differences among G1P[8] strains from the study with vaccine strains. Stool samples collected from children <5 years were screened for rotavirus antigen by enzyme linked immunosorbent assay. The samples that tested positive for rotavirus were subjected to VP7 and VP4 semi-nested RT-PCR. Sanger sequencing was performed in randomly chosen VP7 and VP4 rotavirus strains. Phylogenetic analysis showed less homology between study strains and vaccine strains and they were placed in different lineages. The VP7 and VP4 proteins of rotavirus were analyzed by two different platforms to identify the amino acid substitutions in the epitope regions. Nine amino acid substitutions with respect to Rotarix®, RotaTeq® and Rotasiil®-V66A, A/T68S, Q72R, N94S, D100E, T113I, S123N, M217T, and I281T were observed in VP7. There were five amino acid substitutions-S145G, N/D195G, N113D, N/I78T, E150D in VP4 (VP8 portion) with respect to Rotarix® and RotaTeq® vaccine strains. M217T substitution in VP7 (epitope 7-2) and N113D, D195G substitution in VP4 (epitope 8-3, 8-1) confer changes in polarity/electrical charge with respect to vaccine strains, thus indicating the need for continued surveillance.
Subject(s)
Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Antigens, Viral/genetics , Capsid Proteins/genetics , Child , Epitopes/genetics , Genotype , Humans , India/epidemiology , PhylogenyABSTRACT
ABSTRACT: This report from the Australian Rotavirus Surveillance Network describes the circulating rotavirus genotypes identified in children and adults during the period 1 January - 31 December 2020. During this period, 229 faecal specimens were referred for rotavirus G- and P- genotype analysis, including 189 samples that were confirmed as rotavirus positive. Of these, 98/189 were wildtype rotavirus strains and 86/189 were identified as vaccine-like. A further five samples could not be determined as wildtype or vaccine-like due to poor sequence reads. Genotype analysis of the 98 wildtype rotavirus samples from both children and adults demonstrated that G3P[8] was the dominant genotype identified for the third consecutive year, identified in 27.6% of samples, followed by G2P[4] in 20.4% of samples. Forty-six percent of rotavirus positive samples received were identified as vaccine-like, highlighting the need to add caution in interpreting rotavirus positive results in children aged 0-8 months. This surveillance period was significantly impacted by the coronavirus disease 2019 ( COVID-19 ) pandemic. The reduction in rotavirus notifications reflected reduced healthcare-seeking behaviour and a decrease in community spread, with 'community lockdowns', school and day-care centre closure and improved compliance with hand hygiene. Fewer stool samples were collected throughout Australia during this period. There was a reluctance to store samples at collaborating laboratories and uncertainties regarding the safety and feasibility of the transport of samples to the central laboratory during the closure of state and territory borders. Systems have now been adapted to manage and send biological samples safely and confidently. Ongoing rotavirus surveillance is crucial to identify changes in genotypic patterns and to provide diagnostic laboratories quality assurance by reporting incidences of wildtype, vaccine-like, or false positive rotavirus results.
Subject(s)
COVID-19 , Gastroenteritis , Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Adult , Australia/epidemiology , Child , Communicable Disease Control , Humans , Population Surveillance , Rotavirus/genetics , Rotavirus Infections/epidemiology , Rotavirus Infections/prevention & control , SARS-CoV-2ABSTRACT
Rotarix® vaccine was implemented nationwide in Zambia in 2013. In this study, four unusual strains collected in the post-vaccine period were subjected to whole genome sequencing and analysis. The four strains possessed atypical genotype constellations, with at least one reassortant genome segment within the constellation. One of the strains (UFS-NGS-MRC-DPRU4749) was genetically and phylogenetically distinct in the VP4 and VP1 gene segments. Pairwise analyses demonstrated several amino acid disparities in the VP4 antigenic sites of this strain compared to that of Rotarix®. Although the impact of these amino acid disparities remains to be determined, this study adds to our understanding of the whole genomes of reassortant strains circulating in Zambia following Rotarix® vaccine introduction.
Subject(s)
Genome, Viral , Reassortant Viruses/genetics , Rotavirus Infections/virology , Rotavirus/genetics , Antigens, Viral/chemistry , Antigens, Viral/immunology , Capsid Proteins/chemistry , Capsid Proteins/genetics , Capsid Proteins/immunology , Epitopes , Female , Genotype , Humans , Infant , Male , Phylogeny , Rotavirus Vaccines , Sequence Analysis, DNA , Vaccines, Attenuated , Viral Proteins/chemistry , Viral Proteins/genetics , Viral Proteins/immunology , Whole Genome Sequencing , ZambiaABSTRACT
While rotavirus vaccine programs effectively protect against severe rotavirus gastroenteritis, rotavirus vaccine strains have been identified in the stool of vaccinated children and their close contacts suffering from acute gastroenteritis. The prevalence of vaccine strains, the emergence of vaccine-derived strains, and their role in acute gastroenteritis are not well studied. We developed a locked nucleic acid reverse transcription real-time PCR assay (LNA-RTqPCR) to detect the monovalent rotavirus vaccine (RV1) Rotarix nonstructural protein 2 (NSP2) in children with acute gastroenteritis and healthy controls, and validated it using sequence-confirmed RV1 strains. The association between RV1-derived strains and gastroenteritis was determined using logistic regression. The new assay exhibited 100% (95% CI 91.7%, 100%) diagnostic sensitivity and 99.4% (95% CI 96.2%, 100%) diagnostic specificity, with a detection limit of 9.86 copies/reaction and qPCR efficiency of 99.7%. Using this assay, we identified the presence of RV1-derived NSP2 sequences in 7.7% of rotavirus gastroenteritis cases and 98.6% of rotavirus-positive healthy children (94.4% had previously received the RV1). Among gastroenteritis cases, those whose stool contained RV1-derived strains had milder gastroenteritis symptoms compared to that of natural rotavirus infections. We observed no significant association between RV1-derived strains and gastroenteritis (odds ratio [OR] 0.98; 95% CI 0.60, 1.72). Our study demonstrated that the new assay is suitable for monitoring RV1-derived rotavirus strain circulation and that the RV1-derived strains are not associated with development of gastroenteritis symptoms.
Subject(s)
Gastroenteritis , Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Alberta/epidemiology , Child , Gastroenteritis/epidemiology , Humans , Infant , Rotavirus/genetics , Rotavirus Infections/epidemiology , Vaccines, AttenuatedABSTRACT
The human rotavirus vaccine (HRV; Rotarix, GSK) is available as liquid (Liq) and lyophilized (Lyo) formulations, but only Lyo HRV is licensed in India. In this phase III, randomized, open-label trial (NCT02141204), healthy Indian infants aged 6-10 weeks received 2 doses (1 month apart) of either Liq HRV or Lyo HRV. Non-inferiority of Liq HRV compared to Lyo HRV was assessed in terms of geometric mean concentrations (GMCs) of anti-RV immunoglobulin A (IgA), 1-month post-second dose (primary objective). Reactogenicity/safety were also evaluated. Seroconversion was defined as anti-RV IgA antibody concentration ≥20 units [U]/mL in initially seronegative infants (anti-RV IgA antibody concentration <20 U/mL) or ≥2-fold increase compared with pre-vaccination concentration in initially seropositive infants. Of the 451 enrolled infants, 381 (189 in Liq HRV and 192 in Lyo HRV group) were included in the per-protocol set. The GMC ratio (Liq HRV/Lyo HRV) was 0.93 (95% confidence interval [CI]: 0.65-1.34), with the lower limit of the 95% CI reaching ≥0.5, the pre-specified statistical margin for non-inferiority. In the Liq HRV and Lyo HRV groups, 42.9% and 44.3% (baseline) and 71.4% and 73.4% (1-month post-second dose) of infants had anti-RV IgA antibody concentration ≥20 U/mL, and overall seroconversion rates were 54.5% and 50.0%. Incidences of solicited and unsolicited adverse events were similar between groups and no vaccine-related serious adverse events were reported. Liq HRV was non-inferior to Lyo HRV in terms of antibody GMCs and showed similar reactogenicity/safety profiles, supporting the use of Liq HRV in Indian infants.
PLAIN LANGUAGE SUMMARYWhat is the context?Rotavirus is the most common cause of acute gastronenteritis and contributes to the high number of hospitalizations and deaths in young children worldwide.Vaccination against rotavirus has led to a significant decrease in rotavirus-related infections.The human rotavirus vaccine Rotarix (GSK) is currently used as a liquid or lyophilized formulation.In clinical trials conducted in European and North American infants, the liquid vaccine showed ability to induce immune response and safety comparable to the lyophilized formulation.Only the lyophilized vaccine is currently marketed in india.What is new?We compared the 2-dose liquid and lyophilized human rotavirus vaccines in indian infants in a phase III clinical trial:The ability to induce immune response for thw liquid formulation was not inferior to that observed for the lyophilized vaccine.The safety profiles of the 2 formulations were comparable.Why is this important?This study shows that the liquid human rotavirus vaccine can be administrated to infants from india.
Subject(s)
Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Antibodies, Viral , Humans , Immunogenicity, Vaccine , Immunoglobulin A , Infant , Rotavirus Infections/prevention & control , Rotavirus Vaccines/adverse effects , Vaccines, AttenuatedABSTRACT
BACKGROUND: Despite the global roll-out of rotavirus vaccines (RotaTeq/Rotarix / ROTAVAC/Rotasiil), mortality and morbidity due to group A rotavirus (RVA) remains high in sub-Saharan Africa, causing 104,000 deaths and 600,000 hospitalizations yearly. In Cameroon, Rotarix™ was introduced in March 2014, but, routine laboratory diagnosis of rotavirus infection is not yet a common practice, and vaccine effectiveness studies to determine the impact of vaccine introduction have not been done. Thus, studies examining RVA prevalence post vaccine introduction are needed. The study aim was to determine RVA prevalence in severe diarrhoea cases in Littoral region, Cameroon and investigate the role of other diarrheagenic pathogens in RVA-positive cases. METHODS: We carried out a study among hospitalized children < 5 years of age, presenting with acute gastroenteritis in selected hospitals of the Littoral region of Cameroon, from May 2015 to April 2016. Diarrheic stool samples and socio-demographic data including immunization and breastfeeding status were collected from these participating children. Samples were screened by ELISA (ProSpecT™ Rotavirus) for detection of RVA antigen and by gel-based RT-PCR for detection of the VP6 gene. Co-infection was assessed by multiplexed molecular detection of diarrheal pathogens using the Luminex xTAG GPP assay. RESULTS: The ELISA assay detected RVA antigen in 54.6% (71/130) of specimens, with 45, positive by VP6 RT-PCR and 54, positive using Luminex xTAG GPP. Luminex GPP was able to detect all 45 VP6 RT-PCR positive samples. Co-infections were found in 63.0% (34/54) of Luminex positive RVA infections, with Shigella (35.3%; 12/34) and ETEC (29.4%; 10/34) detected frequently. Of the 71 ELISA positive RVA cases, 57.8% (41/71) were fully vaccinated, receiving two doses of Rotarix. CONCLUSION: This study provides insight on RVA prevalence in Cameroon, which could be useful for post-vaccine epidemiological studies, highlights higher than expected RVA prevalence in vaccinated children hospitalized for diarrhoea and provides the trend of RVA co-infection with other enteric pathogens. RVA genotyping is needed to determine circulating rotavirus genotypes in Cameroon, including those causing disease in vaccinated children.
Subject(s)
Antigens, Viral/isolation & purification , Capsid Proteins/isolation & purification , Coinfection/epidemiology , Diarrhea/virology , Rotavirus Infections/epidemiology , Rotavirus/genetics , Biological Assay , Cameroon/epidemiology , Child, Hospitalized , Child, Preschool , Coinfection/diagnosis , Enzyme-Linked Immunosorbent Assay , Female , Humans , Infant , Male , Prevalence , Reverse Transcriptase Polymerase Chain Reaction , Rotavirus Infections/diagnosis , Rotavirus Infections/drug therapy , Rotavirus Vaccines/therapeutic use , Vaccination , Vaccines, Attenuated/therapeutic useABSTRACT
Rotavirus A (RV) is the primary cause of gastroenteritis in children worldwide and a leading cause of gastroenteritis in children younger than three years, with a significant burden both globally and in Ireland. Rotavirus vaccine (Rotarix™) was introduced into Ireland in 2016. The aim of this study was to determine the diversity and frequency of, and predominant, RV genotypes, nosocomial acquisition, viral co-infections and severity of RV infection in Ireland in the post-vaccination year, from November 18th 2016 to November 18th 2017. The study included all children up to 3 years of age who had presented to Mayo University Hospital or were admitted with vomiting and diarrhoea, and had their stool tested for rotavirus and other viruses by real-time PCR in the National Virus Reference Laboratory. The Vesikari Scoring System was used to assess disease severity. The results showed that rotavirus was a leading cause of gastroenteritis (37 patients, 24.6 % of a total of 150 patients) and gastroenteritis-related hospitalisation (27 patients were admitted, 21 % of a total of 128 patients). Severe rotaviral gastroenteritis was noted in 78 % of all RV gastroenteritis (37 patients). The RV strain G1P[8], including the vaccine G1P[8] strain (Rotarix™), was the most predominant genotype (47 %), followed by G2P[4] (31 %), G4P[8] (8%), G12P[8] (8%) and G9P[8] (6%). RV co-infection with other viruses was detected in four cases (11 %), of whom three cases (75 %) were severe. Rotarix™ was detected in six vaccinated patients (35 %), 50 % were mild disease. Nosocomial infection was detected in one case. These results indicated that RV remained the leading cause of paediatric gastroenteritis during the post vaccination year in Ireland.
Subject(s)
Coinfection , Gastroenteritis , Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Child , Coinfection/epidemiology , Feces , Gastroenteritis/epidemiology , Genotype , Humans , Infant , Ireland/epidemiology , Prospective Studies , Rotavirus/genetics , Rotavirus Infections/epidemiology , Rotavirus Infections/prevention & control , Severity of Illness IndexABSTRACT
This study evaluated the long-term impact of rotavirus vaccination on prevalence, seasonality, and genotype distribution in Gwangju, Korea for 13 seasons. Rotavirus was identified using ELISA and then sequenced for G and P genotypes by Reverse Transcription Polymerase Chain Reactions for diarrhoeagenic patient specimens from local hospitals between January 2008 and August2020. Of 26,902 fecal samples, 2919 samples (10.9%) were ELISA positive. The prevalence declined from 16.3% in pre-vaccine era to 5.4% in post-vaccine era. In the pre-vaccine period, G1P[8] was the most common genotype, followed by G2P[4], G3P[8], and G9P[8], etc. In the transitional period, the proportion of G2P[4] became the dominant genotype and G1P[8] was still commonly identified. In contrast, the novel genotype G8P[8] was predominant in the post-vaccine period. Meanwhile, G2P[4] and G8P[8] were major genotypes in both Rotarix and RotaTeq groups. The substantial decline of G1P[8] prevalence, reemergence of G1P[8], G3P[8], and G2P[4] rotavirus strains, and surge of the rare G8P[8] after vaccine introduction were interesting points to note. The continuous surveillance on the genotypes of RV will be needed to understand rotavirus epidemiology and their evolutionary patterns, as caution is required when interpreting temporal changes in RV genotype dynamic.
ABSTRACT
The introduction of the rotavirus vaccine, Rotarix, into the Fiji National Immunisation Program in 2012 has reduced the burden of rotavirus disease and hospitalisations in children less than 5 years of age. The aim of this study was to describe the pattern of rotavirus genotype diversity from 2005 to 2018; to investigate changes following the introduction of the rotavirus vaccine in Fiji. Faecal samples from children less than 5 years with acute diarrhoea between 2005 to 2018 were analysed at the WHO Rotavirus Regional Reference Laboratory at the Murdoch Children's Research Institute, Melbourne, Australia, and positive samples were serotyped by EIA (2005-2006) or genotyped by heminested RT-PCR (2007 onwards). We observed a transient increase in the zoonotic strain equine-like G3P[8] in the initial period following vaccine introduction. G1P[8] and G2P[4], dominant genotypes prior to vaccine introduction, have not been detected since 2015 and 2014, respectively. A decrease in rotavirus genotypes G2P[8], G3P[6], G8P[8] and G9P[8] was also observed following vaccine introduction. Monitoring the rotavirus genotypes that cause diarrhoeal disease in children in Fiji is important to ensure that the rotavirus vaccine will continue to be protective and to enable early detection of new vaccine escape strains if this occurs.
ABSTRACT
ABSTRACT: This report, from the Australian Rotavirus Surveillance Program and collaborating laboratories Australia-wide, describes the rotavirus genotypes identified in children and adults with acute gastroenteritis during the period 1 January to 31 December 2018. During this period, 690 faecal specimens were referred for rotavirus G- and P- genotype analysis, including 607 samples that were confirmed as rotavirus positive. Of these, 457/607 were wild-type rotavirus strains and 150/607 were identified as rotavirus vaccine-like. Genotype analysis of the 457 wild-type rotavirus samples from both children and adults demonstrated that G3P[8] was the dominant genotype nationally, identified in 52% of samples, followed by G2P[4] (17%). The Australian National Immunisation Program, which previously included both RotaTeq and Rotarix vaccines, changed to Rotarix exclusively on 1 July 2017. Continuous surveillance is needed to identify if the change in vaccination schedule could affect rotavirus genotype distribution and diversity in Australia.
Subject(s)
Rotavirus Infections/epidemiology , Rotavirus Infections/prevention & control , Rotavirus Vaccines/immunology , Australia/epidemiology , Child, Preschool , Epidemiological Monitoring , Feces/virology , Female , Gastroenteritis/epidemiology , Gastroenteritis/virology , Genotype , Humans , Immunization Programs , Infant , Infant, Newborn , Male , Population Surveillance , Rotavirus/genetics , Rotavirus/immunology , Rotavirus Infections/virology , Rotavirus Vaccines/administration & dosage , Vaccines, AttenuatedABSTRACT
ABSTRACT: This report, from the Australian Rotavirus Surveillance Program and collaborating laboratories Australia-wide, describes the rotavirus genotypes identified in children and adults with acute gastroenteritis during the period 1 January to 31 December 2019. During this period, 964 faecal specimens had been referred for rotavirus G- and P- genotype analysis, including 894 samples that were confirmed as rotavirus positive. Of these, 724/894 were wild-type rotavirus strains and 169/894 were identified as vaccine-like. A single sample could not be determined as wild-type or vaccine-like due to poor sequencing. Genotype analysis of the 724 wild-type rotavirus samples from both children and adults demonstrated that G3P[8] was the dominant genotype nationally, identified in 46.7% of samples, followed by G2P[4] in 8.8% of samples. The Australian National Immunisation Program (NIP) changed to the exclusive use of Rotarix as of 1 July 2017. The NIP had previously included two live-attenuated oral vaccines: Rotarix (monovalent, human) and RotaTeq (pentavalent, human-bovine reassortant) in a state-based vaccine selection. Continuous surveillance is imperative to determine the effect of this change in rotavirus vaccine schedule on the genotype distribution and diversity in Australia.
Subject(s)
Immunization Programs/statistics & numerical data , Rotavirus Infections/epidemiology , Rotavirus Infections/prevention & control , Animals , Australia/epidemiology , Cattle , Child, Preschool , Epidemiological Monitoring , Feces/virology , Female , Gastroenteritis/epidemiology , Gastroenteritis/prevention & control , Gastroenteritis/virology , Humans , Infant , Infant, Newborn , Male , Population Surveillance , Rotavirus/genetics , Rotavirus/isolation & purification , Rotavirus Infections/virology , Rotavirus Vaccines/administration & dosage , Rotavirus Vaccines/immunology , Vaccines, AttenuatedABSTRACT
OBJECTIVES: Rotavirus (RV) genotypes vary geographically, and this can affect vaccine effectiveness (VE). This study investigated the genotype distribution of RV and explored VE before introducing the RV vaccine to the national immunization programme in Vietnam. METHODS: This hospital-based surveillance study was conducted at Children's Hospital 1, Ho Chi Minh City in 2013-2018. Stool samples and relevant data, including vaccination history, were collected from children aged <5 years who were hospitalized with gastroenteritis. RV was detected using enzyme immunoassays and then genotyped. Children aged ≥6 months were included in the VE analysis. RESULTS: Overall, 5176 children were included in this study. RV was detected in 2421 children (46.8%). RV positivity decreased over the study period and was associated with age, seasonality, location and previous vaccination. Among 1105 RV-positive samples, G3P[8] was the most prevalent genotype (43.1%), followed by G8P[8] (19.7%), G1P[8] (12.9%) and G2P[4] (12.9%). Overall VE was 69.7% [95% confidence interval (CI) 53.3-80.6%] in fully vaccinated children and 58.6% (95% CI 44.1-69.4%) in children who had received at least one dose of RV vaccine. VE was highest for G3P[8] (95% CI 75.1-84.5%) and lowest for G2P[4] (95% CI 32.4-57.2%). CONCLUSIONS: RV remains a major cause of acute gastroenteritis requiring hospitalization in southern Vietnam. The RV vaccine is effective, but its effectiveness varies with RV genotype.