Project description:Several studies report norovirus as the new leading cause of severe gastroenteritis in children after the global introduction of rotavirus vaccines. Burkina Faso introduced general rotavirus vaccination with the oral pentavalent vaccine RotaTeq in November 2013 and quickly reached a vaccine coverage of >90%. This study describes detection rates, clinical profiles and the molecular epidemiology of norovirus and rotavirus infections in 146 children aged <5 years with severe acute gastroenteritis in Ouagadougou, consecutively enrolled from a hospital between January 2015 and December 2015. Virus detection was performed with an antigen test or real-time polymerase chain reaction (PCR) and genotyping was performed by nucleotide sequencing or multiplex PCR. Rotavirus was found in 14% and norovirus in 20% of faecal samples. Norovirus infection was significantly more associated with severe dehydration compared to rotavirus (P < 0.001). Among genotyped norovirus samples 48% (12/25) belonged to GII.4 which caused significantly more diarrhoeal episodes than non-GII.4 genotypes (P = 0.01). The most common rotavirus genotypes were G2P[4] (30%), G12P[6] (25%) and G12P[8] (20%). Fifty percent of the rotavirus positive children were infected with fully or partly heterotypic strains. In conclusion, this study found a higher proportion of norovirus causing more severe symptoms in children with diarrhoea in Burkina Faso after the introduction of rotavirus vaccination.
Project description:BackgroundAcute gastroenteritis caused by bacteria, virus and parasite is an important cause of childhood morbidity and mortality in developing countries. Rotavirus and norovirus have been recognized as the most common pathogens causing acute gastroenteritis among children. However, there is still no valuable data about infections of rotavirus and norovirus in children in Ji'nan, an eastern city in China. The aims of the present study are to determine the incidence of rotavirus and norovirus associated acute gastroenteritis in Ji'nan among children, to characterize rotavirus and norovirus strains circulating during this period; and to provide useful epidemiological and clinical data.MethodsFecal specimens and clinical data were collected from 767 children (502 outpatients and 265 inpatients) under 5 years of age with acute diarrhea at Shandong University Qilu Hospital and Qilu children's Hospital in Ji'nan, China between February 2011 and January 2012. Virus RNA was extracted, amplified, electrophoresed, sequenced and phylogenetically analyzed to determine the prevalent genotypes. Chi-square and U test were used to compare characteristics of clinical manifestation in each group.ResultsOf the 767 specimens 263 (34.3%) were positive for rotavirus and 80 (10.4%) were positive for norovirus. Among 263 rotavirus positive cases, G3 (40.7%) was the most prevalent serotype, P[8] (46.8%) was the dominant genotype and G3P[8] (31.9%) was the most common combination. All of the norovirus strains belonged to GII genogroup including GII.3, GII.4 and GII.6, of which GII.4 (61.2%) was the predominant genotype. Phylogenetic analysis of the GII.4 sequences showed that 18 GII.4 strains belonged to GII.4 2004-2006 cluster and 31 GII.4 strains were divided into GII.4 2006b cluster. A peak number of rotavirus infections was observed during the cold season from November to next January. Higher rates of norovirus infections were detected from September to November. Most patients with rotavirus and norovirus associated diarrhea experienced vomiting (88.2% and 67.5%, respectively) and fever (79.1% and 46.3%, respectively).ConclusionsThe present study showed that rotavirus and norovirus were still the important causative agents of pediatric diarrhea in Ji'nan during this period.
Project description:BACKGROUND: Acute gastroenteritis is a serious cause of child mortality and morbidity in resource-limited countries. A viral etiology is most common, and rotavirus and norovirus are reported to be the leading causative agents. There are still few epidemiological data on the simultaneous occurrence of these viruses in Morocco. The aim of this study was to provide useful epidemiological data on the gastroenteritis associated with rotavirus and norovirus among children aged less than 5 years. METHODS: From January to December 2011, 335 samples were tested for rotavirus and norovirus using enzyme-linked immunosorbent assay, reverse-transcription-polymerase chain reaction (RT-multiplex PCR) and real-time RT-PCR. Partial sequences of the norovirus were phylogenetically analyzed to determine the genotype. RESULTS: The overall rates of rotavirus and norovirus infections were 26.6% and 16.1%, respectively. Mixed viral infections were detected in 9 of 335 stool specimens (2.7%).The most common genotype combination in the rotavirus strains was G1[P8] (51.7%), followed by G2[P4] (10.1%), G2[P8] (4.5%), G9[P8] (3.4%), G4[P8] (3.4%), and G1[P6] (2.3%). Among patients positive for norovirus, 42 (77.8%) tested positive for GII and 12 (22.2%) for GI. Thirty-three (78.6%) of the norovirus GII-positive cases were successfully characterized. Genotype GII.4 was the most prevalent (n?=?27; 81.8%), followed by GII.3 (n?=?2; 6.1%), GII.13 (n?=?2; 6.1%), GII.16 (n?=?1; 3%), and GII.17 (n?=?1; 3%). CONCLUSION: This study suggests that in Morocco, norovirus is the most frequent cause of acute gastroenteritis after rotavirus, but further enteric viruses need to be integrated in the surveillance system so that a conclusion could be drawn.
Project description:Lanzhou lamb rotavirus vaccine (LLR) is an oral live attenuated vaccine first licensed in China in 2000. To date, > 60 million doses of LLR have been distributed to children. However, very little is known about faecal shedding of LLR in children. Therefore, faecal samples (n = 1,184) were collected from 114 children for 15 days post-vaccination in September-November 2011/2012. Faecal shedding and viral loads were determined by an enzyme immunoassay kit (EIA) and real-time RT-PCR. The complete genome was sequenced and the vaccine strain was isolated by culture in MA104 cells. Approximately 14.0% (16/114) of children had rotavirus-positive samples by EIA for at least 1 day post-vaccination. Viral loads in EIA-positive samples ranged from < 1.0 × 103 to 1.9 × 108 copies/g. Faecal shedding occurred as early as post-vaccination day 2 and as late as post-vaccination day 13 and peaked on post-vaccination day 5-10. One LLR strain was isolated by culture in MA104 cells. Sequence analysis showed 99% identity with LLR prototype strain. Faecal shedding of LLR in stool is common within 15 days of LLR vaccination, indicating vaccine strains can replicate in human enteric tissues.
Project description:Knowledge of background rates of adverse events is crucial to assess vaccine safety concerns. We used data from a rotavirus vaccine study (Ruiz-Palacios et al., NEJM, 2006) including 63,225 infants from 11 Latin American countries to investigate reporting rates of serious adverse events (SAEs) among these infants, and describe rates by country, gender, age, and season.For this randomized, double-blind, placebo-controlled, phase 3 trial, investigators from Argentina, Brazil, Chile, Colombia, Dominican Republic, Honduras, Mexico, Nicaragua, Panama, Peru, and Venezuela recruited 6-to-13-week-old healthy infants. The infants received 2 oral doses of vaccine or placebo. The study population was followed 100 d for the assessment of adverse events. SAEs were captured by an active surveillance system.Strong differences in event rates could be observed between countries (min. 48.1/10,000 person-years in Dominican Republic/Peru; max. 296.2/10,000 person-years in Brazil) and between genders: gastroenteritis, pneumonia, bronchiolitis and bronchitis occurred significantly more frequently in males. In addition, infections and infestations, and most disorders, including immune system and cardiac disorders, were more frequent at earlier ages. Finally, looking at seasonality we noted higher rates of SAEs in the second half of the year in all countries except Mexico.Significant differences in reporting rates of SAEs between countries, gender and calendar months illustrate the importance of knowing the local epidemiology when interpreting SAEs. Data from clinical trials can be used to better understand background rates of diseases that may be perceived as potential adverse events following immunization.
Project description:Rotavirus (RV)-specific secretory immunoglobulin (RV-SIg) has been previously detected in serum of naturally RV infected children and shown to reflect the intestinal Ig immune response. Total plasma SIgA and plasma RV-SIg were evaluated by ELISA in children with gastroenteritis due or not due to RV infection and in 50 children vaccinated with the attenuated RIX4414 human RV vaccine and 62 placebo recipients. RV-SIg was only detected in children with evidence of previous RV infection or with acute RV gastroenteritis. Vaccinees had higher RV-SIg titers than placebo recipients and RV-SIg titers increased after the second vaccine dose. RV-SIg measured after the second dose correlated with protection when vaccinees and placebo recipients were analyzed jointly. RV-SIg may serve as a valuable correlate of protection for RV vaccines.
Project description:Infection with the meningococcus is one of the main causes of meningitis and septicaemia worldwide. Humans are the only natural reservoir for the meningococcus which is found primarily as a commensal inhabitant in the nasopharynx in ~10% of adults, and may be found in over 25% of individuals during adolescence. Prompt recognition of meningococcal infection and early aggressive treatment are essential in order to reduce mortality, which occurs in up to 10% of those with invasive meningococcal disease (IMD). This figure may be significantly higher in those with inadequate or delayed treatment. Early administration of effective parenteral antimicrobial therapy and prompt recognition and appropriate management of the complications of IMD, including circulatory shock and raised intracranial pressure (ICP), are critical to help improve patient outcome. This review summarizes clinical features of IMD and current treatment recommendations. We will discuss the evidence for immunization and effects of vaccine strategies, particularly following implementation of effective vaccines against Group B meningococcus.
Project description:Background. Rotavirus (RV) is the commonest pathogen in the hospital and primary care settings, followed by Adenovirus (AV) and Norovirus (NV). Only few studies that assess the burden of RV gastroenteritis at the community level have been carried out. Objectives. To estimate incidence, disease characteristics, seasonal distribution, and working days lost by parents of RV, AV, and NV gastroenteritis leading to a family pediatrician (FP) visit among children < 5 years. Methods. 12-month, observational, prospective, FP-based study has been carried out using Pedianet database. Results. RVGE incidence was 1.04 per 100 person-years with the highest incidence in the first 2 years of life. Incidences of AVGEs (1.74) and NVGEs (1.51) were slightly higher with similar characteristics regarding age distribution and symptoms. Risk of hospitalisation, access to emergency room (ER), and workdays lost from parents were not significantly different in RVGEs compared to the other viral infections. Conclusions. Features of RVGE in terms of hospitalisation length and indirect cost are lower than those reported in previous studies. Results of the present study reflect the large variability of data present in the literature. This observation underlines the utility of primary care networks for AGE surveillance and further studies on community-acquired gastroenteritis in children.
Project description:Rotavirus (RV) and norovirus (NoV) are the two major causes of viral gastroenteritis (GE) in children worldwide. We have developed an injectable vaccine design to prevent infection or GE induced with these enteric viruses. The trivalent combination vaccine consists of NoV capsid (VP1) derived virus-like particles (VLPs) of GI-3 and GII-4 representing the two major NoV genogroups and tubular RV recombinant VP6 (rVP6), the most conserved and abundant RV protein. Each component was produced in insect cells by a recombinant baculovirus expression system and combined in vitro. The vaccine components were administered intramuscularly to BALB/c mice either separately or in the trivalent combination. High levels of NoV and RV type specific serum IgGs with high avidity (>50%) as well as intestinal IgGs were detected in the immunized mice. Cross-reactive IgG antibodies were also elicited against heterologous NoV VLPs not used for immunization (GII-4 NO, GII-12 and GI-1 VLPs) and to different RVs from cell cultures. NoV-specific serum antibodies blocked binding of homologous and heterologous VLPs to the putative receptors, histo-blood group antigens, suggesting broad NoV neutralizing activity of the sera. Mucosal antibodies of mice immunized with the trivalent combination vaccine inhibited RV infection in vitro. In addition, cross-reactive T cell immune responses to NoV and RV-specific antigens were detected. All the responses were sustained for up to six months. No mutual inhibition of the components in the trivalent vaccine combination was observed. In conclusion, the NoV GI and GII VLPs combination induced broader cross-reactive and potentially neutralizing immune responses than either of the VLPs alone. Therefore, trivalent vaccine might induce protective immune responses to the vast majority of circulating NoV and RV genotypes.
Project description:The genetic susceptibility to and vaccine effectiveness against rotavirus gastroenteritis were different in distinct ethnic groups. The case-control study was aimed to evaluate the effectiveness of rotavirus vaccines and associations between the histo-blood group antigens and susceptibility to rotavirus infections in a Taiwanese population. Cases were children <18 years old who were hospitalized because of laboratory-confirmed rotavirus infection. Controls were healthy children matched to cases by age and gender. The secretor status and Lewis antigen and ABO types were determined by molecular methods. A total of 68 cases and 133 controls were included. Rotavirus immunization was recorded in 8 (12%) cases and 77 (58%) controls, indicating a vaccine effectiveness of 90.3% (95% confidence interval [CI], 78.1% - 95.7%). The secretor and Lewis-positive genotypes were independently associated with increased risk of rotavirus infections (matched odds ratio [mOR] 28.5, 95% CI 2.94-277, P?=?0.003 and mOR 16.8, 95% CI 1.08-2601, P?=?0.04, respectively). The distribution of ABO blood types did not differ significantly between cases and controls (P?=?0.47). In conclusion, Taiwanese children with the secretor genotype and Lewis-positive genotype were at increased risk of moderate-to-severe rotavirus infections. The illness can be effectively prevented by immunization in this population.