Geyer, Annelise; Banyai, Krisztian; Page, Nicola; Aminu, Maryam; Armah, George E.; Hull, Jennifer; Steele, Duncan A.; Glass, Roger I.; Gentsch, Jon R.
We report characterization of a genotype G5P human rotavirus (HRV) from a child in Cameroon who had diarrhea. Sequencing of all 11 gene segments showed similarities to >5 genes each from porcine and human rotaviruses. This G5P strain exemplifies the importance of heterologous animal rotaviruses in generating HRV genetic diversity through reassortment. PMID:19116059
Esona, M D; Geyer, A; Page, N; Trabelsi, A; Fodha, I; Aminu, M; Agbaya, V A; Tsion, B; Kerin, T K; Armah, G E; Steele, A D; Glass, R I; Gentsch, J R
Global rotavirus surveillance has led to the detection of many unusual human rotavirus (HRV) genotypes. During 1996-2004 surveillance within the African Rotavirus Network (ARN), six P,G8 and two P,G8 human rotavirus strains were identified. Gene fragments (RT-PCR amplicons) of all 11-gene segments of these G8 strains were sequenced in order to elucidate their genetic and evolutionary relationships. Phylogenetic and sequence analyses of each gene segment revealed high similarities (88-100% nt and 91-100% aa) for all segments except for gene 4 encoding VP4 proteins P and P. For most strains, almost all of the genes of the ARN strains other than neutralizing antigens are related to typical human strains of Wa genogroup. The VP7, NSP2, and NSP5 genes were closely related to cognate genes of animal strains (83-99% and 97-99% aa identity). This study suggests that the ARN G8 strains might have arisen through VP7 or VP4 gene reassortment events since most of the other gene segments resemble those of common human rotaviruses. However, VP7, NSP2 (likely), and NSP5 (likely) genes are derived potentially from animals consistent with a zoonotic introduction. Although these findings help elucidate rotavirus evolution, sequence studies of cognate animal rotavirus genes are needed to conclusively determine the specific origin of those genes relative to both human and animal rotavirus strains. Copyright 2009 Wiley-Liss, Inc.
Molyneaux, P J
Rotaviruses are the most important cause of severe gastro-enteritis in infants and young children. However, the determinants of protective immunity are poorly understood. Human immunity to rotavirus can be acquired passively or actively. It may be humoral or cell-mediated, protective or non-protective, homotypic or heterotypic and mucosal or systemic, or any combination of these. Mucosal immunity is protective against rotavirus illness, but not against infection, whereas systemic immunity reflects exposure, but probably has little if any role in protection. Both local and cell-mediated immunity are likely to be important in protection. However, there is no agreement as to a reliable surrogate marker of small intestinal protective immunity, and little is known about small intestinal cell-mediated immunity in man, especially infants. Passive mucosal immunity, but not systemic immunity, may contribute to protection in breast-fed infants, and in those at increased risk of serious illness who have been given oral immunoglobulin, either as prophylaxis or therapeutically. Animal and adult studies may have only limited relevance to those who are at greatest risk of serious illness. However, it is probably from such studies that hypotheses about small intestinal cell-mediated immunity in the protection of infants against rotavirus infection in man remain unclear, and this continues to hinder vaccine research.
Kuldeep S Chattha
Full Text Available Rotaviruses (RV are a major cause of gastroenteritis in children. Widespread vitamin A deficiency is associated with reduced efficacy of vaccines and higher incidence of diarrheal infections in children in developing countries. We established a vitamin A deficient (VAD gnotobiotic piglet model that mimics subclinical vitamin A deficiency in children to study its effects on an oral human rotavirus (HRV vaccine and virulent HRV challenge. Piglets derived from VAD and vitamin A sufficient (VAS sows were orally vaccinated with attenuated HRV or mock, with/without supplemental vitamin A and challenged with virulent HRV. Unvaccinated VAD control piglets had significantly lower hepatic vitamin A, higher severity and duration of diarrhea and HRV fecal shedding post-challenge as compared to VAS control pigs. Reduced protection coincided with significantly higher innate (IFNα cytokine and CD8 T cell frequencies in the blood and intestinal tissues, higher pro-inflammatory (IL12 and 2-3 fold lower anti-inflammatory (IL10 cytokines, in VAD compared to VAS control pigs. Vaccinated VAD pigs had higher diarrhea severity scores compared to vaccinated VAS pigs, which coincided with lower serum IgA HRV antibody titers and significantly lower intestinal IgA antibody secreting cells post-challenge in the former groups suggesting lower anamnestic responses. A trend for higher serum HRV IgG antibodies was observed in VAD vs VAS vaccinated groups post-challenge. The vaccinated VAD (non-vitamin A supplemented pigs had significantly higher serum IL12 (PID2 and IFNγ (PID6 compared to vaccinated VAS groups suggesting higher Th1 responses in VAD conditions. Furthermore, regulatory T-cell responses were compromised in VAD pigs. Supplemental vitamin A in VAD pigs did not fully restore the dysregulated immune responses to AttHRV vaccine or moderate virulent HRV diarrhea. Our findings suggest that that VAD in children in developing countries may partially contribute to more
Full Text Available To estimate the frequency, molecular epidemiological and clinical associations of infection with the newly described species C variants of human rhinoviruses (HRV, 3243 diagnostic respiratory samples referred for diagnostic testing in Edinburgh were screened using a VP4-encoding region-based selective polymerase chain reaction (PCR for HRV-C along with parallel PCR testing for 13 other respiratory viruses. HRV-C was the third most frequently detected behind respiratory syncytial virus (RSV and adenovirus, with 141 infection episodes detected among 1885 subjects over 13 months (7.5%. Infections predominantly targeted the very young (median age 6-12 months; 80% of infections in those <2 years, occurred throughout the year but with peak incidence in early winter months. HRV-C was detected significantly more frequently among subjects with lower (LRT and upper respiratory tract (URT disease than controls without respiratory symptoms; HRV-C mono-infections were the second most frequently detected virus (behind RSV in both disease presentations (6.9% and 7.8% of all cases respectively. HRV variants were classified by VP4/VP2 sequencing into 39 genotypically defined types, increasing the current total worldwide to 60. Through sequence comparisons of the 5'untranslated region (5'UTR, the majority grouped with species A (n = 96; 68%, described as HRV-Ca, the remainder forming a phylogenetically distinct 5'UTR group (HRV-Cc. Multiple and bidirectional recombination events between HRV-Ca and HRV-Cc variants and with HRV species A represents the most parsimonious explanation for their interspersed phylogeny relationships in the VP4/VP2-encoding region. No difference in age distribution, seasonality or disease associations was identified between HRV-Ca and HRV-Cc variants. HRV-C-infected subjects showed markedly reduced detection frequencies of RSV and other respiratory viruses, providing evidence for a major interfering effect of HRV-C on susceptibility to
Wen, Ke; Li, Guohua; Yang, Xingdong; Bui, Tammy; Bai, Muqun; Liu, Fangning; Kocher, Jacob; Yuan, Lijuan
The distribution and dynamic changes of CD4+ CD25+ FoxP3+ and CD4+ CD25− FoxP3+ regulatory T (Treg) cells induced by human rotavirus (HRV) infection and vaccination were examined in neonatal gnotobiotic pigs infected with virulent HRV (VirHRV) or vaccinated with attenuated HRV (AttHRV). Subsets of gnotobiotic pigs in the AttHRV and control groups were challenged with VirHRV at post-inoculation day (PID) 28. We demonstrated that VirHRV infection or AttHRV vaccination reduced frequencies and numbers of tissue-residing Treg cells, and decreased the frequencies of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) producing CD4+ CD25− Treg cells in ileum, spleen and blood at PID 28. The frequencies of IL-10 and TGF-β producing CD4+ CD25− Treg cells in all sites at PID 28 were significantly inversely correlated with the protection rate against VirHRV-caused diarrhoea (r = −1, P protective immunity against rotavirus. Our results highlighted the importance of CD4+ CD25− Treg cells over CD4+ CD25+ Treg cells in rotavirus infection and immunity. AttHRV vaccination (induction of immune effector responses) reduced the expansion of CD4+ CD25− Treg cells in ileum seen in the challenged naive pigs during the acute phase of VirHRV infection and preserved normal levels of intestinal TGF-β producing Treg cells post-challenge. The reduced suppressive effect of Treg cells in AttHRV-vaccinated pigs would unleash effector/memory T-cell activation upon challenge. Preserving TGF-β producing CD4+ CD25− Treg cells is important in maintaining homeostasis. Based on our findings, a model is proposed to depict the dynamic equilibrium course of Treg and effector T-cell responses after primary rotavirus infection/vaccination and challenge. PMID:22716916
De Grazia, Simona; Martella, Vito; Rotolo, Valentina; Bonura, Floriana; Matthijnssens, Jelle; Bányai, Krisztián; Ciarlet, Max; Giammanco, Giovanni M
Group A human rotavirus (HRV) strains with a bovine-like (G6) major outer capsid protein VP7 were first detected in Palermo, Italy, in the late 1980s, and subsequently worldwide. During a 25-year rotavirus surveillance period, additional HRV G6 strains, associated with either a P or P VP4 genotype, have been detected sporadically, but repeatedly, in Palermo. Whether these G6 HRVs were transmitted to humans directly from an animal reservoir or could have circulated at low prevalence in susceptible individuals is uncertain. Upon sequence analyses of the VP7, VP4, VP6, NSP4 and NSP5 gene segments, all the Italian HRV strains displayed a conserved genotype constellation, G6-P/-I2-E2-H3. Intra-genotypic lineages and/or sub-lineages were observed among the various HRV strains, with some lineage/sublineage combinations being retained over time. Interestingly, two epidemiologically unrelated G6P viruses, collected in the same rotavirus season, were found to have a clonal origin. In conclusion, our results indicate not only diverse origin of animal derived G6 HRVs in Palermo but also suggest human-to-human transmission of certain strains. Copyright © 2011 Elsevier B.V. All rights reserved.
Xue, Bin; Jin, Min; Yang, Dong; Guo, Xuan; Chen, Zhaoli; Shen, Zhiqiang; Wang, Xinwei; Qiu, Zhigang; Wang, Jingfeng; Zhang, Bin; Li, Junwen
Despite the health risks posed by waterborne human rotavirus (HRV), little information is available concerning the effectiveness of chlorine or chlorine dioxide (ClO2), two common disinfectants of public water sources, against HRV and their effects on its genome remain poorly understood. This study investigated the effects of chlorine and ClO2 on purified HRV by using cell culture and RT-PCR to assess virus infectivity and genetic integrity, respectively. The disinfection efficacy of ClO2 was found to be higher than that of chlorine. According to the efficiency factor Hom model, Ct value (mg/L min) ranges required for a 4-log reduction of HRV at 20 °C by chlorine and ClO2 were 5.55-5.59 and 1.21-2.47 mg/L min, respectively. Detection of the 11 HRV genome segments revealed that damage to the 1227-2354 bp of the VP4 gene was associated with the disappearance of viral infectivity by chlorine. However, no complete accordance between culturing and RT-PCR assays was observed after treatment of HRV with ClO2. These results collectively indicate that the current practice of chlorine disinfection may be inadequate to manage the risk of waterborne HRV infection, and offer the potential to monitor the infectivity of HRV adapting PCR-based protocols in chlorine disinfection. Copyright © 2013 Elsevier Ltd. All rights reserved.
Full Text Available Rotavirus vaccines are now globally recommended by the World Health Organization (WHO, but in early 2009 WHO's Strategic Advisory Group of Experts on Immunization reviewed available data and concluded that there was no evidence for the efficacy or effectiveness of a two-dose schedule of the human rotavirus vaccine (HRV; Rotarix given early at 6 and 10 wk of age. Additionally, the effectiveness of programmatic rotavirus vaccination, including possible indirect effects, has not been assessed in low-resource populations in Asia.In Bangladesh, we cluster-randomized (1:1 142 villages of the Matlab Health and Demographic Surveillance System to include two doses of HRV with the standard infant vaccines at 6 and 10 wk of age or to provide standard infant vaccines without HRV. The study was initiated November 1, 2008, and surveillance was conducted concurrently at Matlab Diarrhoea Hospital and two community treatment centers to identify children less than 2 y of age presenting with acute rotavirus diarrhea (ARD through March 31, 2011. Laboratory confirmation was made by enzyme immunoassay detection of rotavirus antigen in stool specimens. Overall effectiveness of the HRV vaccination program (primary objective was measured by comparing the incidence rate of ARD among all children age-eligible for vaccination in villages where HRV was introduced to that among such children in villages where HRV was not introduced. Total effectiveness among vaccinees and indirect effectiveness were also evaluated. In all, 6,527 infants were age-eligible for vaccination in 71 HRV villages, and 5,791 in 71 non-HRV villages. In HRV villages, 4,808 (73.7% infants received at least one dose of HRV. The incidence rate of ARD was 4.10 cases per 100 person-years in non-HRV villages compared to 2.8 per 100 person-years in HRV villages, indicating an overall effectiveness of 29.0% (95% CI, 11.3% to 43.1%. The total effectiveness of HRV against ARD among vaccinees was 41.4% (95% CI
... and characterisation by SDS-PAGE showed the presence of human group C rotaviruses. Conclusion:This is the first report of group C rotaviruses in Kenya. Further studies are underway to continue the surveillance of rotavirus strains in Kenya; as this information will be useful in planning rotavirus vaccine trials in Africa.
Torres, A; Ji-Huang, L
Pigs exposed in utero to human rotavirus (HRV) strain Wa serotype 1 from 15 to 36 days prior to birth responded immunologically by modifying their clinical response to neonatal oral challenge with a pathogenic dose of homologous Wa or heterologous M serotype 3 HRV. In these cases, diarrhea was prevented in 12 of 14 pigs and greatly reduced in the other two. However, fecal virus shedding was not significantly modified, since it was detected in 12 of 14 pigs. These results suggest the existence of a closer antigenic relationship between these two different HRV serotypes which may only be expressed in an in vivo test system. Exposure of fetal pigs to HRV DS-1 serotype 2 failed to cause infection or to induce any protection when pigs were challenged at birth with HRV Wa. This model for cross-protection studies in gnotobiotic piglets offers good possibilities for the evaluation of potential HRV vaccine candidates, for the in vivo study of antigenic similarities between rotavirus serotypes, and for the understanding of protective immune responses against diarrhea and virus shedding.
Full Text Available BACKGROUND: Human rhinoviruses (HRVs are the most frequently detected pathogens in acute respiratory tract infections (ARTIs and yet little is known about the prevalence, recurrence, structure and clinical impact of individual members. During 2007, the complete coding sequences of six previously unknown and highly divergent HRV strains were reported. To catalogue the molecular and clinical features distinguishing the divergent HRV strains, we undertook, for the first time, in silico analyses of all available polyprotein sequences and performed retrospective reviews of the medical records of cases in which variants of the prototype strain, HRV-QPM, had been detected. METHODOLOGY/PRINCIPLE FINDINGS: Genomic analyses revealed that the six divergent strains, residing within a clade we previously called HRV A2, had the shortest polyprotein of all picornaviruses investigated. Structure-based amino acid alignments identified conserved motifs shared among members of the genus Rhinovirus as well as substantive deletions and insertions unique to the divergent strains. Deletions mostly affected regions encoding proteins traditionally involved in antigenicity and serving as HRV and HEV receptor footprints. Because the HRV A2 strains cannot yet be cultured, we created homology models of predicted HRV-QPM structural proteins. In silico comparisons confirmed that HRV-QPM was most closely related to the major group HRVs. HRV-QPM was most frequently detected in infants with expiratory wheezing or persistent cough who had been admitted to hospital and required supplemental oxygen. It was the only virus detected in 65% of positive individuals. These observations contributed to an objective clinical impact ranging from mild to severe. CONCLUSIONS: The divergent strains did not meet classification requirements for any existing species of the genus Rhinovirus or Enterovirus. HRV A2 strains should be partitioned into at least one new species, putatively called Human
Shao, Lulu; Fischer, David D; Kandasamy, Sukumar; Rauf, Abdul; Langel, Stephanie N; Wentworth, David E; Stucker, Karla M; Halpin, Rebecca A; Lam, Ham Ching; Marthaler, Douglas; Saif, Linda J; Vlasova, Anastasia N
The changing epidemiology of group A rotavirus (RV) strains in humans and swine, including emerging G9 strains, poses new challenges to current vaccines. In this study, we comparatively assessed the pathogenesis of porcine RV (PRV) G9P and evaluated the short-term cross-protection between this strain and human RV (HRV) Wa G1P in gnotobiotic pigs. Complete genome sequencing demonstrated that PRV G9P possessed a human-like G9 VP7 genotype but shared higher overall nucleotide identity with historic PRV strains. PRV G9P induced longer rectal virus shedding and RV RNAemia in pigs than HRV Wa G1P and generated complete short-term cross-protection in pigs challenged with HRV or PRV, whereas HRV Wa G1P induced only partial protection against PRV challenge. Moreover, PRV G9P replicated more extensively in porcine monocyte-derived dendritic cells (MoDCs) than did HRV Wa G1P. Cross-protection was likely not dependent on serum virus-neutralizing (VN) antibodies, as the heterologous VN antibody titers in the sera of G9P-inoculated pigs were low. Thus, our results suggest that heterologous protection by the current monovalent G1P HRV vaccine against emerging G9 strains should be evaluated in clinical and experimental studies to prevent further dissemination of G9 strains. Differences in the pathogenesis of these two strains may be partially attributable to their variable abilities to replicate and persist in porcine immune cells, including dendritic cells (DCs). Additional studies are needed to evaluate the emerging G9 strains as potential vaccine candidates and to test the susceptibility of various immune cells to infection by G9 and other common HRV/PRV genotypes. The changing epidemiology of porcine and human group A rotaviruses (RVs), including emerging G9 strains, may compromise the efficacy of current vaccines. An understanding of the pathogenesis and genetic, immunological, and biological features of the new emerging RV strains will
Medici, Maria Cristina; Martinelli, Monica; Arcangeletti, Maria Cristina; Pinardi, Federica; De Conto, Flora; Dodi, Icilio; Virdis, Raffaele; Abelli, Laura Anna; Aloisi, Annalisa; Zerbini, Laura; Valcavi, Pierpaolo; Calderaro, Adriana; Bernasconi, Sergio; Izzi, Gian Carlo; Dettori, Giuseppe; Chezzi, Carlo
Human rotavirus (HRV) is recognized as the most common cause of severe gastroenteritis in children under 5 years of age. Due to the lack of recent reports about the surveillance of HRV infection in Italy, in this study we assessed the prevalence rate of HRV infection on 1,340 stool samples belonging to 1,264 pediatric patients hospitalized with acute gastroenteritis in the period January 2000--December 2002. The stool samples were submitted to virological investigations by electron microscopy (EM) and conventional cell culture, as well as from January 2002 by RT-PCR for norovirus detection. Reovirus-like particles observed by EM were identified by electropherotyping. Single HRV infections were detected in 302 cases (23.9%, ranging from 19.1% in 2000 to 30.2% in 2001). Mixed infections were observed in 28 cases in which HRV was found to be associated with adenovirus in 16 cases (1.3%), with picornavirus in 4 (0.3%), and with norovirus in 8 (2.1% of the 388 cases examined in 2002). The 3 major epidemic periods of HRV infections were March--May 2000 (66 cases), December 2000--May 2001 (128 cases) and September 2001--April 2002 (105 cases) with peaks in March, January and March, and January, respectively. In the periods of major incidence, single HRV infection accounted even for 52.5% of the gastroenteritis cases monthly examined. According to age distribution, 68.9% (208 cases) of HRV infected children was under 4 years (69.6%: 230/330 cases, including mixed infections) and 16.9% (51 cases) was in the 5-12-year age-group. The epidemiological aspects of HRV infection, also compared to other enteric virus infections, will contribute to assess the magnitude of the problem of HRV in different settings and to devise strategies for intervention.
Full Text Available Rotavirus A (RVA is a dominant causative agent of acute gastroenteritis in children worldwide. G2P is one of the most common genotypes among human rotavirus (HRV strains, and has been persistently prevalent in South Asia including Bangladesh. In the present study, whole genome sequences of a total of 16 G2P HRV strains (8 strains each in 2010 and 2013 detected in Mymensingh, north-central Bangladesh were determined. These strains had typical DS-1-like genotype constellation. Most of gene segments from DS-1 genogroup exhibited high level sequence identities to each other (>98%, while slight diversity was observed for VP1, VP3, and NSP4 genes. By phylogenetic analysis, individual RNA segments were classified into one (V or two-three lineages (V–VI or V–VII. In terms of lineages (sublineages of 11 gene segments, the 16 Bangladeshi strains could be further classified into four clades (A-D containing 8 lineage constellations, revealing the presence of three clades (A-C with three lineage constellations in 2010, and a single clade (D with four constellations in 2013. Therefore, co-existence of multiple G2P HRV strains with different lineage constellations, and change in clades for the study period were demonstrated. Although amino acids in the antigenic regions on VP7 and VP4 were mostly identical to those of global G2P strains after 2000, VP4 of clade D RVAs in 2013 had alanine and proline at positions 88 and 114, respectively, which are novel substitutions compared with recent global G2P strains. Replacement of lineage constellations associated with unique amino acid changes in the antigenic region in VP4 suggested continuous genetic evolutionary state for emerging new G2P rotavirus strains in Bangladesh.
Xue, Bin; Li, Chenyu; Zhang, Bin; Zhao, Tianyu; Shen, Zhiqiang; Qiu, Zhigang; Jin, Min; Wang, Jingfeng; Li, Junwen
Human rotaviruses (HRVs) are the major cause of acute diarrhea in infants and young children. Here, a real-time reverse transcription polymerase chain reaction assay targeting the rotaviral VP4 gene (VP4-RT-qPCR) was established to evaluate the inactivation of HRV upon chlorine disinfection, based on a previous report that damage to the 1227-2354bp region of the VP4 gene was associated with eliminated HRV infectivity by chlorine. In this study, inactivation of HRV by 0.6mg/L free chlorine was assessed in phosphate buffered saline (PBS; pH 7.2), and tap and river water samples, using both TCID50 and RT-qPCR (VP2- and VP4-RT-qPCR) assays, respectively. Among the samples tested, the VP2-RT-qPCR method did not show significant inactivation after chlorine disinfection; however, the reduction in VP4-RT-qPCR signal was correlated with decreased HRV infectivity. Moreover, the higher sensitivity of the VP4-RT-qPCR assay allowed for assessment of chlorine HRV inactivation at longer exposure times compared with the conventional TCID50 assay. Collectively, these results indicated that the VP4-RT-qPCR assay is a rapid, sensitive, and reliable tool to detect infectious HRV following chlorine inactivation, and highlights the potential for further development of qPCR/RT-qPCR assays to provide information regarding viral infectivity from drinking water plants. Copyright © 2017 Elsevier GmbH. All rights reserved.
Gentsch, Jon R; Laird, Ashley R; Bielfelt, Brittany; Griffin, Dixie D; Banyai, Krisztian; Ramachandran, Madhu; Jain, Vivek; Cunliffe, Nigel A; Nakagomi, Osamu; Kirkwood, Carl D; Fischer, Thea K; Parashar, Umesh D; Bresee, Joseph S; Jiang, Baoming; Glass, Roger I
The development of rotavirus vaccines that are based on heterotypic or serotype-specific immunity has prompted many countries to establish programs to assess the disease burden associated with rotavirus infection and the distribution of rotavirus strains. Strain surveillance helps to determine whether the most prevalent local strains are likely to be covered by the serotype antigens found in current vaccines. After introduction of a vaccine, this surveillance could detect which strains might not be covered by the vaccine. Almost 2 decades ago, studies demonstrated that 4 globally common rotavirus serotypes (G1-G4) represent >90% of the rotavirus strains in circulation. Subsequently, these 4 serotypes were used in the development of reassortant vaccines predicated on serotype-specific immunity. More recently, the application of reverse-transcription polymerase chain reaction genotyping, nucleotide sequencing, and antigenic characterization methods has confirmed the importance of the 4 globally common types, but a much greater strain diversity has also been identified (we now recognize strains with at least 42 P-G combinations). These studies also identified globally (G9) or regionally (G5, G8, and P2A) common serotype antigens not covered by the reassortant vaccines that have undergone efficacy trials. The enormous diversity and capacity of human rotaviruses for change suggest that rotavirus vaccines must provide good heterotypic protection to be optimally effective.
Celina G Vega
Full Text Available Group A Rotaviruses are the most common cause of severe, dehydrating diarrhea in children worldwide. The aim of the present work was to evaluate protection against rotavirus (RV diarrhea conferred by the prophylactic administration of specific IgY antibodies (Ab to gnotobiotic piglets experimentally inoculated with virulent Wa G1P human rotavirus (HRV. Chicken egg yolk IgY Ab generated from Wa HRV hyperimmunized hens specifically recognized (ELISA and neutralized Wa HRV in vitro. Supplementation of the RV Ab free cow milk diet with Wa HRV-specific egg yolk IgY Ab at a final ELISA Ab titer of 4096 (virus neutralization -VN- titer = 256 for 9 days conferred full protection against Wa HRV associated diarrhea and significantly reduced virus shedding. This protection was dose-dependent. The oral administration of semi-purified passive IgY Abs from chickens did not affect the isotype profile of the pig Ab secreting cell (ASC responses to Wa HRV infection, but it was associated with significantly fewer numbers of HRV-specific IgA ASC in the duodenum. We further analyzed the pigś immune responses to the passive IgY treatment. The oral administration of IgY Abs induced IgG Ab responses to chicken IgY in serum and local IgA and IgG Ab responses to IgY in the intestinal contents of neonatal piglets in a dose dependent manner. To our knowledge, this is the first study to show that IgY Abs administered orally as a milk supplement passively protect neonatal pigs against an enteric viral pathogen (HRV. Piglets are an animal model with a gastrointestinal physiology and an immune system that closely mimic human infants. This strategy can be scaled-up to inexpensively produce large amounts of polyclonal IgY Abs from egg yolks to be applied as a preventive and therapeutic passive Ab treatment to control RV diarrhea.
Hagbom, Marie; Sharma, Sumit; Lundgren, Ove; Svensson, Lennart
While the clinical importance of human rotavirus (RV) disease is well recognized and potent vaccines have been developed, our understanding of how human RV causes diarrhoea, vomiting and death remains unresolved. The fact that oral rehydration corrects electrolyte and water loss, indicates that enterocytes in the small intestine have a functional sodium-glucose co-transporter. Moreover, RV infection delays gastric emptying and loperamide appears to attenuate RV diarrhoea, thereby suggesting activation of the enteric nervous system. Serotonin (5-HT) receptor antagonists attenuate vomiting in young children with gastroenteritis while zinc and enkephalinase inhibitors attenuate RV-induced diarrhoea. In this review we discuss clinical symptoms, pathology, histology and treatment practices for human RV infections and compile the data into a simplified disease model. Copyright © 2012 Elsevier B.V. All rights reserved.
Nakagomi, Toyoko; Nakagomi, Osamu; Dove, Winifred; Doan, Yen Hai; Witte, Desiree; Ngwira, Bagrey; Todd, Stacy; Steele, A Duncan; Neuzil, Kathleen M; Cunliffe, Nigel A
The human, G1P rotavirus vaccine (Rotarix) significantly reduced severe rotavirus gastroenteritis episodes in a clinical trial in South Africa and Malawi, but vaccine efficacy was lower in Malawi (49.5%) than reported in South Africa (76.9%) and elsewhere. The aim of this study was to examine the molecular relationships of circulating wild-type rotaviruses detected during the clinical trial in Malawi to RIX4414 (the strain contained in Rotarix) and to common human rotavirus strains. Of 88 rotavirus-positive, diarrhoeal stool specimens, 43 rotaviruses exhibited identifiable RNA migration patterns when examined by polyacrylamide gel electrophoresis. The genes encoding VP7, VP4, VP6 and NSP4 of 5 representative strains possessing genotypes G12P, G1P, G9P, and G8P were sequenced. While their VP7 (G) and VP4 (P) genotype designations were confirmed, the VP6 (I) and NSP4 (E) genotypes were either I1E1 or I2E2, indicating that they were of human rotavirus origin. RNA-RNA hybridization using 21 culture-adapted strains showed that Malawian rotaviruses had a genomic RNA constellation common to either the Wa-like or DS-1 like human rotaviruses. Overall, the Malawi strains appear similar in their genetic make-up to rotaviruses described in countries where vaccine efficacy is greater, suggesting that the lower efficacy in Malawi is unlikely to be explained by the diversity of circulating strains. PMID:22520123
Hoshino, Yasutaka; Jones, Ronald W; Ross, Jerri; Kapikian, Albert Z
Rotavirus gastroenteritis remains the leading cause of severe diarrheal disease in infants and young children worldwide, and thus, a safe and effective rotavirus vaccine is urgently needed in both developing and developed countries. Various candidate rotavirus vaccines that were developed by us and others have been or are being evaluated in different populations in various parts of the world. We have recently confirmed that a porcine rotavirus Gottfried strain bears a P (VP4) serotype (P2B) closely related to human rotavirus P serotype 2A which is of epidemiologic importance in some regions of the world. Based on the modified Jennerian approach to immunization, we have constructed 11 Gottfried-based single VP7 or VP4 gene substitution reassortant vaccine candidates which could provide: (i) an attenuation phenotype of a porcine rotavirus in humans; and (ii) antigenic coverage for G serotypes 1-6 and 8-10 and P serotype 1A, 1B and 2A. In addition, following immunization of guinea pigs with Gottfried VP4, we found low but consistent levels of neutralizing antibodies to VP4 with P1A or P1B specificity, both of which are of global epidemiologic importance. Thus, porcine-based VP7 reassortant rotavirus vaccines may provide an advantage over rhesus- or bovine-based VP7 reassortant vaccines since the VP4s of the latter vaccines do not evoke antibodies capable of neutralizing the viruses bearing P1A, P1B or P2A VP4.
Ward, R L
Immune responses following either natural or experimental rotavirus infection provide protection against subsequent rotavirus illnesses, and the mechanisms involved have been examined in humans and animals. In adult volunteers challenged with human rotaviruses, protection has been shown to correlate with serum and intestinal antibodies; however, titers of no specific antibody could be used reliably as a marker of protection, including neutralizing antibody to the challenge virus. Studies in children confirmed these general associations between antibody titers and protection, but the serotype specificity of antibody and its role in protection remained unclear. Studies in mice suggested antibody, CD8 cells, and a third, undetermined, factor as mediators of protection. Antibody appeared to be most important, both in resolution of infection and protection against subsequent infection, but its activity was not serotype specific. CD8 cells helped resolve rotavirus infection but were less important in protection against reinfection. The third factor remains to be identified.
CDC's Dr. Jon Gentsch discusses rotaviruses, the most important cause of severe gastroenteritis in children less than five years of age. Essentially, all children around the world get the disease during the first few years of life. Created: 1/6/2009 by Emerging Infectious Diseases. Date Released: 1/6/2009.
Danchin, M; Kirkwood, C D; Lee, K J; Bishop, R F; Watts, E; Justice, F A; Clifford, V; Cowley, D; Buttery, J P; Bines, J E
RV3 is a human neonatal rotavirus strain (G3P) that has been associated with asymptomatic neonatal infection and replicates well in the infant gut. RV3-BB rotavirus vaccine has been developed as a rotavirus vaccine candidate for administration at birth. A single-centre, double-blind, randomised placebo-controlled Phase I study evaluated the safety and tolerability of a single oral dose of the second generation RV3-BB rotavirus vaccine (8.3×10(6)FFU/mL) in 20 adults, 20 children and 20 infants (10 vaccine and 10 placebo per age cohort). Vaccine take was defined as seroconversion (a 3-fold increase in serum anti-rotavirus IgA or serum neutralising antibody (SNA) from baseline at day 28 post-dose) or evidence of RV3-BB viral replication in the faeces by RT-PCR analysis 3-6 days post-vaccination. RV3-BB presence was confirmed by sequence analysis. The RV3-BB vaccine was well tolerated in all participants, with no pattern of adverse events shown to be associated with the study vaccine. In the infant cohort, vaccine take was demonstrated in 8/9 infants following a single dose of vaccine compared with 2/7 placebo recipients. In the infant vaccine group, 5/9 infants exhibited either IgA or SNA seroconversion and 7/9 infants had evidence of RV3-BB replication on days 3-6, compared with 2/7 infants who seroconverted and 0/10 infants with evidence of replication in the placebo group. Two infants in the placebo group had serological evidence of a rotavirus infection within the 28-day study period: one demonstrated an IgA and the other an SNA response, with wild-type virus replication detected in another infant. A single dose of RV3-BB rotavirus vaccine was well tolerated in adults, children and infants. Most infants (8/9) who received RV3-BB demonstrated vaccine take following a single dose. These data support progression of RV3-BB to Phase II immunogenicity and efficacy trials. Copyright © 2013 Elsevier Ltd. All rights reserved.
Cowley, Daniel; Boniface, Karen; Bogdanovic-Sakran, Nada; Kirkwood, Carl D; Bines, Julie E
The RV3-BB human neonatal rotavirus vaccine aims to provide protection from severe rotavirus disease from birth. A phase IIa safety and immunogenicity trial was undertaken in Dunedin, New Zealand between January 2012 and April 2014. Healthy, full-term (≥ 36 weeks gestation) babies, who were 0-5 d old were randomly assigned (1:1:1) to receive 3 doses of oral RV3-BB vaccine with the first dose given at 0-5 d after birth (neonatal schedule), or the first dose given at about 8 weeks after birth (infant schedule), or to receive placebo (placebo schedule). Vaccine take (serum immune response or stool shedding of vaccine virus after any dose) was detected after 3 doses of RV3-BB vaccine in >90% of participants when the first dose was administered in the neonatal and infant schedules. The aim of the current study was to characterize RV3-BB shedding and virus replication following administration of RV3-BB in a neonatal and infant vaccination schedule. Shedding was defined as detection of rotavirus by VP6 reverse transcription polymerase chain reaction (RT-PCR) in stool on days 3-7 after administration of RV3-BB. Shedding of rotavirus was highest following vaccination at 8 weeks of age in both neonatal and infant schedules (19/30 and 17/27, respectively). Rotavirus was detected in stool on days 3-7, after at least one dose of RV3-BB, in 70% (21/30) of neonate, 78% (21/27) of infant and 3% (1/32) placebo participants. In participants who shed RV3-BB, rotavirus was detectable in stool on day 1 following RV3-BB administration and remained positive until day 4-5 after administration. The distinct pattern of RV3-BB stool viral load demonstrated using a NSP3 quantitative qRT-PCR in participants who shed RV3-BB, suggests that detection of RV3-BB at day 3-7 was the result of replication rather than passage through the gastrointestinal tract.
Rotavirus is the most common cause of severe gastroenteritis in children younger than 3 years of age worldwide. New rotavirus vaccine candidates were required to confer early protection against the most common rotavirus serotypes and to be well tolerated and not associated with intussusception. RIX4414 is a human-attenuated G1(P8) oral rotavirus vaccine administered in two doses at approximately 6-24 weeks of age. The first dose may be administered from the age of 6 weeks. There should be an interval of at least 4 weeks between doses and the vaccination course should preferably be given before 16 weeks of age and must be completed, according to the manufacturer, by the age of 24 weeks. In a worldwide development program involving more than 70,000 children in six Phase I-III field trials, this vaccine proved to be nonreactogenic, well tolerated and not associated with intussusception. The vaccine provides over 85-96% protection against moderate-to-severe gastroenteritis caused by G1 and non-G1 serotypes, as demonstrated in Latin American and European clinical trial settings, respectively; and reduces gastroenteritis-related hospitalizations by more than 40% in Latin America and by 75% in European settings.
Laucirica, Daniel R; Triantis, Vassilis; Schoemaker, Ruud; Estes, Mary K; Ramani, Sasirekha
Background: Oligosaccharides in milk act as soluble decoy receptors and prevent pathogen adhesion to the infant gut. Milk oligosaccharides reduce infectivity of a porcine rotavirus strain; however, the effects on human rotaviruses are less well understood. Objective: In this study, we determined the effect of specific and abundant milk oligosaccharides on the infectivity of 2 globally dominant human rotavirus strains. Methods: Four milk oligosaccharides-2'-fucosyllactose (2'FL), 3'-sialyllactose (3'SL), 6'-sialyllactose (6'SL), and galacto-oligosaccharides-were tested for their effects on the infectivity of human rotaviruses G1P and G2P through fluorescent focus assays on African green monkey kidney epithelial cells (MA104 cells). Oligosaccharides were added at different time points in the infectivity assays. Infections in the absence of oligosaccharides served as controls. Results: When compared with infections in the absence of glycans, all oligosaccharides substantially reduced the infectivity of both human rotavirus strains in vitro; however, virus strain-specific differences in effects were observed. Compared with control infections, the maximum reduction in G1P infectivity was seen with 2'FL when added after the onset of infection (62% reduction, P < 0.01), whereas the maximum reduction in G2P infectivity was seen with the mixture of 3'SL + 6'SL when added during infection (73% reduction, P < 0.01). The mixture of 3'SL + 6'SL at the same ratio as is present in breast milk was more potent in reducing G2P infectivity (73% reduction, P < 0.01) than when compared with 3'SL (47% reduction) or 6'SL (40% reduction) individually. For all oligosaccharides the reduction in infectivity was mediated by an effect on the virus and not on the cells. Conclusions: Milk oligosaccharides reduce the infectivity of human rotaviruses in MA104 cells, primarily through an effect on the virus. Although breastfed infants are directly protected, the addition of specific
Elizabeth P. Ryan
Full Text Available Human rotavirus (HRV is a leading cause of severe childhood diarrhea, and there is limited vaccine efficacy in the developing world. Neonatal gnotobiotic pigs consuming a prophylactic synbiotic combination of probiotics and rice bran (Pro+RB did not exhibit HRV diarrhea after challenge. Multiple immune, gut barrier protective, and anti-diarrheal mechanisms contributed to the prophylactic efficacy of Pro+RB when compared to probiotics (Pro alone. In order to understand the molecular signature associated with diarrheal protection by Pro+RB, a global non-targeted metabolomics approach was applied to investigate the large intestinal contents and serum of neonatal gnotobiotic pigs. The ultra-high performance liquid chromatography-tandem mass spectrometry platform revealed significantly different metabolites (293 in LIC and 84 in serum in the pigs fed Pro+RB compared to Pro, and many of these metabolites were lipids and amino acid/peptides. Lipid metabolites included 2-oleoylglycerol (increased 293.40-fold in LIC of Pro+RB, p = 3.04E-10, which can modulate gastric emptying, andhyodeoxycholate (decreased 0.054-fold in the LIC of Pro+RB, p = 0.0040 that can increase colonic mucus production to improve intestinal barrier function. Amino acid metabolites included cysteine (decreased 0.40-fold in LIC, p = 0.033, and 0.62-fold in serum, p = 0.014 of Pro+RB, which has been found to reduce inflammation, lower oxidative stress and modulate mucosal immunity, and histamine (decreased 0.18-fold in LIC, p = 0.00030, of Pro+RB and 1.57-fold in serum, p = 0.043, which modulates local and systemic inflammatory responses as well as influences the enteric nervous system. Alterations to entire LIC and serum metabolic pathways further contributed to the anti-diarrheal and anti-viral activities of Pro+RB such as sphingolipid, mono/diacylglycerol, fatty acid, secondary bile acid, and polyamine metabolism. Sphingolipid and long chain fatty acid profiles influenced the
Nealon, Nora Jean; Yuan, Lijuan; Yang, Xingdong; Ryan, Elizabeth P
Human rotavirus (HRV) is a leading cause of severe childhood diarrhea, and there is limited vaccine efficacy in the developing world. Neonatal gnotobiotic pigs consuming a prophylactic synbiotic combination of probiotics and rice bran (Pro+RB) did not exhibit HRV diarrhea after challenge. Multiple immune, gut barrier protective, and anti-diarrheal mechanisms contributed to the prophylactic efficacy of Pro+RB when compared to probiotics (Pro) alone. In order to understand the molecular signature associated with diarrheal protection by Pro+RB, a global non-targeted metabolomics approach was applied to investigate the large intestinal contents and serum of neonatal gnotobiotic pigs. The ultra-high performance liquid chromatography-tandem mass spectrometry platform revealed significantly different metabolites (293 in LIC and 84 in serum) in the pigs fed Pro+RB compared to Pro, and many of these metabolites were lipids and amino acid/peptides. Lipid metabolites included 2-oleoylglycerol (increased 293.40-fold in LIC of Pro+RB, p = 3.04E-10), which can modulate gastric emptying, andhyodeoxycholate (decreased 0.054-fold in the LIC of Pro+RB, p = 0.0040) that can increase colonic mucus production to improve intestinal barrier function. Amino acid metabolites included cysteine (decreased 0.40-fold in LIC, p = 0.033, and 0.62-fold in serum, p = 0.014 of Pro+RB), which has been found to reduce inflammation, lower oxidative stress and modulate mucosal immunity, and histamine (decreased 0.18-fold in LIC, p = 0.00030, of Pro+RB and 1.57-fold in serum, p = 0.043), which modulates local and systemic inflammatory responses as well as influences the enteric nervous system. Alterations to entire LIC and serum metabolic pathways further contributed to the anti-diarrheal and anti-viral activities of Pro+RB such as sphingolipid, mono/diacylglycerol, fatty acid, secondary bile acid, and polyamine metabolism. Sphingolipid and long chain fatty acid profiles influenced the ability of HRV to
Kapikian, A Z; Hoshino, Y; Chanock, R M; Perez-Schael, I
Rotaviruses are the single most important cause of severe diarrhea of infants and young children world-wide. Deaths from rotavirus diarrhea occur infrequently in developed countries; however, in developing countries, rotaviruses are estimated to cause over 870000 deaths in the under five-year age group. There is, therefore, a vital need for a vaccine to prevent severe rotavirus diarrhea in infants and young children. The most extensively evaluated strategy for rotavirus vaccination has been the "Jennerian" approach in which an antigenically related rotavirus strain from an animal host (bovine or simian [rhesus monkey]) is used as the immunogen to induce protection against the four epidemiologically important group A human rotavirus serotypes. These orally administered vaccines were safe and immunogenic but had only limited success because serotype-specific immunity was not induced consistently in the under six-month age group. Therefore, a modified "Jennerian" approach was adopted with the goal of attaining broader antigenic coverage. In this approach four serotypes are combined to form a quadrivalent vaccine comprised of (i) rhesus rotavirus (RRV) which provides coverage for VP7 serotype 3, and (ii) three human-RRV reassortants each with ten RRV genes and a single human rotavirus gene that encodes VP7 serotype 1, 2, or 4 specificity. This modified "Jennerian" approach appears to be quite promising in preventing severe diarrhea in field trials. However, if this approach fails to yield an optimal level of protection consistently, additional modified "Jennerian" strategic, are under development that consider not only human rotavirus VP7 but also human rotavirus VP4, the other outer capsid protein. In addition, a non-"Jennerian" approach includes the development of cold-adapted human rotavirus strains or cold-adapted human rotavirus reassortants as vaccine candidates.
Zaman, K; Fleming, Jessica A; Victor, John C; Yunus, Mohammad; Bari, Tajul Islam A; Azim, Tasnim; Rahman, Mustafizur; Mowla, Syed Mohammad Niaz; Bellini, William J; McNeal, Monica; Icenogle, Joseph P; Lopman, Ben; Parashar, Umesh; Cortese, Margaret M; Steele, A Duncan; Neuzil, Kathleen M
The burden of rotavirus morbidity and mortality is high in children aged rotavirus immunization in the second year. An additional dose of rotavirus vaccine may enhance the immune response and lengthen the period of protection against disease, but coadministration of this dose should not interfere with immune responses to concurrently given vaccines. A total of 480 9-month-old participants from Matlab, Bangladesh, were enrolled in a study with a primary objective to establish noninferiority of concomitant administration of measles-rubella vaccine (MR) and a third dose of human rotavirus vaccine (HRV; MR + HRV), compared with MR given alone. Secondary objectives included noninferiority of rubella antibody seroconversion and evaluating rotavirus IgA/IgG seroresponses in MR + HRV recipients. Two months after vaccination, 75.3% and 74.3% of MR + HRV and MR recipients, respectively, had seroprotective levels of measles virus antibodies; 100.0% and 99.6%, respectively, showed anti-rubella virus immunoglobulin G (IgG) seroprotection. In the MR + HRV group, antirotavirus immunoglobulin A and IgG seropositivity frequencies before vaccination (52.7% and 66.3%, respectively) increased to 69.6% and 88.3% after vaccination. Vaccine-induced measles and rubella antibody responses are not negatively affected by concomitant administration of HRV. The HRV dose increases antirotavirus serum antibody titers and the proportion of infants with detectable antirotavirus antibody. NCT01700621. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.
Wyatt, R G; Greenberg, H B; James, W D; Pittman, A L; Kalica, A R; Flores, J; Chanock, R M; Kapikian, A Z
Twenty different human rotavirus reassortants were characterized serologically by a plaque reduction assay as belonging to one of three distinct serotypes. Fourteen were similar if not identical to our prototype Wa strain; two were like the prototype DS-1 strain, and four belonged to a third serotype for which a prototype has not yet been selected. Hyperimmune sera raised against the three serotypes were required to distinguish among them, since postinfection sera had lower titers and were more cross-reactive than hyperimmune sera. These results confirmed the ability of a qualitative cytopathic neutralization test to predict correctly the Wa or DS-1 serotype. A strain of rhesus rotavirus (MMU 18006) was identified as belonging to the newly defined third serotype. Finally, an attempt was made to correlate previously published serotype analysis by neutralization of fluorescent cell-forming units with the results determined by the plaque reduction neutralization assay.
Saif, L J; Ward, L A; Yuan, L; Rosen, B I; To, T L
Gnotobiotic piglets serve as a useful animal model for studies of human rotavirus infections, including disease pathogenesis and immunity. An advantage of piglets over laboratory animal models is their prolonged susceptibility to human rotavirus-induced disease, permitting cross-protection studies and an analysis of active immunity. Major advances in rotavirus research resulting from gnotobiotic piglet studies include: 1) the adaptation of the first human rotavirus to cell culture after passage and amplification in piglets; 2) delineation of the independent roles of the two rotavirus outer capsid proteins (VP4 and VP7) in induction of neutralizing antibodies and cross-protection; and 3) recognition of a potential role for a nonstructural protein (NSP4) in addition to VP4 and VP7, in rotavirus virulence. Current studies of the pathogenesis of group A human rotavirus infections in gnotobiotic piglets in our laboratory have confirmed that villous atrophy is induced in piglets given virulent but not cell culture attenuated human rotavirus (G1, P1A, Wa strain) and have revealed that factors other than villous atrophy may contribute to the early diarrhea induced. A comprehensive examination of these factors, including a proposed role for NSP4 in viral-induced cytopathology, may reveal new mechanisms for induction of viral diarrhea. Finally, to facilitate and improve rotavirus vaccination strategies, our current emphasis is on the identification of correlates of protective active immunity in the piglet model of human rotavirus-induced diarrhea. Comparison of cell-mediated and antibody immune responses induced by infection with a virulent human rotavirus (to mimic host response to natural infection) with those induced by a live attenuated human rotavirus (to mimic attenuated oral vaccines) in the context of homotypic protection has permitted an analysis of correlates of protective immunity. Results of these studies have indicated that the magnitude of the immune response
Midthun, K; Greenberg, H B; Hoshino, Y; Kapikian, A Z; Wyatt, R G; Chanock, R M
A series of reassortants was isolated from coinfection of cell cultures with a wild-type animal rotavirus and a "noncultivatable" human rotavirus. Wild-type bovine rotavirus (UK strain) was reassorted with human rotavirus strains D, DS-1, and P; wild-type rhesus rotavirus was reassorted with human rotavirus strains D and DS-1. The D, DS-1, and P strains represent human rotavirus serotypes 1, 2, and 3, respectively. Monospecific antiserum (to bovine rotavirus, NCDV strain) or a set of monoclonal antibodies to the major outer capsid neutralization glycoprotein, VP7 (of the rhesus rotavirus), was used to select for reassortants with human rotavirus neutralization specificity. This selection technique yielded many reassortants which received only the gene segment coding for the major neutralization protein from the human rotavirus parent, whereas the remaining genes were derived from the animal rotavirus parent. Single human rotavirus gene substitution reassortants of this sort represent potential live vaccine strains.
Wang, Haifeng; Gao, Kan; Wen, Ke; Allen, Irving Coy; Li, Guohua; Zhang, Wenming; Kocher, Jacob; Yang, Xingdong; Giri-Rachman, Ernawati; Li, Guan-Hong; Clark-Deener, Sherrie; Yuan, Lijuan
A better understanding of mechanisms underlying dose-effects of probiotics in their applications as treatments of intestinal infectious or inflammatory diseases and as vaccine adjuvant is needed. In this study, we evaluated the modulatory effects of Lactobacillus rhamnosus GG (LGG) on transplanted human gut microbiota (HGM) and on small intestinal immune cell signaling pathways in gnotobiotic pigs vaccinated with an oral attenuated human rotavirus (AttHRV) vaccine. Neonatal HGM transplanted pigs were given two doses of AttHRV on 5 and 15 days of age and were divided into three groups: none-LGG (AttHRV), 9-doses LGG (AttHRV + LGG9X), and 14-doses LGG (AttHRV + LGG14X) (n = 3-4). At post-AttHRV-inoculation day 28, all pigs were euthanized and intestinal contents and ileal tissue and mononuclear cells (MNC) were collected. AttHRV + LGG14X pigs had significantly increased LGG titers in the large intestinal contents and shifted structure of the microbiota as indicated by the formation of a cluster that is separated from the cluster formed by the AttHRV and AttHRV + LGG9X pigs. The increase in LGG titers concurred with significantly increased ileal HRV-specific IFN-γ producing T cell responses to the AttHRV vaccine reported in our previous publication, suggesting pro-Th1 adjuvant effects of the LGG. Both 9- and 14-doses LGG fed pig groups had significantly higher IkBα level and p-p38/p38 ratio, while significantly lower p-ERK/ERK ratio than the AttHRV pigs, suggesting activation of regulatory signals during immune activation. However, 9-doses, but not 14-doses LGG fed pigs had enhanced IL-6, IL-10, TNF-α, TLR9 mRNA levels, and p38 MAPK and ERK expressions in ileal MNC. Increased TLR9 mRNA was in parallel with higher mRNA levels of cytokines, p-NF-kB and higher p-p38/p38 ratio in MNC of the AttHRV + LGG9X pigs. The relationship between modulation of gut microbiota and regulation of host immunity by different doses of probiotics is complex. LGG
Davey, Heather M; Muscatello, David J; Wood, James G; Snelling, Thomas L; Ferson, Mark J; Macartney, Kristine K
Australia was one of the first countries to introduce nationally funded rotavirus vaccination. The program has had a substantial impact on both rotavirus and all-cause acute gastroenteritis (AGE) hospitalisations and rotavirus laboratory tests. Evidence for an impact on Emergency Department (ED) presentations is limited. This study assessed changes in ED presentations for rotavirus in children aged rotavirus vaccine (RV1, Rotarix(®), GlaxoSmithKline Australia Pty Ltd., Victoria, Australia). A time series analysis to examine trends in total non-admitted ED presentations for all-cause AGE and in the rotavirus-attributable fraction using data on rotavirus positive laboratory tests. A decline in the rate of non-admitted ED presentations for all-cause AGE was observed for all ages, being most notable in 1 year old children. Compared with the pre-vaccination period, we estimated the average weekly rate was lower across the first 4.5 years of the program for both all-cause AGE (18.3%; 70.5 versus 57.5 per 100,000 population) and rotavirus attributable (55.4%; 17.3 versus 7.7 per 100,000 population) presentations. In the fourth year of the program, estimated annual rotavirus attributable presentations were 77% lower than the pre-vaccination annual mean (996 versus 4300 per year). The program was associated with a substantial decline in rotavirus attributable non-admitted AGE presentations to ED among children aged <5 years. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.
Construction of four double gene substitution human x bovine rotavirus reassortant vaccine candidates: each bears two outer capsid human rotavirus genes, one encoding P serotype 1A and the other encoding G serotype 1, 2, 3, or 4 specificity.
Hoshino, Y; Jones, R W; Chanock, R M; Kapikian, A Z
Previously, four human x bovine rotavirus reassortant candidate vaccines, each of which derived ten genes from bovine rotavirus UK strain and only the outer capsid protein VP7-gene from human rotavirus strain D (G serotype 1), DS-1 (G serotype 2), P (G serotype 3), or ST3 (G serotype 4), were developed [Midthun et al., (1985): Journal of Virology 53:949-954; (1986): Journal of Clinical Microbiology 24:822-826]. Such human x bovine reassortant vaccines should theoretically provide antigenic coverage for the four epidemiologically most important VP7(G) serotypes 1, 2, 3, and 4. In an attempt to increase the antigenicity of VP7-based human x animal reassortant rotavirus vaccines which derive a single VP7-encoding gene from the human strain and the remaining ten genes from the animal strain, we generated double gene substitution reassortants. This was done by incorporating another protective antigen (VP4) of an epidemiologically important human rotavirus by crossing human rotavirus Wa strain (P serotype 1A), with each of the human x bovine single VP7-gene substitution rotavirus reassortants. In this way four separate double gene substitution rotavirus reassortants were generated. Each of these reassortants bears the VP4-encoding gene from human rotavirus Wa strain, the VP7-encoding gene from human rotavirus strain D, DS-1, P, or ST3, and the remaining nine genes from bovine rotavirus strain UK. The safety, antigenicity, and protective efficacy of individual components as well as combinations of strains are currently under evaluation.
Hruska, J F; Notter, M F; Menegus, M A; Steinhoff, M C
RNA polymerase activity was detected in six stools which were partially purified by high-speed centrifugation from infants with rotavirus gastroenteritis, but was not detected in five stools which were negative for rotavirus by counterimmunoelectrophoresis and radioimmunoassay. The polymerase activity was associated with the 1.38-g/ml rotavirus band after purification in a CsCl gradient. PMID:207902
Bui, Tammy; Li, Guohua; Kim, Inyoung; Wen, Ke; Twitchell, Erica L; Hualei, Shaoh; Ramesh, Ashwin K; Weiss, Mariah D; Yang, Xingdong; Glark-Deener, Sherrie G; Choy, Robert Km; Yuan, Lijuan
Diarrheal disease is the second leading cause of death in children younger than 5 y, and the most common cause of acute watery diarrhea in young children worldwide is rotaviral infection. Medicines to specifically reduce diarrhea would be a desirable adjunctive treatment to supportive fluid therapy to decrease the mortality rate of diarrheal diseases. In this study, we evaluated the efficacy of an antisecretory drug, racecadotril, in treating human rotavirus (HRV)-induced diarrhea in a neonatal gnotobiotic pig model. In total, 27 gnotobiotic pigs were randomly assigned (n = 9 per group) to receive either racecadotril, chlorpromazine (positive-control drug), or PBS (mock treatment) after inoculation with HRV. Pigs were weighed daily and rectal swabs were collected to determine fecal consistency scores and virus shedding. Rotaviral infection was confirmed by ELISA and cell culture immunofluorescence. Overall, the racecadotril-treated pigs had less severe illness than either the chlorpromazine- or mock-treated groups; this conclusion was supported by the lower fecal-consistency scores, shorter duration of diarrhea, and significant gain in body weight during the course of the study of the racecadotril-treated pigs. Through its influence on decreasing intestinal hypersecretion, racecadotril was better able to control the clinical signs of rotaviral infection in the gnotobiotic pigs. These results lend support for using racecadotril as a treatment for rotaviral diarrhea.
Chen, Y S; Vaughn, J M
The inactivation of single-particle stocks of human (type 2, Wa) and simian (SA-11) rotaviruses by chlorine dioxide was investigated. Experiments were conducted at 4 degrees C in a standard phosphate-carbonate buffer. Both virus types were rapidly inactivated, within 20 s under alkaline conditions, when chlorine dioxide concentrations ranging from 0.05 to 0.2 mg/liter were used. Similar reductions of 10(5)-fold in infectivity required additional exposure time of 120 s at 0.2 mg/liter for Wa and at 0.5 mg/liter for SA-11, respectively, at pH 6.0. The inactivation of both virus types was moderate at neutral pH, and the sensitivities to chlorine dioxide were similar. The observed enhancement of virucidal efficiency with increasing pH was contrary to earlier findings with chlorine- and ozone-treated rotavirus particles, where efficiencies decreased with increasing alkalinity. Comparison of 99.9% virus inactivation times revealed ozone to be the most effective virucidal agent among these three disinfectants. PMID:2160222
Midthun, K; Greenberg, H B; Hoshino, Y; Kapikian, A Z; Wyatt, R G; Chanock, R M
A series of reassortants was isolated from coinfection of cell cultures with a wild-type animal rotavirus and a "noncultivatable" human rotavirus. Wild-type bovine rotavirus (UK strain) was reassorted with human rotavirus strains D, DS-1, and P; wild-type rhesus rotavirus was reassorted with human rotavirus strains D and DS-1. The D, DS-1, and P strains represent human rotavirus serotypes 1, 2, and 3, respectively. Monospecific antiserum (to bovine rotavirus, NCDV strain) or a set of monoclon...
Gauchan, Punita; Sasaki, Eriko; Nakagomi, Toyoko; Do, Loan Phuong; Doan, Yen Hai; Mochizuki, Masami; Nakagomi, Osamu
Feline rotaviruses, members of the species Rotavirus A, are an infrequent source of zoonotic infections, and were previously shown by RNA-RNA hybridization assays to possess two distinct genomic RNA constellations, represented by strains FRV-1 and FRV64. Due to the lack of whole genome sequence information for FRV-1, human rotavirus strain AU-1 has been used as a surrogate for the genotype constellation of feline rotaviruses. The aim of this study was to determine the whole genome sequence of FRV-1 and FRV64 to help understand the genetic relationships among existing feline rotaviruses from the evolutionary perspective. The genotype constellations of FRV-1 and FRV64 were G3-P-I3-R3-C3-M3-A3-N3-T3-E3-H3 and G3-P-I3-R3-C2-M3-A9-N2-T3-E3-H6, respectively. FRV-1 has a genotype constellation identical to that of the AU-1 strain. Although for individual genes they shared lineages, with the exception of genes encoding VP2, VP6 and VP7, the sequence identity between FRV-1 and AU-1 was considered to be sufficiently high for the AU-1 to be regarded as an example of the direct transmission of a feline rotavirus to a child. On the other hand, the FRV64 strain was not only similar in all the 11 genome segments to another feline rotavirus strain, Cat97, but also to canine rotavirus strains (K9 and CU-1) and feline/canine-like human rotavirus strains (Ro1845 and HCR3A). In conclusion, this study revealed intermingled sharing of genotypes and lineages among feline rotaviruses, suggesting the occurrence of frequent reassortment events over the course of evolution to emerge in four genotype constellations represented by FRV-1, FRV64/Cat97, Cat2 and BA222 strains. © 2015 The Authors.
Lanata, C F; Black, R E; Flores, J; Lazo, F; Butron, B; Linares, A; Huapaya, A; Ventura, G; Gil, A; Kapikian, A Z
In a four cell trial, a single 10(4) plaque-forming unit dose of rhesus rotavirus (RRV) vaccine (serotype G3), a human rotavirus-rhesus rotavirus reassortant vaccine with serotype G1 specificity, a similar vaccine with serotype G2 specificity, or a placebo was administered with buffer orally at 2 months of age to 800 Peruvian infants. Only the RRV vaccine was associated with a febrile response (< 38 degrees C) that occurred in 9% of the infants on day 4 after vaccination. Diarrhea or other side-effects were not associated with administration of vaccine. Vaccine strains were shed by only 12-18% of the infants as determined by examination of a single stool specimen obtained on days 4 or 5 after vaccination. Fifty per cent of vaccines developed an IgA ELISA seroresponse; however, a serotype-specific seroresponse by plaque reduction neutralization was demonstrated in < 20% of the participants against each of the three candidate vaccine strains. Vaccine efficacy was evaluated by twice-weekly home surveillance for diarrheal diseases during 24 months post-immunization. Rotavirus diarrheal episodes were identified by ELISA. Only the RRV vaccine had a significant protective efficacy (29%, p = 0.03, chi-square test) against rotavirus diarrhea. Analysis of vaccine efficacy against rotavirus episodes of any severity in which no other enteropathogen was isolated showed a trend towards higher vaccine efficacy. In addition, a similar trend was observed in rotavirus-only episodes in which there was some degree of dehydration or when health services were utilized. Serotype G1 or G2 rotavirus strains were most prevalent during surveillance. Neither serotype G1 or serotype G2 vaccines were protective against serotype 1 or 2 rotavirus diarrhea, respectively. The serotype G2 vaccine was 84% protective against serotype 1 and 2 dehydrating rotavirus diarrhea in the small numbers of individuals evaluated. We conclude that one dose of 10(4) p.f.u. of the RRV, serotype G1, or serotype G2
Romero-Maraccini, Ofelia C.
Human rotavirus Wa and porcine rotavirus OSU solutions were irradiated with simulated solar UV and visible light in the presence of different photosensitizers dissolved in buffered solutions. For human rotavirus, the exogenous effects were greater than the endogenous effects under irradiation with full spectrum and UVA and visible light at 25 C. For porcine rotavirus, the exogenous effects with UVA and visible light irradiation were only observed at high temperatures, >40 C. The results from dark experiments conducted at different temperatures suggest that porcine rotavirus has higher thermostability than human rotavirus. Concentrations of 3′-MAP excited triplet states of 1.8 fM and above resulted in significant human rotavirus inactivation. The measured excited triplet state concentrations of ≤0.45 fM produced by UVA and visible light irradiation of natural dissolved organic matter solutions were likely not directly responsible for rotavirus inactivation. Instead, the linear correlation for human rotavirus inactivation rate constant (kobs) with the phenol degradation rate constant (kexp) found in both 1 mM NaHCO3 and 1 mM phosphate-buffered solutions suggested that OH radical was a major reactive species for the exogenous inactivation of rotaviruses. Linear correlations between rotavirus kobs and specific UV254 nm absorbance of two river-dissolved organic matter and two effluent organic matter isolates indicated that organic matter aromaticity may help predict formation of radicals responsible for rotavirus inactivation. The results from this study also suggested that the differences in rotavirus strains should be considered when predicting solar inactivation of rotavirus in sunlit surface waters. © 2013 American Chemical Society.
Armah, George; Lewis, Kristen D C; Cortese, Margaret M; Parashar, Umesh D; Ansah, Akosua; Gazley, Lauren; Victor, John C; McNeal, Monica M; Binka, Fred; Steele, A Duncan
The recommended schedule for receipt of 2-dose human rotavirus vaccine (HRV) coincides with receipt of the first and second doses of diphtheria, pertussis, and tetanus vaccine (ie, 6 and 10 weeks of age, respectively). Alternative schedules and additional doses of HRV have been proposed and may improve vaccine performance in low-income countries. In this randomized trial in rural Ghana, HRV was administered at ages 6 and 10 weeks (group 1), 10 and 14 weeks (group 2), or 6, 10, and 14 weeks (group 3). We compared serum antirotavirus immunoglobulin A (IgA) seroconversion (≥20 U/mL) and geometric mean concentrations (GMCs) between group 1 and groups 2 and 3. Ninety-three percent of participants (424 of 456) completed the study per protocol. In groups 1, 2, and 3, the IgA seroconversion frequencies among participants with IgA levels of correlate of protection, a postmarketing effectiveness study is required to determine whether the improvement in immune response translates into a public health benefit in low-income countries. NCT015751. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.
Barbova, A I
Adsorptive activity of enterosgel has been studied as applied to different strains of rotaviruses of man and animals. Optimal amounts of the sorbent and pH values of the reaction medium at which rotaviruses were most efficiently sorbed from the virus-containing liquid were determined experimentally.
Jun 17, 2014 ... transplacental antibodies and breast milk, which contain lactadherin.[11‑13] Repeated rotavirus ... the asymptomatic infection in older children and adults. Two licensed rotavirus vaccines have shown ... as age, sex, home address, onset of diarrhea, and sources of drinking water were obtained through a.
Background: Diarrhea is a major cause of childhood morbidity and mortality in the developing countries. Rotavirus is a major cause of acute watery diarrhea. Aim: This study aims at characterizing the prevalent rotavirus G-genotypes among under.five children presenting with acute watery diarrhea in Benin City, Nigeria.
Due to HIV/AIDS scourge in Kenya, it is possible that rotavirus-related gastroenteritis has been aggravated in adults. The Global Alliance for Immunizations has ranked rotavirus infection a priority for vaccine, and, to ensure its success, there is a need to document the local strain(s) circulating in different regions. Methods: A ...
Komoto, Satoshi; Tacharoenmuang, Ratana; Guntapong, Ratigorn; Ide, Tomihiko; Tsuji, Takao; Yoshikawa, Tetsushi; Tharmaphornpilas, Piyanit; Sangkitporn, Somchai; Taniguchi, Koki
The emergence and rapid spread of novel DS-1-like G1P human rotaviruses in Japan were recently reported. More recently, such intergenogroup reassortant strains were identified in Thailand, implying the ongoing spread of unusual rotavirus strains in Asia. During rotavirus surveillance in Thailand, three DS-1-like intergenogroup reassortant strains having G3P (RVA/Human-wt/THA/SKT-281/2013/G3P and RVA/Human-wt/THA/SKT-289/2013/G3P) and G2P (RVA/Human-wt/THA/LS-04/2013/G2P) genotypes were identified in fecal samples from hospitalized children with acute gastroenteritis. In this study, we sequenced and characterized the complete genomes of strains SKT-281, SKT-289, and LS-04. On whole genomic analysis, all three strains exhibited unique genotype constellations including both genogroup 1 and 2 genes: G3-P-I2-R2-C2-M2-A2-N2-T2-E2-H2 for strains SKT-281 and SKT-289, and G2-P-I2-R2-C2-M2-A2-N2-T2-E2-H2 for strain LS-04. Except for the G genotype, the unique genotype constellation of the three strains (P-I2-R2-C2-M2-A2-N2-T2-E2-H2) is commonly shared with DS-1-like G1P strains. On phylogenetic analysis, nine of the 11 genes of strains SKT-281 and SKT-289 (VP4, VP6, VP1-3, NSP1-3, and NSP5) appeared to have originated from DS-1-like G1P strains, while the remaining VP7 and NSP4 genes appeared to be of equine and bovine origin, respectively. Thus, strains SKT-281 and SKT-289 appeared to be reassortant strains as to DS-1-like G1P, animal-derived human, and/or animal rotaviruses. On the other hand, seven of the 11 genes of strain LS-04 (VP7, VP6, VP1, VP3, and NSP3-5) appeared to have originated from locally circulating DS-1-like G2P human rotaviruses, while three genes (VP4, VP2, and NSP1) were assumed to be derived from DS-1-like G1P strains. Notably, the remaining NSP2 gene of strain LS-04 appeared to be of bovine origin. Thus, strain LS-04 was assumed to be a multiple reassortment strain as to DS-1-like G1P, locally circulating
Full Text Available The emergence and rapid spread of novel DS-1-like G1P human rotaviruses in Japan were recently reported. More recently, such intergenogroup reassortant strains were identified in Thailand, implying the ongoing spread of unusual rotavirus strains in Asia. During rotavirus surveillance in Thailand, three DS-1-like intergenogroup reassortant strains having G3P (RVA/Human-wt/THA/SKT-281/2013/G3P and RVA/Human-wt/THA/SKT-289/2013/G3P and G2P (RVA/Human-wt/THA/LS-04/2013/G2P genotypes were identified in fecal samples from hospitalized children with acute gastroenteritis. In this study, we sequenced and characterized the complete genomes of strains SKT-281, SKT-289, and LS-04. On whole genomic analysis, all three strains exhibited unique genotype constellations including both genogroup 1 and 2 genes: G3-P-I2-R2-C2-M2-A2-N2-T2-E2-H2 for strains SKT-281 and SKT-289, and G2-P-I2-R2-C2-M2-A2-N2-T2-E2-H2 for strain LS-04. Except for the G genotype, the unique genotype constellation of the three strains (P-I2-R2-C2-M2-A2-N2-T2-E2-H2 is commonly shared with DS-1-like G1P strains. On phylogenetic analysis, nine of the 11 genes of strains SKT-281 and SKT-289 (VP4, VP6, VP1-3, NSP1-3, and NSP5 appeared to have originated from DS-1-like G1P strains, while the remaining VP7 and NSP4 genes appeared to be of equine and bovine origin, respectively. Thus, strains SKT-281 and SKT-289 appeared to be reassortant strains as to DS-1-like G1P, animal-derived human, and/or animal rotaviruses. On the other hand, seven of the 11 genes of strain LS-04 (VP7, VP6, VP1, VP3, and NSP3-5 appeared to have originated from locally circulating DS-1-like G2P human rotaviruses, while three genes (VP4, VP2, and NSP1 were assumed to be derived from DS-1-like G1P strains. Notably, the remaining NSP2 gene of strain LS-04 appeared to be of bovine origin. Thus, strain LS-04 was assumed to be a multiple reassortment strain as to DS-1-like G1P, locally
Pêra, Francisco F P G; Mutepfa, David L R; Khan, Ayesha M; Els, Johann H; Mbewana, Sandiswa; van Dijk, Alberdina A A; Rybicki, Edward P; Hitzeroth, Inga I
Human rotaviruses are the main cause of severe gastroenteritis in children and are responsible for over 500 000 deaths annually. There are two live rotavirus vaccines currently available, one based on human rotavirus serotype G1P, and the other a G1-G4 P pentavalent vaccine. However, the recent emergence of the G9 and other novel rotavirus serotypes in Africa and Asia has prompted fears that current vaccines might not be fully effective against these new varieties. We report an effort to develop an affordable candidate rotavirus vaccine against the new emerging G9P (RVA/Human-wt/ZAF/GR10924/1999/G9P) strain. The vaccine is based on virus-like particles which are both highly immunogenic and safe. The vaccine candidate was produced in Nicotiana benthamiana by transient expression, as plants allow rapid production of antigens at lower costs, without the risk of contamination by animal pathogens. Western blot analysis of plant extracts confirmed the successful expression of two rotavirus capsid proteins, VP2 and VP6. These proteins assembled into VLPs resembling native rotavirus particles when analysed by transmission electron microscopy (TEM). Expression of the rotavirus glycoprotein VP7 and the spike protein VP4 was also tried. However, VP7 expression caused plant wilting during the course of the time trial and expression could never be detected for either protein. We therefore created three fusion proteins adding the antigenic part of VP4 (VP8*) to VP6 in an attempt to produce more appropriately immunogenic particles. Fusion protein expression in tobacco plants was detected by western blot using anti-VP6 and anti-VP4 antibodies, but no regular particles were observed by TEM, even when co-expressed with VP2. Our results suggest that the rotavirus proteins produced in N. benthamiana are candidates for a subunit vaccine specifically for the G9P rotavirus strain. This could be more effective in developing countries, thereby possibly providing a higher
... are also common in babies with rotavirus.Before rotavirus vaccine, rotavirus disease was a common and serious health ... to 60 died. Since the introduction of the rotavirus vaccine, hospitalizations and emergency visits for rotavirus have dropped ...
Herrera Daniel; Vásquez Camilo; Corthésy Blaise E.; Franco M. A.; Angel Juana
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 a...
Full Text Available A non-human primate model was used to evaluate its potential for identification of rotavirus viral protein 6 (VP6 CD4+ T cell epitopes. Four juvenile rhesus macaques were inoculated with a mixed inoculum (G1P and G9P of human rotaviruses. Infection accompanied by G1P shedding was achieved in the two macaques that had no rotavirus immunoglobulin A (IgA in plasma. To measure the interferon gamma (IFN-γ and tumor necrosis factor (TNF anti-viral cytokines produced by peripheral CD4+ cells that recognize VP6 epitopes, whole blood cells from one infected macaque were stimulated in vitro with VP6 peptides. Stimulation with peptide pools derived from the simian rotavirus VP6 161–395 region revealed reactivity of CD4+ T cells with the VP6 281–331 domain. A VP6 301–315 region was identified as the epitope responsible for IFN-γ production while a broader VP6 293–327 domain was linked to TNF production. These results suggest that human rotavirus-infected macaques can be used for identification of additional epitopes and domains to address specific questions related to the development of pediatric vaccines.
Heide, van der R.; Koopmans, M.P.G.; Shekary, N.; Houwers, D.J.; Duynhoven, van Y.; Poel, van der W.H.M.
To gain more insight into interspecies transmission of rotavirus group A, human and animal fecal samples were collected between 1997 and 2001 in The Netherlands. A total of 110 human stool samples were successfully P and G genotyped by reverse transcriptase PCR. All strains belonged to the main
Chattha, Kuldeep S; Vlasova, Anastasia N; Kandasamy, Sukumar; Esseili, Malak A; Siegismund, Christine; Rajashekara, Gireesh; Saif, Linda J
Breast milk (colostrum [col]/milk) components and gut commensals play important roles in neonatal immune maturation, establishment of gut homeostasis and immune responses to enteric pathogens and oral vaccines. We investigated the impact of colonization by probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (Bb12) with/without col/milk (mimicking breast/formula fed infants) on B lymphocyte responses to an attenuated (Att) human rotavirus (HRV) Wa strain vaccine in a neonatal gnotobiotic pig model. Col/milk did not affect probiotic colonization in AttHRV vaccinated pigs. However, unvaccinated pigs fed col/milk shed higher numbers of probiotic bacteria in feces than non-col/milk fed colonized controls. In AttHRV vaccinated pigs, col/milk feeding with probiotic treatment resulted in higher mean serum IgA HRV antibody titers and intestinal IgA antibody secreting cell (ASC) numbers compared to col/milk fed, non-colonized vaccinated pigs. In vaccinated pigs without col/milk, probiotic colonization did not affect IgA HRV antibody titers, but serum IgG HRV antibody titers and gut IgG ASC numbers were lower, suggesting that certain probiotics differentially impact HRV vaccine responses. Our findings suggest that col/milk components (soluble mediators) affect initial probiotic colonization, and together, they modulate neonatal antibody responses to oral AttHRV vaccine in complex ways. Copyright © 2013 Elsevier Ltd. All rights reserved.
Background: Rotavirus (RV) is the most common cause of severe diarrhea in children <5 years of age worldwide accounting for 527,000 deaths annually. Over 80% of these deaths occur in South Asia and sub-Saharan Africa. RV vaccines have significantly reduced RV-associated morbidity and mortalities in several ...
The molecular epidemiology of rotavirus infection in white children in Pretoria was investigated over a 2-year period. Rotalvirus-positive specimens from 322 infants and young children submitted to private patl1ology laboratories were analysed by polyacrylamide-gel electrophoresis of the viral RNA. A predominance of long ...
Wen, Xiaobo; Cao, Dianjun; Jones, Ronald W.; Li, Jianping; Szu, Shousun; Hoshino, Yasutaka
Two currently licensed live oral rotavirus vaccines (Rotarix® and RotaTeq®) are highly efficacious against severe rotavirus diarrhea. However, the efficacy of such vaccines in selected low-income African and Asian countries is much lower than that in middle or high-income countries. Additionally, these two vaccines have recently been associated with rare case of intussusception in vaccinated infants. We developed a novel recombinant subunit parenteral rotavirus vaccine which may be more effective in low-income countries and also avert the potential problem of intussusception. Truncated recombinant VP8* (ΔVP8*) protein of human rotavirus strain Wa P, DS-1 P or 1076 P expressed in E. coli was highly soluble and was generated in high yield. Guinea pigs hyperimmunized intramuscularly with each of the ΔVP8* proteins (i.e., (P, P or P) developed high levels of homotypic as well as variable levels of heterotypic neutralizing antibodies. Moreover, the selected ΔVP8* proteins when administered to mice at a clinically relevant dosage, route and schedule, elicited high levels of serum anti-VP8* IgG and/or neutralizing antibodies. Our data indicated that the ΔVP8* proteins may be a plausible additional candidate as new parenteral rotavirus vaccines. PMID:22885016
Wen, Xiaobo; Cao, Dianjun; Jones, Ronald W; Li, Jianping; Szu, Shousun; Hoshino, Yasutaka
Two currently licensed live oral rotavirus vaccines (Rotarix® and RotaTeq®) are highly efficacious against severe rotavirus diarrhea. However, the efficacy of such vaccines in selected low-income African and Asian countries is much lower than that in middle or high-income countries. Additionally, these two vaccines have recently been associated with rare case of intussusception in vaccinated infants. We developed a novel recombinant subunit parenteral rotavirus vaccine which may be more effective in low-income countries and also avert the potential problem of intussusception. Truncated recombinant VP8* (ΔVP8*) protein of human rotavirus strain Wa P, DS-1 P or 1076 P expressed in Escherichia coli was highly soluble and was generated in high yield. Guinea pigs hyperimmunized intramuscularly with each of the ΔVP8* proteins (i.e., P, P or P) developed high levels of homotypic as well as variable levels of heterotypic neutralizing antibodies. Moreover, the selected ΔVP8* proteins when administered to mice at a clinically relevant dosage, route and schedule, elicited high levels of serum anti-VP8* IgG and/or neutralizing antibodies. Our data indicated that the ΔVP8* proteins may be a plausible additional candidate as new parenteral rotavirus vaccines. Published by Elsevier Ltd.
Do, Loan Phuong; Nakagomi, Toyoko; Nakagomi, Osamu
Rotavirus strains with a rearranged 11th genome segment may show super-short RNA electropherotypes. Examples from human strains were limited to seven strains, 69M, 57M, B37, Mc345, AU19, B4106 and BE2001, which have a variety of G and P genotypes. AU19 is a rare G1P human rotavirus strain detected in a Japanese infant with severe acute gastroenteritis. This study was undertaken to better understand the origin of AU19 by determining the genotype constellation of AU19. Upon nearly-full genome sequencing, AU19 had a G1-P-I5-R1-C1-M1-A8-N1-T1-E1-H2 genotype constellation. Possession of I5 and A8 genotypes is indicative of its porcine rotavirus origin, whereas possession of H2 genotype is indicative of its DS-1 like human rotavirus origin. At the phylogenetic lineage level for the genome segments that share the genotype between porcine and human rotaviruses, the VP1-4, VP7, NSP3-4 genes were most closely related to those of porcine rotaviruses, but the origin of the NSP2 gene was inconclusive. As to the NSP5 gene, the lineage containing AU19 and the other three super-short human strains, 69M, 57M and B37, carrying the H2 genotype (H2b) clustered with the lineage to which DS-1- like short strains belonged (H2a) albeit with an insignificant bootstrap support. Taken all these observations together, AU19 was likely to emerge as a consequence of interspecies transmission of a porcine rotavirus to a child coupled with the acquisition of a rare H2b genotype by genetic reassortment probably from a co-circulating human strain. The addition of the AU19 NSP5 sequence to much homogeneous H2b genotypes shared by previous super-short rotavirus strains made the genetic diversity of H2b genotypes as diverse as that of the H2a genotype, lending support to the hypothesis that super-short strains carrying H2b genotype have long been circulating unnoticed in the human population. Copyright © 2013 Elsevier B.V. All rights reserved.
Cheuvart, Brigitte; Neuzil, Kathleen M; Steele, A Duncan; Cunliffe, Nigel; Madhi, Shabir A; Karkada, Naveen; Han, Htay Htay; Vinals, Carla
Clinical trials of the human rotavirus vaccine Rotarix™ (RV1) have demonstrated significant reductions in severe rotavirus gastroenteritis (RVGE) in children worldwide. However, no correlate of vaccine efficacy (VE) has yet been established. This paper presents 2 analyses which aimed to investigate whether serum anti-RV IgA measured by ELISA 1 or 2 mo post-vaccination can serve as a correlate of efficacy against RVGE: (1) In a large Phase III efficacy trial (Rota-037), the Prentice criteria for surrogate endpoints was applied to anti-RV IgA seropositivity 1 mo post-vaccination. These criteria determine whether a significant vaccine group effect can be predicted from the surrogate, namely seropositivity (anti-RV IgA concentration>20 U/mL); (2) Among other GSK-sponsored RV1 VE studies, 8 studies which assessed immunogenicity at 1 or 2 mo post-vaccination in all or a sub-cohort of enrolled subjects and had at least 10 RVGE episodes were included in a meta-analysis to measure the regression between clinical VE and VE predicted from immunogenicity (VE1). In Rota-037, anti-RV IgA seropositivity post-vaccination was associated with a lower incidence of any or severe RVGE, however, the proportion of vaccine group effect explained by seropositivity was only 43.6% and 32.7% respectively. This low proportion was due to the vaccine group effect observed in seronegative subjects. In the meta-analysis, the slope of the regression between clinical VE and VE1 was statistically significant. These two independent analyses support the hypothesis that post-vaccination anti-RV IgA seropositivity (antibody concentration ≥20 U/mL) may serve as a useful correlate of efficacy in clinical trials of RV1 vaccines.
Madhi, Shabir A; Cunliffe, Nigel A; Steele, Duncan; Witte, Desirée; Kirsten, Mari; Louw, Cheryl; Ngwira, Bagrey; Victor, John C; Gillard, Paul H; Cheuvart, Brigitte B; Han, Htay H; Neuzil, Kathleen M
Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children. We conducted a randomized, placebo-controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total) and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live, oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine (in addition to one dose of placebo) or three doses of vaccine - the pooled vaccine group - or three doses of placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were graded with the use of the Vesikari scale. A total of 4939 infants were enrolled and randomly assigned to one of the three groups; 1647 infants received two doses of the vaccine, 1651 infants received three doses of the vaccine, and 1641 received placebo. Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year). Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group. Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life
Herrera, Daniel; Vásquez, Camilo; Corthésy, Blaise; Franco, Manuel A; Angel, Juana
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.
Tam, Ka Ian; Roy, Sunando; Esona, Mathew D; Jones, Starlene; Sobers, Stephanie; Morris-Glasgow, Victoria; Rey-Benito, Gloria; Gentsch, Jon R; Bowen, Michael D
Since 2004, the Pan American Health Organization (PAHO) has carried out rotavirus surveillance in Latin America and the Caribbean. Here we report the characterization of human rotavirus with the novel G-P combination of G4P, detected through PAHO surveillance in Barbados. Full genome sequencing of strain RVA/Human-wt/BRB/CDC1133/2012/G4P revealed that its genotype is G4-P-I1-R1-C1-M1-A8-N1-T1-E1-H1. The possession of a Genogroup 1 (Wa-like) backbone distinguishes this strain from other P rotavirus strains. Phylogenetic analyses suggested that this strain was likely generated by genetic reassortment between human, porcine and possibly other animal rotavirus strains and identified 7 lineages within the P genotype. The results of this study reinforce the potential role of interspecies transmission in generating human rotavirus diversity through reassortment. Continued surveillance is important to determine if rotavirus vaccines will protect against strains that express the P rotavirus genotype. Published by Elsevier B.V.
Goveia, Michelle G; Rodriguez, Zoe M; Dallas, Michael J; Itzler, Robbin F; Boslego, John W; Heaton, Penny M; DiNubile, Mark J
Premature infants seem to be at greater risk of hospitalization from rotavirus gastroenteritis than term infants. Safety and efficacy of the pentavalent human-bovine (WC3) reassortant rotavirus vaccine were assessed in premature infants enrolled in the large-scale, blinded, placebo-controlled rotavirus efficacy and safety trial (REST). Healthy infants 6-12 weeks of chronologic age at study entry were randomized to receive 3 oral doses of pentavalent rotavirus vaccine or placebo at 4- to 10-week intervals. Infants born at rotavirus gastroenteritis were defined as forceful vomiting and/or > or =3 watery or looser-than-normal stools within a 24-hour period, accompanied by detection of rotavirus antigen in the stool. A total of 2070 infants between 25 and 36 gestational weeks received at least 1 dose of vaccine or placebo; 1005 vaccine recipients and 1061 placebo recipients were evaluable for safety. Serious adverse events occurred in 55 vaccine recipients (5.5%) and 62 placebo recipients (5.8%). In a nested substudy of 308 premature infants evaluable for detailed safety (154 in each group), the frequencies of fever, diarrhea, vomiting, and irritability were comparable between vaccine and placebo recipients. Overall, 3 doses of the pentavalent vaccine reduced the rate of hospitalizations and emergency department visits in premature infants due to rotavirus gastroenteritis by 100% (95% CI: 82.2-100) compared with placebo. The vaccine also prevented 73.0% (95% CI: -2.2-95.2) of rotavirus gastroenteritis cases of any severity. In this post hoc analysis of healthy premature infants, the pentavalent rotavirus vaccine was generally well-tolerated and substantially reduced rotavirus-attributable hospitalizations and emergency department visits compared with placebo. Overall, vaccine safety and efficacy seemed to be generally comparable to the results in the REST study population as a whole. These results support vaccinating healthy premature infants on the same schedule as
Background Rotaviruses are the most important cause of severe acute gastroenteritis worldwide in children rotavirus vaccine Rotarix™ significantly reduced severe rotavirus gastroenteritis episodes in a Phase III clinical trial conducted in infants in South Africa and Malawi. This paper examines rotavirus vaccine efficacy in preventing severe rotavirus gastroenteritis, during infancy, caused by the various G and P rotavirus types encountered during the first rotavirus-season. Methods Healthy infants aged 5–10 weeks were enrolled and randomized into three groups to receive either two (10 and 14 weeks) or three doses of Rotarix™ (together forming the pooled Rotarix™ group) or three doses of placebo at a 6,10,14-week schedule. Weekly home visits were conducted to identify gastroenteritis episodes. Rotaviruses were detected by ELISA and genotyped by RT-PCR and nucleotide sequencing. The percentage of infants with severe rotavirus gastroenteritis caused by the circulating G and P types from 2 weeks post-last dose until one year of age and the corresponding vaccine efficacy was calculated with 95% CI. Results Overall, 4939 infants were vaccinated and 4417 (pooled Rotarix™ = 2974; placebo = 1443) were included in the per protocol efficacy cohort. G1 wild-type was detected in 23 (1.6%) severe rotavirus gastroenteritis episodes from the placebo group. This was followed in order of detection by G12 (15 [1%] in placebo) and G8 types (15 [1%] in placebo). Vaccine efficacy against G1 wild-type, G12 and G8 types were 64.1% (95% CI: 29.9%; 82%), 51.5% (95% CI:-6.5%; 77.9%) and 64.4% (95% CI: 17.1%; 85.2%), respectively. Genotype P was the predominant circulating P type and was detected in 38 (2.6%) severe rotavirus gastroenteritis cases in placebo group. The remaining circulating P types comprised of P (20 [1.4%] in placebo) and P (13 [0.9%] in placebo). Vaccine efficacy against P was 59.1% (95% CI: 32.8%; 75.3%), P was 70.9% (95% CI: 37
Cho, Min-Kyu; Jheong, Weon-Hwa; Lee, Sung-Geun; Park, Chul Jong; Jung, Kum Hee; Paik, Soon-Young
A rotavirus G1P strain C1-81 was isolated from a 5-month-old female infant admitted to hospital with fever and severe diarrhea in Incheon, South Korea. To investigate its full genomic relatedness and its group, the full genome of strain C1-81 was determined. Based on a full genome classification system, C1-81 was shown to possess the typical Wa-like genotype constellation: G1-P-I1-R1-C1-M1-A1-N1-T1-E1-H1. On the basis of sequence similarities, the strain was shown to be the closest related strain to contemporary human rotavirus strains with recent strains isolated in Asia. This C1-81 strain showed the highest degree of nucleic acid similarity (98.8% and 97%) to G1 B4633-03 and P (Thai-1604 and Dhaka8-02), respectively. This is the first report that group A rotavirus was analyzed with G1P in South Korea. The study of the complete genome of the virus will help understanding of the evolution of rotavirus. Copyright © 2012 Wiley Periodicals, Inc.
Full Text Available Abstract Background Rotaviruses are the most important cause of severe acute gastroenteritis worldwide in children Rotarix™ significantly reduced severe rotavirus gastroenteritis episodes in a Phase III clinical trial conducted in infants in South Africa and Malawi. This paper examines rotavirus vaccine efficacy in preventing severe rotavirus gastroenteritis, during infancy, caused by the various G and P rotavirus types encountered during the first rotavirus-season. Methods Healthy infants aged 5–10 weeks were enrolled and randomized into three groups to receive either two (10 and 14 weeks or three doses of Rotarix™ (together forming the pooled Rotarix™ group or three doses of placebo at a 6,10,14-week schedule. Weekly home visits were conducted to identify gastroenteritis episodes. Rotaviruses were detected by ELISA and genotyped by RT-PCR and nucleotide sequencing. The percentage of infants with severe rotavirus gastroenteritis caused by the circulating G and P types from 2 weeks post-last dose until one year of age and the corresponding vaccine efficacy was calculated with 95% CI. Results Overall, 4939 infants were vaccinated and 4417 (pooled Rotarix™ = 2974; placebo = 1443 were included in the per protocol efficacy cohort. G1 wild-type was detected in 23 (1.6% severe rotavirus gastroenteritis episodes from the placebo group. This was followed in order of detection by G12 (15 [1%] in placebo and G8 types (15 [1%] in placebo. Vaccine efficacy against G1 wild-type, G12 and G8 types were 64.1% (95% CI: 29.9%; 82%, 51.5% (95% CI:-6.5%; 77.9% and 64.4% (95% CI: 17.1%; 85.2%, respectively. Genotype P was the predominant circulating P type and was detected in 38 (2.6% severe rotavirus gastroenteritis cases in placebo group. The remaining circulating P types comprised of P (20 [1.4%] in placebo and P (13 [0.9%] in placebo. Vaccine efficacy against P was 59.1% (95% CI: 32.8%; 75.3%, P was 70.9% (95% CI: 37.5%; 87
Human and bovine rotavirus strain antigens for evaluation of immunogenicity in a randomized, double-blind, placebo-controlled trial of a single dose live attenuated tetravalent, bovine-human-reassortant, oral rotavirus vaccine in Indian adults.
Paul, Anu; Babji, Sudhir; Sowmyanarayanan, T V; Dhingra, Mandeep Singh; Ramani, Sasirekha; Kattula, Deepthi; Kang, Gagandeep
A single dose of live attenuated tetravalent (G1-G4) bovine human reassortant rotavirus vaccine (BRV-TV) was administered to healthy Indian adult volunteers, who were assessed for safety and immunogenicity of the vaccine with 3:1 randomization to vaccine or placebo. All 20 adult male volunteers in the study had rotavirus specific serum IgA at baseline. There were no side effects or adverse events reported. Administration of BRV-TV was not associated with fever, diarrhea, or altered liver transaminases. Rotavirus IgA seroconversion post single dose administration was 27%. This study shows that BRV-TV is non-reactogenic, safe and immunogenic in adults. The IgA units estimated for the same sample using human G1P rotavirus strain as the antigen were consistently higher than with the bovine G6P WC3 strain and the human G2P DS-1 strain antigen. The use of different human and bovine rotavirus strains as antigens in a quantitative rotavirus specific serum IgA assay resulted in different estimations of IgA antibody in the same sample. Copyright © 2014 Elsevier Ltd. All rights reserved.
Midthun, K; Kapikian, A Z
Rotavirus vaccine development has focused on the delivery of live attenuated rotavirus strains by the oral route. The initial "Jennerian" approach involving bovine (RIT4237, WC3) or rhesus (RRV) rotavirus vaccine candidates showed that these vaccines were safe, well tolerated, and immunogenic but induced highly variable rates of protection against rotavirus diarrhea. The goal of a rotavirus vaccine is to prevent severe illness that can lead to dehydration in infants and young children in both developed and developing countries. These studies led to the concept that a multivalent vaccine that represented each of the four epidemiologically important VP7 serotypes might be necessary to induce protection in young infants, the target population for vaccination. Human-animal rotavirus reassortants whose gene encoding VP7 was derived from their human rotavirus parent but whose remaining genes were derived from the animal rotavirus parent were developed as vaccine candidates. The greatest experience with a multivalent vaccine to date has been gained with the quadrivalent preparation containing RRV (VP7 serotype 3) and human-RRV reassortants of VP7 serotype 1, 2, and 4 specificity. Preliminary efficacy trial results in the United States have been promising, whereas a study in Peru has shown only limited protection. Human-bovine reassortant vaccines, including a candidate that contains the VP4 gene of a human rotavirus (VP4 serotype 1A), are also being studied.
Liu, Fangning; Li, Guohua; Wen, Ke; Bui, Tammy; Cao, Dianjun; Zhang, Yanming; Yuan, Lijuan
Previous studies of epithelial immune responses to rotavirus infection have been conducted in transformed cell lines. In this study, we evaluated a non-transformed porcine jejunum epithelial cell line (IPEC-J2) as an in-vitro model of rotavirus infection and probiotic treatment. Cell-culture-adapted porcine rotavirus (PRV) OSU strain, or human rotavirus (HRV) Wa strain, along with Lactobacillus acidophilus (LA) or Lactobacillus rhamnosus GG (LGG) were used to inoculate IPEC-J2 cells. LA or LGG treatment was applied pre- or post-rotavirus infection. We demonstrated that IPEC-J2 cells were productively infected by PRV. LA or LGG treatment of the cells did not reduce virus replication. PRV infection increased MUC3 mucin secretion. LGG treatment post-rotavirus infection reduced the mucin secretion response induced by PRV; LGG alone increased the production of membrane-associated MUC3 mucin. LA treatment prior to rotavirus infection significantly increased PRV replication and the IL-6 response to PRV infection, which is consistent with the adjuvant effect of LA. LGG treatment post-rotavirus infection downregulated the IL-6 response, confirming the anti-inflammatory effect of LGG. IPEC-J2 cells expressed toll-like receptor (TLR) 2, TLR3, and TLR9 constitutively. TLR2 expression was upregulated by LGG and peptidoglycan, corresponding to the decreased IL-6 response, indicating that the protective effect of LGG is associated with upregulation of TLR2 expression on intestinal epithelial cells. The IPEC-J2 cell model of PRV infection is a completely homologous system. It is a valuable model for studying the interactions among rotavirus-host-probiotics, and the mechanisms behind the immunomodulating effect of probiotic bacteria on innate immune responses.
Vollet, J J; Ericsson, C D; Gibson, G; Pickering, L K; DuPont, H L; Kohl, S; Conklin, R H
The role of human rotavirus in adult diarrhea was evaluated in 164 newly arrived US students attending summer school at an urban Mexican university. Rotavirus was identified in stool samples by electron microscopy. Rotavirus was found in 26 of 109 students with diarrhea (24%) and in 8 of 55 asymptomatic control students (15%). Although bacterial pathogens were recovered from virus positive students with diarrhea, viral shedding also occurred independently of other agents. Clinical disease in students excreting only rotavirus tended to be mild and was accompanied by a low density of viral shedding. Food consumption in the home and at public eating establishments was examined the week before illness. While the location of food consumption was found to be important in the acquisition of diarrhea, there was no apparent relationship of the site where meals were eaten and the acquisition of rotavirus by students newly arrived in Mexico. These data support our previous study in a US student population residing in a rural setting in Mexico and implicate rotavirus as a cause of diarrhea among students traveling to Mexico from the United States. The present study offers additional evidence that rotavirus infection in this population might be spread by a nonfood vehicle of transmission which differs from spread of enterotoxigenic E coli, Shigella, or Salmonella strains in the same population.
Generation and characterization of six single VP4 gene substitution reassortant rotavirus vaccine candidates: each bears a single human rotavirus VP4 gene encoding P serotype 1A or 1B and the remaining 10 genes of rhesus monkey rotavirus MMU18006 or bovine rotavirus UK.
Hoshino, Yasutaka; Jones, Ronald W; Chanock, Robert M; Kapikian, Albert Z
The global disease burden of rotavirus diarrhea in infants and young children has stimulated interest in the biological and clinical characteristics of these agents, leading to intensive efforts to develop a vaccine. A rhesus rotavirus (RRV)-based quadrivalent vaccine ("RotaShield") was licensed and administered to about 1 million infants and found to be highly effective. However, it was withdrawn because of a link with intussusception. This vaccine was developed according to a modified "Jennerian" approach in which one of the two major outer capsid proteins (VP7) shares neutralization specificity with one of the four epidemiologically important human rotavirus serotypes. The other outer capsid protein (VP4) is derived solely from RRV and is distinct from the VP4 of the four human rotavirus serotypes of epidemiologic importance. In an effort to further increase the immunogenicity of the existing VP7-based RRV quadrivalent vaccine, we generated three single VP4 gene substitution reassortant rotavirus candidate vaccines, each of which bears a single human rotavirus VP4 gene encoding P serotype 1A or 1B specificity while the remaining 10 genes are derived from the rhesus rotavirus. By incorporating one or two of these strains into the quadrivalent vaccine, a pentavalent or hexavalent RRV-based vaccine could be formulated thus providing antigenic coverage not only for VP7 serotype 1, 2, 3 and 4 but also for VP4 serotype 1A or 1B, thus possibly augmenting its immunogenicity. Similarly, three single VP4 gene (P1A or P1B) substitution reassortants have also been generated in a background of 10 bovine (UK) rotavirus genes for addition to a second generation UK-based quadrivalent vaccine.
B. R. Alkali
Full Text Available This study was conducted to detect and characterize prevalent human group A rotavirus strains from 200 diarrheic children in Sokoto, Nigeria, by ELISA, monoclonal antibody (Mab serotyping and Reverse Transcription-Polymerase Chain Reaction (RT-PCR techniques. Rotavirus was detected in 25.5% of the children. The G-serotypes observed in circulation were G4: 16 (59.3%, G1: 4 (14.8%, G2: 3 (11.1%, G3: 3 (11.1%, and G12: 1 (3.7%. The monoclonal antibody (Mab serotyping detected G1 and G3 but did not detect G4 and G2 serotypes. The Mab typing of the G1 and G3 serotypes was consistent with the result of the RT-PCR. The VP4 genotypes detected were P 3 (13%, P 11 (47.8%, and the rare human P genotype (P, found in 9 patients (39.1%. Nine strains identified with the common G and P combinations were G4 P 5 (56%, G4 P 1 (11%, G1 P 2 (22%, and G3 P 1 (11%, while seven strains with unusual combinations or rare G or P genotypes identified were G12 P 1 (14%, G2 P 2 (29%, and G4 P 4 (57%. To our knowledge this is the first molecular study of human rotavirus and report of rare human G and P serotypes in Sokoto State.
Medici, Maria Cristina; Tummolo, Fabio; Guerra, Paola; Arcangeletti, Maria Cristina; Chezzi, Carlo; De Conto, Flora; Calderaro, Adriana
Intragenotypic heterogeneity of co-circulating rotaviruses is remarkable. Sequence and phylogenetic analyses of the rotavirus VP7 and VP4 genes were performed on selected human G4P strains identified in Parma, Northern Italy, during 2004-2005 and 2008-2012. All the strains clustered into lineages Ic (VP7) and P-III (VP4) in different subclusters with a nucleotide sequence variation up to 4 %. VP7 and VP4 amino acid sequences of the Italian rotaviruses showed multiple changes with the corresponding reference strains as well as with vaccine viruses in the neutralizing epitopes. There is concern that the progressive intra-lineage diversification in the VP7 and VP4 through the accumulation of point mutations and amino acid differences between vaccine strains and currently circulating rotaviruses could generate, over the years, vaccine-resistant variants.
Nyaga, Martin M; Jere, Khuzwayo C; Esona, Mathew D; Seheri, Mapaseka L; Stucker, Karla M; Halpin, Rebecca A; Akopov, Asmik; Stockwell, Timothy B; Peenze, Ina; Diop, Amadou; Ndiaye, Kader; Boula, Angeline; Maphalala, Gugu; Berejena, Chipo; Mwenda, Jason M; Steele, A Duncan; Wentworth, David E; Mphahlele, M Jeffrey
Group A rotaviruses (RVA) are among the main global causes of severe diarrhea in children under the age of 5years. Strain diversity, mixed infections and untypeable RVA strains are frequently reported in Africa. We analysed rotavirus-positive human stool samples (n=13) obtained from hospitalised children under the age of 5years who presented with acute gastroenteritis at sentinel hospital sites in six African countries, as well as bovine and porcine stool samples (n=1 each), to gain insights into rotavirus diversity and evolution. Polyacrylamide gel electrophoresis (PAGE) analysis and genotyping with G-(VP7) and P-specific (VP4) typing primers suggested that 13 of the 15 samples contained more than 11 segments and/or mixed G/P genotypes. Full-length amplicons for each segment were generated using RVA-specific primers and sequenced using the Ion Torrent and/or Illumina MiSeq next-generation sequencing platforms. Sequencing detected at least one segment in each sample for which duplicate sequences, often having distinct genotypes, existed. This supported and extended the PAGE and RT-PCR genotyping findings that suggested these samples were collected from individuals that had mixed rotavirus infections. The study reports the first porcine (MRC-DPRU1567) and bovine (MRC-DPRU3010) mixed infections. We also report a unique genome segment 9 (VP7), whose G9 genotype belongs to lineage VI and clusters with porcine reference strains. Previously, African G9 strains have all been in lineage III. Furthermore, additional RVA segments isolated from humans have a clear evolutionary relationship with porcine, bovine and ovine rotavirus sequences, indicating relatively recent interspecies transmission and reassortment. Thus, multiple RVA strains from sub-Saharan Africa are infecting mammalian hosts with unpredictable variations in their gene segment combinations. Whole-genome sequence analyses of mixed RVA strains underscore the considerable diversity of rotavirus sequences and
Maldonado, Antonio; Franco, María C; Blanco, Alberto; Villalobos de B, Luz; Martínez, Rosa; Hagel, Isabel; González, Rosabel; Bastardo, Jesús W
The detection rate of group A human rotavirus (HRV-A), as well as its association with clinical and epidemiological parameters, was studied in children younger than 5 years old with acute diarrhea attending to the University Hospital "Antonio Patricio de Alcalá" of Cumaná, between march 2006 and september 2007. Of 241 fecal samples collected in this study, 47 (19.5%) were positive to HRV-A by immunoassay. Rotavirus were present throughout the study and the major detection rates were on march, april and may of 2006 (rates were 30,0%, 28,6% y 43,8%, respectively) and september of 2007 (37,5%). Thirty four percent of cases with HRV-A occurred in children of 7 - 12 months and males were the most affected (55.3%), as well as the worker and marginal socioeconomic classes (72,4%). Children that not received maternal feeding were the group mainly infected by HRV-A (61.7%). Most of the children (72.4%) had one to four evacuations/day, with few vomits (38.2%) and fever (10.6%). Almost all the feces (83.0%) had a liquid or semi-liquid aspect. When these results were compared with previous data of the same geographic area, we observed a two-fold decrease of the detection rate of HRV-A and the clinical symptoms were the same as reported by other authors. Of 32 children vaccinated against rotavirus, 30 (93.8%) did not have HVR-A in their feces and there was a significant association between the vaccinated children and protection.
Deal, Emily M; Jaimes, Maria C; Crawford, Sue E; Estes, Mary K; Greenberg, Harry B
.... Although increased levels of systemic type I interferon (IFNalpha and beta) correlate with accelerated resolution of rotavirus disease, multiple rotavirus strains, including rhesus rotavirus (RRV...
Varyukhina, Svetlana; Freitas, Miguel; Bardin, Sabine; Robillard, Emilie; Tavan, Emmanuelle; Sapin, Catherine; Grill, Jean-Pierre; Trugnan, Germain
Rotaviruses attach to intestinal cells in a process that requires glycan recognition. Some bacteria from the gut microflora have been shown to modify cell-surface glycans. In this study, human intestinal cultured cells were incubated with bacteria-derived soluble factors and infected with rotavirus. Results show that only bacterial soluble factors that increase cell-surface galactose namely, those of Bacteroides thetaiotaomicron and Lactobacillus casei were able to efficiently block rotavirus infections. Increasing cell-surface galactose using galactosyltransferase resulted in a similar blockage of rotavirus infections. These results indicate that manipulation of cell-surface intestinal glycans by bacterial soluble factors can prevent rotavirus infection in a species-specific manner, and should now be considered a potential therapeutic approach against rotavirus infection. Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
Yodmeeklin, Arpaporn; Khamrin, Pattara; Chuchaona, Watchaporn; Kumthip, Kattareeya; Kongkaew, Aphisek; Vachirachewin, Ratchaya; Okitsu, Shoko; Ushijima, Hiroshi; Maneekarn, Niwat
Whole genomes of G9P human (RVA/Human-wt/THA/CMH-S070-13/2013/G9P) and porcine (RVA/Pig-wt/THA/CMP-015-12/2012/G9P) rotaviruses concurrently detected in the same geographical area in northern Thailand were sequenced and analyzed for their genetic relationships using bioinformatic tools. The complete genome sequence of human rotavirus RVA/Human-wt/THA/CMH-S070-13/2013/G9P was most closely related to those of porcine rotavirus RVA/Pig-wt/THA/CMP-015-12/2012/G9P and to those of porcine-like human and porcine rotaviruses reference strains than to those of human rotavirus reference strains. The genotype constellation of G9P detected in human and piglet were identical and displayed as the G9-P-I5-R1-C1-M1-A8-N1-T1-E1-H1 genotypes with the nucleotide sequence identities of VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4, and NSP5 at 99.0%, 99.5%, 93.2%, 97.7%, 97.7%, 85.6%, 89.5%, 93.2%, 92.9%, 94.0%, and 98.1%, respectively. The findings indicate that human rotavirus strain RVA/Human-wt/THA/CMH-S070-13/2013/G9P containing the genome segments of porcine genetic backbone is most likely a human rotavirus of porcine origin. Our data provide an evidence of interspecies transmission and whole-genome transmission of nonreassorted G9P porcine RVA to human occurring in nature in northern Thailand. Copyright © 2016. Published by Elsevier B.V.
Tam, Ka Ian; Roy, Sunando; Esona, Mathew D.; Jones, Starlene; Sobers, Stephanie; Morris-Glasgow, Victoria; Rey-Benito, Gloria; Gentsch, Jon R.; Bowen, Michael D.
Since 2004, the Pan American Health Organization (PAHO) has carried out rotavirus surveillance in Latin America and the Caribbean. Here we report the characterization of human rotavirus with the novel G-P combination of G4P, detected through PAHO surveillance in Barbados. Full genome sequencing of strain RVA/Human-wt/BRB/CDC1133/2012/G4P revealed that its genotype is G4-P-I1-R1-C1-M1-A8-N1-T1-E1-H1. The possession of a Genogroup 1 (Wa-like) backbone distinguishes this strain from ...
Lynch, Maureen; Bresee, Joseph S.; Gentsch, Jon R.; Glass, Roger I.
The past few years have seen important developments in understanding the epidemiological and virological characteristics of rotaviruses, and rapid progress has been made in rotavirus vaccine development, but further challenges remain before a vaccine is introduced into widespread use. The licensure of the first rotavirus vaccine, a tetravalent rhesus-based rotavirus vaccine, in the United States in 1998, marked a significant advance in preventing the morbidity associated with rotavirus diarrhea. The association between the tetravalent rhesus-based rotavirus vaccine and intussusception has created significant hurdles as well as new opportunities to study the pathogenesis of rotavirus and rotavirus vaccine infection. Several other rotavirus vaccine candidates are in late stages of development, and results from trials have been encouraging.
Emily M Deal
Full Text Available Rotaviruses are the leading cause of severe dehydrating diarrhea in children worldwide. Rotavirus-induced immune responses, especially the T and B cell responses, have been extensively characterized; however, little is known about innate immune mechanisms involved in the control of rotavirus infection. Although increased levels of systemic type I interferon (IFNalpha and beta correlate with accelerated resolution of rotavirus disease, multiple rotavirus strains, including rhesus rotavirus (RRV, have been demonstrated to antagonize type I IFN production in a variety of epithelial and fibroblast cell types through several mechanisms, including degradation of multiple interferon regulatory factors by a viral nonstructural protein. This report demonstrates that stimulation of highly purified primary human peripheral plasmacytoid dendritic cells (pDCs with either live or inactivated RRV induces substantial IFNalpha production by a subset of pDCs in which RRV does not replicate. Characterization of pDC responses to viral stimulus by flow cytometry and Luminex revealed that RRV replicates in a small subset of human primary pDCs and, in this RRV-permissive small subset, IFNalpha production is diminished. pDC activation and maturation were observed independently of viral replication and were enhanced in cells in which virus replicates. Production of IFNalpha by pDCs following RRV exposure required viral dsRNA and surface proteins, but neither viral replication nor activation by trypsin cleavage of VP4. These results demonstrate that a minor subset of purified primary human peripheral pDCs are permissive to RRV infection, and that pDCs retain functionality following RRV stimulus. Additionally, this study demonstrates trypsin-independent infection of primary peripheral cells by rotavirus, which may allow for the establishment of extraintestinal viremia and antigenemia. Importantly, these data provide the first evidence of IFNalpha induction in primary
Deal, Emily M; Jaimes, Maria C; Crawford, Sue E; Estes, Mary K; Greenberg, Harry B
Rotaviruses are the leading cause of severe dehydrating diarrhea in children worldwide. Rotavirus-induced immune responses, especially the T and B cell responses, have been extensively characterized; however, little is known about innate immune mechanisms involved in the control of rotavirus infection. Although increased levels of systemic type I interferon (IFNalpha and beta) correlate with accelerated resolution of rotavirus disease, multiple rotavirus strains, including rhesus rotavirus (RRV), have been demonstrated to antagonize type I IFN production in a variety of epithelial and fibroblast cell types through several mechanisms, including degradation of multiple interferon regulatory factors by a viral nonstructural protein. This report demonstrates that stimulation of highly purified primary human peripheral plasmacytoid dendritic cells (pDCs) with either live or inactivated RRV induces substantial IFNalpha production by a subset of pDCs in which RRV does not replicate. Characterization of pDC responses to viral stimulus by flow cytometry and Luminex revealed that RRV replicates in a small subset of human primary pDCs and, in this RRV-permissive small subset, IFNalpha production is diminished. pDC activation and maturation were observed independently of viral replication and were enhanced in cells in which virus replicates. Production of IFNalpha by pDCs following RRV exposure required viral dsRNA and surface proteins, but neither viral replication nor activation by trypsin cleavage of VP4. These results demonstrate that a minor subset of purified primary human peripheral pDCs are permissive to RRV infection, and that pDCs retain functionality following RRV stimulus. Additionally, this study demonstrates trypsin-independent infection of primary peripheral cells by rotavirus, which may allow for the establishment of extraintestinal viremia and antigenemia. Importantly, these data provide the first evidence of IFNalpha induction in primary human pDCs by a ds
Swiatek, Dayna L; Palombo, Enzo A; Lee, Alvin; Coventry, Michael J; Britz, Margaret L; Kirkwood, Carl D
This study describes the characterisation of G8 rotavirus strains isolated from humans with acute gastroenteritis. Six G8 strains were detected in Australia between 2002 and 2008. Four were G8P strains, one was G8P+ and one was G8 P non-typeable. By polyacrylamide gel electrophoresis and enzyme immunoassay analysis, four G8 strains with visible RNA exhibited a long electropherotype and five G8 strains displayed subgroup I specificity. Sequence analysis of the VP7 gene indicated that the G8 strains exhibited the highest nucleotide and amino acid identity with a G8P bovine rotavirus strain detected in Japan. VP4 sequence data of one G8P strain revealed that the closest identity was to another human-bovine-like strain detected in Australia, MG6, a G6P strain. The identification of G8 strains causing disease further extends the number of G8P strains detected in Australian children, and indicates that there is a rare but ongoing presence of uncommon human strains within the community in Australia. Copyright 2009 Elsevier B.V. All rights reserved.
Cheuvart, Brigitte; Friedland, Leonard R; Abu-Elyazeed, Remon; Han, Htay Htay; Guerra, Yolanda; Verstraeten, Thomas
An oral, live attenuated human rotavirus vaccine, RIX4414 has been developed to prevent rotavirus gastroenteritis. An integrated safety summary of 8 randomized, placebo-controlled, double-blind phase II and III trials of vaccine at potency licensed for use worldwide was performed. Healthy 1- to 18-week-old infants (N = 71209) were enrolled to receive 2 doses of RIX4414/placebo according to 0, 1 or 0, 2 month schedules. Solicited (fever, fussiness/irritability, loss of appetite, vomiting, diarrhea, cough/rhinorrhea) and unsolicited adverse events (AEs) were recorded for 8 days and 31 days, respectively, after each dose. Serious adverse events (SAEs) including intussusception and death were collected throughout the entire study periods. Potential imbalances were defined as the 95% confidence interval (CI) for the relative risk (RR) stratified by trials excluding "1." Solicited AEs were evaluated in 3286 RIX4414 vaccinees and 2015 placebo recipients. Among solicited AEs, no imbalance was noted between groups. SAEs, including death and intussusception, were evaluated in 36755 RIX4414 and 34454 placebo recipients. Within 31 days after each dose, no imbalances were noted between the groups for all SAEs (RR = 0.9; 95% CI: 0.81, 1.01), deaths (RR = 1.64; 95% CI: 0.92, 3.02), and intussusception (RR 1.23; 95% CI: 0.41, 3.90). SAEs because of gastrointestinal diseases including diarrhea, gastroenteritis (all cause and due to rotavirus), dehydration, and intestinal ileus occurred significantly less often in RIX4414 than placebo recipients. Across the phase II and III clinical trials, the reactogenicity and safety profile between RIX4414 and placebo was similar, in particular with no increased risk of intussusception.
Trinh, Quang Duy; Nguyen, Tuan Anh; Phan, Tung Gia; Khamrin, Pattara; Yan, Hainian; Hoang, Phuc Le; Maneekarn, Niwat; Li, Yan; Yagyu, Fumihiro; Okitsu, Shoko; Ushijima, Hiroshi
Over the last decade, rotavirus G1 has represented the most common genotype worldwide. Since 2000, the prevalence of rotavirus G1 has decreased in some countries such as Japan and China. To monitor the trend of the VP7 encoding gene of rotavirus G1, we performed a sequence analysis of 74 G1 rotavirus strains isolated in Japan, China, Thailand, and Vietnam during the period from 2002 to 2005. The phylogenetic tree showed that all of the studied G1 strains from the four countries clustered into lineage III, the same as the majority of the G1 strains isolated in China and Japan in 1990 and 1991. Examination of the deduced amino acid sequences of the G1 strains from China and Japan revealed an amino acid substitution at position 91 (Asn instead of Thr) in antigenic region A when compared to the G1 strains isolated in China and Japan in 1990, 1991, and global reference strains. For the G1 strains from Thailand and Vietnam, there were three amino acid substitutions, not belonging to any antigenic regions. The study showed that there have been no considerable changes of human rotavirus G1 isolated in Japan, China, Thailand, and Vietnam. Further studies need to be carried out for a better understanding of why such changes in the prevalence of rotavirus G1 occur in these countries.
Esona, Mathew D; Page, Nicola A; Akran, Veronique A; Armah, George E; Steele, A Duncan
During routine rotavirus surveillance projects in Cameroon and Cote d'Ivoire, 2 fecal samples collected from 2 children 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 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 G10 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.
... Organization PATH's Rotavirus Vaccine Program American Academy of Pediatrics ... fight bacteria not viruses. Rotavirus infection can cause severe vomiting and diarrhea. This can lead to dehydration (loss of body ...
Lack of Correlation between Virus Barosensitivity and the Presence of a Viral Envelope during Inactivation of Human Rotavirus, Vesicular Stomatitis Virus, and Avian Metapneumovirus by High-Pressure Processing▿
Lou, Fangfei; Neetoo, Hudaa; Li, Junan; Chen, Haiqiang; Li, Jianrong
High-pressure processing (HPP) is a nonthermal technology that has been shown to effectively inactivate a wide range of microorganisms. However, the effectiveness of HPP on inactivation of viruses is relatively less well understood. We systematically investigated the effects of intrinsic (pH) and processing (pressure, time, and temperature) parameters on the pressure inactivation of a nonenveloped virus (human rotavirus [HRV]) and two enveloped viruses (vesicular stomatitis virus [VSV] and avian metapneumovirus [aMPV]). We demonstrated that HPP can efficiently inactivate all tested viruses under optimal conditions, although the pressure susceptibilities and the roles of temperature and pH substantially varied among these viruses regardless of the presence of a viral envelope. We found that VSV was much more stable than most food-borne viruses, whereas aMPV was highly susceptible to HPP. When viruses were held for 2 min under 350 MPa at 4°C, 1.1-log, 3.9-log, and 5.0-log virus reductions were achieved for VSV, HRV, and aMPV, respectively. Both VSV and aMPV were more susceptible to HPP at higher temperature and lower pH. In contrast, HRV was more easily inactivated at higher pH, although temperature did not have a significant impact on inactivation. Furthermore, we demonstrated that the damage of virion structure by disruption of the viral envelope and/or capsid is the primary mechanism underlying HPP-induced viral inactivation. In addition, VSV glycoprotein remained antigenic although VSV was completely inactivated. Taken together, our findings suggest that HPP is a promising technology to eliminate viral contaminants in high-risk foods, water, and other fomites. PMID:22003028
Medici, Maria Cristina; Tummolo, Fabio; Martella, Vito; Arcangeletti, Maria Cristina; De Conto, Flora; Chezzi, Carlo; Fehér, Enikő; Marton, Szilvia; Calderaro, Adriana; Bányai, Krisztián
Group C rotaviruses (RVC) are enteric pathogens of humans and animals. Whole-genome sequences are available only for few RVCs, leaving gaps in our knowledge about their genetic diversity. We determined the full-length genome sequence of two human RVCs (PR2593/2004 and PR713/2012), detected in Italy from hospital-based surveillance for rotavirus infection in 2004 and 2012. In the 11 RNA genomic segments, the two Italian RVCs segregated within separate intra-genotypic lineages showed variation ranging from 1.9 % (VP6) to 15.9 % (VP3) at the nucleotide level. Comprehensive analysis of human RVC sequences available in the databases allowed us to reveal the existence of at least two major genome configurations, defined as type I and type II. Human RVCs of type I were all associated with the M3 VP3 genotype, including the Italian strain PR2593/2004. Conversely, human RVCs of type II were all associated with the M2 VP3 genotype, including the Italian strain PR713/2012. Reassortant RVC strains between these major genome configurations were identified. Although only a few full-genome sequences of human RVCs, mostly of Asian origin, are available, the analysis of human RVC sequences retrieved from the databases indicates that at least two intra-genotypic RVC lineages circulate in European countries. Gathering more sequence data is necessary to develop a standardized genotype and intra-genotypic lineage classification system useful for epidemiological investigations and avoiding confusion in the literature.
Melisa Berenice Bonica
Full Text Available Group A rotaviruses (RVA are responsible for causing infantile diarrhea both in humans and animals. The molecular characteristics of lapine RVA strains are only studied to a limited extent and so far G3P and G3P were found to be the most common G/P-genotypes. During the 2012-2013 rotavirus season in Belgium, a G3P RVA strain was isolated from stool collected from a two-year-old boy. We investigated whether RVA/Human-wt/BEL/BE5028/2012/G3P is completely of lapine origin or the result of reassortment event(s. Phylogenetic analyses of all gene segments revealed the following genotype constellation: G3-P-I2-R2-C2-M3-A9-N2-T6-E5-H3 and indicated that BE5028 probably represents a rabbit to human interspecies transmission able to cause disease in a human child. Interestingly, BE5028 showed a close evolutionary relationship to RVA/Human-wt/BEL/B4106/2000/G3P, another lapine-like strain isolated in a Belgian child in 2000. The phylogenetic analysis of the NSP3 segment suggests the introduction of a bovine(-like NSP3 into the lapine RVA population in the past 12 years. Sequence analysis of NSP5 revealed a head-to-tail partial duplication, combined with two short insertions and a deletion, indicative of the continuous circulation of this RVA lineage within the rabbit population.
Objectives: Rotaviruses have a wide host range, infecting many animal species as well as humans. The segmented nature of the genome suggests that rotaviruses are able to form new strains by a mechanism of reassortment. Animal rotaviruses are regarded as a potential reservoir for genetic diversity of human rotaviruses.
El-Attar, L; Oliver, S L; Mackie, A; Charpilienne, A; Poncet, D; Cohen, J; Bridger, J C
Rotavirus-like particles (VLPs) have shown promise as rotavirus vaccine candidates in mice, rabbits and pigs. In pigs, VLP vaccines reduced rotavirus shedding and disease but only when used in conjunction with live attenuated human rotavirus. Using a porcine rotavirus pig model, rotavirus antigen shedding was reduced by up to 40% after vaccination with VLPs including the neutralizing antigens VP7 and VP8* when used in combination with the adjuvant polyphosphazene poly[di(carbozylatophenoxy)phoshazene] (PCPP). In contrast, complete protection from rotavirus antigen shedding and disease was induced by vaccination with the virulent porcine rotavirus PRV 4F. This is the first study to demonstrate some post-challenge reductions in rotavirus antigen shedding in a pig model of rotavirus disease after vaccination with VLPs without combining with infectious rotavirus.
Talissa de Moraes Tavares
Full Text Available Nonstructural protein 4 (NSP4, encoded by group A rotavirus genome segment 10, is a multifunctional protein and the first recognized virus-encoded enterotoxin. The NSP4 gene has been sequenced, and five distinct genetic groups have been described: genotypes A-E. NSP4 genotypes A, B, and C have been detected in humans. In this study, the NSP4-encoding gene of human rotavirus strains of different G and P genotypes collected from children between 1987 and 2003 in three cities of West Central region of Brazil was characterized. NSP4 gene of 153 rotavirus-positive fecal samples was amplified by reverse transcriptase-polymerase chain reaction and then sequenced. For phylogenetic analysis, NSP4 nucleotide sequences of these samples were compared to nucleotide sequences of reference strains available in GenBank. Two distinct NSP4 genotypes could be identified: 141 (92.2% sequences clustered with NSP4 genotype B, and 12 sequences (7.8% clustered with NSP4 genotype A. These results reinforce that further investigations are needed to assess the validity of NSP4 as a suitable target for epidemiologic surveillance of rotavirus infections and vaccine development.
Yuan, L; Kang, S Y; Ward, L A; To, T L; Saif, L J
Newborn gnotobiotic pigs were inoculated twice perorally (p.o.) (group 1) or intramuscularly (i.m.) (group 2) or three times i.m. (group 3) with inactivated Wa strain human rotavirus and challenged with virulent Wa human rotavirus 20 to 24 days later. To assess correlates of protection, antibody-secreting cells (ASC) were enumerated in intestinal and systemic lymphoid tissues from pigs in each group at selected postinoculation days (PID) or postchallenge days. Few virus-specific ASC were detected in any tissues of group 1 pigs prior to challenge. By comparison, groups 2 and 3 had significantly greater numbers of virus-specific immunoglobulin M (IgM) ASC in intestinal and splenic tissues at PID 8 and significantly greater numbers of virus-specific IgG ASC and IgG memory B cells in spleen and blood at challenge. However, as for group 1, few virus-specific IgA ASC or IgA memory B cells were detected in any tissues of group 2 and 3 pigs. Neither p.o. nor i.m. inoculation conferred significant protection against virulent Wa rotavirus challenge (0 to 6% protection rate), and all groups showed significant anamnestic virus-specific IgG and IgA ASC responses. Hence, high numbers of IgG ASC or memory IgG ASC in the systemic lymphoid tissues at the time of challenge did not correlate with protection. Further, our findings suggest that inactivated Wa human rotavirus administered either p.o. or parenterally is significantly less effective in inducing intestinal IgA ASC responses and conferring protective immunity than live Wa human rotavirus inoculated orally, as reported earlier (L. Yuan, L. A. Ward, B. I. Rosen, T. L. To, and L. J. Saif, J. Virol. 70:3075-3083, 1996). Thus, more efficient mucosal delivery systems and rotavirus vaccination strategies are needed to induce intestinal IgA ASC responses, identified previously as a correlate of protective immunity to rotavirus.
Wen, Xiaobo; Cao, Dianjun; Jones, Ronald W.; Li, Jianping; Szu, Shousun; Hoshino, Yasutaka
Two currently licensed live oral rotavirus vaccines (Rotarix® and RotaTeq®) are highly efficacious against severe rotavirus diarrhea. However, the efficacy of such vaccines in selected low-income African and Asian countries is much lower than that in middle or high-income countries. Additionally, these two vaccines have recently been associated with rare case of intussusception in vaccinated infants. We developed a novel recombinant subunit parenteral rotavirus vaccine which may be more effec...
Than, Van Thai; Jeong, Sunyoung; Kim, Wonyong
Rotavirus infections continue to be the leading cause of severe diarrhea in young Korean children. Rotavirus data acquired from uninterrupted surveillance studies between 1989 and 2009 in South Korea were analyzed to better understand the genetic diversity and evolution. The relationship between rotaviruses and the currently licensed rotavirus vaccine viruses was also examined. The most prevalent rotavirus strains, with genotype G1P, followed by G3P, G4P, and G2P, accounted for approximately 76.7% of the total identified strains, and more recently, rotavirus G9P has significance increased to be the fifth most common genotype. Phylogenetic analyses underscored the heterogeneity between viral populations within each genotype, with different lineages and sub-lineages. Although the currently licensed rotavirus vaccines are effective, safe, and economical, additional data from rotavirus monitoring is necessary to evaluate the efficacy of these vaccines for their sustained use in South Korea. The present study provides comprehensive and up-to-date information regarding the epidemiology, genetic diversity, and evolution of the circulating rotaviruses in South Korea. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.
Yuan, L; Ward, L A; Rosen, B I; To, T L; Saif, L J
Neonatal gnotobiotic pigs orally inoculated with virulent (intestinal-suspension) Wa strain human rotavirus (which mimics human natural infection) developed diarrhea, and most pigs which recovered (87% protection rate) were immune to disease upon homologous virulent virus challenge at postinoculation day (PID) 21. Pigs inoculated with cell culture-attenuated Wa rotavirus (which mimics live oral vaccines) developed subclinical infections and seroconverted but were only partially protected agai...
Deal, Emily M.; Jaimes, Maria C.; Crawford, Sue E.; Estes, Mary K.; Greenberg, Harry B.
Rotaviruses are the leading cause of severe dehydrating diarrhea in children worldwide. Rotavirus-induced immune responses, especially the T and B cell responses, have been extensively characterized; however, little is known about innate immune mechanisms involved in the control of rotavirus infection. Although increased levels of systemic type I interferon (IFNalpha and beta) correlate with accelerated resolution of rotavirus disease, multiple rotavirus strains, including rhesus rotavirus (R...
Only a few ovine rotaviruses have been isolated and characterized so far. Recently, the G and P types circulating in ovines have been identified. The ovine rotavirus strain NT isolated from a diarrheic lamb in China is being considered as a promising vaccine candidate for human infants. Keywords: Ovine, Rotavirus ...
Jul 10, 2017 ... experiment. Body weight. Growth retardation was observed from day 7 P.I. in all infected group till the end of the study. The effects of Rotavirus and ... Table 2: Mean body weights of birds inoculated orally with Rotavirus, Salmonella or Rotavirus/Salmonella .... species and humans (Mettifogo et al., 2014).
Ngabo, Fidèle; Levin, Ann; Wang, Susan A; Gatera, Maurice; Rugambwa, Celse; Kayonga, Celestin; Donnen, Philippe; Lepage, Philippe; Hutubessy, Raymond
Detailed cost evaluations of delivery of new vaccines such as pneumococcal conjugate, human papillomavirus (HPV), and rotavirus vaccines in low and middle-income countries are scarce. This paper differs from others by comparing the costs of introducing multiple vaccines in a single country and then assessing the financial and economic impact at the time and implications for the future. The objective of the analysis was to understand the introduction and delivery cost per dose or per child of the three new vaccines in Rwanda to inform domestic and external financial resource mobilization. Start-up, recurrent, and capital costs from a government perspective were collected in 2012. Since pneumococcal conjugate and HPV vaccines had already been introduced, cost data for those vaccines were collected retrospectively while prospective (projected) costing was done for rotavirus vaccine. The financial unit cost per fully immunized child (or girl for HPV vaccine) of delivering 3 doses of each vaccine (without costs related to vaccine procurement) was $0.37 for rotavirus (RotaTeq(®)) vaccine, $0.54 for pneumococcal (Prevnar(®)) vaccine in pre-filled syringes, and $10.23 for HPV (Gardasil (®)) vaccine. The financial delivery costs of Prevnar(®) and RotaTeq(®) were similar since both were delivered using existing health system infrastructure to deliver infant vaccines at health centers. The total financial cost of delivering Gardasil(®) was higher than those of the two infant vaccines due to greater resource requirements associated with creating a new vaccine delivery system in for a new target population of 12-year-old girls who have not previously been served by the existing routine infant immunization program. The analysis indicates that service delivery strategies have an important influence on costs of introducing new vaccines and costs per girl reached with HPV vaccine are higher than the other two vaccines because of its delivery strategy. Documented information
Bridger, J C
Novel (non-group A) rotaviruses have many of the morphological, biochemical and biological properties described originally for group A rotaviruses but they do not share the same group antigens. By negative-stain electron microscopy, novel rotaviruses have the characteristic rotavirus morphology, although with some novel rotaviruses the characteristic single- and double-shelled particles may not be readily apparent. Comparison of novel rotaviruses in serological tests has revealed the existence of at least six rotavirus serogroups, A to F, with the original rotaviruses belonging to group A. As with group A rotaviruses, viruses from different animal species, including man, can belong to the same serogroup. A further point of difference between novel and group A rotaviruses is their genome profiles, which lack the triplet of segments in the 7-8-9 region of group A rotaviruses. This is a useful diagnostic aid. Novel rotaviruses have been found in farm animals and man. They can cause enteritis experimentally and infect villus enterocytes. In chickens, turkeys, lambs and pigs the viruses and/or antibody to them are commonly found, in association with either clinical or subclinical infection. In humans one type of novel virus has emerged as a cause of severe diarrhoeal disease in adults. The possible reasons for the relatively recent discovery of the novel rotaviruses are discussed.
Midgley, S; Böttiger, B; Jensen, T G; Friis-Møller, A; Person, L K; Nielsen, L; Barzinci, S; Fischer, T K
One of the leading causes of severe childhood gastroenteritis are group A rotaviruses, and they have been found to be associated with ∼40% of the annual gastroenteritis-associated hospitalizations in young Danish children rotavirus strains circulating among young children rotavirus positive stool samples were genotyped in the study period, and the majority of samples (74%) were from hospitalized children. G and P genotypes were successfully determined for 826 of samples, with G1P being the most commonly detected genotype. Detection of G1 showed a decreasing trend over time, and an inverse trend was seen for the emerging G9P. The common human genotypes (G1/G3/G4/G9P and G2P) were detected in the majority of samples (n=733, 88.2%). Rare genotype combinations such as G6P were detected in genotype strains and strains which failed to amplify in genotyping RT-PCR were subjected to genetic characterization by sequencing one or all of the following genes; VP7, VP4, VP6 and NSP4. Sequences of sufficient length and quality were available for all 4 genes for 28 strains. Phylogenetic analysis revealed that reassortant G9P strains circulated with 3 different genotype combinations. As rotavirus vaccines are not widely used in Denmark or its neighboring countries, the diversity of rotavirus strains identified in this study most likely reflects naturally occurring selection pressures and viral evolution. Copyright © 2014 Elsevier B.V. All rights reserved.
Li, Min; Monaco, Marcia H; Wang, Mei; Comstock, Sarah S; Kuhlenschmidt, Theresa B; Fahey, George C; Miller, Michael J; Kuhlenschmidt, Mark S; Donovan, Sharon M
The impact of human milk oligosaccharides (HMO) on mucosal immunity, gut microbiota and response to rotavirus (RV) infection was investigated in the piglet model. Newborn piglets were fed with formula alone (FF) or formula supplemented with 4 g l(-1) HMO (HMO) or a prebiotic mixture of 9:1 short-chain galactooligosaccharides (3.6 g l(-1)) and long-chain fructooligosaccharides (0.4 g l(-1)) (PRE) (n=19-21 per group) for 15 days. Piglets (n=7-8) in each dietary group were orally infected with porcine rotavirus (RV) OSU strain on d10, and stool consistency was assessed daily. Blood, small intestine and colonic contents were collected at day 15. Serum RV-specific antibody concentrations, intestinal histomorphology, RV non-structural protein-4 (NSP4) and cytokine mRNA expression were assessed. Colonic content pH, dry matter (DM) and short-chain fatty acid concentrations were measured. Ascending colonic microbiota was analyzed by 16S rRNA gene v1-3 region pyrosequencing. HMO- and PRE-fed groups had shorter duration of diarrhea than FF piglets. Infection changed intestinal histomorphology, increased serum RV-specific antibody response and intestinal RV NSP4 expression, and modulated ileal cytokine expression. HMO enhanced T helper type 1 (interferon-gamma) and anti-inflammatory (interleukin-10) cytokines in the ileum, while prebiotics promoted RV-specific immunoglobulin M response to the infection. RV infection and HMO supplementation altered intraluminal environment and gut microbiota. HMO increased pH and lowered DM of colonic contents and enhanced the abundance of unclassified Lachnospiraceae, which contains numerous butyrate-producing bacteria. In conclusion, HMO and prebiotics did not prevent the onset of RV infection but reduced the duration of RV-induced diarrhea in piglets, in part, by modulating colonic microbiota and immune response to RV infection.
Phua, Kong Boo; Lim, Fong Seng; Quak, Seng Hock; Lee, Bee Wah; Teoh, Yee Leong; Suryakiran, Pemmaraju V; Han, Htay Htay; Bock, Hans L
This was the first study conducted to evaluate the efficacy of 2 oral doses of the human rotavirus vaccine, RIX4414 in Singaporean infants during the first 3 years of life. Healthy infants, 11 to 17 weeks of age were enrolled in this randomised (1:1), double-blinded, placebo-controlled study to receive 2 oral doses of RIX4414 vaccine/placebo following a 0-, 1-month schedule. Vaccine efficacy against severe rotavirus (RV) gastroenteritis (Vesikari score ≥11) caused by wild-type RV strains from a period starting from 2 weeks post-Dose 2 until 2 and 3 years of age was calculated with 95% confidence interval (CI). Immunogenicity and safety of the vaccine were also assessed. Of 6542 infants enrolled, 6466 were included in the efficacy analysis and a subset of 100 infants was included in the immunogenicity analysis. Fewer severe RV gastroenteritis episodes were reported in the RIX4414 group when compared to placebo at both 2 and 3 year follow-up periods. Vaccine efficacy against severe RV gastroenteritis at the respective time points were 93.8% (95% CI, 59.9 to 99.9) and 95.2% (95% CI, 70.5 to 99.9). One to 2 months post-Dose 2 of RIX4414, 97.5% (95% CI, 86.8 to 99.9) of infants seroconverted for anti-RV IgA antibodies. The number of serious adverse events recorded from Dose 1 until 3 years of age was similar in both groups. Two oral doses of RIX4414 vaccine was immunogenic and provided high level of protection against severe RV gastroenteritis in Singaporean children, during the first 3 years of life when the disease burden is highest.
Wright, P F; King, J; Araki, K; Kondo, Y; Thompson, J; Tollefson, S J; Kobayashi, M; Kapikian, A Z
Two rotavirus vaccine strains representing VP7 serotypes 1 and 2 derived by reassortment between a rhesus rotavirus master strain, MMU18006, and either of two human rotavirus strains were administered simultaneously to infants and young children to assess potential interactions between strains. Children were observed in a day care setting for 10 days after vaccine administration for clinical symptoms, evidence of vaccine transmission, and patterns of viral shedding. Serum and local antibody responses were measured. The ratio of input virus strongly influenced the amount of each strain recovered from the child. Regardless of dose of virus administered, the neutralizing antibody response to the VP7 glycoprotein, the serotype determinant, was diminished in a bivalent preparation compared with a monovalent vaccine. Additional strategies must be sought to induce immunity against the multiple serotypes of human rotavirus before broad immunity will be established.
Moreno, Sandra; Alvarado, Mónica Viviana; Bermúdez, Andrea; Gutiérrez, María Fernanda
Quibdó, the capital of Chocó Province, is one of the poorest cities in Colombia. Enteric viruses such as rotavirus and hepatitis A virus was found to occur commonly in city drinking water and indicated poor water quality and high risk of becoming infected. The source of these viruses was unknown, but humans and cattle were suspect sources. City water was assessed to determine source and persistence of diarrhea and hepatitis among the human populations in the environs of Quibdó. Four thousand liters of water were collected, filtered by tangential ultrafiltration and centrifuged in Centriprep Ultracel YM-50 tubes. Sixty samples of untreated and 20 of treated water were probed by RT-PCR. Six samples were positive for rotavirus and 2 for hepatitis A virus in both, treated and non treated water. DNA sequence analysis identified the presence of human G2 rotavirus and human hepatitis A virus. The evidence indicated a high level of contamination with pathogenic viruses in consumable water sources in Quibdó, Colombia.
Yuan, L; Ward, L A; Rosen, B I; To, T L; Saif, L J
Neonatal gnotobiotic pigs orally inoculated with virulent (intestinal-suspension) Wa strain human rotavirus (which mimics human natural infection) developed diarrhea, and most pigs which recovered (87% protection rate) were immune to disease upon homologous virulent virus challenge at postinoculation day (PID) 21. Pigs inoculated with cell culture-attenuated Wa rotavirus (which mimics live oral vaccines) developed subclinical infections and seroconverted but were only partially protected against challenge (33% protection rate). Isotype-specific antibody-secreting cells (ASC were enumerated at selected PID in intestinal (duodenal and ileal lamina propria and mesenteric lymph node [MLN]) and systemic (spleen and blood) lymphoid tissues by using enzyme-linked immunospot assays. At challenge (PID 21), the numbers of virus-specific immunoglobulin A (IgA) ASC, but not IgG ASC, in intestines and blood were significantly greater in virulent-Wa rotavirus-inoculated pigs than in attenuated-Wa rotavirus-inoculated pigs and were correlated (correlation coefficients: for duodenum and ileum, 0.9; for MLN, 0.8; for blood, 0.6) with the degree of protection induced. After challenge, the numbers of IgA and IgG virus-specific ASC and serum-neutralizing antibodies increased significantly in the attenuated-Wa rotavirus-inoculated pigs but not in the virulent-Wa rotavirus-inoculated pigs (except in the spleen and except for IgA ASC in the duodenum). The transient appearance of IgA ASC in the blood mirrored the IgA ASC responses in the gut, albeit at a lower level, suggesting that IgA ASC in the blood of humans could serve as an indicator for IgA ASC responses in the intestine after rotavirus infection. To our knowledge, this is the first report to study and identify intestinal IgA ASC as a correlate of protective active immunity in an animal model of human-rotavirus-induced disease.
Kobayashi, M; Araki, K; Thompson, J; Tollefson, S J; Wright, P F
Rotavirus vaccine strains representing serotypes 1 and 2 have been derived by reassortment between genes of a rhesus rotavirus master strain, MMU18006, and the gene from human viruses coding for VP7, a surface protein with neutralizing determinants. As simultaneous administration of these two human rotavirus reassortants had resulted in disappointing strain-specific immunity, these two vaccines were administered sequentially to infants and young children to assess whether immunity to both serotypes could be achieved with two monovalent doses. Following initial immunization with RRVxDS-1, a serotype 2 vaccine, 12 of 13 shed virus and showed serologic responses to multiple rotavirus proteins. However, with subsequent administration of RRVxD, serotype 1, only 2 of 12 shed virus, and an enhancement or broadening of the immune response was not uniformly seen. Although rhesus rotavirus vaccines are immunogenic with primary administration of monovalent vaccine in seronegative children, and supplemental seroresponses are seen with a second dose, other strategies or new vaccine candidates must be sought to induce immunity against the multiple serotypes of human rotavirus.
Parreño, V; Hodgins, D C; de Arriba, L; Kang, S Y; Yuan, L; Ward, L A; Tô, T L; Saif, L J
The effects of passive antibodies on protection and active immune responses to human rotavirus were studied in gnotobiotic pigs. Pigs were injected at birth with saline or sow serum of high (immunized) or low (control) antibody titre and subsets of pigs were fed colostrum and milk from immunized or control sows. Pigs were inoculated at 3-5 days of age and challenged at 21 days post-inoculation (p.i.) with virulent Wa human rotavirus. Pigs receiving immune serum with or without immune colostrum/milk were partially protected against diarrhoea and virus shedding after inoculation, but had significantly lower IgA antibody titres in serum and small intestinal contents at 21 days p.i. and lower protection rates after challenge compared with pigs given control or no maternal antibodies. IgG antibody titres were consistently higher in small than in large intestinal contents. Pigs given control serum with control colostrum/milk had lower rates of virus shedding after inoculation than those given control serum alone. In summary, high titres of circulating maternal antibodies with or without local (milk) antibodies provided passive protection after inoculation but suppressed active mucosal antibody responses. These findings may have implications for the use of live, oral rotavirus vaccines in breast-fed infants.
Leung, A K; Pai, C H
Rotavirus gastroenteritis is a leading cause of morbidity and mortality, especially in developing countries. Dehydration, which is often isotonic, occurs in 40 to 80% of patients. Rehydration and maintenance of proper fluid and electrolyte balance remains the mainstay of treatment. In recent years, development of efficient diagnostic methods has led to better understanding of the morphology of the virus, the epidemiology and natural history, as well as the importance of rotavirus disease. Rapid progress in the development and improvement of rotavirus vaccines has also been made. Among the vaccine candidates currently available, both the bovine rotavirus strain RIT 4237 and the rhesus rotavirus strain MMU 18006 have undergone extensive clinical trials and both have shown promising results.
Auditya Purwandini Sutarto
Full Text Available The widespread implementation of advanced and complex systems requires predominantly operators’ cognitive functions and less importance of human manual control. On the other hand, most operators perform their cognitive functions below their peak cognitive capacity level due to fatigue, stress, and boredom. Thus, there is a need to improve their cognitive functions during work. The goal of this paper is to present a psychophysiology training approach derived from cardiovascular response named heart rate variability (HRV biofeedback. Description of resonant frequency biofeedback - a specific HRV training protocol - is discussed as well as its supported researches for the performance enhancement. HRV biofeedback training works by teaching people to recognize their involuntary HRV and to control patterns of this physiological response. The training is directed to increase HRV amplitude that promotes autonomic nervous system balance. This balance is associated with improved physiological functioning as well as psychological benefits. Most individuals can learn HRV biofeedback training easily which involves slowing the breathing rate (around six breaths/min to each individual’s resonant frequency at which the amplitude of HRV is maximized. Maximal control over HRV can be obtained in most people after approximately four sessions of training. Recent studies have demonstrated the effectiveness of HRV biofeedback to the improvement of some cognitive functions in both simulated and real industrial operators.
De Donno Antonella
Full Text Available Abstract Background In recent years, rotavirus genotyping by RT-PCR has provided valuable information about the diversity of rotaviruses (RV circulating throughout the world. The purpose of the present study was to monitor the prevalence of the different G and P genotypes of rotaviruses circulating in Salento and detect any uncommon or novel types. Methods During the period from January 2006 to December 2007, a total of 243 rotavirus positive stool samples were collected from children with diarrhoea admitted to four Hospitals in the province of Lecce (Copertino, Galatina, Gallipoli and Tricase. All the specimens were tested for RV by real time PCR and genotyped for VP7 (G-type and VP4 (P-type gene by reverse transcription (RT and multiplex PCR using different type specific primers. Results In course of this study we identified 4 common G&P combinations viz. G2P, G1P, G2P and G9P amongst 59.8% of the typeable rotavirus positives. Rotavirus G2P was recognized as the most widespread genotype during the sentinel-based survey in Salento. The detection of other novel and unusual strains, such as G2P, G4P, G8P, G9P and G10P is noteworthy. Furthermore, a significant number of mixed infections were observed during the survey period but G3P rotaviruses were not detected. Conclusion This study highlights the genetic diversity among rotaviruses isolated from children in Salento and the emergence of some novel strains. Therefore, it is highly essential to continuously monitor for these strains so as to assess the impact of vaccines on RV strains circulating in Salento and understand the effect of strain variation on efficacy of presently available vaccines.
Theamboonlers, A; Maiklang, O; Thongmee, T; Chieochansin, T; Vuthitanachot, V; Poovorawan, Y
This study has identified diverse and re-assorted group A rotavirus (RVA) strains by sequence and phylogenetic analysis of the 11 genomic segments. The 22 cases investigated in this study were collected from children with diarrhea between 2008 and 2011. The RVA genomic constellations identified in this study were identified as G1-P-I1-R1-C1-M1-A1-N1-T1-E1-H1 22.7% (5/22); G2-P-I2-R2-C2-M2-A2-N2-T2-E2-H2 27.3% (6/22); G3-P-I1-R1-C1-M1-A1-N1-T1-E1-H1 18.2% (4/22); G3-P-I3-R3-C3-M3-A3-N3-T3-E3-H6 4.6% (1/22); G9-P-I1-R1-C1-M1-A1-N1-T1-E1-H1 9.1% (2/22); G12-P-I1-R1-C1-M1-A1-N1-T1-E1-H1 4.6% (1/22) and G12-P-I1-R1-C1-M1-A1-N1-T1-E1-H1 13.6% (3/22). Two RVA strains, possessing a complete AU-1-like genomic backbone, showed re-assortment for genes 3 and 11, revealing possible zoonotic re-assortment events between human and canine strains. In addition, one of the analyzed strains revealed a G12 specificity for VP7 in combination with a porcine-like P VP4 and a complete Wa-like constellation. Continuous surveillance of rotavirus strains and their evolution may be useful for understanding the emergence of novel strains through interspecies genome re-assortment between human and animal viruses. Copyright © 2013 Elsevier B.V. All rights reserved.
Marton, Szilvia; Dóró, Renáta; Fehér, Enikő; Forró, Barbara; Ihász, Katalin; Varga-Kugler, Renáta; Farkas, Szilvia L; Bányai, Krisztián
Genotype P rotaviruses in humans are thought to be zoonotic strains originating from bovine or ovine host species. Over the past 30 years only few genotype P strains were identified in Hungary totaling<0.1% of all human rotaviruses whose genotype had been determined. In this study we report the genome sequence and phylogenetic analysis of a human genotype G8P strain, RVA/Human-wt/HUN/182-02/2001/G8P. The whole genome constellation (G8-P-I2-R2-C2-M2-A11-N2-T6-E2-H3) of this strain was shared with another Hungarian zoonotic G8P strain, RVA/Human-wt/HUN/BP1062/2004/G8P, although phylogenetic analyses revealed the two rotaviruses likely had different progenitors. Overall, our findings indicate that human G8P rotavirus detected in Hungary in the past originated from independent zoonotic events. Further studies are needed to assess the public health risk associated with infections by various animal rotavirus strains. Copyright Â© 2016. Published by Elsevier B.V.
Bhandari, Nita; Rongsen-Chandola, Temsunaro; Bavdekar, Ashish; John, Jacob; Antony, Kalpana; Taneja, Sunita; Goyal, Nidhi; Kawade, Anand; Kang, Gagandeep; Rathore, Sudeep Singh; Juvekar, Sanjay; Muliyil, Jayaprakash; Arya, Alok; Shaikh, Hanif; Abraham, Vinod; Vrati, Sudhanshu; Proschan, Michael; Kohberger, Robert; Thiry, Georges; Glass, Roger; Greenberg, Harry B; Curlin, George; Mohan, Krishna; Harshavardhan, G V J A; Prasad, Sai; Rao, T S; Boslego, John; Bhan, Maharaj Kishan
Rotavirus gastroenteritis is one of the leading causes of diarrhea in Indian children less than 2 years of age. The 116E rotavirus strain was developed as part of the Indo-US Vaccine Action Program and has undergone efficacy trials. This paper reports the efficacy and additional safety data in children up to 2 years of age. In a double-blind placebo controlled multicenter trial, 6799 infants aged 6-7 weeks were randomized to receive three doses of an oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6, 10, and 14 weeks. The primary outcome was severe (≥11 on the Vesikari scale) rotavirus gastroenteritis. Efficacy outcomes and adverse events were ascertained through active surveillance. We randomly assigned 4532 and 2267 subjects to receive vaccine and placebo, respectively, with over 96% subjects receiving all three doses of the vaccine or placebo. The per protocol analyses included 4354 subjects in the vaccine and 2187 subjects in the placebo group. The overall incidence of severe RVGE per 100 person years was 1.3 in the vaccine group and 2.9 in the placebo recipients. Vaccine efficacy against severe rotavirus gastroenteritis in children up to 2 years of age was 55.1% (95% CI 39.9 to 66.4; pvaccine efficacy in the second year of life of 48.9% (95% CI 17.4 to 68.4; p=0.0056) was only marginally less than in the first year of life [56.3% (95% CI 36.7 to 69.9; pvaccine dose and all were reported only after the third dose. The sustained efficacy of the 116E in the second year of life is reassuring. The trial is registered with Clinical Trial Registry-India (# CTRI/2010/091/000102) and Clinicaltrials.gov (# NCT01305109). Copyright © 2014. Published by Elsevier Ltd.
Kaur, Balvinder; Durek, Joseph J.; O'Kane, Barbara L.; Tran, Nhien; Moses, Sophia; Luthra, Megha; Ikonomidou, Vasiliki N.
Heart rate variability (HRV) can be an important indicator of several conditions that affect the autonomic nervous system, including traumatic brain injury, post-traumatic stress disorder and peripheral neuropathy , ,  & . Recent work has shown that some of the HRV features can potentially be used for distinguishing a subject's normal mental state from a stressed one ,  & . In all of these past works, although processing is done in both frequency and time domains, few classification algorithms have been explored for classifying normal from stressed RRintervals. In this paper we used 30 s intervals from the Electrocardiogram (ECG) time series collected during normal and stressed conditions, produced by means of a modified version of the Trier social stress test, to compute HRV-driven features and subsequently applied a set of classification algorithms to distinguish stressed from normal conditions. To classify RR-intervals, we explored classification algorithms that are commonly used for medical applications, namely 1) logistic regression (LR)  and 2) linear discriminant analysis (LDA) . Classification performance for various levels of stress over the entire test was quantified using precision, accuracy, sensitivity and specificity measures. Results from both classifiers were then compared to find an optimal classifier and HRV features for stress detection. This work, performed under an IRB-approved protocol, not only provides a method for developing models and classifiers based on human data, but also provides a foundation for a stress indicator tool based on HRV. Further, these classification tools will not only benefit many civilian applications for detecting stress, but also security and military applications for screening such as: border patrol, stress detection for deception ,, and wounded-warrior triage .
Juarez, Paloma; Fernandez-del-Carmen, Asun; Rambla, Jose L; Presa, Silvia; Mico, Amparo; Granell, Antonio; Orzaez, Diego
The production of neutralizing immunoglobulin A (IgA) in edible fruits as a means of oral passive immunization is a promising strategy for the inexpensive treatment of mucosal diseases. This approach is based on the assumption that the edible status remains unaltered in the immunoglobulin-expressing fruit, and therefore extensive purification is not required for mucosal delivery. However, unintended effects associated with IgA expression such as toxic secondary metabolites and protein allergens cannot be dismissed a priori and need to be investigated. This paper describes a collection of independent transgenic tomato lines expressing a neutralizing human IgA against rotavirus, a mucosal pathogen producing severe diarrhea episodes. This collection was used to evaluate possible unintended effects associated with recombinant IgA expression. A comparative analysis of protein and secondary metabolite profiles using wild type lines and other commercial varieties failed to find unsafe features significantly associated with IgA expression. Preliminary, the data indicate that formulations derived from IgA tomatoes are as safe for consumption as equivalent formulations derived from wild type tomatoes.
Padilla-Noriega, Luis; Méndez-Toss, Martha; Menchaca, Griselda; Contreras, Juan F.; Romero-Guido, Pedro; Puerto, Fernando I.; Guiscafré, Héctor; Mota, Felipe; Herrera, Ismael; Cedillo, Roberto; Muñoz, Onofre; Calva, Juan; Guerrero, María de Lourdes; Coulson, Barbara S.; Greenberg, Harry B.; López, Susana; Arias, Carlos F.
In the present investigation we characterized the antigenic diversity of the VP4 and VP7 proteins in 309 and 261 human rotavirus strains isolated during two consecutive epidemic seasons, respectively, in three different regions of Mexico. G3 was found to be the prevalent VP7 serotype during the first year, being superseded by serotype G1 strains during the second season. To antigenically characterize the VP4 protein of the strains isolated, we used five neutralizing monoclonal antibodies (MAbs) which showed specificity for VP4 serotypes P1A, P1B, and P2 in earlier studies. Eight different patterns of reactivity with these MAbs were found, and the prevalence of three of these patterns varied from one season to the next. The P genotype of a subset of 52 samples was determined by PCR. Among the strains characterized as genotype P and P there were three and five different VP4 MAb reactivity patterns, respectively, indicating that the diversity of neutralization epitopes in VP4 is greater than that previously appreciated by the genomic typing methods. PMID:9620401
Yu, Ying; Lasanajak, Yi; Song, Xuezheng; Hu, Liya; Ramani, Sasirekha; Mickum, Megan L.; Ashline, David J.; Prasad, B. V. Venkataram; Estes, Mary K.; Reinhold, Vernon N.; Cummings, Richard D.; Smith, David F.
Human milk contains a rich set of soluble, reducing glycans whose functions and bioactivities are not well understood. Because human milk glycans (HMGs) have been implicated as receptors for various pathogens, we explored the functional glycome of human milk using shotgun glycomics. The free glycans from pooled milk samples of donors with mixed Lewis and Secretor phenotypes were labeled with a fluorescent tag and separated via multidimensional HPLC to generate a tagged glycan library containing 247 HMG targets that were printed to generate the HMG shotgun glycan microarray (SGM). To investigate the potential role of HMGs as decoy receptors for rotavirus (RV), a leading cause of severe gastroenteritis in children, we interrogated the HMG SGM with recombinant forms of VP8* domains of the RV outer capsid spike protein VP4 from human neonatal strains N155(G10P) and RV3(G3P) and a bovine strain, B223(G10P). Glycans that were bound by RV attachment proteins were selected for detailed structural analyses using metadata-assisted glycan sequencing, which compiles data on each glycan based on its binding by antibodies and lectins before and after exo- and endo-glycosidase digestion of the SGM, coupled with independent MSn analyses. These complementary structural approaches resulted in the identification of 32 glycans based on RV VP8* binding, many of which are novel HMGs, whose detailed structural assignments by MSn are described in a companion report. Although sialic acid has been thought to be important as a surface receptor for RVs, our studies indicated that sialic acid is not required for binding of glycans to individual VP8* domains. Remarkably, each VP8* recognized specific glycan determinants within a unique subset of related glycan structures where specificity differences arise from subtle differences in glycan structures. PMID:25048705
Agbemabiese, Chantal Ama; Nakagomi, Toyoko; Doan, Yen Hai; Nakagomi, Osamu
Human G8 Rotavirus A (RVA) strains are commonly detected in Africa but are rarely detected in Japan and elsewhere in the world. In this study, the whole genome sequence of the first human G8 RVA strain designated AU109 isolated in a child with acute gastroenteritis in 1994 was determined in order to understand how the strain was generated including the host species origin of its genes. The genotype constellation of AU109 was G8-P-I2-R2-C2-M2-A2-N2-T2-E2-H2. Phylogenetic analyses of the 11 genome segments revealed that its VP7 and VP1 genes were closely related to those of a Hungarian human G8P RVA strain and these genes shared the most recent common ancestors in 1988 and 1982, respectively. AU109 possessed an NSP2 gene closely related to those of Chinese sheep and goat RVA strains. The remaining eight genome segments were closely related to Japanese human G2P strains which circulated around 1985-1990. Bayesian evolutionary analyses revealed that the NSP2 gene of AU109 and those of the Chinese sheep and goat RVA strains diverged from a common ancestor around 1937. In conclusion, AU109 was generated through genetic reassortment event where Japanese DS-1-like G2P strains circulating around 1985-1990 obtained the VP7, VP1 and NSP2 genes from unknown ruminant G8 RVA strains. These observations highlight the need for comprehensive examination of the whole genomes of RVA strains of less explored host species. Copyright © 2015 Elsevier B.V. All rights reserved.
Khuzwayo C Jere
Full Text Available Rotavirus virus-like particles (RV-VLPs are potential alternative non-live vaccine candidates due to their high immunogenicity. They mimic the natural conformation of native viral proteins but cannot replicate because they do not contain genomic material which makes them safe. To date, most RV-VLPs have been derived from cell culture adapted strains or common G1 and G3 rotaviruses that have been circulating in communities for some time. In this study, chimaeric RV-VLPs were generated from the consensus sequences of African rotaviruses (G2, G8, G9 or G12 strains associated with either P, P or P genotypes characterised directly from human stool samples without prior adaptation of the wild type strains to cell culture. Codon-optimised sequences for insect cell expression of genome segments 2 (VP2, 4 (VP4, 6 (VP6 and 9 (VP7 were cloned into a modified pFASTBAC vector, which allowed simultaneous expression of up to four genes using the Bac-to-Bac Baculovirus Expression System (BEVS; Invitrogen. Several combinations of the genome segments originating from different field strains were cloned to produce double-layered RV-VLPs (dRV-VLP; VP2/6, triple-layered RV-VLPs (tRV-VLP; VP2/6/7 or VP2/6/7/4 and chimaeric tRV-VLPs. The RV-VLPs were produced by infecting Spodoptera frugiperda 9 and Trichoplusia ni cells with recombinant baculoviruses using multi-cistronic, dual co-infection and stepwise-infection expression strategies. The size and morphology of the RV-VLPs, as determined by transmission electron microscopy, revealed successful production of RV-VLPs. The novel approach of producing tRV-VLPs, by using the consensus insect cell codon-optimised nucleotide sequence derived from dsRNA extracted directly from clinical specimens, should speed-up vaccine research and development by by-passing the need to adapt rotaviruses to cell culture. Other problems associated with cell culture adaptation, such as possible changes in epitopes, can also be
Jere, Khuzwayo C; O'Neill, Hester G; Potgieter, A Christiaan; van Dijk, Alberdina A
Rotavirus virus-like particles (RV-VLPs) are potential alternative non-live vaccine candidates due to their high immunogenicity. They mimic the natural conformation of native viral proteins but cannot replicate because they do not contain genomic material which makes them safe. To date, most RV-VLPs have been derived from cell culture adapted strains or common G1 and G3 rotaviruses that have been circulating in communities for some time. In this study, chimaeric RV-VLPs were generated from the consensus sequences of African rotaviruses (G2, G8, G9 or G12 strains associated with either P, P or P genotypes) characterised directly from human stool samples without prior adaptation of the wild type strains to cell culture. Codon-optimised sequences for insect cell expression of genome segments 2 (VP2), 4 (VP4), 6 (VP6) and 9 (VP7) were cloned into a modified pFASTBAC vector, which allowed simultaneous expression of up to four genes using the Bac-to-Bac Baculovirus Expression System (BEVS; Invitrogen). Several combinations of the genome segments originating from different field strains were cloned to produce double-layered RV-VLPs (dRV-VLP; VP2/6), triple-layered RV-VLPs (tRV-VLP; VP2/6/7 or VP2/6/7/4) and chimaeric tRV-VLPs. The RV-VLPs were produced by infecting Spodoptera frugiperda 9 and Trichoplusia ni cells with recombinant baculoviruses using multi-cistronic, dual co-infection and stepwise-infection expression strategies. The size and morphology of the RV-VLPs, as determined by transmission electron microscopy, revealed successful production of RV-VLPs. The novel approach of producing tRV-VLPs, by using the consensus insect cell codon-optimised nucleotide sequence derived from dsRNA extracted directly from clinical specimens, should speed-up vaccine research and development by by-passing the need to adapt rotaviruses to cell culture. Other problems associated with cell culture adaptation, such as possible changes in epitopes, can also be circumvented
Jere, Khuzwayo C.; O'Neill, Hester G.; Potgieter, A. Christiaan; van Dijk, Alberdina A.
Rotavirus virus-like particles (RV-VLPs) are potential alternative non-live vaccine candidates due to their high immunogenicity. They mimic the natural conformation of native viral proteins but cannot replicate because they do not contain genomic material which makes them safe. To date, most RV-VLPs have been derived from cell culture adapted strains or common G1 and G3 rotaviruses that have been circulating in communities for some time. In this study, chimaeric RV-VLPs were generated from the consensus sequences of African rotaviruses (G2, G8, G9 or G12 strains associated with either P, P or P genotypes) characterised directly from human stool samples without prior adaptation of the wild type strains to cell culture. Codon-optimised sequences for insect cell expression of genome segments 2 (VP2), 4 (VP4), 6 (VP6) and 9 (VP7) were cloned into a modified pFASTBAC vector, which allowed simultaneous expression of up to four genes using the Bac-to-Bac Baculovirus Expression System (BEVS; Invitrogen). Several combinations of the genome segments originating from different field strains were cloned to produce double-layered RV-VLPs (dRV-VLP; VP2/6), triple-layered RV-VLPs (tRV-VLP; VP2/6/7 or VP2/6/7/4) and chimaeric tRV-VLPs. The RV-VLPs were produced by infecting Spodoptera frugiperda 9 and Trichoplusia ni cells with recombinant baculoviruses using multi-cistronic, dual co-infection and stepwise-infection expression strategies. The size and morphology of the RV-VLPs, as determined by transmission electron microscopy, revealed successful production of RV-VLPs. The novel approach of producing tRV-VLPs, by using the consensus insect cell codon-optimised nucleotide sequence derived from dsRNA extracted directly from clinical specimens, should speed-up vaccine research and development by by-passing the need to adapt rotaviruses to cell culture. Other problems associated with cell culture adaptation, such as possible changes in epitopes, can also be circumvented
Teimoori, Ali; Soleimanjahi, Hoorieh; Makvandi, Manoochehr
Rotavirus (RV) is a major cause of gastroenteritis in infants and children and is one of the most severe public health problems. Rotaviruses outer layer contains two proteins including VP4 and VP7. These proteins are necessary for host-cell binding and penetration. TLP (triple layer virus particle) of RV is a complete infectious virion that binds to the target cells and internalized at the cytoplasm. The DLP (double layer virus particle) is a non-infectious particle that is formed through exclusion of the outer layer proteins including VP4 and VP7. These DLPs are the transcriptionally active forms of rotavirus. The aim of this study was to transfer DLP of RV into cytoplasm of MA104 cells by Lipofectamine and to analyze their replication. Initially, rotavirus was purified by CsCl discontinuous gradient and DLP was separated from TLP based on density differences. For confirmation, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of the proteins were conducted Then the purified DLP of RV was transferred into MA104 cells using Lipofectamine. We attempt to avoid the attachment and entry of the rotavirus by using Lipofectamine to mediate the delivery of viral particles directly into the cytoplasm. DLP was endocytosed into the cytoplasm following treatment by Lipofectamine and then replicated in cytoplasm. Therefore the non-infectious DLPs were became infectious if introduced into the cytoplasm of permissive and cancerous cells, without passing attachment and entry process.
Zhou, Yan; Wu, Jinyuan; Geng, Panpan; Kui, Xiang; Xie, Yuping; Zhang, Lei; Liu, Yaling; Yin, Na; Zhang, Guangming; Yi, Shan; Li, Hongjun; Sun, Maosheng
Rotavirus infection is an important cause of acute gastroenteritis in children, but the interaction between rotavirus and host cells is not completely understood. We isolated a wildtype (wt) rotavirus strain, ZTR-68(P  G1), which is derived from an infant with diarrhea in southwest China in 2010. In this study, we investigated host cellular miRNA expression profiles changes in response to ZTR-68 in early stage of infection to investigate the role of miRNAs upon rotavirus infection. Differentially expressed miRNAs were identified by deep sequencing and qRT-PCR and the function of their targets predicted by Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation. A total of 36 candidate miRNAs were identified. Comparative analysis indicated that 29 miRNAs were significantly down-regulated and 7 were up-regulated after infection. The data were provided contrasting the types of microRNAs in two different permissive cell lines (HT29 and MA104). The target assays results showed that mml-miR-7 and mml-miR-125a are involved in anti-rotavirus and virus-host interaction in host cells. These results offer clues for identifying potential candidates in vector-based antiviral strategies. J. Med. Virol. 88:1497-1510, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
... that causes gastroenteritis. Symptoms include severe diarrhea, vomiting, fever, and dehydration. Almost all children in the U.S. are likely to be infected with rotavirus before their 5th birthday. Infections happen most often ...
... Organization PATH's Rotavirus Vaccine Program American Academy of Pediatrics ... symptoms to appear. Children who get infected may have severe watery diarrhea, often with vomiting, fever, and abdominal pain. Vomiting ...
Flores, J; Perez-Schael, I; Blanco, M; Vilar, M; Garcia, D; Perez, M; Daoud, N; Midthun, K; Kapikian, A Z
The reactions to and antigenicity of two human-rhesus rotavirus (RRV) reassortants (human rotavirus strain D x RRV and human rotavirus strain DS1 x RRV) with the VP7 neutralization specificity of a serotype 1 or serotype 2 rotavirus were evaluated in a placebo-controlled double-blind trial in 116 1- to 5-month-old infants in Caracas, Venezuela. The children were randomly divided into five groups to receive orally the following inocula: (i) 10(4) PFU of D x RRV reassortant; (ii) 10(4) PFU of DS1 x RRV reassortant; (iii) 10(4) PFU of RRV; (iv) 5 x 10(3) PFU of D x RRV and 5 x 10(3) PFU of RRV; and (v) placebo. The children were examined daily for 7 days following vaccine administration; 8 to 26% of the vaccinated infants developed a mild febrile reaction which in most cases lasted only 1 day. Seroresponses to rotavirus were observed in 39 to 65% of the vaccinees by plaque neutralization assay and in 57 to 88% by an immunoglobulin A enzyme-linked immunosorbent assay. Vaccine shedding was detected in 53 to 86% of the vaccinees. Analysis of neutralization antibody responses indicates that the VP4 protein represents an important component of the response induced by the vaccines.
Ianiro, Giovanni; Delogu, Roberto; Fiore, Lucia; Ruggeri, Franco M
Group A rotaviruses (RVA) are the leading cause of acute gastroenteritis in young (humans worldwide are associated with the five major G/P combinations G1P, G2P, G3P, G4P and G9P. During RVA gastroenteritis surveillance in Italy, a total of 1112 samples collected from children hospitalized with acute gastroenteritis in 2013 were RVA positive and were genotyped following standardized protocols from the EuroRotaNet. Most strains analyzed belonged to the five major human genotypes. Among these common strains, 22 G4P RVA strains from different Italian regions were subjected to nucleotide sequencing of their VP4, VP6, VP7 and NSP4 genes to investigate their evolution. The phylogenetic analysis showed that the Italian strains belonged to lineage G4-I for VP7 and to lineage P-III for VP4, in line with the modern G4P RVA strains detected in children worldwide. The phylogenetic trees revealed high degrees of nucleotide identity between the RVA strains involved in this study and G4P strains detected previously in Europe, Asia and Africa, but also demonstrated at least three separate evolution clusters within the same lineage. Based on the amino acid sequences deduced for their hypervariable regions, both the VP7 and VP8* proteins of the Italian G4P RVA strains presented amino acid substitutions near known neutralizing epitopes. Copyright © 2015 Elsevier B.V. All rights reserved.
Teimoori, Ali; Soleimanjahi, Hoorieh; Makvandi, Manoochehr
Background: Rotavirus (RV) is a major cause of gastroenteritis in infants and children and is one of the most severe public health problems. Rotaviruses outer layer contains two proteins including VP4 and VP7. These proteins are necessary for host-cell binding and penetration. TLP (triple layer virus particle) of RV is a complete infectious virion that binds to the target cells and internalized at the cytoplasm. The DLP (double layer virus particle) is a non-infectious particle that is formed...
Moon, Sung-Sil; Velasquez, Daniel; Jones, Stephanie; Koen, Anthonet; van Niekerk, Nadia; Jiang, Baoming; Parashar, Umesh D; Madhi, Shabir A
Abstract Objective To investigate the effect of abstention from breastfeeding, for an hour before and after each vaccination, on the immune responses of infants to two doses of rotavirus vaccine. Methods In Soweto, South Africa, mother–infant pairs who were uninfected with human immunodeficiency virus (HIV) were enrolled as they presented for the “6-week” immunizations of the infants. Each infant was randomly assigned to Group 1 – in which breastfeeding was deferred for at least 1 h before and after each dose of rotavirus vaccine – or Group 2 – in which unrestricted breastfeeding was encouraged. Enzyme-linked immunosorbent assays were used to evaluate the titres of rotavirus-specific IgA in samples of serum collected from each infant immediately before each vaccine dose and 1 month after the second dose. Among the infants, a fourfold or greater increase in titres of rotavirus-specific IgA following vaccination was considered indicative of seroconversion. Findings The evaluable infants in Group 1 (n = 98) were similar to those in Group 2 (n = 106) in their baseline demographic characteristics and their pre-vaccination titres of anti-rotavirus IgA. After the second vaccine doses, geometric mean titres of anti-rotavirus IgA in the sera of Group-1 infants were similar to those in the sera of Group-2 infants (P = 0.685) and the frequency of seroconversion in the Group-1 infants was similar to that in the Group-2 infants (P = 0.485). Conclusion Among HIV-uninfected South African infants, abstention from breastfeeding for at least 1 h before and after each vaccination dose had no significant effect on the infants’ immune response to a rotavirus vaccine. PMID:24700991
Kindler, Eveline; Trojnar, Eva; Heckel, Gerald; Otto, Peter H; Johne, Reimar
Rotaviruses are a leading cause of viral acute gastroenteritis in humans and animals. Eight different rotavirus species (A-H) have been defined based on antigenicity and nucleotide sequence identities of the VP6 gene. Here, the first complete genome sequences of rotavirus F (strain 03V0568) and G (strain 03V0567) with lengths of 18,341 and 18,186bp, respectively, are described. Both viruses have open reading frames for rotavirus proteins VP1 to VP7 and NSP1 to NSP5 located at the 11 genome segments. Nucleotide sequence identities to other rotaviruses ranged between 29.8% (NSP1 gene) and 61.7% (VP1 gene) for rotavirus F and between 29.3% (NSP1-2 gene) and 65.9% (NSP2 gene) for rotavirus G, thus confirming their classification as separate virus species. Encoded proteins revealed remarkable sequence differences among the rotavirus species. In contrast, the non-coding 5'-terminal sequences of the genome segments are highly conserved among all rotavirus species. Different 3'-terminal consensus sequences are found between rotavirus A/D/F, rotavirus C and rotavirus B/G/H. Phylogenetic analyses indicated a separation of rotaviruses in two major clades consisting of rotavirus A/C/D/F and rotavirus B/G/H. Within these clades, rotavirus F mainly clustered with rotavirus D and rotavirus G with rotavirus B. In addition, differentiation among mammalian and avian rotavirus A strains, host-specific evolution of rotavirus B and C as well as an ancient reassortment event between avian rotavirus A and D are indicated by the phylogenetic data. These results underline the high diversity of rotaviruses as a result of a complex evolutionary history. Copyright © 2012 Elsevier B.V. All rights reserved.
Bok, K; Palacios, G; Sijvarger, K; Matson, D; Gomez, J
Because rotavirus diarrhea can be reduced through vaccination and because current vaccine candidates provide protection against only the most common G antigenic types (G1 to G4), detection of uncommon G types is one of the main goals of rotavirus surveillance. After a 2-year nationwide rotavirus surveillance study in Argentina concluded, surveillance was continued and an increase of G9 prevalence in several Argentine cities was detected. During this period G9 strains predominated in the south, and a gradient of decreasing G9 prevalence was observed from south to north (41 to 0%). Sequence analysis of gene 9, encoding the G antigen, showed that Argentine strains cluster with most G9 isolates from other countries, showing less than 2% nucleotide divergence among them, but are distinctive from them in that they present some unique amino acid changes. Our results agree with reports of increased G9 prevalence in other parts of the world, suggesting the need to incorporate G9 into candidate rotavirus vaccines.
Chakravarti, Anita; Chauhan, Mayank Singh; Sharma, Anju; Verma, Vikas
Rotavirus gastroenteritis is a major cause of severe dehydrating diarrhea in children worldwide. Rotavirus G and P genotyping is essential for epidemiological surveillance and for better formulation of candidate rotavirus vaccines. Out of 862 diarrheal stool samples collected from hospitalized children aged rotavirus by ELISA. G and P genotyping was performed on 100 randomly selected positive samples using a seminested multiplex RT-PCR assay. The result of G genotyping indicates G1 (60%) was the most predominant VP7 type, followed by G2 (16%), G9 (8%) and G3 (3%). Two cases of G12 genotype were also observed. P genotypes identified were P (40%) followed by P (26%) and P (17%). The most common G-P combinations were G1P (26%), followed by G1P and G1P. Mixed infection involved 28% of strains. In this study the G1 and P genotypes were the leading G and P types. Two cases with G12 genotype were also observed during the study.
Kirkwood, Carl D; Buttery, Jim
Rotavirus vaccines offer the best hope to reduce the toll of acute rotaviral gastroenteritis in both developed and developing countries. An association with intussusception (IS) led to the withdrawal of the first licensed rotavirus vaccine in the USA in 1999, forcing a re-evaluation of the safety profile of potentially lifesaving vaccines. Development of new rotavirus vaccine candidates has continued, with a bovine-human reassortant vaccine and an attenuated human monovalent vaccine commencing Phase III trials. Several other candidates are in early Phase I and II clinical trials. The creation of innovative funding strategies to support vaccine development and production, specifically in developing countries, aim to make vaccines available where rotavirus causes the greatest impact.
policlonal contra β3 y establecer que β3 y PDI se unen in vitro, luego de incubar las proteínas aisladas con el rotavirus ECwt, e in vivo, después de incubar el rotavirus con las vellosidades aisladas del intestino delgado de ratón lactante de la cepa ICR.Background. Commercial integrin β3 is currently not available and commercial PDI is too expensive, which is making access difficult to these proteins needed for conducting experiments aimed at the establishment of possible interactions between integrin β3 and PDI and wild type rotavirus strains. Objective. To explore a methodology allowing isolation of proteins β3 and PDI from human platelets to be used as antigens in the generation of rabbit polyclonal antibodies useful in the assessment of interactions between these proteins and rotavirus ECwt. Materials and methods. Proteins β3 and PDI from human platelet lysates were separated using preparative electrophoresis under reducing conditions and then eluted. Interactions of these proteins with rotavirus ECwt were analyzed using co-immunoprecipitation, Western blotting and capture ELISA. Results. Proteins from human platelet lysates were separated by preparative electrophoresis under reducing conditions. The identification of proteins β3 and PDI present in a gel slice was performed through their reaction with commercial antibodies in a Western blotting analysis. Protein purity was established after electroelution from a gel slice. Polyclonal antibodies against protein β3 were generated in rabbit. Incubation of eluted proteins β3 and PDI with rotavirus ECwt showed in co-immunoprecipitation and ELISA assays that these proteins bound virus in vitro. The same binding was showed to occur when rotavirus was incubated with isolated small intestinal villi from suckling mice. Conclusions. Relatively high amounts of proteins β3 and PDI were partially purified from human platelets by preparative electrophoresis. The isolation of these proteins allowed the generation of
Zeller, Mark; Patton, John T.; Heylen, Elisabeth; De Coster, Sarah; Ciarlet, Max; Van Ranst, Marc
Two live-attenuated rotavirus group A (RVA) vaccines, Rotarix (G1P) and RotaTeq (G1-G4, P), have been successfully introduced in many countries worldwide, including Belgium. The parental RVA strains used to generate the vaccines were isolated more than 20 years ago in France (G4 parental strain in RotaTeq) and the United States (all other parental strains). At present, little is known about the relationship between currently circulating human RVAs and the vaccine strains. In this study, we determined sequences for the VP7 and VP4 outer capsid proteins of representative G1P, G2P, G3P, G4P, G9P, and G12P RVAs circulating in Belgium during 2007 to 2009. The analyses showed that multiple amino acid differences existed between the VP7 and VP4 antigenic epitopes of the vaccine viruses and the Belgian isolates, regardless of their G and P genotypes. However, the highest variability was observed among the circulating G1P RVA strains and the G1 and P components of both RVA vaccines. In particular, RVA strains of the P lineage 4 (OP354-like) showed a significant number of amino acid differences with the P VP4 of both vaccines. In addition, the circulating Belgian G3 RVA strains were found to possibly possess an extra N-linked glycosylation site compared to the G3 RVA vaccine strain of RotaTeq. These results indicate that the antigenic epitopes of RVA strains contained in the vaccines differ substantially from those of the currently circulating RVA strains in Belgium. Over time, these differences might result in selection for strains that escape the RVA neutralizing-antibody pressure induced by vaccines. PMID:22189107
Desselberger, Ulrich; Manktelow, Emily; Li, Wilson; Cheung, Winsome; Iturriza-Gómara, Miren; Gray, Jim
Rotaviruses (RVs) are an important cause of acute gastroenteritis in infants and young children worldwide, resulting in more than 600 000 deaths per annum, mainly in developing countries. Since the 1980s, there has been intensive research on the development of RV vaccine candidates, and since 2006 two vaccines have been licensed in many countries. The scientific literature since the 1970s has been consulted, and the results of original research carried out in authors' laboratories were used. There are firmly established data on virus particle structure, genome composition, gene-protein assignment, protein-function assignment (incomplete), virus classification, the mechanisms of several steps of the replication cycle (adsorption, primary transcription, virus maturation-all partial), several mechanisms of pathogenesis, aspects of the immune response, diagnosis, illness and treatment, epidemiology and vaccine development. Research on the following areas is still in full flux and in part not generally accepted: several steps of the replication cycle (mechanism of viral entry into host cells, mechanisms of packaging and reassortment of viral RNAs, morphogenesis of subviral particles in viroplasms and maturation of virus particles in the rough endoplasmic reticulum (RER) with temporary acquisition and subsequent loss of an envelope), the true correlates of protection and the long-term effectiveness of RV vaccines. GROWING RESEARCH: Recently, a system that allows carrying out reverse genetics with some of the RV genes has been established which, however, has limitations. There is intensive research ongoing, which is trying to develop better and universally applicable reverse genetics systems. There is broad research on the molecular mechanisms of the immune response and on which immunological parameter correlates best with lasting protection from severe RV disease. Research into other than live attenuated vaccines is growing. The establishment of better reverse genetics
Komoto, Satoshi; Tacharoenmuang, Ratana; Guntapong, Ratigorn; Ide, Tomihiko; Sinchai, Phakapun; Upachai, Sompong; Fukuda, Saori; Yoshikawa, Tetsushi; Tharmaphornpilas, Piyanit; Sangkitporn, Somchai; Taniguchi, Koki
An unusual rotavirus strain with the G9P genotype (RVA/Human-wt/THA/KKL-117/2014/G9P) was identified in a stool specimen from a 10-month-old child hospitalized with severe diarrhoea. In this study, we sequenced and characterized the complete genome of strain KKL-117. On full-genomic analysis, strain KKL-117 was found to have the following genotype constellation: G9-P-I5-R1-C1-M1-A8-N1-T1-E1-H1. The non-G/P genotype constellation of this strain (I5-R1-C1-M1-A8-N1-T1-E1-H1) is commonly shared with rotavirus strains from pigs. Furthermore, phylogenetic analysis indicated that each of the 11 genes of strain KKL-117 appeared to be of porcine origin. Our observations provide important insights into the dynamic interactions between human and porcine rotavirus strains.
Bhandari, Nita; Rongsen-Chandola, Temsunaro; Bavdekar, Ashish; John, Jacob; Antony, Kalpana; Taneja, Sunita; Goyal, Nidhi; Kawade, Anand; Kang, Gagandeep; Rathore, Sudeep Singh; Juvekar, Sanjay; Muliyil, Jayaprakash; Arya, Alok; Shaikh, Hanif; Abraham, Vinod; Vrati, Sudhanshu; Proschan, Michael; Kohberger, Robert; Thiry, Georges; Glass, Roger; Greenberg, Harry B; Curlin, George; Mohan, Krishna; Harshavardhan, GVJA; Prasad, Sai; Rao, TS; Boslego, John; Bhan, Maharaj Kishan
Background Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed for developing countries. Methods In a double-blind placebo controlled multicentre trial, 6799 infants aged 6 to 7 weeks were randomised to receive three doses of an oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6, 10, and 14 weeks. Primary outcome was severe (≥11 on the Vesikari scale) rotavirus gastroenteritis. Efficacy outcomes and adverse events were ascertained through active surveillance. Findings At analyses, the median age was 17·2 months; over 96% subjects received all three doses of the vaccine/placebo and ~1% were lost to follow up. 4532 and 2267 subjects were randomly assigned to receive vaccine and placebo, respectively. The per protocol analyses included 4354 subjects in the vaccine and 2187 subjects in the placebo group. 71 events of severe rotavirus gastroenteritis were reported in 4752 person years among the vaccinees compared to 76 events in 2360 person years in the placebo recipients; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0–66·9; Protavirus gastroenteritis episode was 55 (95% CI 37–97). The incidence of severe rotavirus gastroenteritis/100 person years was 1·5 in vaccine and 3·2 in placebo group and an incidence rate ratio of 0·46 (95% CI 0·33–0·65). The absolute rate reduction for severe rotavirus gastroenteritis was 1·7 (95% CI 2·5–0·9). Efficacy against severe gastroenteritis of any aetiology was 18·6% (95% CI 1·9–32·3); it was 24·1% (95% CI 5·8–38·7) in the first year of life. The prevalence of immediate, solicited, and serious adverse events were similar in both groups. There were six cases of intussusception amongst 4532 vaccinees and two amongst 2267 placebo recipients (P=0·73). All intussusception cases occurred after the third dose. Among vaccine and placebo recipients
Uhnoo, I; Svensson, L
During a prospective 1-year study rotavirus isolates from 169 children with gastroenteritis were investigated by polyacrylamide gel electrophoresis. A total of 118 (70%) of the strains analyzed contained sufficient viral nucleic acid to give visible electrophoretic patterns; 36% were identified as strains belonging to subgroup 1 (short patterns), and 64% were identified as strains belonging to subgroup 2 (long patterns). The two subgroups cocirculated at equal frequencies during the first 7 m...
Alexandre C. Linhares
-se que a implementação de vacinas de elevada eficácia na prevenção de tumores benignos e malignos causados por alguns tipos de HPV leve a uma queda acentuada das taxas desses tumores, os quais afetam milhões de pessoas em todo o mundo.OBJECTIVE: To briefly review strategies aimed at the development of rotavirus and HPV vaccines, with emphasis on the current status of studies assessing the safety, reactogenicity, immunogenicity and efficacy of recently developed vaccines. SOURCES OF DATA: This review focuses on articles published from 1996 to 2006, mainly those from the last five years, with special emphasis on data obtained from recently completed studies involving a new live attenuated human rotavirus vaccine and a virus-like particle (HPV vaccine. SUMMARY OF THE FINDINGS: Strategies for developing rotavirus vaccines ranged from Jennerian approaches to the new human-derived rotavirus vaccine. Currently, two rotavirus vaccines are recognized as both efficacious and safe: a pentavalent human-bovine reassortant vaccine and a vaccine derived from an attenuated rotavirus of human origin. The second of these has been evaluated in more than 70,000 infants all over the world. Prophylactic vaccines against HPV have been tested in more than 25,000 young individuals around the world. Results from phase II and III clinical studies indicate that such vaccines against the most common types of HPV, those linked to both genital warts and 70% of cervical cancers, are safe and highly efficacious. CONCLUSIONS: A future rotavirus immunization program covering 60 to 80% of infants worldwide is likely to reduce by at least 50% the number of rotavirus-associated hospitalizations and deaths. It is also reasonable to expect that implementation of HPV prophylactic vaccines will reduce the burden of the HPV-related diseases that presently impact millions of people around the world.
Grdadolnik, Urška; Sočan, Maja
Socio-economic inequalities may have an impact on the uptake of selfpaid vaccines. The aim of the study was to identify the effect of some socio economic determinants on vaccination rates with self-paid human papilloma virus (HPV) and rotavirus (RV) vaccines. Vaccination coverage data, available in electronic database cepljenje.net (administered by the National Institute of Public Health), were collected at administrative unit level. The socio-economic determinants (the average gross pay in euros, the unemployment rate, the educational and households structure, the population density, the number of inhabitants, the number of children aged from 0 to 4, the number of women aged from 15 to 30) were extracted from Statistical Office of the Republic of Slovenia web page. The strength of the correlation between socioeconomic variables and self-paid HPV and RV vaccination rates was determined. Rotavirus vaccination rates show a slight negative correlation with the number of residents per administrative unit (ρ=-0.29, p=0.04), and no correlation with other socio-economic variables. Likewise, no correlation has been found between HPV vaccination rates and the selected socio-economic variables. Ecological study did not reveal any correlations between socio economic variables and vaccination rates with RV and HPV self-paid vaccines on administrative unit level.
Annarita, Petrinca; Grassi, Tiziana; Donia, Domenica; De Donno, Antonella; Idolo, Adele; Alfio, Cristaldi; Alessandri, Claudia; Alberto, Spanò; Divizia, Maurizio
Rotaviruses are one of the most important causes of gastroenteritis in children under 5 years old. Analysis of G and P rotavirus genotypes in circulation is crucial in evaluating the appropriacy of mass vaccination of children worldwide. Overall, 592 stool samples were collected in Tirana (Albania), the Salento peninsula (South Italy), and three different hospitals in Rome (Central Italy). Of the total samples, 31.3% were rotavirus positive in Albania, 78.3% in the Salento, and 40.3% in Rome. The samples collected in Tirana and Rome were G-P typed, whereas the samples collected in the Salento were only G typed. Overall, in Italy the most frequent combinations were G4 P (54.5%), G1 P (27.3%), and G2 P (18.2%); in Albania they were G9 P (72.1%), G4 P (8.8%), G1 P (5.9%), and G2 P (2.9%). The prevalence in Albania of atypical combinations was 7.4% for G4 P and 2.9% for G9 P. Phylogenetic analysis was also performed to assess the genetic relatedness of the strains. J. Med. Virol. 82:510-518, 2010. (c) 2010 Wiley-Liss, Inc.
Steele, A. Duncan; Madhi, Shabir A.; Cunliffe, Nigel A.; Vesikari, Timo; Phua, Kong Boo; Lim, Fong Seng; Nelson, E. Anthony S.; Lau, Yu-Lung; Huang, Li-Min; Karkada, Naveen; Debrus, Serge; Han, Htay Htay; Benninghoff, Bernd
ABSTRACT Variability in rotavirus gastroenteritis (RVGE) epidemiology can influence the optimal vaccination schedule. We evaluated regional trends in the age of RVGE episodes in low- to middle- versus high-income countries in three continents. We undertook a post-hoc analysis based on efficacy trials of a human rotavirus vaccine (HRV; Rotarix™, GSK Vaccines), in which 1348, 1641, and 5250 healthy infants received a placebo in Europe (NCT00140686), Africa (NCT00241644), and Asia (NCT00197210, NCT00329745). Incidence of any/severe RVGE by age at onset was evaluated by active surveillance over the first two years of life. Severity of RVGE episodes was assessed using the Vesikari-scale. The incidence of any RVGE in Africa was higher than in Europe during the first year of life (≤2.78% vs. ≤2.03% per month), but much lower during the second one (≤0.86% versus ≤2.00% per month). The incidence of severe RVGE in Africa was slightly lower than in Europe during the first year of life. Nevertheless, temporal profiles for the incidence of severe RVGE in Africa and Europe during the first (≤1.00% and ≤1.23% per month) and second (≤0.53% and ≤1.13% per month) years of life were similar to those of any RVGE. Any/severe RVGE incidences peaked at younger ages in Africa vs. Europe. In high-income Asian regions, severe RVGE incidence (≤0.31% per month) remained low during the study. The burden of any RVGE was higher earlier in life in children from low- to middle- compared with high-income countries. Differing rotavirus vaccine schedules are likely warranted to maximize protection in different settings. PMID:27260009
Bwogi, Josephine; Jere, Khuzwayo C; Karamagi, Charles; Byarugaba, Denis K; Namuwulya, Prossy; Baliraine, Frederick N; Desselberger, Ulrich; Iturriza-Gomara, Miren
Rotaviruses of species A (RVA) are a common cause of diarrhoea in children and the young of various other mammals and birds worldwide. To investigate possible interspecies transmission of RVAs, whole genomes of 18 human and 6 domestic animal RVA strains identified in Uganda between 2012 and 2014 were sequenced using the Illumina HiSeq platform. The backbone of the human RVA strains had either a Wa- or a DS-1-like genetic constellation. One human strain was a Wa-like mono-reassortant containing a DS-1-like VP2 gene of possible animal origin. All eleven genes of one bovine RVA strain were closely related to those of human RVAs. One caprine strain had a mixed genotype backbone, suggesting that it emerged from multiple reassortment events involving different host species. The porcine RVA strains had mixed genotype backbones with possible multiple reassortant events with strains of human and bovine origin.Overall, whole genome characterisation of rotaviruses found in domestic animals in Uganda strongly suggested the presence of human-to animal RVA transmission, with concomitant circulation of multi-reassortant strains potentially derived from complex interspecies transmission events. However, whole genome data from the human RVA strains causing moderate and severe diarrhoea in under-fives in Uganda indicated that they were primarily transmitted from person-to-person.
Gilger, M A; Matson, D O; Conner, M E; Rosenblatt, H M; Finegold, M J; Estes, M K
Some rotavirus strains, including vaccine candidates, have been demonstrated to cause hepatitis in immunodeficient and malnourished mice and to grow in human liver cells. To determine whether rotavirus spreads outside the intestine in naturally infected children, we examined tissues from four immunodeficient children affected with severe combined immunodeficiency disease, acquired immunodeficiency disease syndrome, or DiGeorge syndrome. Chronic rotavirus-related diarrhea, which persisted until death, had also developed in each child. Using indirect immunoperoxidase techniques, we identified rotavirus antigen in the liver and kidney with a hyperimmune guinea pig antiserum prepared to double-shelled rotavirus particles. Similar immunostaining with an antiserum to a rotavirus nonstructural protein (NS26) provided evidence of active virus replication. The observed reactivity was eliminated specifically when serial sections were immunostained with the same antiserum that had been absorbed with either double-shelled rotavirus particles or NS26. Immunostaining was not observed in the liver of children with other diseases (alpha 1-antitrypsin deficiency, inspissated bile syndrome, and acute rejection of a transplanted liver). These findings demonstrate that rotavirus infections in children can extend beyond the intestinal tract. Further studies are warranted to determine whether extraintestinal rotavirus replication occurs in children without severe immunodeficiency, such as malnourished children.
Omenaca, Felix; Sarlangue, Jean; Szenborn, Leszek; Nogueira, Marta; Suryakiran, Pemmaraju V; Smolenov, Igor V; Han, Htay H
Rotavirus disease is more severe in preterm infants than in full-term infants. This study assessed the safety, reactogenicity and immunogenicity of a human rotavirus vaccine, RIX4414, in European preterm infants. A total of 1009 preterm infants were randomized (2:1, vaccine:placebo) and stratified into 2 groups: 20% of early (27-30 weeks, group 1) and 80% of late (31-36 weeks, group 2) gestational age preterm infants in each group. Two doses of RIX4414/placebo were administered to these preterm infants according to the recommended chronologic age for full-term infants with an interval of 30-83 days between doses. Serious adverse events were recorded throughout the study period. Solicited and unsolicited adverse events were recorded for 15 and 31 days post-each dose. Antirotavirus IgA concentrations (enzyme-linked immunosorbent assay cutoff = 20 U/mL) and geometric mean concentration were determined pre-dose 1 and 30-83 days post-dose 2 in a subset of 300 infants. This study is registered with ClinicalTrials.gov, number NCT00420745 (eTrack106481). Serious adverse events were reported at a similar frequency in both groups (P = 0.266). Fifty-seven infants reported at least 1 serious adverse event (5.1% [3.5-7.0] in the RIX4414 group and 6.8% [4.3-10.0] in the placebo group). During the 15-day postvaccination follow-up period, diarrhea, vomiting and fever occurred at a similar frequency in both groups; fever could have been due to concomitant vaccines. Five cases (RIX4414 = 3, Placebo = 2) of rotavirus gastroenteritis were reported. The onset of rotavirus gastroenteritis in the RIX4414 group was 1-5 days after vaccination (vaccine strain identified in all cases) and in the placebo group it was 3-4 days after receiving placebo (wild-type rotavirus identified from both cases). Antirotavirus IgA seroconversion rates at 30-83 days post-dose 2 were 85.7% (79.0-90.9) in the RIX4414 group and 16.0% (8.8-25.9) in the placebo group. Geometric mean concentrations were 202.2 U
Nakagomi, Toyoko; Doan, Yen Hai; Dove, Winifred; Ngwira, Bagrey; Iturriza-Gómara, Miren; Nakagomi, Osamu
Rotavirus A, the most common cause of severe diarrhoea in children worldwide, occurs in five major VP7 (G) and VP4 (P) genotype combinations, comprising G1P, G2P, G3P, G4P and G9P. However, G8, a common bovine rotavirus genotype, has been reported frequently among children in African countries. Surveillance of rotavirus gastroenteritis conducted in a sentinel hospital in Blantyre, Malawi between 1997 and 2007 provided a rare opportunity to examine the whole genotype constellation of G8 strains and their evolution over time. A sample of 27 (9.0 %) of 299 G8 strains was selected to represent each surveillance year and a range of P genotypes, which shifted in predominance from P to P and P during the study period. Following cell culture adaptation, whole genome sequencing demonstrated that the genetic background of 26 strains possessed the DS-1 genotype constellation. A single G8P strain was a reassortant in which both NSP2 and NSP5 genes from strains with the Wa genotype constellation had been inserted into a strain with the DS-1 genotype background. Phylogenetic analysis suggested frequent reassortment among co-circulating strains with the DS-1 genotype constellation. Little evidence was identified to suggest the introduction of contemporary bovine rotavirus genes into any of the 27 G8 strains examined. In conclusion, Malawian G8 strains are closely related to other human strains with the DS-1 genotype constellation. They have evolved over the last decade through genetic reassortment with other human rotaviruses, changing their VP4 genotypes while maintaining a conserved genotype constellation for the remaining structural and non-structural proteins. PMID:23407423
Nakagomi, Toyoko; Doan, Yen Hai; Dove, Winifred; Ngwira, Bagrey; Iturriza-Gómara, Miren; Nakagomi, Osamu; Cunliffe, Nigel A
Rotavirus A, the most common cause of severe diarrhoea in children worldwide, occurs in five major VP7 (G) and VP4 (P) genotype combinations, comprising G1P, G2P, G3P, G4P and G9P. However, G8, a common bovine rotavirus genotype, has been reported frequently among children in African countries. Surveillance of rotavirus gastroenteritis conducted in a sentinel hospital in Blantyre, Malawi between 1997 and 2007 provided a rare opportunity to examine the whole genotype constellation of G8 strains and their evolution over time. A sample of 27 (9.0 %) of 299 G8 strains was selected to represent each surveillance year and a range of P genotypes, which shifted in predominance from P to P and P during the study period. Following cell culture adaptation, whole genome sequencing demonstrated that the genetic background of 26 strains possessed the DS-1 genotype constellation. A single G8P strain was a reassortant in which both NSP2 and NSP5 genes from strains with the Wa genotype constellation had been inserted into a strain with the DS-1 genotype background. Phylogenetic analysis suggested frequent reassortment among co-circulating strains with the DS-1 genotype constellation. Little evidence was identified to suggest the introduction of contemporary bovine rotavirus genes into any of the 27 G8 strains examined. In conclusion, Malawian G8 strains are closely related to other human strains with the DS-1 genotype constellation. They have evolved over the last decade through genetic reassortment with other human rotaviruses, changing their VP4 genotypes while maintaining a conserved genotype constellation for the remaining structural and non-structural proteins.
Full Genome Characterization of Novel DS-1-Like G8P Rotavirus Strains that Have Emerged in Thailand: Reassortment of Bovine and Human Rotavirus Gene Segments in Emerging DS-1-Like Intergenogroup Reassortant Strains.
Full Text Available The emergence and rapid spread of unusual DS-1-like intergenogroup reassortant rotavirus strains have been recently reported in Asia, Australia, and Europe. During rotavirus surveillance in Thailand in 2013-2014, novel DS-1-like intergenogroup reassortant strains having G8P genotypes (i.e., strains KKL-17, PCB-79, PCB-84, PCB-85, PCB-103, SKT-107, SWL-12, NP-130, PCB-656, SKT-457, SSKT-269, and SSL-55 were identified in stool samples from hospitalized children with severe diarrhea. In this study, we determined and characterized the complete genomes of these 12 strains (seven strains, KKL-17, PCB-79, PCB-84, PCB-85, PCB-103, SKT-107, and SWL-12, found in 2013 (2013 strains, and five, NP-130, PCB-656, SKT-457, SSKT-269, and SSL-55, in 2014 (2014 strains. On full genomic analysis, all 12 strains showed a unique genotype constellation comprising a mixture of genogroup 1 and 2 genes: G8-P-I2-R2-C2-M2-A2-N2-T2-E2-H2. With the exception of the G genotype, the unique genotype constellation of the 12 strains (P-I2-R2-C2-M2-A2-N2-T2-E2-H2 was found to be shared with DS-1-like intergenogroup reassortant strains. On phylogenetic analysis, six of the 11 genes of the 2013 strains (VP4, VP2, VP3, NSP1, NSP3, and NSP5 appeared to have originated from DS-1-like intergenogroup reassortant strains, while the remaining four (VP7, VP6, VP1, and NSP2 and one (NSP4 gene appeared to be of bovine and human origin, respectively. Thus, the 2013 strains appeared to be reassortant strains as to DS-1-like intergenogroup reassortant, bovine, bovine-like human, and/or human rotaviruses. On the other hand, five of the 11 genes of the 2014 strains (VP4, VP2, VP3, NSP1, and NSP3 appeared to have originated from DS-1-like intergenogroup reassortant strains, while three (VP7, VP1, and NSP2 and one (NSP4 were assumed to be of bovine and human origin, respectively. Notably, the remaining two genes, VP6 and NSP5, of the 2014 strains appeared to have originated from locally
Bernstein, David I
Rotaviral gastroenteritis is a serious public health problem in both developed and developing countries. The disease is ubiquitous, affecting nearly all children by the age of 5 years. It is the most common cause of hospitalizations for gastroenteritis among children in the United States (30%-70% depending on the season) and is associated with direct and indirect costs of approximately $1 billion per year. Symptoms of rotaviral gastroenteritis are nonspecific (ie, diarrhea, vomiting, and fever), with disease severity varying considerably. Diagnostic confirmation of rotaviral gastroenteritis requires laboratory tests (most commonly enzyme immunoassay or latex agglutination); however, because specific diagnosis is costly and does not affect treatment, laboratory tests are generally not performed. Because no antiviral therapies are currently available, treatment of rotavirus infection is supportive and primarily aimed at the replacement of fluid and electrolyte losses. Based on the observations that improved sanitation does not decrease disease prevalence and that hospitalizations remain high despite the availability and use of oral rehydrating solutions, the primary public health intervention for rotavirus infection is vaccination. Current vaccines (ie, RotaTeq, Merck and Company; Rotarix, GlaxoSmithKline) are effective for reducing rotaviral gastroenteritis (particularly severe disease), emergency department visits, and hospitalizations. Rotavirus vaccination is now included as part of the routine vaccination schedule for all infants in the United States.
Midthun, K; Kapikian, A Z
Rotavirus vaccine development has focused on the delivery of live attenuated rotavirus strains by the oral route. The initial "Jennerian" approach involving bovine (RIT4237, WC3) or rhesus (RRV) rotavirus vaccine candidates showed that these vaccines were safe, well tolerated, and immunogenic but induced highly variable rates of protection against rotavirus diarrhea. The goal of a rotavirus vaccine is to prevent severe illness that can lead to dehydration in infants and young children in both...
Jucélia Stadinicki dos Santos
Full Text Available From January/2000 to December/2003, 550 diarrheic fecal samples from the children and adults were collected in several geographical regions of Paraná State, Brazil. The enzyme immunoassay showed 120 (21.8% samples positive for the group A rotaviruses. One hundred and fourteen samples were genotyped by multiplex-nested-PCR assay. The highest frequency (77.5% of the positive samples (n=93 was observed in the children under 5 years old. Rotavirus diarrhea was more frequent in the cold and dry seasons of the four evaluated years. The most frequent genotypes were: G1 (50.9%, G4 (9.6%, G9 (7.0%, G2 (1.7%, G3 (0.9%, P[ 8] (71.9%, and P[ 4] (3.5%. The P[ 8] G1 (46.5% and P[ 8] G4 (9.6% were the main combinations found to P and G genotypes. The mixed infections, characterized by the rotaviruses with more than one genotype G or P, and nontypeable rotavirus were observed in 8.8, 3.5, and 16.7% of the samples, respectively. The identification of the G9 genotype in the rotavirus strains tested along the four years of studies ratifies the emergency of this genotype also in Paraná State, South region of Brazil, as the worldwide.No período de janeiro de 2000 a dezembro de 2003 foram colhidas, em várias regiões geográficas do Estado do Paraná, 550 amostras fecais de crianças e adultos com quadro clínico de diarréia aguda. Por meio de ensaio imunoenzimático comercial, 120 (21,8% amostras foram positivas para o rotavírus grupo A. Dessas, 114 amostras foram genotipadas por meio da multiplex-nested-PCR. A maior freqüência (77,5% de amostras positivas (n=93 foi observada em crianças menores de cinco anos de idade. A maior concentração de casos positivos para o rotavírus ocorreu nos meses frios e secos dos quatro anos avaliados. Os genotipos de maior ocorrência foram: G1 (50,9%, G4 (9,6%, G9 (7,0%, G2 (1,7%, G3 (0,9%, P[ 8] (71,9% e P[ 4] (3,5%. P[ 8] G1 (46,5% e P[ 8] G4 (9,6% foram as associações de genotipos P e G mais encontradas. Infec
Darveau, André; Fliss, Ismaïl
Rotavirus is the leading cause of severe acute gastroenteritis among children worldwide. Despite effective vaccines, inexpensive alternatives such as probiotics are needed. The aim of this study was to assess the ability of probiotic candidate Bifidobacterium thermophilum RBL67 to inhibit rotavirus infection. Bacterial adhesion to intestinal cells and interference with viral attachment were evaluated in vitro. B. thermophilum RBL67 displayed adhesion indexes of 625 ± 84 and 1958 ± 318 on Caco-2 and HT-29 cells respectively and was comparable or superior to four other bifidobacteria, including B. longum ATCC 15707 and B. pseudolongum ATCC 25526 strains. Incubation of B. thermophilum RBL67 for 30 min before (exclusion) and simultaneously (competition) with human rotavirus strain Wa decreased virus attachment by 2.0 ± 0.1 and 1.5 ± 0.1 log10 (by 99.0% and 96.8% respectively). Displacement of virus already present was negligible. In CD-1 suckling mice fed B. thermophilum RBL67 challenged with simian rotavirus SA-11, pre-infection feeding with RBL 67 was more effective than post-infection feeding, reducing the duration of diarrhea, limiting epithelial lesions, reducing viral replication in the intestine, accelerating recovery, and stimulating the humoral specific IgG and IgM response, without inducing any adverse effect. B. thermophilum RBL67 had little effect on intestinal IgA titer. These results suggest that humoral immunoglobulin might provide protection against the virus and that B. thermophilum RBL67 has potential as a probiotic able to inhibit rotavirus infection and ultimately reduce its spread. PMID:27727323
Bishop, R F
Candidate rotavirus vaccines tested to date have been developed using a 'Jennerian' approach. Strains of bovine and simian rotaviruses that are naturally attenuated for humans have been assessed and found to confer immunity that is serotype specific in a varying proportion of recipients. The spectrum of protection has been widened by developing reassortants in which the bovine or simian gene coding for VP7 (the major outer capsid protein) has been replaced by the corresponding gene from human VP7 types 1, 2, 3 or 4. Once the protective antigen(s) are identified it may be possible to develop subunit vaccines that eliminate side effects sometimes observed with live vaccine candidates.
Cunliffe, Nigel A; Witte, Desiree; Ngwira, Bagrey M; Todd, Stacy; Bostock, Nancy J; Turner, Ann M; Chimpeni, Philips; Victor, John C; Steele, A Duncan; Bouckenooghe, Alain; Neuzil, Kathleen M
Rotavirus gastroenteritis is a major cause of morbidity and mortality among African infants and young children. A phase III, placebo-controlled, multi-centre clinical trial of a live, oral G1P human rotavirus vaccine (RIX4414) undertaken in Malawi and South Africa significantly reduced the incidence of severe rotavirus gastroenteritis in the first year of life. We now report on vaccine efficacy in the Malawi cohort of children who were followed into the second year of life. A total of 1,773 healthy infants were enrolled in Blantyre, Malawi into three groups. Two groups received three doses of RIX4414 or placebo at age 6, 10, and 14 weeks and the third group received placebo at 6 weeks and RIX4414 at age 10 and 14 weeks. Subjects were followed by weekly home visits for episodes of gastroenteritis until 1 year of age, and were then re-consented for further follow-up to 18-24 months of age. Severity of gastroenteritis episodes was graded according to the Vesikari scoring system. Seroconversion for anti-rotavirus IgA was determined on a subset of children by using ELISA on pre- and post-vaccine blood samples. Rotavirus VP7 (G) and VP4 (P) genotypes were determined by RT-PCR. A total of 70/1030 (6.8%, 95% CI 5.3 - 8.5) subjects in the pooled (2 dose plus 3 dose) RIX4414 group compared with 53/483 (11.0%, 8.3 – 14.1) subjects in the placebo group developed severe rotavirus gastroenteritis in the entire follow-up period (Vaccine Efficacy 38.1% (9.8 – 57.3). The point estimate of efficacy in the second year of life (17.6%; −59.2 – 56.0) was lower than in the first year of life (49.4%; 19.2 – 68.3). There were non-significant trends towards a higher efficacy in the second year of life among children who received the three-dose schedule compared with the two-dose schedule, and a higher anti-rotavirus IgA seroresponse rate in the three-dose RIX4414 group. Rotavirus strains detected included genotype G12 (31%); G9 (23%); and G8 (18%); only 18% of strains belonged
Ndze, Valentine N; Papp, Hajnalka; Achidi, Eric A; Gonsu, Kamga H; László, Brigitta; Farkas, Szilvia; Kisfali, Péter; Melegh, Béla; Esona, Mathew D; Bowen, Michael D; Bányai, K; Gentsch, Jon R; Odama, Abena M T
In this study the emergence of rotavirus A genotype G12 in children G genotyped by reverse transcriptase PCR. Six different rotavirus VP7 genotypes were detected, including G1, G2, G3, G8, G9, and G12 in combinations with P, P and P VP4 genotypes. Genotype G12 predominated in combination with P (54.1%) and P (10.4%) genotypes followed by G1P (8.2%), G3P (6.7%), G2P (5.9%), G8P (3.7%), G2P (0.7%), G3P (0.7%), and G9P (0.7%). Genotype P strains in combination with various G-types represented a substantial proportion (N=44, 32.6%) of the genotyped strains. Partially typed strains included G12P[NT] (2.2%); G3P[NT] (0.7%); G(NT)P (1.5%); and G(NT)P (0.7%). Mixed infections were found in five specimens (3.7%) in several combinations including G1+ G12P, G2+ G3P + P, G3+ G8P, G3 + G12P + P, and G12P +P. The approximately 10% relative frequency of G12P strains detected in this study suggests that this strain is emerging in Cameroon and should be monitored carefully as rotavirus vaccine is implemented in this country, as it shares neither G- nor P-type specificity with strains in the RotaTeq® and Rotarix® vaccines. These findings are consistent with other recent reports of the global spread and increasing epidemiologic importance of G12 and P strains. Copyright © 2013 Wiley Periodicals, Inc.
Than, Van Thai; Park, Jong-Hwa; Chung, In Sik; Kim, Jong Bum; Kim, Wonyong
A rare rotavirus, RVA/Human-wt/KOR/CAU12-2/2012/G11P, was isolated from a 16-year-old female with fever and diarrhea during the 2012 rotavirus surveillance in South Korea using a cell culture system, and its full genome sequence was determined and analyzed. Strain CAU12-2 exhibited a G11-P-I12-R1-C1-M1-A1-N1-T1-E1-H1 genotype constellation. Phylogenetic analysis of this strain revealed that it is a human-porcine reassortant of two distant relatives of the G11 strains circulating in the world. The VP7 and VP4 genes are most closely related to those of human G11P viruses (Dhaka6, KTM368, and N-38 strains) identified in South Asia, whereas the VP1 gene originated from a porcine G11P virus (YM strain) that was identified in South America. The VP6 gene was found to belong to the new genotype I12. This study indicates that the G11-P-I12 genotype was introduced into the South Korean population by interspecies transmissions of human and animal rotaviruses, followed by multiple reassortment events.
Full Text Available Rotaviruses are a major etiologic agent of gastroenteritis in infants and young children worldwide. Since the latter of the 1990s, G3 human rotaviruses referred to as "new variant G3" have emerged and spread in China, being a dominant genotype until 2010, although their genomic evolution has not yet been well investigated.The complete genomes of 33 G3P human rotavirus strains detected in Wuhan, China, from 2000 through 2013 were analyzed. Phylogenetic trees of concatenated sequences of all the RNA segments and individual genes were constructed together with published rotavirus sequences.Genotypes of 11 gene segments of all the 33 strains were assigned to G3-P-I1-R1-C1-M1-A1-N1-T1-E1-H1, belonging to Wa genogroup. Phylogenetic analysis of the concatenated full genome sequences indicated that all the modern G3P strains were assigned to Cluster 2 containing only one clade of G3P strains in the US detected in the 1970s, which was distinct from Cluster 1 comprising most of old G3P strains. While main lineages of all the 11 gene segments persisted during the study period, different lineages appeared occasionally in RNA segments encoding VP1, VP4, VP6, and NSP1-NSP5, exhibiting various allele constellations. In contrast, only a single lineage was detected for VP7, VP2, and VP3 genes. Remarkable lineage shift was observed for NSP1 gene; lineage A1-2 emerged in 2007 and became dominant in 2008-2009 epidemic season, while lineage A1-1 persisted throughout the study period.Chinese G3P rotavirus strains have evolved since 2000 by intra-genogroup reassortment with co-circulating strains, accumulating more reassorted genes over the years. This is the first large-scale whole genome-based study to assess the long-term evolution of common human rotaviruses (G3P in an Asian country.
Wang, Yuan-Hong; Pang, Bei-Bei; Ghosh, Souvik; Zhou, Xuan; Shintani, Tsuzumi; Urushibara, Noriko; Song, Yu-Wei; He, Ming-Yang; Liu, Man-Qing; Tang, Wei-Feng; Peng, Jin-Song; Hu, Quan; Zhou, Dun-Jin; Kobayashi, Nobumichi
Background Rotaviruses are a major etiologic agent of gastroenteritis in infants and young children worldwide. Since the latter of the 1990s, G3 human rotaviruses referred to as “new variant G3” have emerged and spread in China, being a dominant genotype until 2010, although their genomic evolution has not yet been well investigated. Methods The complete genomes of 33 G3P human rotavirus strains detected in Wuhan, China, from 2000 through 2013 were analyzed. Phylogenetic trees of concatenated sequences of all the RNA segments and individual genes were constructed together with published rotavirus sequences. Results Genotypes of 11 gene segments of all the 33 strains were assigned to G3-P-I1-R1-C1-M1-A1-N1-T1-E1-H1, belonging to Wa genogroup. Phylogenetic analysis of the concatenated full genome sequences indicated that all the modern G3P strains were assigned to Cluster 2 containing only one clade of G3P strains in the US detected in the 1970s, which was distinct from Cluster 1 comprising most of old G3P strains. While main lineages of all the 11 gene segments persisted during the study period, different lineages appeared occasionally in RNA segments encoding VP1, VP4, VP6, and NSP1-NSP5, exhibiting various allele constellations. In contrast, only a single lineage was detected for VP7, VP2, and VP3 genes. Remarkable lineage shift was observed for NSP1 gene; lineage A1-2 emerged in 2007 and became dominant in 2008–2009 epidemic season, while lineage A1-1 persisted throughout the study period. Conclusion Chinese G3P rotavirus strains have evolved since 2000 by intra-genogroup reassortment with co-circulating strains, accumulating more reassorted genes over the years. This is the first large-scale whole genome-based study to assess the long-term evolution of common human rotaviruses (G3P) in an Asian country. PMID:24676363
Van Damme Pierre
Full Text Available Abstract Background The Rotavirus Efficacy and Safety Trial was a placebo-controlled Phase III study that evaluated the safety and efficacy of a three-dose pentavalent rotavirus vaccine (RV5 including its effect on healthcare utilization for rotavirus gastroenteritis (RVGE. The per-protocol (PP analyses, which counted events occurring 14 days after dose 3 among infants without protocol violations, have already been published. This paper evaluates the consistency of the healthcare utilization results based on the modified intention to treat (MITT analyses with the PP analyses. The MITT analyses include all infants receiving at least one dose of vaccine or placebo and follow-up begins after dose 1. The paper also explores the consistency of the results for different subgroups of the study population with different types of surveillance. Methods Data on healthcare utilization for acute gastroenteritis were collected via telephone interviews after administration of the first dose. Parents were either contacted every 6 weeks or every 2 weeks depending on the substudy in which they were enrolled. Those contacted every 2 weeks were also asked to complete symptom diaries. Poisson regression was used to evaluate the effect of RV5 on the rates of RVGE-associated healthcare encounters in all of the analyses. Results In the first 2 years after vaccination, RV5 reduced the combined rate of hospitalizations and emergency department (ED visits 88.9% (95% CI: 84.9, 91.9 for all RVGE regardless of serotype in the MITT analysis compared with a 94.5% (95% CI: 91.2, 96.6 reduction based on the G1-G4 PP analysis. By type of surveillance, the rate reductions for the G1-G4 PP analysis were 91.0% (95% CI: 81.7, 95.5 and 95.9% (95% CI: 92.2, 97.8 among parents contacted every 2 weeks (number evaluable = 4,451 and every 6 weeks (number evaluable = 52,683 respectively. Conclusions Our analyses demonstrated that the effect of RV5 on reducing the rate of hospitalizations
Zhou, Nan; Lv, Dong; Wang, Suting; Lin, Xiaojuan; Bi, Zhenwang; Wang, Haiyan; Wang, Pei; Zhang, Huaning; Tao, Zexin; Hou, Peibin; Song, Yanyan; Xu, Aiqiang
Rotavirus is the leading viral agent for pediatric gastroenteritis. However, the case-based surveillance for rotavirus is limited in China, and its circulation in the environment is not well investigated. From 2013 to 2014, rotavirus was detected in raw sewage samples of Jinan and Linyi by quantitative PCR (qPCR) and conventional reverse transcription PCR (RT-PCR). After sequenced and genotyped, sequences analysis was conducted. A total of 46 sewage samples were collected monthly for the detection of rotavirus, and rotavirus was positive in 43 samples (93.5 %, 43/46). By quantitative assessment, the concentrations of rotavirus in raw sewage ranged from 4.1 × 10(3) to 1.3 × 10(6) genome copies (GC)/L in Jinan, and from 1.5 × 10(3) to 3.0 × 10(5) GC/L in Linyi. A total of 318 sequences of 5 G-genotypes and 318 sequences of 5 P-genotypes were obtained. G9 (91.8 %, 292/318) and P (56.0 %, 178/318) were the most common G- and P-genotype, respectively. Multiple transmission lineages were recognized in these genotypes. Interestingly, an intragenic recombination event between two G9 lineages was observed. This study provided the first report of comprehensive environmental surveillance for rotavirus in China. The results suggest that the concentration of rotavirus in raw sewage was high, and multiple rotavirus transmission lineages continuously co-circulated in Shandong.
Bellaiche, M; Viala, J; Degas, V; Cézard, J-P
Rotavirus is the most frequent virus found in childhood gastroenteritis. A rotavirus viremia is observed in 19 to 63 % of cases, for three days at the beginning of infection. Then, rotavirus can reach several organs as liver (hepatitis in 1/3 of case), nervous central system (2 % of encephalitis could be linked to rotavirus), or more infrequently mesenteric lymph nodes, lung or heart. However, the link between rotavirus and systemic manifestations has not been well established. Further studies are necessary to confirm the role of rotavirus in these organ's lesions.
Dennehy, Penelope H
Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and has a major global impact on childhood morbidity and mortality. Vaccination is the only control measure likely to have a significant impact on the incidence of severe dehydrating rotavirus disease. Rotavirus disease prevention efforts suffered a great setback in 1999 with the withdrawal of the RRV-TV vaccine less than a year after its introduction. Several new rotavirus vaccine candidates have now been developed and are undergoing clinical trials. New safe and effective rotavirus vaccines offer the best hope of reducing the toll of acute rotavirus gastroenteritis in both developed and developing countries.
Thaís Aparecida Vieira Reis
Full Text Available Abstract Human adenovirus species F (HAdV-F type 40 and 41 are commonly associated with acute diarrheal disease (ADD across the world. Despite being the largest state in southeastern Brazil and having the second largest number of inhabitants, there is no information in the State of Minas Gerais regarding the role of HAdV-F in the etiology of ADD. This study was performed to determine the prevalence, to verify the epidemiological aspects of infection, and to characterize the strains of human adenoviruses (HAdV detected. A total of 377 diarrheal fecal samples were obtained between January 2007 and August 2011 from inpatient and outpatient children of age ranging from 0 to 12 years. All samples were previously tested for rotavirus, norovirus, and astrovirus, and 314 of 377 were negative. The viral DNA was extracted, amplified using the polymerase chain reaction and the HAdV-positive samples were sequenced and phylogenetically analyzed. Statistical analyses were performed using the Chi-square test (p < 0.05, considering two conditions: the total of samples tested (377 and the total of negative samples for the remaining viruses tested (314. The overall prevalence of HAdV was 12.47% (47/377; and in 76.60% (36/47 of the positive samples, this virus was the only infectious agent detected. The phylogenetic analysis of partial sequences of 32 positive samples revealed that they all clustered with the HAdV-F type 41. The statistical analysis showed that there was no correlation between the onset of the HAdV infection and the origin of the samples (inpatients or outpatients in the two conditions tested: the total of samples tested (p = 0.598 and the total of negative samples for the remaining viruses tested (p = 0.614. There was a significant association in the occurrence of infection in children aged 0–12 months for the condition 1 (p = 0.030 as well as condition 2 (p = 0.019. The occurrence of infections due to HAdV did not coincide with a pattern of
Glass, Roger I; Parashar, Umesh D; Bresee, Joseph S; Turcios, Reina; Fischer, Thea K; Widdowson, Marc-Alain; Jiang, Baoming; Gentsch, Jon R
Rotavirus is the most common cause of severe diarrhoea in children worldwide and diarrhoeal deaths in children in developing countries. Accelerated development and introduction of rotavirus vaccines into global immunisation programmes has been a high priority for many international agencies, including WHO and the Global Alliance for Vaccines and Immunizations. Vaccines have been developed that could prevent the enormous morbidity and mortality from rotavirus and their effect should be measurable within 2-3 years. Two live oral rotavirus vaccines have been licensed in many countries; one is derived from an attenuated human strain of rotavirus and the other combines five bovine-human reassortant strains. Each vaccine has proven highly effective in preventing severe rotavirus diarrhoea in children and safe from the possible complication of intussusception. In developed countries, these vaccines could substantially reduce the number and associated costs of child hospitalisations and clinical visits for acute diarrhoea. In developing countries, they could reduce deaths from diarrhoea and improve child survival through programmes for childhood immunisations and diarrhoeal disease control. Although many scientific, programmatic, and financial challenges face the global use of rotavirus vaccines, these vaccines-and new candidates in the pipeline-hold promise to make an immediate and measurable effect to improve child health and survival from this common burden affecting all children.
Full Text Available Abstract Background Rotavirus genotyping is performed by using reverse transcription PCR with type-specific-primers. Because the high rotavirus mutation rate generates an extensive genomic variation, different G-type-specific primer sets are applied in different geographical locations. In Bangladesh, a significant proportion (36.9% of the rotavirus strains isolated in 2002 could not be G-typed using the routinely used primer set. To investigate the reason why the strains were untypeable, nucleotide sequencing of the VP7 genes was performed. Results Four nucleotide substitutions at the G1 primer-binding site of the VP7 gene of Bangladeshi G1 rotaviruses rendered a major proportion of circulating strains untypeable using the routine primer set. Using an alternative primer set, we could identify G1 rotaviruses as the most prevalent genotype (44.8%, followed by G9 (21.7%, G2 (15.0% and G4 (13.8%. Conclusion Because of the natural variation in the rotaviral gene sequences, close monitoring of rotavirus genotyping methods is important.
Nguyen, Tuan Anh; Khamrin, Pattara; Trinh, Quang Duy; Phan, Tung Gia; Pham, Le Duc; Hoang, Le Phuc; Hoang, Kim Trong; Yagyu, Fumihiro; Okitsu, Shoko; Ushijima, Hiroshi
Nucleotide and amino acid sequences of the VP8* gene of five Vietnamese P rotavirus strains detected from hospitalized patients with acute gastroenteritis were analyzed and compared with other human and porcine P rotaviruses. It is of interest that these strains had greatest identity with two Italian porcine rotavirus strains, 134/04-10 and 134/04-11. To our knowledge, these five Vietnamese rotaviruses are the rare P rotavirus strains belonging to lineage I that cluster into sublineage Ic with porcine rotaviruses, and not into sublineage Ia, as other human P rotaviruses have done so far. Sequence analysis of the VP7 gene of these P rotavirus strains was also performed. The results showed that the Vietnamese G9P strain had high similarity with other human G9 rotaviruses, confirming a human-animal reassortant virus, whereas other three G4P strains had best identity with porcine G4 rotavirus strains, suggesting interspecies transmission of rotavirus between porcine and humans. This result provides the important data on molecular characteristics of Vietnamese rotaviruses, and highlights interspecies transmission events of rotaviruses in Vietnam as well as in Asia. (c) 2007 Wiley-Liss, Inc.
Pourasgari, Farzaneh; Ahmadian, Shahin; Salmanian, Ali Hatef; Sarbolouki, Mohammad Nabi; Massumi, Mohammad
The efficiency of dendrosome (a gene porter) was assessed in transferring recombinant human rotavirus VP2 cDNA into A549, a human lung cell line. After gene transferring, transmission electron microscopy showed core-like particles (CLPs) formation in the transfected cells both with dendrosome and lipofectamine porters. In addition, western blotting analysis showed that the expression of VP2 gene was almost equal in the dendrosome and lipofectamine-transfected cells. Also, the cytotoxicity studies revealed that dendrosome had a lower cytotoxicity than lipofectamine. Therefore, our study may introduce dendrosome as a possible carrier for gene transferring into the human lung cell line, especially, for intranasally administration of DNA vaccines.
Rippinger, Christine M; Patton, John T; McDonald, Sarah M
Rotaviruses (RVs) cause severe gastroenteritis in infants and young children; yet, several strains have been isolated from newborns showing no signs of clinical illness. Two of these neonatal strains, RV3 (G3P) and 116E (G9P), are currently being developed as live-attenuated vaccines. In this study, we sequenced the eleven-segmented double-stranded RNA genomes of cell culture-adapted RV3 and 116E and compared their genes and protein products to those of other RVs. Using amino acid alignments and structural predictions, we identified residues of RV3 or 116E that may contribute to attenuation or influence vaccine efficacy. We also discovered residues of the VP4 attachment protein that correlate with the capacity of some P strains, including RV3, to infect newborns versus older infants. The results of this study enhance our understanding of the molecular determinants of RV3 and 116E attenuation and are expected to aid in the ongoing development of these vaccine candidates. Published by Elsevier Inc.
Zade, Jagdish K; Kulkarni, Prasad S; Desai, Sajjad A; Sabale, Rajendra N; Naik, Sameer P; Dhere, Rajeev M
A bovine rotavirus pentavalent vaccine (BRV-PV) containing rotavirus human-bovine (UK) reassortant strains of serotype G1, G2, G3, G4 and G9 has been developed by the Serum Institute of India Ltd, in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), USA. The vaccine underwent animal toxicity studies and Phase I and II studies in adults, toddlers and infants. It has been found safe and immunogenic and will undergo a large Phase III study to assess efficacy against severe rotavirus gastroenteritis. Copyright © 2014. Published by Elsevier Ltd.
Ianiro, Giovanni; Delogu, Roberto; Fiore, Lucia; Ruggeri, Franco M
Group A rotaviruses (RVA) are the leading cause of acute gastroenteritis in young children, causing up to 450,000 deaths worldwide, mostly in developing countries. Most of RVA human infections in developed countries are related to five major G/P combinations: G1P, G2P, G3P, G4P and G9P. During the surveillance activity of RotaNet-Italy, three uncommon G3P RVA strains, designated as RVA/Human-wt/ITA/NA01/2009/G3P, RVA/Human-wt/ITA/NA06/2009/G3P, and RVA/Human-wt/ITA/NA19/2009/G3P, were identified in the stools of children with diarrhea hospitalized in Southern Italy in 2009. Samples NA01, NA06 and NA19 were characterized as genotype G3P. To investigate the three strains further, partial sequencing of the eleven genomic segments was performed. RVA strains NA01, NA06 and NA19 were found to share the rare genotype constellation: G3-P-I2-R2-C2-M2-A2-N2-T2-E2-H2, which had not been reported previously in continental Italy. The phylogenetic analysis of the eleven genomic segments showed no evidence of zoonosis or inter-species reassortment at the origin of the Italian G3P strains, indicating that they possessed DS-1-like genomic constellations similar to those detected previously in human cases in Africa and Europe. The analysis of the hypervariable regions of VP7 and VP4 (VP8*) revealed high amino acid identity between the Italian G3P RVA strains involved in this study. Copyright © 2015 Elsevier B.V. All rights reserved.
Trinh, Quang Duy; Pham, Ngan Thi Kim; Nguyen, Tuan Anh; Phan, Tung Gia; Yan, Hainian; Hoang, Le Phuc; Khamrin, Pattara; Maneekarn, Niwat; Li, Yan; Okitsu, Shoko; Mizuguchi, Masashi; Ushijima, Hiroshi
Sequence and phylogenetic analyses of the rotavirus VP7 gene were performed on 52 human G2 and G4 strains isolated in Japan, China, Thailand, and Vietnam during 2001-2003. All genotype G2 strains included in the study clustered into lineage II of the phylogenetic tree, together with the majority of global G2 strains detected since 1995. The amino acid substitution at position 96 from aspartic acid to asparagine was noted among the emerging or re-emerging G2 rotavirus strains in Japan, Thailand, and Vietnam during 2002-2003. Genotype G4 strains detected in Vietnam grouped into lineage Ia of the phylogenetic tree, whereas Japanese G4 strains clustered in lineage Ic which included emerging G4 strains from Argentina, Italy, Paraguay, and Uruguay. It is noteworthy that an insertion of asparagine was found at position 76 in all the Japanese strains and that its presence might be involved in the emergence of G4 rotavirus in Japan during 2002-2003. (c) 2010 Wiley-Liss, Inc.
Eichelberger, Maryna C; Sperber, Ellen; Wagner, Mariam; Hoshino, Yasutaka; Dudas, Robert; Hodgins, Vicki; Marron, Jennifer; Nehring, Pamela; Casey, Roberta; Burns, Barbara; Karron, Ruth; Clements-Mann, Mary Lou; Kapikian, Albert Z
The safety, infectivity, and immunogenicity of two human-bovine reassortant rotavirus candidate vaccines were evaluated in adults, children, and infants. One of these, Wa x UK, contained a single human rotavirus gene from the Wa strain that encoded VP4 P1A specificity in a background of 10 bovine genes including the VP7 gene that encodes G6 specificity, whereas the other, Wa x (DS-1 x UK), possessed the human rotavirus VP4 gene from the Wa strain as well as the human VP7 gene from strain DS-1 that encoded G2 specificity. Each of these vaccines appeared to be well-tolerated and immunogenic in infants less than 6 months of age following a single oral dose, and therefore should be evaluated further as vaccine candidates. Copyright 2002 Wiley-Liss, Inc.
Abdel-Haq, Nahed; Amjad, Muhammad; McGrath, Eric; Chearskul, Pimpanada; Amer, Ahdi; Salimnia, Hossein; Asmar, Basim I
Between January 2007 and April 2009, rotavirus (RV)-positive stool samples from 238 children with acute gastroenteritis, seen at Children's Hospital of Michigan in Detroit, USA, were collected and RV genotyping was performed. G and P genotypes were determined by RT-PCR and nucleotide sequencing was conducted on selected G9 and P strains. Correlation between the severity of gastroenteritis episode and the infecting G genotype was done using a 14-point scoring system. The predominant G genotype was G9 (39.5 %), followed by G1 (35.3 %) and G4 (15.5 %), while P was the most prevalent P genotype (66.5 %), followed by P (21.9 %) and P (11.2 %). The gene combinations G1P and G9P were the most prevalent (21.4 % and 20.6 %, respectively), followed by G4P (13 %) and G9P (8.8 %). Immunization data showed that only 17/238 (7.1 %) children received ≥one dose of RV vaccine (the pentavalent vaccine RotaTeq or the monovalent vaccine Rotarix) and that 10/17 were infected with G4P strains. Severity of RV gastroenteritis episodes was not related to the infecting G genotype. Our results suggest a high proportion of genotype G9 strains in combination with P, P and P specificity circulating in the metropolitan Detroit area. While the protective efficacy of the RV vaccines has been demonstrated against G9P strains, the level of cross-protection offered by the vaccines against G9 strains with P and P genotypes in the Detroit paediatric population remains to be determined.
Yamamoto, Seiji P; Kaida, Atsushi; Ono, Atsushi; Kubo, Hideyuki; Iritani, Nobuhiro
In a surveillance system in Osaka City, Japan, 48 sporadic rotavirus A (RVA) infections were detected during 2008/2009-2011/2012 seasons. The G/P-genotypes of detected RVAs were G1P, G2P, G3P, G9P, and G9P. Although G9P is a rare genotype that had not been reported in Japan, it was the second most prevalent genotype, following G1P, and accounted for 35.3% of RVA cases in the 2011/2012 season. Further genotyping revealed that the G9P strain had genotype 2 internal protein genes except for NSP3: G9-P-I2-R2-C2-M2-A2-N2-T1-E2-H2. Among detected RVA strains, G9P and some G9P strains shared high nucleotide identity in VP7 and NSP3 genes. Phylogenetic and BLAST search analyses showed that the G9P strain in Japan shared high nucleotide identity in genotype 2 genes with common G2P strains circulating globally, but was distinct from other G9P strains circulating worldwide. These results suggest that the G9P strain in Japan may have emerged through an independent reassortment between G9P and G2P. Finally, the role of NSP3 protein in the circulating RVA from an amino acid comparison between T1- and T2-type NSP3 is discussed. These findings provide an important insight into less problematic combinations of circulating RVA genes derived from different genotypes. © 2015 Wiley Periodicals, Inc.
Midgley, S. E.; Hjulsager, Charlotte Kristiane; Larsen, Lars Erik
Group A rotaviruses infect humans and a variety of animals. In July 2006 a rare rotavirus strain with G8P specificity was identified in the stool samples of two adult patients with diarrheoa, who lived in the same geographical area in Denmark. Nucleotide sequences of the VP7, VP4, VP6, and NSP4...... genes of the identified strains were identical. Phylogenetic analyses showed that both Danish G8P strains clustered with rotaviruses of animal, mainly, bovine and caprine, origin. The high genetic relatedness to animal rotaviruses and the atypical epidemiological features suggest that these human G8...
Hagbom, Marie; Istrate, Claudia; Engblom, David; Karlsson, Thommie; Rodriguez-Diaz, Jesus; Buesa, Javier; Taylor, John A; Loitto, Vesa-Matti; Magnusson, Karl-Eric; Ahlman, Håkan; Lundgren, Ove; Svensson, Lennart
Rotavirus (RV) is the major cause of severe gastroenteritis in young children. A virus-encoded enterotoxin, NSP4 is proposed to play a major role in causing RV diarrhoea but how RV can induce emesis, a hallmark of the illness, remains unresolved. In this study we have addressed the hypothesis that RV-induced secretion of serotonin (5-hydroxytryptamine, 5-HT) by enterochromaffin (EC) cells plays a key role in the emetic reflex during RV infection resulting in activation of vagal afferent nerves connected to nucleus of the solitary tract (NTS) and area postrema in the brain stem, structures associated with nausea and vomiting. Our experiments revealed that RV can infect and replicate in human EC tumor cells ex vivo and in vitro and are localized to both EC cells and infected enterocytes in the close vicinity of EC cells in the jejunum of infected mice. Purified NSP4, but not purified virus particles, evoked release of 5-HT within 60 minutes and increased the intracellular Ca²⁺ concentration in a human midgut carcinoid EC cell line (GOT1) and ex vivo in human primary carcinoid EC cells concomitant with the release of 5-HT. Furthermore, NSP4 stimulated a modest production of inositol 1,4,5-triphosphate (IP₃), but not of cAMP. RV infection in mice induced Fos expression in the NTS, as seen in animals which vomit after administration of chemotherapeutic drugs. The demonstration that RV can stimulate EC cells leads us to propose that RV disease includes participation of 5-HT, EC cells, the enteric nervous system and activation of vagal afferent nerves to brain structures associated with nausea and vomiting. This hypothesis is supported by treating vomiting in children with acute gastroenteritis with 5-HT₃ receptor antagonists.
Full Text Available Rotavirus (RV is the major cause of severe gastroenteritis in young children. A virus-encoded enterotoxin, NSP4 is proposed to play a major role in causing RV diarrhoea but how RV can induce emesis, a hallmark of the illness, remains unresolved. In this study we have addressed the hypothesis that RV-induced secretion of serotonin (5-hydroxytryptamine, 5-HT by enterochromaffin (EC cells plays a key role in the emetic reflex during RV infection resulting in activation of vagal afferent nerves connected to nucleus of the solitary tract (NTS and area postrema in the brain stem, structures associated with nausea and vomiting. Our experiments revealed that RV can infect and replicate in human EC tumor cells ex vivo and in vitro and are localized to both EC cells and infected enterocytes in the close vicinity of EC cells in the jejunum of infected mice. Purified NSP4, but not purified virus particles, evoked release of 5-HT within 60 minutes and increased the intracellular Ca²⁺ concentration in a human midgut carcinoid EC cell line (GOT1 and ex vivo in human primary carcinoid EC cells concomitant with the release of 5-HT. Furthermore, NSP4 stimulated a modest production of inositol 1,4,5-triphosphate (IP₃, but not of cAMP. RV infection in mice induced Fos expression in the NTS, as seen in animals which vomit after administration of chemotherapeutic drugs. The demonstration that RV can stimulate EC cells leads us to propose that RV disease includes participation of 5-HT, EC cells, the enteric nervous system and activation of vagal afferent nerves to brain structures associated with nausea and vomiting. This hypothesis is supported by treating vomiting in children with acute gastroenteritis with 5-HT₃ receptor antagonists.
Scheier, Eric; Aviner, Shraga
Rotavirus gastroenteritis is a prevalent childhood illness rarely complicated by secondary bacterial sepsis. Although there are case reports of septicemia after rotavirus infection, there are no recent reviews on this topic. To add new cases of septicemia after rotavirus to the literature, review the few cases of septicemia after rotavirus that have been reported, calculate the incidence of septicemia in children hospitalized for rotavirus gastroenteritis, and discuss the characteristics of septicemia after rotavirus infection and implications for current pediatric practice. We identified children whose illness was complicated by septicemia from among all hospitalizations at our facility for rotavirus gastroenteritis from May 1999 through May 2010. We also review the few cases reported in the English literature. We identified two cases of septicemia from among 632 hospitalizations for rotavirus gastroenteritis in this time period, for an incidence rate of 0.32%, which is comparable to other estimates in the English literature. The typical course for cases of bacterial superinfection involves a second peak of high fever; other clinical signs are variable. Septicemia after rotavirus gastroenteritis is a rare but dangerous entity. Early identification of a child developing bacterial superinfection after rotavirus, as in any case of sepsis, is of the utmost importance, as is obtaining blood cultures in a child with a rotavirus infection and a second fever spike.
Moon, Sung-Sil; Groome, Michelle J; Velasquez, Daniel E; Parashar, Umesh D; Jones, Stephanie; Koen, Antoinette; van Niekerk, Nadia; Jiang, Baoming; Madhi, Shabir A
Live oral rotavirus (RV) vaccines have shown modest efficacy among children in African countries for reasons that are not completely understood. We examined the possible inhibitory effect of preexisting antirotavirus antibodies on immunogenicity of monovalent RV vaccine (RV1). Mother-infant pairs were enrolled at presentation for their routine immunization visit in Soweto, South Africa, when infants were aged 5-8 weeks. Infant serum samples were obtained before the first and second doses of RV1 and 1 month after the second dose. Maternal serum and breast milk samples were obtained prior to administration of each dose of RV1 to infants. RV-specific immunoglobulin G (IgG), IgA, and neutralizing activity in sera of infants and serum or breast milk samples of mothers were measured using enzyme-linked immunosorbent assays or a microneutralization test. Of the 107 serum pairs from infants who were seronegative for RV IgA at enrollment, we observed a strong positive association between IgG titers in pre-dose 1 sera of infants and mothers and significant negative associations between IgG titers in pre-dose 1 sera of infants and seroconversion to RV1 post-dose 1. Similarly, mothers whose infants' IgA seroconverted after RV1 had significantly lower pre-dose 1 IgG titers in sera than those whose infants did not seroconvert. High levels of preexisting serum IgG, including transplacentally acquired maternal IgG, appeared to have an inhibitory effect on the immunogenicity of RV1 among infants and may, in part, contribute to lower efficacy of RV vaccines in this and other low-income settings. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Krisna Nur Andriana Pangesti
Full Text Available AbstrakRotavirus adalah penyebab utama gastroenteritis pada anak-anak. Insiden diare yang disebabkan rotavirus di Indonesia terjadi sepanjang tahun dengan jumlah kematian mencapai sekitar 10.088 anak per tahun. Virus ini ditularkan melalui rute tinja-oral dengan tingkat transmisi tinggi. Lebih dari 50 kombinasi galur G - P yang dikenal sebagai galur yang menginfeksi manusia dengan serotipe dominan akan bervariasi antar wilayah dan tahun. Di Indonesia, berbagai penelitian rotavirus menunjukkan bahwa variasi tipe VP7 (G9 dan VP4 (P merupakan kombinasi genotipe paling sering muncul. Metode pencegahan yang paling mungkin dan sangat diperlukan untuk mengontrol transmisi dan mencegah penyakit yang disebabkan oleh virus ini adalah dengan vaksinasi. Berbagai macam jenis vaksin Rotavirus dikembangkan untuk memberikan kekebalan sebaik infeksi alamiah dan meminimalisasi efek samping yang terjadi. Untuk itu pengawasan yang baik pra dan pasca perizinan diperlukan untuk memantau efek samping dari vaksin yang ada. Infeksi Rotavirus menyebabkan beban penyakit dan ekonomi yang tinggi sehingga vaksin dapat dipertimbangkan sebagai salah satu cara pencegahan yang baik.Kata kunci : Rotavirus, vaksin, diareAbstractRotaviruses are the leading cause of gastroenteritis in young children. The incidence of diarrhea due to rotavirus in Indonesia is evenly throughout the year with the mortality approximately of 10,088 children in a year. These viruses are transmitted by fecal-oral route with high rate of transmission. More than 50 combinations G-P known as strain that infect human with the predominant serotypes will vary between region and year. In Indonesia, rotavirus studies showed that a variety of VP7 type (G9 and VP4 type (P were the genotype combinations most frequently encountered. The most likely methods of prevention and control of transmission for the disease caused by this virus are vaccination. Various types of rotavirus vaccine were developed to provide
Broor, Shobha; Ghosh, Dhrubaa; Mathur, Purva
Rotaviruses cause an estimated 140 million cases of gastroenteritis and 800,000 deaths in children between the ages of 6 months to 2 yr in developing countries. In India, one of every 250 children or about 100-150,000 children die of rotavirus diarrhoea each year. The prevalence of rotavirus diarrhoea in India has been found to vary from 5-71 per cent in hospitalized children rotavirus diarrhoea in India varies in different geographical regions with high incidence in winter months at low relative humidity in north India. The distinctive features of rotavirus infection in India include the occurrence of severe disease at an early age and common neonatal rotavirus infections which are often asymptomatic. Rotavirus shows genetic and antigenic diversity in terms of subgroup, electropherotypes and G and P serotypes/genotypes. There are a few studies in terms of prevalence of different antigenic and genetic variants from various regions of India. In most studies on subgroup distribution from India a higher prevalence of subgroup II was reported compared to subgroup I. Electropherotyping has also demonstrated that a number of multiple electropherotypes co-circulate at one time in a particular community leading to extensive genomic variation and the appearance of new strains which may become the predominant electropherotype during the peak season. The most common G types reported from India are G1 and G2 and P types are P and P. A significant number of children also have mixed rotavirus infections. G9 strains are also quite commonly seen in Indian children. In addition P6 strains of probable bovine origin have been reported from India. A novel neonatal strain P type 11 human rotavirus (116 E) was isolated from neonates in Delhi, the VP4 of which was closely related to the bovine serotype G10P strain B223 and VP7 was closely related to the human serotype G9 strain. Another neonatal strain G10P was reported from Bangalore. G10P strains also have a high
Tacharoenmuang, Ratana; Komoto, Satoshi; Guntapong, Ratigorn; Ide, Tomihiko; Haga, Kei; Katayama, Kazuhiko; Kato, Takema; Ouchi, Yuya; Kurahashi, Hiroki; Tsuji, Takao; Sangkitporn, Somchai; Taniguchi, Koki
An unusual rotavirus strain, SKT-27, with the G6P genotypes (RVA/Human-wt/THA/SKT-27/2012/G6P), was identified in a stool specimen from a hospitalized child aged eight months with severe diarrhea. In this study, we sequenced and characterized the complete genome of strain SKT-27. On whole genomic analysis, strain SKT-27 was found to have a unique genotype constellation: G6-P-I2-R2-C2-M2-A3-N2-T6-E2-H3. The non-G/P genotype constellation of this strain (I2-R2-C2-M2-A3-N2-T6-E2-H3) is commonly shared with rotavirus strains from artiodactyls such as cattle. Phylogenetic analysis indicated that nine of the 11 genes of strain SKT-27 (VP7, VP4, VP6, VP2-3, NSP1, NSP3-5) appeared to be of artiodactyl (likely bovine) origin, while the remaining VP1 and NSP2 genes were assumed to be of human origin. Thus, strain SKT-27 was found to have a bovine rotavirus genetic backbone, and thus is likely to be of bovine origin. Furthermore, strain SKT-27 appeared to be derived through interspecies transmission and reassortment events involving bovine and human rotavirus strains. Of note is that the VP7 gene of strain SKT-27 was located in G6 lineage-5 together with those of bovine rotavirus strains, away from the clusters comprising other G6P strains in G6 lineages-2/6, suggesting the occurrence of independent bovine-to-human interspecies transmission events. To our knowledge, this is the first report on full genome-based characterization of human G6P strains that have emerged in Southeast Asia. Our observations will provide important insights into the origin of G6P strains, and into dynamic interactions between human and bovine rotavirus strains.
Full Text Available An unusual rotavirus strain, SKT-27, with the G6P genotypes (RVA/Human-wt/THA/SKT-27/2012/G6P, was identified in a stool specimen from a hospitalized child aged eight months with severe diarrhea. In this study, we sequenced and characterized the complete genome of strain SKT-27. On whole genomic analysis, strain SKT-27 was found to have a unique genotype constellation: G6-P-I2-R2-C2-M2-A3-N2-T6-E2-H3. The non-G/P genotype constellation of this strain (I2-R2-C2-M2-A3-N2-T6-E2-H3 is commonly shared with rotavirus strains from artiodactyls such as cattle. Phylogenetic analysis indicated that nine of the 11 genes of strain SKT-27 (VP7, VP4, VP6, VP2-3, NSP1, NSP3-5 appeared to be of artiodactyl (likely bovine origin, while the remaining VP1 and NSP2 genes were assumed to be of human origin. Thus, strain SKT-27 was found to have a bovine rotavirus genetic backbone, and thus is likely to be of bovine origin. Furthermore, strain SKT-27 appeared to be derived through interspecies transmission and reassortment events involving bovine and human rotavirus strains. Of note is that the VP7 gene of strain SKT-27 was located in G6 lineage-5 together with those of bovine rotavirus strains, away from the clusters comprising other G6P strains in G6 lineages-2/6, suggesting the occurrence of independent bovine-to-human interspecies transmission events. To our knowledge, this is the first report on full genome-based characterization of human G6P strains that have emerged in Southeast Asia. Our observations will provide important insights into the origin of G6P strains, and into dynamic interactions between human and bovine rotavirus strains.
young infants, a clinical trial of a human rotavirus vaccine clearly demonstrated the potential for rotavirus vaccination to greatly reduce the morbidity and mortality due to rotavirus diarrhoea in Malawi. This new enteric vaccine initiative represents a major opportunity to improve the health and survival of Malawian children.
Ward, Richard L; McNeal, Monica M
Several nonliving rotavirus vaccine candidates have been evaluated in animal models. Among them is the VP6 protein that comprises the intermediate layer of the rotavirus particle. This protein was expressed as a chimera with maltose binding protein (MBP::VP6) and was administered intranasally to mice. When later challenged with rotavirus, vaccinated mice were nearly 100% protected from fecal shedding of rotavirus, a result strictly dependent on coadministration of an effective adjuvant. Protection was stimulated by only 1 dose of MBP::VP6, remained fully intact for at least 1 year, was effective in all strains of mice tested, and could also be effectively delivered orally or intrarectally. When VP6 was derived from a human rotavirus, it stimulated protection comparable to that found when derived from the challenge murine EDIM strain. In contrast to live rotavirus vaccines, CD4(+) T cells were found to be the only lymphocytes required for protection. If VP6 elicits comparable protection in humans, it would represent a potential second-generation vaccine candidate.
Clements-Mann, M L; Makhene, M K; Mrukowicz, J; Wright, P F; Hoshino, Y; Midthun, K; Sperber, E; Karron, R; Kapikian, A Z
Live rotavirus vaccine candidates representing VP7 serotypes 1, 2, 3 or 4 derived by reassortment between bovine UK rotavirus and human rotavirus strains D, DS-1, P or ST3 were evaluated for safety and immunogenicity in adults, children and infants. Infection was defined by evidence of rotavirus shed in stools or a 4-fold or greater increase in serum rotavirus-specific IgA or IgG ELISA or plaque reduction neutralization antibody. A single oral dose (10(5.3) or 10(5.8) pfu) of reassortant virus was well tolerated and infected most infants: 10/20 (50%) by D x UK; 9/11 (82%) by DS-1 x UK; 8/10 (80%) by P x UK and 13/14 (93%) by ST3 x UK. All 14 infants given two doses of D x UK were infected. These findings demonstrating satisfactory levels of attenuation, safety, infectivity and immunogenicity of each reassortant in infants warrant additional studies of a candidate vaccine containing these four strains.
Abstract. Background: Recent estimates attribute 527 000 deaths in children less than five years of age to rotavirus diarrhea annually, with 145 000 occurring in sub-Saharan Africa. Human astroviruses have been identified as one of the most frequent causes of infantile diarrhea, second in incidence only to rotavirus.
Midgley, Sofie; Gram, N.; Hjulsager, Charlotte Kristiane
adults are sent a questionnaire to identify potential risk factors. Rotavirus type A infection can also occur in a range of animals, including domestic dogs, cats, cattle, horses, and birds. There is some data suggesting direct transmission between animals and humans. Rotavirus typing is carried out...
Cheuvart, Brigitte; Neuzil, Kathleen M; Steele, A Duncan; Cunliffe, Nigel; Madhi, Shabir A; Karkada, Naveen; Han, Htay Htay; Vinals, Carla
Clinical trials of the human rotavirus vaccine Rotarix? (RV1) have demonstrated significant reductions in severe rotavirus gastroenteritis (RVGE) in children worldwide. However, no correlate of vaccine efficacy (VE) has yet been established. This paper presents 2 analyses which aimed to investigate whether serum anti-RV IgA measured by ELISA 1 or 2 mo post-vaccination can serve as a correlate of efficacy against RVGE: (1) In a large Phase III efficacy trial (Rota-037), the Prentice criteria f...
Saluja, Tarun; Palkar, Sonali; Misra, Puneet; Gupta, Madhu; Venugopal, Potula; Sood, Ashwani Kumar; Dhati, Ravi Mandyam; Shetty, Avinash; Dhaded, Sangappa Malappa; Agarkhedkar, Sharad; Choudhury, Amlan; Kumar, Ramesh; Balasubramanian, Sundaram; Babji, Sudhir; Adhikary, Lopa; Dupuy, Martin; Chadha, Sangeet Mohan; Desai, Forum; Kukian, Darshna; Patnaik, Badri Narayan; Dhingra, Mandeep Singh
Rotavirus remains the leading cause of diarrhoea among children TV) over the licensed human-bovine pentavalent rotavirus vaccine RV5. Phase III single-blind study (parents blinded) in healthy infants randomized (1:1) to receive three doses of BRV-TV or RV5 at 6-8, 10-12, and 14-16weeks of age. All concomitantly received a licensed diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b conjugate vaccine (DTwP-HepB-Hib) and oral polio vaccine (OPV). Immunogenic non-inferiority was evaluated in terms of the inter-group difference in anti-rotavirus serum IgA seroresponse (primary endpoint), and seroprotection/seroresponse rates to DTwP-HepB-Hib and OPV vaccines. Seroresponse was defined as a ≥4-fold increase in titers from baseline to D28 post-dose 3. Non-inferiority was declared if the difference between groups (based on the lower limit of the 95% confidence interval [CI]) was above -10%. Each subject was evaluated for solicited adverse events 7days and unsolicited & serious adverse events 28days following each dose of vaccination. Of 1195 infants screened, 1182 were randomized (590 to BRV-TV; 592 to RV5). Non-inferiority for rotavirus serum IgA seroresponse was not established: BRV-TV, 47.1% (95%CI: 42.8; 51.5) versus RV5, 61.2% (95%CI: 56.8; 65.5); difference between groups, -14.08% (95%CI: -20.4; -7.98). Serum IgA geometric mean concentrations at D28 post-dose 3 were 28.4 and 50.1U/ml in BRV-TV and RV5 groups, respectively. For all DTwP-HepB-Hib and OPV antigens, seroprotection/seroresponse was elicited in both groups and the -10% non-inferiority criterion between groups was met. There were 16 serious adverse events, 10 in BRV-TV group and 6 in RV5 group; none were classified as vaccine related. Both groups had similar vaccine safety profiles. BRV-TV was immunogenic but did not meet immunogenic non-inferiority criteria to RV5 when administered concomitantly with routine pediatric antigens in infants. Copyright © 2017 Elsevier Ltd. All rights
Ahmed, Salwa; Klena, John; Albana, Antun; Alhamdani, Faisal; Oskoff, John; Soliman, Mireille; Heylen, Elisabeth; Teleb, Nadia; Husain, Tupur; Matthijnssens, Jelle
Fecal samples from 976 children with gastroenteritis were collected and analyzed for group A rotavirus (RVA), in three different cities in Iraq between January 2008 and December 2008. RVA antigen was detected in 394 (40%) of the samples, and 98 samples were available for further genotype analyses using multiplex RT-PCR and sequence analyses for untypeable strains. The G/P-genotype combination was determined for 69 samples, and 19, 2 and 8 samples remained P-untypeable, G-untypeable and G/P-untypeable (UT), respectively. The most prevalent genotype was G2 (40%, 39/98) most often associated with P. G1 was the second most common genotype (16%, 16/98) mainly associated with P and P[UT]. G3, G4 and G9 were detected at a lower prevalence (3%, 11%, 3%, respectively), mainly associated with P. Surprisingly, five G8P, and seven G12 RVA strains in combination with P and P were also detected for the first time in Iraq. Overall, a striking high prevalence of 47% of the analyzed samples possessed the P genotype (65% of the P-typed RVA strains). Atypical genotype combinations such as G1P, G1P, G2P or strains with mixed G-types were detected sporadically. The detection of unusual G8P RVA strains prompted us to further analyze the NSP2, NSP3, NSP4 and NSP5 gene segments of three selected G8P strains, resulting in their designation to the N2, T2, E2 and H2 genotypes, respectively. The VP7, VP4, NSP2, NSP3 and NSP5 gene segments clustered closely with common human RVA strains, whereas the NSP4 gene sequences were found to cluster with animal derived RVA strains, suggesting a potential reassortment event. The high prevalence of RVA strains with the G8, G12 and P genotypes in combination with a DS-1-like genotype constellation in Iraq, needs to be monitored closely as these RVA strains might challenge the effectiveness of current RVA vaccines. Published by Elsevier B.V.
... not optimal. Signs and Symptoms Kids with a rotavirus infection have fever , nausea, and vomiting , often followed by abdominal cramps ... advice if your child has signs of a rotavirus infection, including watery diarrhea, fever, nausea, and vomiting. Call immediately if your child ...
... is taken in its entirety from the CDC Rotavirus Vaccine Information Statement (VIS): www.cdc.gov/vaccines/hcp/ ... are also common in babies with rotavirus. Before rotavirus vaccine, rotavirus disease was a common and serious health ...
Midgley, Sofie E.; Bányai, Krisztián; Buesa, Javier
Group A rotaviruses can infect both humans and animals. Individual rotavirus strains can occasionally cross species barriers and might hereby contribute to the emergence of new genotypes in heterologous hosts. The incidence and impact of zoonotic rotavirus are not well defined, and one reason...... collected from swine and cattle, both healthy and diarrhoeic, and tested for rotaviruses. Viruses from positive stools were genotyped and a subset of strains was characterized by nucleotide sequencing and phylogenetic analysis of the VP7 (G) and VP4 (P) genes. Rotaviruses were detected in 43% of bovine...... described genotype specificities, P and P, were identified in swine. When compared at the nucleotide sequence level, the identified porcine rotavirus strains and contemporary human strains grouped together phylogenetically, whereas bovine rotavirus strains formed separate clades. These data...
Moreno, J; Ramos-Castro, J; Movellan, J; Parrado, E; Rodas, G; Capdevila, L
Our aim is to demonstrate the usefulness of photoplethysmography (PPG) for analyzing heart rate variability (HRV) using a standard 5-min test at rest with paced breathing, comparing the results with real RR intervals and testing supine and sitting positions. Simultaneous recordings of R-R intervals were conducted with a Polar system and a non-contact PPG, based on facial video recording on 20 individuals. Data analysis and editing were performed with individually designated software for each instrument. Agreement on HRV parameters was assessed with concordance correlations, effect size from ANOVA and Bland and Altman plots. For supine position, differences between video and Polar systems showed a small effect size in most HRV parameters. For sitting position, these differences showed a moderate effect size in most HRV parameters. A new procedure, based on the pixels that contained more heart beat information, is proposed for improving the signal-to-noise ratio in the PPG video signal. Results were acceptable in both positions but better in the supine position. Our approach could be relevant for applications that require monitoring of stress or cardio-respiratory health, such as effort/recuperation states in sports. © Georg Thieme Verlag KG Stuttgart · New York.
Ward, Richard L; McNeal, Monica M; Steele, A Duncan
A "Meeting on Upstream Rotavirus Vaccines and Emerging Vaccine Producers" was held at the World Health Organization in Geneva, Switzerland on March 28-30, 2006. The purpose was to discuss, evaluate, and weigh the importance of additional rotavirus vaccine candidates following the successful international licensure of rotavirus vaccines by two major pharmaceutical companies (GlaxoSmithKline and Merck) that had been in development for many years. Both licensed vaccines are composed of live rotaviruses that are delivered orally as have been all candidate rotavirus vaccines evaluated in humans. Each is built on the experience gained with previous candidates whose development had either been discontinued or, in the case of the previously licensed rhesus rotavirus reassortant vaccine (Rotashield), was withdrawn by its manufacturer after the discovery of a rare association with intussusception. Although which alternative candidate vaccines should be supported for development and where this should be done are controversial topics, there was general agreement expressed at the Geneva meeting that further development of alternative candidates is a high priority. This development will help insure that the most safe, effective and economic vaccines are available to children in Third World nations where the vast majority of the >600,000 deaths due to rotavirus occur each year. This review is intended to provide the history and present status of rotavirus vaccines as well as a perspective on the future development of candidate vaccines as a means of promulgating plans suggested at the Geneva meeting.
Kumar, Ashok; Basu, Sriparna; Vashishtha, Vipin; Choudhury, Panna
Rotavirus is the most common cause of severe diarrhea in infants and young children worldwide. The burden of rotavirus diarrhea in Indian children is not well established. The present study reviewed the epidemiology of rotavirus diarrhea in hospitalized children and in the community, molecular serotyping and under-five mortality caused by rotavirus diarrhea. Publications, reporting rotavirus diarrhea in Indian children, were retrieved through a systematic search of databases including Medline, PubMed, IndMed, websites of WHO, UNICEF, National Family Health Survey, Ministry of Health and Family Welfare, and Government of India. Human studies in English language were included. Age group selected was 0 month to 5 years. No restrictions were applied in terms of study design and time frame. Stool sample positivity varied from 4.6% in Kolkata to 89.8% in Manipur, among hospitalized children, and from 4% in Delhi to 33.7% in Manipur in community. Most cases of rotavirus diarrhea in India are caused by G1, G2, and G untypeable strains with distinct regional variations. Rotavirus was identified as an etiological agent in 5.2 to 80.5% cases of nosocomial diarrhea. Data are lacking for rotavirus mortality.
Wang, Ching-Min; Chen, Shou-Chien; Chen, Kow-Tong
Rotaviruses remain the major cause of childhood diarrheal disease worldwide and of diarrheal deaths of infants and children in developing countries. The huge burden of childhood rotavirus-related diarrhea in the world continues to drive the remarkable pace of vaccine development. Research articles were searched using terms "rotavirus" and "rotavirus vaccine" in MEDLINE and PubMed. Articles not published in the English language, articles without abstracts, and opinion articles were excluded from the review. After preliminary screening, all articles were reviewed and synthesized to provide an overview of current vaccines and vaccination programs. In this review of the global rotavirus vaccines and vaccination programs, the principles of rotavirus vaccine development and the efficacy of the currently licensed vaccines from both developed and developing countries were summarized. Rotavirus is a common cause of diarrhea in children in both developed and developing countries. Rotavirus vaccination is a cost-effective measure to prevent rotavirus diarrhea.
Shif, I; Silberstein, I; Aboudy, Y; Mendelson, E; Mates, A; Gotlieb-Stematsky, T
Each of three consecutive cold seasons (November-March) in the town of Tiberias, Israel, was dominated by one particular rotavirus serotype causing acute diarrhoea in the community: the 1987/88 season by serotype-2; 1988/89 by serotype-1 and 1989/90 by serotype-4. Each season was also characterized by a particular pattern of rotaviral RNA when visualized using electrophoresis in gels. RNA profiles of identical rota serotypes and serotypic prevalence for any given cold season were unique for the town of Tiberias and different from other localities throughout Israel. The meaning of these findings in terms of herd immunity is discussed.
Bhandari, Nita; Sharma, Pooja; Glass, Roger I; Ray, Pratima; Greenberg, Harry; Taneja, Sunita; Saksena, Manju; Rao, C Durga; Gentsch, Jon R; Parashar, Umesh; Maldonado, Yvonne; Ward, Richard L; Bhan, M K
We evaluated safety and immunogenicity of two orally administered human rotavirus vaccine candidates 116E and I321. Ninety healthy infants aged 8 weeks received a single dose of 116E (10(5)FFu (florescence focus units)), I321 (10(5)FFu) or placebo. There were no significant differences in the number of adverse events. Fever was reported by 6/30, 1/30 and 5/30 in the 116E, I321 and placebo groups; the corresponding figures for diarrhoea were 5/30, 8/29 and 3/30. Serum IgA seroconversion rates were 73%, 39% and 20% in the 116E, I321 and placebo groups, respectively. Vaccine virus was shed on days 3, 7 or 28 in 11/30 infants of the 116E and none in the other two groups. The 116E strain is attenuated, clinically safe and highly immunogenic with a single dose.
Ward, R L; Bernstein, D I
In a large placebo-controlled efficacy trial of the rhesus tetravalent (RRV-TV) and serotype 1 monovalent (RRV-S1) rotavirus vaccines in multiple sites throughout the United States, protection against rotavirus disease over a 2-year period was found to be 57 and 40%, respectively (Bernstein et al., J. Am. Med. Assoc., 1995, 273, 1191-1196). Sera collected from a subset of subjects during this trial were used to determine possible correlations between rotavirus antibody responses after vaccination and protection. Between 82% (RRV-S1) and 92% (RRV-TV) of the vaccinees seroconverted by at least one of the six antibody assays performed (i.e. rotavirus IgA and neutralizing antibody to RRV and serotype 1-4 human rotaviruses). Rises in neutralizing antibody were due primarily to RRV. The seroconversion rate was only 18-22% to each of the four human rotavirus serotypes following RRV-TV vaccination and was only 43% to serotype 1 human rotavirus after RRV-S1 administration. Furthermore, no correlate of immunity against rotavirus infection or disease was identifiable based on seroconversion to any of the antibodies measured. Likewise, no consistent relationship was found between the titers of any of these six antibodies following vaccination and protection against rotavirus, thus suggesting that serum antibody titers will not be useful markers of protection with these reassortant RRV vaccines. In addition, vaccinated subjects did not develop higher titers of neutralizing antibody to human rotaviruses following a subsequent natural rotavirus illness, a further indication that only weak immune responses to human rotaviruses were stimulated by vaccination with the RRV reassortants.(ABSTRACT TRUNCATED AT 250 WORDS)
Full Text Available Introduction Automatic human emotion recognition is one of the most interesting topics in the field of affective computing. However, development of a reliable approach with a reasonable recognition rate is a challenging task. The main objective of the present study was to propose a robust method for discrimination of emotional responses thorough examination of heart rate variability (HRV. In the present study, considering the non-stationary and non-linear characteristics of HRV, empirical mode decomposition technique was utilized as a feature extraction approach. Materials and Methods In order to induce the emotional states, images indicating four emotional states, i.e., happiness, peacefulness, sadness, and fearfulness were presented. Simultaneously, HRV was recorded in 47 college students. The signals were decomposed into some intrinsic mode functions (IMFs. For each IMF and different IMF combinations, 17 standard and non-linear parameters were extracted. Wilcoxon test was conducted to assess the difference between IMF parameters in different emotional states. Afterwards, a probabilistic neural network was used to classify the features into emotional classes. Results Based on the findings, maximum classification rates were achieved when all IMFs were fed into the classifier. Under such circumstances, the proposed algorithm could discriminate the affective states with sensitivity, specificity, and correct classification rate of 99.01%, 100%, and 99.09%, respectively. In contrast, the lowest discrimination rates were attained by IMF1 frequency and its combinations. Conclusion The high performance of the present approach indicated that the proposed method is applicable for automatic emotion recognition.
Richard L Ward
Full Text Available Richard L Ward1, Monica M McNeal1, A Duncan Steele21Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; 2Initiative for Vaccine Research, World Health Organization, Geneva, SwitzerlandAbstract: A “Meeting on Upstream Rotavirus Vaccines and Emerging Vaccine Producers” was held at the World Health Organization in Geneva, Switzerland on March 28–30, 2006. The purpose was to discuss, evaluate, and weigh the importance of additional rotavirus vaccine candidates following the successful international licensure of rotavirus vaccines by two major pharmaceutical companies (GlaxoSmithKline and Merck that had been in development for many years. Both licensed vaccines are composed of live rotaviruses that are delivered orally as have been all candidate rotavirus vaccines evaluated in humans. Each is built on the experience gained with previous candidates whose development had either been discontinued or, in the case of the previously licensed rhesus rotavirus reassortant vaccine (Rotashield, was withdrawn by its manufacturer after the discovery of a rare association with intussusception. Although which alternative candidate vaccines should be supported for development and where this should be done are controversial topics, there was general agreement expressed at the Geneva meeting that further development of alternative candidates is a high priority. This development will help insure that the most safe, effective and economic vaccines are available to children in Third World nations where the vast majority of the >600,000 deaths due to rotavirus occur each year. This review is intended to provide the history and present status of rotavirus vaccines as well as a perspective on the future development of candidate vaccines as a means of promulgating plans suggested at the Geneva meeting.Keywords: rotavirus vaccines, rotavirus immunity, candidate vaccines
Nakamura, Hisako; Marumo, Kenji; Iwasawa, Atsuo; Tazawa, Setsuko; Kawano, Rumiko; Kikuchi, Toshiki; Nagashima, Goro; Taguchi, Kazumi; Isoyama, Keiichi
Group A rotavirus G-serotyping by polymerase chain reaction (PCR) using university hospital subject samples in September 2003 to August 2004, September 2004 to August 2005, September 2005 to August 2006, and September 2006 to August 2007 showed the most common serotypes G1 and G3, detected in 27 and 33 subjects, compared to 4 subjects in whom serotype G4 was detected. Between 2003 and 2004, serotypes G1 accounted for 50% and G3 for 38%, contrasting with serotype G3 at 79% between 2004 and 2005, serotype G1 at 91% between 2005 and 2006, and serotype G1 and G3 at 37% and 63% between 2006 and 2007, respectively. Serotypes G2 and G9 were not detected at all during any of our time periods. No correlation was seen between subject age and G serotype, although subjects younger than two years old accounted for 73% of subjects. This infection caused combined fever, diarrhea, and vomiting in 48% of subjects but showed no correlation with G serotype. These findings under-score the importance of G-serotyping in understanding rotavirus infection epidemiology at different times and in different locales.
Ray, Pratima; Sharma, S.; Agarwal, R. K.; Longmei, K.; Gentsch, J. R.; Paul, V. K.; Glass, R. I.; Bhan, M. K.
Rotavirus genotype G12 strains were detected for the first time among newborns with asymptomatic rotavirus infection (74% of 39 rotavirus strains isolated from the infected infants were genotype G12) in the nursery of the All India Institute of Medical Sciences during a period from 2005 to 2006. Sequence analysis of the VP7 genes from these neonatal strains indicated a high level of homology to other G12 strains reported worldwide, suggesting the recent emergence of these strains in humans. S...
Dhingra, M S; Kundu, R; Gupta, M; Kanungo, S; Ganguly, N; Singh, M P; Bhattacharya, M K; Ghosh, R; Kumar, R; Sur, D; Chadha, S M; Saluja, T
Rotavirus infections, prevalent in human populations worldwide are mostly caused by Group A viruses. Live attenuated rotavirus vaccines are highly effective in preventing severe rotavirus gastroenteritis. However, the cost of these vaccines and local availability can be a barrier for widespread adoption in public health programs in developing countries where infants suffer a heavy burden of rotavirus related morbidity and mortality. A phase I/II study was carried out with the long term aim to produce a locally licensed vaccine which is equally safe and immunogenic as compared to available licensed vaccines. This study was conducted in two cohorts. In the first cohort, 20 healthy adults were administered a single dose of the rotavirus vaccine (highest antigen concentration planned for infants) or placebo and were followed up for 10 days for safety. Following demonstration of safety in adult volunteers, 100 healthy infants were recruited (cohort 2) and randomly divided into five equal study groups. They were administered three doses of either the investigational rotavirus vaccine (BRV-TV) at one of the three antigen concentrations or Rotateq or Placebo at 6-8, 10-12 and 14-16 weeks of age. All infants were followed up for safety till 28 days after the third dose. Immune response to the vaccine, in terms of seroresponse and geometric mean concentrations, was compared across the five study groups. Increase in anti-rotavirus serum IgA antibodies from baseline, demonstrated higher immune response for all the three antigen concentrations of BRV-TV vaccine and RotaTeq in comparison with the placebo. Sero-response rates for placebo, BRV-TV dose-levels 10(5.0) FFU, 10(5.8) FFU, 10(6.4) FFU, and Rotateq at 28 days post third dose were 11.1%, 27.8%, 41.2%, 83.3%, and 63.2% respectively using the four-fold or more criteria. The BRV-TV vaccine arm corresponding to the highest antigen concentration of 10(6.4) FFU had a higher sero-response rate compared to the active comparator
Full Text Available ... V.E. parents for prevention publications schedules & records support statements vaccine initiative vaccine safety about bucking the ... go to GETVAXED.ORG cme Immunizations Rotavirus One family's struggles with rotavirus We provide this video in ...
Full Text Available ... GETVAXED print ads go to GETVAXED.ORG cme Immunizations Rotavirus One family's struggles with rotavirus We provide ... not possible without a visit to your doctor. Immunizations stop disease from spreading. Check with your family ...
Santosham, Mathuram; Nelson, E Anthony S; Bresee, Joseph S
At the 2006 meeting of the Asian Pacific Pediatric Association (APPA), the Asia Pacific regional rotavirus community and international experts strongly recommended that rotavirus vaccines be used in National Immunization Programmes (NIP) in countries in Asia. Two rotavirus vaccine candidates are currently licensed and have been demonstrated to be safe, well tolerated and highly efficacious. Several additional vaccines are in the late stages of development. The conference participants agreed that decisions on the introduction of rotavirus vaccines may require additional disease burden data in some countries and that economic evaluations will help policymakers reach decisions on nationwide rotavirus vaccine implementation. Other potential issues that arise with vaccine implementation, for example, the concomitant use of rotavirus vaccines with other vaccines, were also discussed. Rotavirus vaccines have the potential to substantially reduce morbidity and mortality from rotavirus disease and impact children's health in Asia.
Midgley, Sofie; Gram, N.; Hjulsager, Charlotte Kristiane
direct transmission between animals and humans. Rotavirus genotyping is carried out in Denmark as part of the EUROTAnet vaccine study. In 2006 a total of 180 samples were successfully typed, and to date 85 samples from 2007 have been typed. 19 samples from pigs and 31 samples from cattle (from 2006......Rotavirus type A infection is a common cause of hospitalisation of children. In addition, almost 30% of diagnosed persons in Denmark are adults. Rotavirus type A infection can also occur in a range of animals, including domestic dogs, cats, cattle, horses, and birds. There is some data suggesting...... and 2007) have also been typed. For the human samples all common human G types (1-4 and 9), as well the emerging G12 were identified, and were found in combination with the common P types (, , and ). Two samples contained a G8 P[goat] rotavirus (G8 98% identical to bovine G8, 96% identical to goat...
Chandler-Bostock, Rebecca; Hancox, Laura R; Nawaz, Sameena; Watts, Oliver; Iturriza-Gomara, Miren; Mellits, Kenneth H; Mellits, Kenneth M
Rotavirus is endemic in pig farms where it causes a loss in production. This study is the first to characterise porcine rotavirus circulating in UK pigs. Samples from diarrheic pigs with rotavirus enteritis obtained between 2010 and 2012 were genotyped in order to determine the diversity of group A rotavirus (GARV) in UK pigs. A wide range of rotavirus genotypes were identified in UK pigs: six G types (VP7); G2, G3, G4, G5, G9 and G11 and six P types (VP4); P, P, P, P, P, and P. With the exception of a single P isolate, there was less than 95% nucleotide identity between sequences from this study and any available rotavirus sequences. The G9 and P genotypes are capable of infecting both humans and pigs, but showed no species cross-over within the UK as they were shown to be genetically distinct, which suggested zoonotic transmission is rare within the UK. We identified the P genotype in one isolate, this genotype is almost exclusively found in humans. The P was linked to a human Irish rotavirus isolate in the same year. The discovery of human genotype P rotavirus in a UK pig confirms this common human genotype can infect pigs and also highlights the necessity of surveillance of porcine rotavirus genotypes to safeguard human as well as porcine health. Copyright © 2014. Published by Elsevier B.V.
Gabbay Yvone B.
Full Text Available Rotavirus was detected by the enzyme-linked immunosorbent assay (ELISA in the faeces of a diarrheic dog. Virus particles with morphology typical of rotavirus were visualized by direct electron microscopy. This sample was subsequently tested for the four main human serotypes (G1-G4, by ELISA with monoclonal antibodies. G genotyping was attempted by RT-PCR using G1-G6 and G8-G11 primers but no positive results could be yielded. Also using RT-PCR it was possible to characterize this canine strain as belonging to P[ 3] genotype. This is the first canine rotavirus detected in Brazil.
... their fifth birthday. It is often accompanied by fever, vomiting as well as diarrhea. Rotavirus is not the only cause of severe diarrhea, ... to top What are other symptoms of rotavirus? Rotavirus often begins with a mild fever and is followed by vomiting and an upset ...
Tapparel, Caroline, E-mail: Caroline.Tapparel@hcuge.ch [Laboratory of Virology, Division of Infectious Diseases and Division of Laboratory Medicine, University of Geneva Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1211 Geneva 14 (Switzerland); Sobo, Komla [Laboratory of Virology, Division of Infectious Diseases and Division of Laboratory Medicine, University of Geneva Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1211 Geneva 14 (Switzerland); Constant, Samuel; Huang, Song [Epithelix sárl, 14 Chemin des Aulx, 1228 Plan les Ouates, Geneva (Switzerland); Van Belle, Sandra; Kaiser, Laurent [Laboratory of Virology, Division of Infectious Diseases and Division of Laboratory Medicine, University of Geneva Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1211 Geneva 14 (Switzerland)
New molecular diagnostic tools have recently allowed the discovery of human rhinovirus species C (HRV-C) that may be overrepresented in children with lower respiratory tract complications. Unlike HRV-A and HRV-B, HRV-C cannot be propagated in conventional immortalized cell lines and their biological properties have been difficult to study. Recent studies have described the successful amplification of HRV-C15, HRV-C11, and HRV-C41 in sinus mucosal organ cultures and in fully differentiated human airway epithelial cells. Consistent with these studies, we report that a panel of clinical HRV-C specimens including HRV-C2, HRV-C7, HRV-C12, HRV-C15, and HRV-C29 types were all capable of mediating productive infection in reconstituted 3D human primary upper airway epithelial tissues and that the virions enter and exit preferentially through the apical surface. Similar to HRV-A and HRV-B, our data support the acid sensitivity of HRV-C. We observed also that the optimum temperature requirement during HRV-C growth may be type-dependent. - Highlights: • A 3D human upper airway epithelia reconstituted in vitro supports HRV-C growth. • HRV-Cs enter and exit preferentially at the apical side of this ALI culture system. • HRV-Cs are acid sensitive. • Temperature sensitivity may be type-dependent for HRV-Cs.
Grimwood, Keith; Lambert, Stephen B; Milne, Richard J
Rotaviruses are the most common cause of severe gastroenteritis in children. By 5 years of age virtually every child worldwide will have experienced at least one rotavirus infection. This leads to an enormous disease burden, where every minute a child dies because of rotavirus infection and another four are hospitalized, at an annual societal cost in 2007 of $US2 billion. Most of the annual 527 000 deaths are in malnourished infants living in rural regions of low and middle income countries. In contrast, most measurable costs arise from medical expenses and lost parental wages in high income countries. Vaccines are the only public health prevention strategy likely to control rotavirus disease. They were developed to mimic the immunity following natural rotavirus infection that confers protection against severe gastroenteritis and consequently reduces the risk of primary healthcare utilization, hospitalization and death. The two currently licensed vaccines--one a single human strain rotavirus vaccine, the other a multiple strain human-bovine pentavalent reassortant rotavirus vaccine--are administered to infants in a two- or three-dose course, respectively, with the first dose given at 6-14 weeks of age. In various settings they are safe, immunogenic and efficacious against many different rotavirus genotypes. In high and middle income countries, rotavirus vaccines confer 85-100% protection against severe disease, while in low income regions of Africa and Asia, protection is less, at 46-77%. Despite this reduced efficacy in low income countries, the high burden of diarrheal disease in these regions means that proportionately more severe cases are prevented by vaccination than elsewhere. Post-licensure effectiveness studies show that rotavirus vaccines not only reduce rotavirus activity in infancy but they also decrease rates of rotavirus diarrhea in older and unimmunized children. A successful rotavirus vaccination program will rely upon sustained vaccine efficacy
Inmunogenicidad, inocuidad y eficacia de una vacuna tetravalente obtenida por recombinación genética de rotavirus aislados de monos rhesus y seres humanos en Belém, Brasil Immunogenicity, safety and efficacy of tetravalent rhesus-human, reassortant rotavirus vaccine in Belém, Brazil
A. C. Linhares
son lo suficientemente alentadores para justificar que en países en desarrollo se hagan otros estudios de esta vacuna con una dosis mayor para tratar de mejorar su inmunogenicidad y eficacia.A tetravalent rhesus-human reassortant rotavirus (RRV-TV vaccine (4 x 10(4 plaque-forming units/dose was evaluated for safety, immunogenicity and efficacy in a prospective, randomized, double-blind, placebo-controlled trial involving 540 Brazilian infants. Doses of vaccine or placebo were given at ages, 1, 3 and 5 months. No significant differences were noted in the occurrence of diarrhoea or vomiting in vaccine and placebo recipients following each dose. Low-grade fever occurred on days 35 in 23% of vaccinees after the first dose, but not after the second or third doses of vaccine. An IgA antibody response to rhesus rotavirus (RRV occurred in 58% of vaccinees and 33% of placebo recipients. Neutralizing antibody responses to individual serotypes did not exceed 20% when measured by fluorescent focus reduction, but exceeded 40% when assayed by plaque reduction neutralization. There were 91 cases of rotavirus diarrhoea among the 3-dose (vaccine or placebo recipients during two years of follow-up, 36 of them among children given the vaccine. Overall vaccine efficacy was 8% (P = 0.005 against any diarrhoea and 35% (P = 0.03 against any rotavirus diarrhoea. Protection during the first year of follow-up, when G serotype 1 rotavirus predominated, was 57% (P = 0.008, but fell to 12% in the second year. Similar results were obtained when analysis was restricted to episodes in which rotavirus was the only identified pathogen. There was a tendency for enhanced protection by vaccine against illness associated with an average of 6 or more stools per day. These results are sufficiently encouraging to warrant further studies of this vaccine in developing countries using a higher dosage in an attempt to improve its immunogenicity and efficacy.
... the vaccine. Why should my child get the rotavirus vaccine? The rotavirus vaccine: Protects your child from rotavirus, ... work to care for your sick child). Is rotavirus vaccine safe? Both rotavirus vaccines (RotaTeq and Rotarix) are ...
Fernando Rosado Spilki
Full Text Available Viral gastroenteritis and other waterborne diseases are a major concern for health in Brazil. A number of studies were conducted about the presence of viruses on water samples from Brazilian areas. However, the knowledge about the occurrence of viral contamination of drinking water sources in rural settings of the country is insufficient. On the present work, 15 samples from 5 dairy farms located at the municipality of Tenente Portela were collected and analysed for the presence of human adenoviruses (HAdV, as well as human enteroviruses (EV and rotaviruses (RV. HAdV was present on 66.66% of the water samples, and have been found in all samples from artesian wells and springs, which are used as sources of drinking water for the individuals inhabiting those farms. EV and RV found only in one sample each. The detection rates of HAdV on the water from these dairy farms are alarming and point towards a situation of elevated environmental contamination by fecal microorganisms of human origin and poor basic sanitation conditions.
Spilki, Fernando Rosado; da Luz, Roger Bordin; Fabres, Rafael Bandeira; Soliman, Mayra Cristina; Kluge, Mariana; Fleck, Juliane Deise; Rodrigues, Manoela Tressoldi; Comerlato, Juliana; Cenci, Alexander; Cerva, Cristine; Dasso, Maurício Gautério; Roehe, Paulo Michel
Viral gastroenteritis and other waterborne diseases are a major concern for health in Brazil. A number of studies were conducted about the presence of viruses on water samples from Brazilian areas. However, the knowledge about the occurrence of viral contamination of drinking water sources in rural settings of the country is insufficient. On the present work, 15 samples from 5 dairy farms located at the municipality of Tenente Portela were collected and analysed for the presence of human adenoviruses (HAdV), as well as human enteroviruses (EV) and rotaviruses (RV). HAdV was present on 66.66% of the water samples, and have been found in all samples from artesian wells and springs, which are used as sources of drinking water for the individuals inhabiting those farms. EV and RV found only in one sample each. The detection rates of HAdV on the water from these dairy farms are alarming and point towards a situation of elevated environmental contamination by fecal microorganisms of human origin and poor basic sanitation conditions.
Robert E. Keane; Paul F. Hessburg; Peter B. Landres; Fred J. Swanson
This paper examines the past, present, and future use of the concept of historical range and variability (HRV) in land management. The history, central concepts, benefits, and limitations of HRV are presented along with a discussion on the value of HRV in a changing world with rapid climate warming, exotic species invasions, and increased land development. This paper...
Follett, E. A.; Sanders, R. C.; Beards, G. M.; Hundley, F.; Desselberger, U.
The molecular epidemiology of rotavirus infections in Glasgow and the west of Scotland during 1981/82 and 1982/83 was investigated by electron microscopy, ELISA testing and RNA migration pattern analysis. In 1981/82, rotaviruses of both the 'long' and the 'short' electropherotype (in different variants) co-circulated from the onset throughout the winter peak of the outbreak. Approximately 80% of the children were infected during the first year of life. No differences in incidence were found between sexes. In 1982/83 the isolated rotaviruses were almost exclusively of the 'long' electropherotype (in different variants) and 36% of the children were infected beyond the first year of life. Rotaviruses of the 'long' electropherotype serologically were of subgroup II and serotype 1 and those of the 'short' electropherotype of subgroup I and serotype 2. Images Fig. 2 PMID:6323577
Bolea, Juan; Laguna, Pablo; Remartínez, José María; Rovira, Eva; Navarro, Augusto; Bailón, Raquel
This paper presents a methodological framework for robust estimation of the correlation dimension in HRV signals. It includes (i) a fast algorithm for on-line computation of correlation sums; (ii) log-log curves fitting to a sigmoidal function for robust maximum slope estimation discarding the estimation according to fitting requirements; (iii) three different approaches for linear region slope estimation based on latter point; and (iv) exponential fitting for robust estimation of saturation level of slope series with increasing embedded dimension to finally obtain the correlation dimension estimate. Each approach for slope estimation leads to a correlation dimension estimate, called D^2, D^2⊥, and D^2max. D^2 and D^2max estimate the theoretical value of correlation dimension for the Lorenz attractor with relative error of 4%, and D^2⊥ with 1%. The three approaches are applied to HRV signals of pregnant women before spinal anesthesia for cesarean delivery in order to identify patients at risk for hypotension. D^2 keeps the 81% of accuracy previously described in the literature while D^2⊥ and D^2max approaches reach 91% of accuracy in the same database. PMID:24592284
Full Text Available This paper presents a methodological framework for robust estimation of the correlation dimension in HRV signals. It includes (i a fast algorithm for on-line computation of correlation sums; (ii log-log curves fitting to a sigmoidal function for robust maximum slope estimation discarding the estimation according to fitting requirements; (iii three different approaches for linear region slope estimation based on latter point; and (iv exponential fitting for robust estimation of saturation level of slope series with increasing embedded dimension to finally obtain the correlation dimension estimate. Each approach for slope estimation leads to a correlation dimension estimate, called D^2, D^2⊥, and D^2max. D^2 and D^2max estimate the theoretical value of correlation dimension for the Lorenz attractor with relative error of 4%, and D^2⊥ with 1%. The three approaches are applied to HRV signals of pregnant women before spinal anesthesia for cesarean delivery in order to identify patients at risk for hypotension. D^2 keeps the 81% of accuracy previously described in the literature while D^2⊥ and D^2max approaches reach 91% of accuracy in the same database.
Kaur, Balvinder; Hutchinson, J. Andrew; Ikonomidou, Vasiliki N.
Stress is a major health concern that not only compromises our quality of life, but also affects our physical health and well-being. Despite its importance, our ability to objectively detect and quantify it in a real-time, non-invasive manner is very limited. This capability would have a wide variety of medical, military, and security applications. We have developed a pipeline of image and signal processing algorithms to make such a system practical, which includes remote cardiac pulse detection based on visible spectrum videos and physiological stress detection based on the variability in the remotely detected cardiac signals. First, to determine a reliable cardiac pulse, principal component analysis (PCA) was applied for noise reduction and independent component analysis (ICA) was applied for source selection. To determine accurate cardiac timing for heart rate variability (HRV) analysis, a blind source separation method based least squares (LS) estimate was used to determine signal peaks that were closely related to R-peaks of the electrocardiogram (ECG) signal. A new metric, differential pulse transit time (dPTT), defined as the difference in arrival time of the remotely acquired cardiac signal at two separate distal locations, was derived. It was demonstrated that the remotely acquired metrics, HRV and dPTT, have potential for remote stress detection. The developed algorithms were tested against human subject data collected under two physiological conditions using the modified Trier Social Stress Test (TSST) and the Affective Stress Response Test (ASRT). This research provides evidence that the variability in remotely-acquired blood wave (BW) signals can be used for stress (high and mild) detection, and as a guide for further development of a real-time remote stress detection system based on remote HRV and dPTT.
Losonsky, G A; Rennels, M B; Lim, Y; Krall, G; Kapikian, A Z; Levine, M M
Thirty-four children 3 to 20 months of age ingested either 10(5), 10(4) or 10(3) plaque-forming units of rhesus rotavirus vaccine, MMU 18006, which possesses human rotavirus serotype 3 neutralization antigen. Immune responses were evaluated by a plaque reduction neutralization (PRN) assay to rotavirus serotypes 1, 2 and 3 and by a serum IgG, IgM and IgA and fecal IgA class-specific enzyme-linked immunosorbent assay. Homotypic PRN antibody seroconversions to serotype 3 rotavirus were detected in 31 of 34 children (91%), whereas rises in heterotypic PRN antibody to human rotavirus serotypes 1 or 2 were found in only 3 of 21 (14%) (p less than 0.00000001). Thirty of the 34 vaccinated children (88%) had at least one class of rotavirus-specific serum antibody detected by enzyme-linked immunosorbent assay. A rotavirus-specific IgA coproantibody response was seen in 11 of 16 children (69%) following vaccination. Two children who had no evidence of PRN antibody to serotype 3 after vaccination had evidence of both a fecal and a serum rotavirus-specific IgA response, suggesting that in these children the response to the vaccine was primarily mucosal. These data show that orally administered rhesus rotavirus vaccine MMU 18006 elicits local intestinal immunity but produces primarily a homotypic serum neutralization response as measured by plaque reduction neutralization assays.
% af danske børn følger det danske børnevaccinationsprogram og bliver vaccineret mod en række infektioner. Der findes i Danmark to velafprøvede og godkendte vacciner mod rotavirus. Begge vacciner gives gennem munden og ikke gennem indsprøjtning i huden, som de øvrige vacciner i det danske...... børnevaccinationsprogram. Verdenssundhedsorganisation (WHO=World Health Organisation) samt nationale og europæiske faglige selskaber har anbefalet at vaccinere mod rotavirus. I en række europæiske lande er vaccination mod rotavirus indført i det nationale børnevaccinationsprogram. Andre europæiske lande har fravalgt...... vaccinen i deres børnevaccinationsprogram, og endnu andre er i en overvejelsesfase. Formålet med denne MTV er at bidrage med et beslutningsgrundlag, der belyser fordele og ulemper ved at indføre vaccination mod rotavirus i det danske børnevaccinationsprogram. MTV´en har belyst: 1) effekt og bivirkninger...
Intellectual property rights and challenges for development of affordable human papillomavirus, rotavirus and pneumococcal vaccines: Patent landscaping and perspectives of developing country vaccine manufacturers.
Chandrasekharan, Subhashini; Amin, Tahir; Kim, Joyce; Furrer, Eliane; Matterson, Anna-Carin; Schwalbe, Nina; Nguyen, Aurélia
The success of Gavi, the Vaccine Alliance depends on the vaccine markets providing appropriate, affordable vaccines at sufficient and reliable quantities. Gavi's current supplier base for new and underutilized vaccines, such as the human papillomavirus (HPV), rotavirus, and the pneumococcal conjugate vaccine is very small. There is growing concern that following globalization of laws on intellectual property rights (IPRs) through trade agreements, IPRs are impeding new manufacturers from entering the market with competing vaccines. This article examines the extent to which IPRs, specifically patents, can create such obstacles, in particular for developing country vaccine manufacturers (DCVMs). Through building patent landscapes in Brazil, China, and India and interviews with manufacturers and experts in the field, we found intense patenting activity for the HPV and pneumococcal vaccines that could potentially delay the entry of new manufacturers. Increased transparency around patenting of vaccine technologies, stricter patentability criteria suited for local development needs and strengthening of IPRs management capabilities where relevant, may help reduce impediments to market entry for new manufacturers and ensure a competitive supplier base for quality vaccines at sustainably low prices. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Heylen, Elisabeth; Zeller, Mark; Ciarlet, Max; Lawrence, Jody; Steele, Duncan; Van Ranst, Marc; Matthijnssens, Jelle
RotaTeqTM is a pentavalent rotavirus vaccine based on a bovine rotavirus genetic backbone in vitro reassorted with human outer capsid genes. During clinical trials of RotaTeqTM in Sub-Saharan Africa, the vaccine efficacy over a 2-year follow-up was lower against the genotypes contained in the vaccine than against the heterotypic G8P and G8P rotavirus strains of which the former is highly prevalent in Africa. Complete genome analyses of 43 complete rotavirus genomes collected during phase III clinical trials of RotaTeqTM in Sub-Saharan Africa, were conducted to gain insight into the high level of cross-protection afforded by RotaTeqTM against these G8 strains. Phylogenetic analysis revealed the presence of a high number of bovine rotavirus gene segments in these human G8 strains. In addition, we performed an in depth analysis on the individual amino acid level which showed that G8 rotaviruses were more similar to the RotaTeqTM vaccine than non-G8 strains. Because RotaTeqTM possesses a bovine genetic backbone, the high vaccine efficacy against G8 strains might be partially explained by the fact that all these strains contain a complete or partial bovine-like backbone. Altogether, this study supports the hypothesis that gene segments other than VP7 and VP4 play a role in vaccine-induced immunity.
Kumar, Arun; Goel, Manish K; Jain, Ram Bilas; Khanna, Pardeep; Vibha, Vibha
Globally, rotavirus diarrhea results in 453,000 deaths in children younger than 5 y—37% of deaths attributable to diarrhea and 5% of all deaths in children younger than 5 y. India alone accounts for 22% (~100,000 deaths) of all deaths attributable to rotavirus infection. Two oral rotavirus vaccines are available: Rotarix, a monovalent P1A G1 vaccine (GlaxoSmithKline), and RotaTeq, a pentavalent bovine-human reassortant vaccine (Merck). Rotarix is administered in a 2-dose schedule with the first and second doses of DTP (DTP1, DTP2). RotaTeq requires a 3-dose schedule with DTP1, DTP2 and DTP3 with an interval of 4–10 weeks between doses. The first dose of either vaccine should be administered to infants aged 6–15 weeks irrespective of the history of previous rotavirus infection, and the maximum age for administering the last dose of either vaccine should be 32 weeks. Although India would require funding from international health organizations/GAVI until new indigenous rotavirus vaccine candidates are developed at a cheaper price, introduction of vaccination into the national immunization program would be a cost-effective step toward control of the rotavirus diarrhea-related morbidity and mortality in India.
Rainwater-Lovett, Kaitlin; Tsutsumi, Hiroyuki
Rotavirus (RV) A is a very common cause of acute diarrhoea in infants and young children worldwide. Most human strains are classified into two major Wa-like and DS-1-like genotype constellations, whilst a minor third strain, AU-1, was described in 1989 among human RV isolates from Japan. AU-1 demonstrates a high degree of homology to a feline RV, FRV-1, which suggests interspecies transmission of feline RV. However, there has been no subsequent report of RVs possessing the AU-1 genotype throughout all 11 genes of the genome. Between March 1997 and December 1999, 157 RV-positive stool samples were collected from Brazilian children, and 16 of the RVs (10.2 %) were P genotype. We analysed eight strains by almost full-genome sequencing. These eight strains were divided into two groups: five AU-1-like and three Wa-like strains. Four of the five AU-1-like strains had the AU-1-like genotype constellation throughout the 11 genes. The remaining AU-1-like strain was considered to be a reassortant strain comprosed of nine, two and one genes from the AU-1-like, Wa-like and G9 strains, respectively. The three Wa-like strains were considered to be reassortants comprising seven to eight genes and three to four genes from Wa-like and non-Wa-like strains, respectively. This report of human G3P RV strains possessing the AU-1 genotype constellation throughout all genes demonstrates the stability and infectivity of the AU-1-like strain with its original genotype over distance and time. PMID:25467218
Kirkwood, Carl D; Ma, Lyou-Fu; Carey, Megan E; Steele, A Duncan
Rotavirus disease is a leading global cause of mortality and morbidity in children under 5years of age. The effectiveness of the two globally used oral rotavirus vaccines quickly became apparent when introduced into both developed and developing countries, with significant reductions in rotavirus-associated mortality and hospitalizations. However, the effectiveness and impact of the vaccines is reduced in developing country settings, where the burden and mortality is highest. New rotavirus vaccines, including live oral rotavirus candidates and non-replicating approaches continue to be developed, with the major aim to improve the global supply of rotavirus vaccines and for local implementation, and to improve vaccine effectiveness in developing settings. This review provides an overview of the new rotavirus vaccines in development by developing country manufacturers and provides a rationale why newer candidates continue to be explored. It describes the new live oral rotavirus vaccine candidates as well as the non-replicating rotavirus vaccines that are furthest along in development. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Ward, Richard L
The rotavirus vaccines that have been evaluated in clinical trials thus far have all been live, attenuated strains delivered orally to mimic natural infections. Early vaccine candidates were animal strains that are naturally attenuated for humans. Due to the lack of consistent protection, these were reassorted with human rotaviruses to create multivalent vaccines with neutralization proteins of the circulating human strains. One of these multivalent candidates, RotaShield, was launched in the US but withdrawn due to association with intussusception. Another vaccine, Rotateq, is expected to be launched by 2006. Human rotaviruses have also been developed as candidate vaccines and Rotarix, which is attenuated by passage in cell culture, has been launched in Mexico and may soon be available worldwide.
Adefisoye, Martins Ajibade; Nwodo, Uchechukwu U; Green, Ezekiel; Okoh, Anthony Ifeanyin
The occurrence of enteric viruses in reclaimed wastewater, their removal by efficient treatment processes and the public health hazards associated with their release into the environments are of great significance in environmental microbiology. In this study, TaqMan-based real-time polymerase chain reaction (qPCR) was used to assess the prevalence of human adenovirus (HAdV), rotavirus (RV) and hepatitis A virus (HAV) in the final effluents of two wastewater treatment plants in the Eastern Cape Province, South Africa, over a twelve-month sampling period. The correlation between the concentrations of viruses in the effluents samples and faecal coliform (FC) densities were assessed as to validate the use of FC as microbiological indicator in water quality assessment. HAdV was detected in 62.5 % (30/48) of the samples with concentrations ranging between 8.4 × 10(1) and 1.0 × 10(5) genome copies/L while HAV and RV were only detected at concentrations below the set detection limits. FCs densities ranged from 1 to 2.7 × 10(4) CFU/100 ml. Adenovirus species HAdV-B (serotype 2) and HAdV-F (serotype 41) were detected in 86.7 % (26/30) and 6.7 % (2/30) of the HAdV-positive samples, respectively. No consistent seasonal trend was observed in HAdV concentrations, however, increased concentrations of HAdV were generally observed in the winter months. Also, there was no correlation between the occurrence of HAdV and FC at both the treatment plants. The persistent occurrence of HAdV in the discharged treated effluents points to the potential public health risk through the release of HAdV into the receiving watersheds, and the possibility of their transmission to human population.
Mesbah, Mostefa; Balakrishnan, Malarvili; Colditz, Paul B; Boashash, Boualem
.... Two different approaches were used to combine this extracted information. The first approach, known as feature fusion, involves combining features extracted from EEG and heart rate variability (HRV...
Rotavirus was first identified as a human pathogen just over 40 years ago, and work on this pathogen in India started shortly thereafter. Subsequent studies have confirmed its pre-eminent role in gastroenteritis in children in India. Standardized surveillance has enabled the documentation of the high burden of disease, and has demonstrated that there is considerable geographic and temporal variation in strain circulation. Internationally licensed vaccines, vaccine candidates based on indigenous strains and out-licensed strains have been tested for safety, immunogenicity and efficacy; three vaccines are now licensed in India and are used in the private sector. Public sector vaccination has begun, and it will be path-breaking for Indian vaccinologists to measure impact of vaccine introduction in terms of safety and effectiveness. So far, India has kept pace with international epidemiologic and vaccine research on rotavirus, and these efforts should continue.
Vonderfecht, S L; Osburn, B I
The local and systemic humoral immune responses to rotavirus were studied in six conventional neonatal calves. Attenuated bovine rotavirus was administered either orally or directly into an isolated intestinal loop. The parameters monitored were neutralizing rotavirus antibody in serum, immunofluorescent and neutralizing rotavirus antibody in intestinal loop washings, and rotavirus antibody-producing cells in intestinal mucosa. An antibody response was observed in the serum and intestinal sec...
Malińska, Marzena; Zużewicz, Krystyna; Bugajska, Joanna; Grabowski, Andrzej
The goal of the study was assessment of the hour-long training involving handling virtual environment (sVR) and watching a stereoscopic 3D movie on the mechanisms of autonomic heart rate (HR) regulation among the subjects who were not predisposed to motion sickness. In order to exclude predispositions to motion sickness, all the participants (n=19) underwent a Coriolis test. During an exposure to 3D and sVR the ECG signal was continuously recorded using the Holter method. For the twelve consecutive 5-min epochs of ECG signal, the analysis of heart rate variability (HRV) in time and frequency domains was conducted. After 30 min from the beginning of the training in handling the virtual workstation a significant increase in LF spectral power was noted. The values of the sympathovagal LF/HF index while sVR indicated a significant increase in sympathetic predominance in four time intervals, namely between the 5th and the 10th minute, between the 15th and the 20th minute, between the 35th and 40th minute and between the 55th and the 60th minute of exposure.
Patel, Manish M.; Pitzer, Virginia; Alonso, Wladimir J.; Vera, David; Lopman, Ben; Tate, Jacqueline; Viboud, Cecile; Parashar, Umesh D.
Background A substantial number of surveillance studies have documented rotavirus prevalence among children admitted for dehydrating diarrhea. We sought to establish global seasonal patterns of rotavirus disease before widespread vaccine introduction. Methods We reviewed studies of rotavirus detection in children with diarrhea published since 1995. We assessed potential relationships between seasonal prevalence and locality by plotting the average monthly proportion of diarrhea cases positive for rotavirus according to geography, country development, and latitude. We used linear regression to identify variables that were potentially associated with the seasonal intensity of rotavirus. Results Among a total of 99 studies representing all six geographical regions of the world, patterns of year-round disease were more evident in low- and low-middle income countries compared with upper-middle and high income countries where disease was more likely to be seasonal. The level of country development was a stronger predictor of strength of seasonality (P=0.001) than geographical location or climate. However, the observation of distinctly different seasonal patterns of rotavirus disease in some countries with similar geographical location, climate and level of development indicate that a single unifying explanation for variation in seasonality of rotavirus disease is unlikely. Conclusion While no unifying explanation emerged for varying rotavirus seasonality globally, the country income level was somewhat more predictive of the likelihood of having seasonal disease than other factors. Future evaluation of the effect of rotavirus vaccination on seasonal patterns of disease in different settings may help understand factors that drive the global seasonality of rotavirus disease. PMID:23190782
Ward, Richard L
Rotaviruses cause extensive morbidity and mortality worldwide each year, supporting the need for a vaccine that is effective against rotavirus disease in all socioeconomic environments. Vaccines evaluated in clinical trials have all been live viruses that are delivered orally to mimic the excellent protection against severe rotavirus disease consistently observed after natural infection. The mechanisms by which either these vaccine candidates or natural rotavirus infections elicit protection are poorly understood. Therefore, it is not surprising that several of these candidate vaccines have provided little or no protection and have been discontinued. Two candidate vaccines are presently in phase III trials. These two were developed on the basis of very different views regarding the importance of one specific immune effector, that is, serotype-specific neutralizing antibody. One of these candidates (RotaTeq) is composed of five bovine/human reassortant rotavirus strains containing neutralization proteins representative of dominant human serotypes. The other candidate (Rotarix) is composed of only a single strain of human rotavirus. Very recent data obtained with Rotarix support the suggestion that factors other than neutralizing antibody can play important roles in protection against rotavirus disease after live rotavirus immunization. These results must be confirmed in subsequent studies in different locales with circulating rotaviruses belonging to a variety of serotypes in order to establish there overall applicability. Mechanisms by which rotavirus immunization with live viruses or other immunogens elicit protection have been most extensively examined in an adult mouse model and were reported to be multi-factorial. That is, CD8 and CD4 T cells as well as B cells were all found to play significant roles. The importance of each lymphocyte population as effectors of protection was found to be dependent on the immunogen and the route of immunization. The results of
Midgley, Sofie; Gram, Nina; Hjulsager, Charlotte Kristiane
Rotavirus group A infection causes gastroenteritis in both humans and a variety of animal species. Both domestic pet species such as cats and dogs, and commercial species such as pigs and cows can be affected. Zoonotic transmission is a possibility and could lead to the introduction into human...
Midgley, Sofie; Gram, Nina; Hjulsager, Charlotte Kristiane
Rotavirus group A infection causes gastroenteritis in both humans and a variety of animal species. Both domestic pet species such as cats and dogs, and commercial species such as pigs and cows can be affected. Zoonotic transmission is a possibility and could lead to the introduction into human...
... representative in the case of a child) receiving vaccines covered under the National Vaccine Injury Compensation... HUMAN SERVICES Centers for Disease Control and Prevention Proposed Vaccine Information Materials for Rotavirus Vaccine AGENCY: Centers for Disease Control and Prevention (CDC), Department of Health and Human...
Ahrens, Esben; Sørensen, Helge Bjarup Dissing; Langberg, Henning
factors that comprise the jitter of a system. We propose a method inspired by the field of signal averaged electrocardiography (SAECG) that allows for a quantification of the jitter of any HRV system that records and stores the raw ECG signal. Furthermore, with this method the differences between the HRV...
Sestak, K; McNeal, M M; Choi, A; Cole, M J; Ramesh, G; Alvarez, X; Aye, P P; Bohm, R P; Mohamadzadeh, M; Ward, R L
The appearance of virus-specific CD4(+) and/or CD8(+) T lymphocytes in peripheral blood of captive juvenile rhesus macaques (Macaca mulatta) was observed following rotavirus infection. These cell-mediated immune responses were measured following experimental or natural infection after rotavirus was isolated from stool specimens of asymptomatic animals. The virus isolated was a new strain of simian rotavirus that we named TUCH (for Tulane University and Cincinnati Children's Hospital). Restimulation of peripheral T lymphocytes by inactivated double- or triple-layered TUCH rotavirus particles containing either VP6 or VP4 and VP7 on their respective surfaces resulted in increased quantities of interleukin-6 (IL-6) and IL-12 in cell culture supernatants. Recall responses to rotavirus by CD4(+) and CD8(+) T lymphocytes were associated with accumulation of intracellular IL-6 and gamma interferon. Antigen presentation of TUCH rotavirus to lymphocytes was mediated via differentiated cultures of monocyte-derived dendritic (HLA-DR(+)) cells. This is the first report demonstrating cell-mediated immune responses to rotavirus in nonhuman primates. Further exploration of rhesus macaques in vaccine trials with human rotavirus vaccine candidates is the major objective of future studies.
Kittigul, Leera; Panjangampatthana, Apinya; Rupprom, Kitwadee; Pombubpa, Kannika
Rotavirus is a common cause of acute diarrhea in young children worldwide. This study investigated the prevalence and molecular characterization of rotavirus in environmental water and oyster samples in Thailand. A total of 114 water samples and 110 oyster samples were collected and tested for group A rotavirus using RT-nested PCR. Rotavirus genotype was identified by phylogenetic analysis of the VP7 genetic sequences. Group A rotavirus was detected in 21 water samples (18.4%) and six oyster samples (5.4%). Twenty five rotavirus strains were successfully sequenced and classified into four genotypes; G1, G2, G3, and G9. Rotavirus G1 (three strains), G2 (three strains), and G9 (two strains) demonstrated the genetic sequences similar to human strains (90%–99% nucleotide identity), whereas G3 (17 strains) was closely related to animal strains (84%–98% nucleotide identity). G1 strains belonged to lineages I (sub-lineage c) and II. G2 strains belonged to lineage II. G9 strains belonged to lineages III (sub-lineage b) and IV. G3 strains belonged to lineages I, III (sub-lineage c), and IV with a predominance of lineage I. The present study provides important information on the rotavirus strains circulating in the environment. PMID:24469269
Uhnoo, I; Dharakul, T; Riepenhoff-Talty, M; Ogra, P L
Rotaviruses are important pathogens causing severe diarrhoea in human infants and young animals. Available information on the pathogenic mechanisms of and the immune response to rotaviruses is reviewed here. Studies in our laboratory using the suckling mouse model have focused on elucidating the nature of interaction between the virus and the gut, and on the importance of T and B cell mediated immunity in protection and recovery from the disease. Our data suggest that the age dependence of mouse rotavirus (MRV) infection is related to the presence of virus-specific receptors on the enterocytes. The uptake of rotavirus antigens appears to be limited to the epithelium associated with Peyer's patches. The antigen is transported to local and regional lymph nodes. Recent studies have indicated that rotavirus infection also increases the uptake of other macromolecules in the intestine. Rotavirus-specific mucosal IgA response seems to be related to the location and magnitude of MRV antigen in the lymph follicles in different segments of the small intestine. Studies in mice with different types of immunodeficiency suggest that a specific immune response is required for complete resolution of virus infection. Several parameters of immunity to rotavirus infection have been examined and, similar to other reports, local immunity in the intestine appears to have the most important role in protection. It also has been observed that nutritional factors may be important in modifying disease. However, there are still many questions to be answered concerning the role of immunity in mediating the pathogenesis of rotavirus infection.
Kapikian, A Z; Wyatt, R G; Greenberg, H B; Kalica, A R; Kim, H W; Brandt, C D; Rodriguez, W J; Parrott, R H; Chanock, R M
Recent studies have shown that in developed countries rotaviruses are the single most important etiologic agents of acute gastroenteritis that requires hospitalization of infants and young children. Although deaths from gastroenteritis are, in general, infrequent in the developed countries, an effective rotavirus vaccine would clearly be of benefit to reduce the heavy toll of morbidity from gastroenteritis due to rotavirus. In the developing countries the impact of diarrheal diseases is staggering. It was recently estimated that in Asia, Africa, and Latin-America during a one-year period there would be 3.5 billion cases of diarrhea and 5-10 million deaths associated with diarrhea; in addition, diarrhea was ranked first in freqency in the categories of disease and mortality. In the developing countries rotaviruses are known to cause diarrhea, but their relative role in this high mortality rate is not yet known. epidemiologic data indicate that development of an effective rotavirus vaccine would reduce morbidity, and they suggest that a vaccine would also reduce a portion of the mortality from diarrheal disease. The prospects and approaches for the development of an effective rotavirus vaccine are presented. The recent successful propagation of rotavirus type 2 in cell culture represents an important step in this regard. In addition, the antigenic relation between human and animal strains offers another possible approach. The need for a live attenuated vaccine is indicated by the prime role played by local intestinal immunity in resistance to rotavirus disease.
Castaldo, R; Xu, W; Melillo, P; Pecchia, L; Santamaria, L; James, C
Mental stress may cause cognitive dysfunctions, cardiovascular disorders and depression. Mental stress detection via short-term Heart Rate Variability (HRV) analysis has been widely explored in the last years, while ultra-short term (less than 5 minutes) HRV has been not. This study aims to detect mental stress using linear and non-linear HRV features extracted from 3 minutes ECG excerpts recorded from 42 university students, during oral examination (stress) and at rest after a vacation. HRV features were then extracted and analyzed according to the literature using validated software tools. Statistical and data mining analysis were then performed on the extracted HRV features. The best performing machine learning method was the C4.5 tree algorithm, which discriminated between stress and rest with sensitivity, specificity and accuracy rate of 78%, 80% and 79% respectively.
Tate, Jacqueline E; Parashar, Umesh D
Vaccines are now available to combat rotavirus, the most common cause of severe diarrhea among children worldwide. We review clinical trial data for available rotavirus vaccines and summarize postlicensure data on effectiveness, impact, and safety from countries routinely using these vaccines in national programs. In these countries, rotavirus vaccines have reduced all-cause diarrhea and rotavirus hospitalizations by 17%-55% and 49%-92%, respectively, and all-cause diarrhea deaths by 22%-50% in some settings. Indirect protection of children who are age-ineligible for rotavirus vaccine has also been observed in some high and upper middle income countries. Experience with routine use of rotavirus vaccines in lower middle income countries has been limited to date, but vaccine introductions in such countries have been increasing in recent years. The risk-benefit analysis of rotavirus vaccines is extremely favorable but other strategies to improve the effectiveness of the vaccine, particularly in lower middle income settings, should be considered. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Jere, K C; Sawyerr, T; Seheri, L M; Peenze, I; Page, N A; Geyer, A; Steele, A D
In an effort to reduce the high mortalities associated with rotavirus infections, a number of African countries are considering introducing human rotavirus vaccines. The demonstrated safety and efficacy of the live-attenuate human rotavirus vaccines in several clinical trials worldwide has accelerated such initiatives. Although the percentage-mortality rates for Sierra Leone are top of the list for rotavirus-associated deaths in Africa, no study has reported the prevalent strains circulating within this country. In this study, stool specimens were collected from 128 Sierra Leonean children presenting with diarrhea in 2005. Almost 37.5% (48/128) were rotavirus positive by EIA, of which 89.6% (43/48) revealed a short electropherotype, and a further 6.98% (3/48) could not be assigned a PAGE pattern. Genotyping analysis revealed G2P (30.23%), G2P (13.95%), G8P (11.63%), G2P (4.65%), G8P (4.65%), and G8P (2%) strains. About 11% were only assigned VP7 genotypes (G2), while 20.9% had mixed G and P types. The frequent detection of G2 rotaviruses could be of concern considering data generated from some studies that suggests lower efficacy of Rotarix® vaccine against G2 rotaviruses. This underscores the need for extensive and continuous regional strain surveillance to support rotavirus vaccines introduction and guide future vaccine development efforts. Such information will be useful before considering administration of specific rotavirus vaccine candidates in countries like Sierra Leone where little is known about circulating rotavirus strains. Copyright © 2011 Wiley-Liss, Inc.
Chigor, Vincent N; Sibanda, Timothy; Okoh, Anthony I
Buffalo River is an important water resource in the Eastern Cape Province of South Africa. The potential risks of infection constituted by exposure to human enteric viruses in the Buffalo River and three source water dams along its course were assessed using mean values and static quantitative microbial risk assessment (QMRA). The daily risks of infection determined by the exponential model [for human adenovirus (HAdV) and enterovirus (EnV)] and the beta-Poisson model (for hepatitis A virus (HAV) and rotavirus (RoV)) varied with sites and exposure scenario. The estimated daily risks of infection values at the sites where the respective viruses were detected, ranged from 7.31 × 10(-3) to 1 (for HAdV), 4.23 × 10(-2) to 6.54 × 10(-1) (RoV), 2.32 × 10(-4) to 1.73 × 10(-1) (HAV) and 1.32 × 10(-4) to 5.70 × 10(-2) (EnV). The yearly risks of infection in individuals exposed to the river/dam water via drinking, recreational, domestic or irrigational activities were unacceptably high, exceeding the acceptable risk of 0.01% (10(-4) infection/person/year), and the guideline value used as by several nations for drinking water. The risks of illness and death from infection ranged from 6.58 × 10(-5) to 5.0 × 10(-1) and 6.58 × 10(-9) to 5.0 × 10(-5), respectively. The threats here are heightened by the high mortality rates for HAV, and its endemicity in South Africa. Therefore, we conclude that the Buffalo River and its source water dams are a public health hazard. The QMRA presented here is the first of its kinds in the Eastern Cape Province and provides the building block for a quantitatively oriented local guideline for water quality management in the Province.
Full Text Available ... not vaccinating the abcs of mmr & dtp thimerosal vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles media room ...
Full Text Available ... hiv/aids overview current news labs links & resources hpv overview why vaccinate posters buttons and banners videos ... q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles media room ...
Full Text Available ... not vaccinating the abcs of mmr & dtp thimerosal vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles media room Flu's Gonna Lose M.O. ...
Full Text Available ... immunizations current news Flu's Gonna Lose hepatitis a & b vaccines im/sq how to do kids infect ... vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles ...
Full Text Available ... freed meet keri russell posters grand article rich media video/audio pneumonia tb overview links & resources families ... hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles media room Flu's Gonna Lose M.O.V.E. ...
The study was carried out to determine the molecular characteristics of the rotavirus strains associated with diarrhea among children in ... The State has 16 local government areas with human population of 2,591,555 (2006 Census). ..... Infection and Immunity in Children 5: 45-54. Gomwalk, N. E., Gosham, L. T. and Umoh, ...
... https://medlineplus.gov/news/fullstory_167720.html Rotavirus Vaccine Cut Kids' Hospitalization, Medical Costs Virus a common ... the sustained impact and effectiveness of the rotavirus vaccine program," study author Dr. Eyal Leshem said in ...
Offit, P A
Although studies of rotavirus immunity in experimental animals and humans have often yielded conflicting data, a preponderance of evidence supports the following answers to the questions initially posed. 1. What is the importance of virus serotype in formulating an optimal vaccine? Both vp4 and vp7 induce virus-neutralizing antibodies after either natural infection or immunization; the capacity of vp4 to induce rotavirus-specific neutralizing antibodies is probably greater than that of vp7. However, protection against disease after immunization of infants and young children is induced by strains heterotypic to the challenge virus (e.g., immunization with WC3 induces protection against disease induced by serotypically distinct human G1 strains). In addition, oral inoculation of infants with primate or bovine reassortant rotaviruses containing genes that encode human vp7 has not consistently induced a higher level of protection against challenge than that induced by parent animal rotaviruses (see Table I). Therefore, although vp4 or vp7 or both are probably important in inducing protection against challenge, it has not been clearly demonstrated that inclusion of the epidemiologically important human (as distinct from animal) P or G type is important in protection against human disease. 2. Which immunological effector arm most likely protects against rotavirus disease? No immunological effector arm clearly explains protection against heterotypic challenge. Protection against disease is not predicted by rotavirus-specific neutralizing antibodies in serum. Rotavirus-specific, binding sIgA in feces [detected by enzyme-linked immunosorbent assay (ELISA)] induced after natural infection does correlate with protection against disease induced by subsequent infection. However, protection after immunization with WC3 may occur in the absence of a detectable fecal sIgA response. The relationship between rotavirus-binding sIgA and sIgA-mediated neutralizing activity directed
Burns, J W; Krishnaney, A A; Vo, P T; Rouse, R V; Anderson, L J; Greenberg, H B
The group A rotaviruses are significant human and veterinary pathogens in terms of morbidity, mortality, and economic loss. Despite its importance, an effective vaccine remains elusive due at least in part to our incomplete understanding of rotavirus immunity and protection. Both large and small animal model systems have been established to address these issues. One significant drawback of these models is the lack of well-characterized wild-type homologous viruses and their cell culture-adapted variants. We have characterized four strains of murine rotaviruses, EC, EHP, EL, and EW, in the infant and adult mouse model using wild-type isolates and cell culture-adapted variants of each strain. Wild-type murine rotaviruses appear to be equally infectious in infant and adult mice in terms of the intensity and duration of virus shedding following primary infection. Spread of infection to naive cagemates is seen in both age groups. Clearance of shedding following primary infection appears to correlate with the development of virus-specific intestinal IgA. Protective immunity is developed in both infant and adult mice following oral infection as demonstrated by a lack of shedding after subsequent wild-type virus challenge. Cell culture-adapted murine rotaviruses appear to be highly attenuated when administered to naive animals and do not spread efficiently to nonimmune cagemates. The availability of these wild-type and cell culture-adapted virus preparations should allow a more systematic evaluation of rotavirus infection and immunity. Furthermore, future vaccine strategies can be evaluated in the mouse model using several fully virulent homologous viruses for challenge.
Payne, Daniel C.; Currier, Rebecca L.; Staat, Mary A.; Sahni, Leila C.; Selvarangan, Rangaraj; Halasa, Natasha B.; Englund, Janet A.; Weinberg, Geoffrey A.; Boom, Julie A.; Szilagyi, Peter G.; Klein, Eileen J.; Chappell, James; Harrison, Christopher J.; Davidson, Barbara S.; Mijatovic-Rustempasic, Slavica; Moffatt, Mary D.; McNeal, Monica; Wikswo, Mary; Bowen, Michael D.; Morrow, Ardythe L.; Parashar, Umesh D.
IMPORTANCE A genetic polymorphism affecting FUT2 secretor status in approximately one-quarter of humans of European descent affects the expression of histo-blood group antigens on the mucosal epithelia of human respiratory, genitourinary, and digestive tracts. These histo-blood group antigens serve as host receptor sites necessary for attachment and infection of some pathogens, including norovirus. OBJECTIVE We investigated whether an association exists between FUT2 secretor status and laboratory-confirmed rotavirus infections in US children. DESIGN, SETTING, AND PARTICIPANTS Multicenter case-control observational study involving active surveillance at 6 US pediatric medical institutions in the inpatient and emergency department clinical settings. We enrolled 1564 children younger than 5 years with acute gastroenteritis (diarrhea and/or vomiting) and 818 healthy controls frequency matched by age and month, from December 1, 2011, through March 31, 2013. MAIN OUTCOMES AND MEASURES Paired fecal-saliva specimens were tested for rotavirus and for secretor status. Comparisons were made between rotavirus test–positive cases and healthy controls stratified by ethnicity and vaccination status. Adjusted multivariable analyses assessed the preventive association of secretor status against severe rotavirus gastroenteritis. RESULTS One (0.5%) of 189 rotavirus test–positive cases was a nonsecretor, compared with 188 (23%) of 818 healthy control participants (P rotavirus gastroenteritis. CONCLUSIONS AND RELEVANCE Severe rotavirus gastroenteritis was virtually absent among US children who had a genetic polymorphism that inactivates FUT2 expression on the intestinal epithelium. We observed a strong epidemiologic association among children with rotavirus gastroenteritis compared with healthy control participants. The exact cellular mechanism behind this epidemiologic association remains unclear, but evidence suggests that it may be rotavirus genotype specific. The lower
Van Thai Than
Full Text Available The epidemiology of human group A rotavirus was analyzed by examining genotypic data acquired from 1989 to 2009 in South Korea. This information was derived from all the available published articles on rotavirus studies in South Korea, retrieved from both the PubMed and KoreaMed databases. Four common G types (G1, G2, G3, and G4 and three common P types (P, P, and P accounted for approximately 93% and 99% of the rotavirus reports, respectively. The G9 type was frequently detected after 2000, and because of this prevalence, it is considered to be the fifth most important G type rotavirus after the G1–G4 genotypes. Less common G types of the virus such as G12, G11, and G10 were detected in some geographic settings, and it is important to consider the context of these subtypes and their epidemiological significance. The P virus genotype was observed in the study and has been discussed in many other studies; however, the P, P and P genotypes were rarely detected in the epidemiological research. In general, the distributions of the G and P genotypes showed temporal and geographical fluctuations, and a nationwide rotavirus vaccine program that targeted these genotypes demonstrated effectiveness in protecting against the circulating rotavirus strains. However, further analysis is needed to determine the true long-term effectiveness of these vaccines; the analysis should also consider the unexpected effects of vaccinations, such as vaccineinduced diseases, herd immunity, and changes in host susceptibilities.
Chiappini, Elena; Azzari, Chiara; Moriondo, Maria; Galli, Luisa; de Martino, Maurizio
Rotavirus infection is usually localized to the intestine but involvement of extra-intestinal sites, including the respiratory tract, liver, kidney, lymph nodes, and central nervous system, has been reported. The extra-intestinal spread of the virus may occur through blood since viraemia has been documented occasionally in animals and humans. Nevertheless, the questions of how common viraemia is in immunocompetent children and whether it is associated with extra-intestinal manifestations remain unsolved. Serum samples from 54 immunocompetent children hospitalized for acute diarrhea were evaluated prospectively for the presence of rotavirus RNA by nested reverse transcriptase-polymerase chain reaction (RT-PCR) to investigate this issue. Rotavirus antigens were detected in the stools of 14 children. A bacterial aetiology was documented in 14 cases, and in the remaining cases the aetiology remained unknown. Rotavirus RNA was detected in the blood of 9/14 (64.3%) rotavirus infected children but in no child with diarrhea of other origin. Positive RT-PCR was associated with high fever and/or evidence of extra-intestinal involvement. All positive samples were collected within 3 days of illness onset, suggesting that viraemia was detectable for only a few days. Children in whom rotavirus was detected only in stool samples had high fever but no other extra-intestinal feature. These data suggest that viraemia is common in children infected with rotavirus, which may be associated with extra-intestinal involvement. Copyright 2005 Wiley-Liss, Inc.
Ward, Richard L; Clark, H Fred; Offit, Paul A
Rotaviruses cause extensive morbidity and mortality worldwide, thus corroborating the need for a vaccine that is effective in all socioeconomic environments. Vaccines evaluated in clinical trials have all been live attenuated rotaviruses that are delivered orally to mimic the excellent protection observed after natural infection. The mechanisms by which these vaccine candidates or wild-type rotaviruses elicit protection are not fully understood. During the 1980s, several candidate vaccines provided little protection, particularly in developing countries, and were discontinued. Two, however, are in the process of being licensed worldwide, and several others are undergoing clinical trials. Development of live rotavirus vaccines has been highly influenced by views regarding the importance of serotype-specific neutralizing antibody. Development of several candidate vaccines is based on the concept that neutralizing antibody is the primary determinant of protection. These candidates, including 1 of the 2 being licensed worldwide (RotaTeq), are composed of multiple rotavirus strains representative of the major human rotavirus serotypes. The other group of candidates has been developed based on the theory that protection is not solely dependent on neutralizing antibody. These candidates are composed of single rotavirus strains and include the other vaccine being licensed worldwide (Rotarix). Studies that provide the basis for each approach will be presented and discussed.
Bines, Julie E; Danchin, Margaret; Jackson, Pamela; Handley, Amanda; Watts, Emma; Lee, Katherine J; West, Amanda; Cowley, Daniel; Chen, Mee-Yew; Barnes, Graeme L; Justice, Frances; Buttery, Jim P; Carlin, John B; Bishop, Ruth F; Taylor, Barry; Kirkwood, Carl D
Despite the success of rotavirus vaccines, suboptimal vaccine efficacy in regions with a high burden of disease continues to present a challenge to worldwide implementation. A birth dose strategy with a vaccine developed from an asymptomatic neonatal rotavirus strain has the potential to address this challenge and provide protection from severe rotavirus disease from birth. This phase 2a randomised, double-blind, three-arm, placebo-controlled safety and immunogenicity trial was undertaken at a single centre in New Zealand between Jan 13, 2012, and April 17, 2014. Healthy, full-term (≥36 weeks gestation) babies, who weighed at least 2500 g, and were 0-5 days old at the time of randomisation were randomly assigned (1:1:1; computer-generated; telephone central allocation) according to a concealed block randomisation schedule to oral RV3-BB vaccine with the first dose given at 0-5 days after birth (neonatal schedule), to vaccine with the first dose given at about 8 weeks after birth (infant schedule), or to placebo. The primary endpoint was cumulative vaccine take (serum immune response or stool shedding of vaccine virus after any dose) after three doses. The immunogenicity analysis included all randomised participants with available outcome data. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611001212943. 95 eligible participants were randomised, of whom 89 were included in the primary analysis. A cumulative vaccine take was detected in 27 (90%) of 30 participants in the neonatal schedule group after three doses of RV3-BB vaccine compared with four (13%) of 32 participants in the placebo group (difference in proportions 0·78, 95% CI 0·55-0·88; pvaccine take after three doses compared with eight (25%) of 32 participants in the placebo group (difference in proportions 0·68, 0·44-0·81; pvaccine was not associated with an increased frequency of fever or gastrointestinal symptoms compared with placebo. RV3-BB vaccine was
Mihalov-Kovács, Eszter; Gellért, Ákos; Marton, Szilvia; Farkas, Szilvia L.; Fehér, Enikő; Oldal, Miklós; Jakab, Ferenc; Martella, Vito
We identified unusual rotavirus strains in fecal specimens from sheltered dogs in Hungary by viral metagenomics. The novel rotavirus species displayed limited genome sequence homology to representatives of the 8 rotavirus species, A–H, and qualifies as a candidate new rotavirus species that we tentatively named Rotavirus I. PMID:25811414
Jiang, Baoming; Gentsch, Jon R; Glass, Roger I
A critical observation in understanding immunity to rotavirus is that children infected with wild virus or vaccinated with oral live vaccines develop a humoral immune response and are protected against severe disease upon reinfection. Nevertheless, much controversy exists as to whether these serum antibodies are directly involved in protection or merely reflect recent infection, leaving the protective role to mucosal or cell-mediated immunity or to other as-yet-undefined mechanisms. We have reviewed data from a variety of studies in humans, including challenge experiments in adult volunteers, longitudinal studies of rotavirus infection in young children, and clinical trials of animal and animal-human reassortant rotavirus vaccines in infants. These data suggest that serum antibodies, if present at critical levels, are either protective themselves or are an important and powerful correlate of protection against rotavirus disease, even though other host effectors may play an important role as well.
Kota, M; Bino, S; Delogu, R; Simaku, A; Neza, B; Ruggeri, F M; Fiore, L
The aim of the study was to estimate the prevalence of rotavirus disease in childrenAlbania, and to monitor and characterize the rotavirus genotypes. Rotavirus was detected in 21% of samples, more frequently in children under 2 years of age, which accounted for 80.8% of all positive cases. Among all rotavirus-positive samples collected, G4P was the most prevalent genotype (38%), followed by G1P (36.6%). The use of safe and effective rotavirus vaccines for the prevention of severe diarrhoea and the reduction of treatment costs will be of great importance for Albania.
data collection. Significant changes in use or care of human subjects, vertebrate animals , biohazards, and/or select agents Nothing to report...they have qualified for an incentive (Amazon gift code) to UNC IRB. Significant changes in use or care of vertebrate animals . Nothing to report...perspective (polyvagal theory) that emphasizes the hierarchical organization of the human mind . Cognitive and behavioral regulation depends on
H. G. Pereira
Full Text Available Particles morphologically identical to rotaviruses were found in the faeces of a nine week-old child with gastroenteritis. Analysis of the viral RNA genome by polyacrylamine gel electrophoresis revealed 10 bands (probably 11 segments some of wich differed in migration rate from those of the great majority of rotaviruses infecting man and other animal hosts. The virus was not detected by a highly sensitive enzyme immunoassay (ELISA and therefore probably lacked the crossreactive antigen(s shared by the majority rotaviruses. This was the only strain with such behaviour among 230 rotaviruses of human origin examined in this laboratory since 1979. The implications of the existence of non-crossreactive rotaviruses are discussed.Partículas morfologicamente idênticas a rotavirus foram encontradas nas fezes de uma criança de dois meses com gastroenterite. Análise do genoma viral por eletroforese em gel de poliacrilamida revelou 10 faixas (provavelmente 11 segmentos de RNA, algumas das quais diferem em velocidade de migração das observadas na grande maioria de rotavirus de hospedeiros humanos e de diversas espécies de animais. O vírus não foi revelado por um ensaio imuno-enzimático de alta sensibilidade, o que sugere a ausência do antígeno de grupo que da reações cruzadas entre a maioria dos rotavirus. O vírus descrito no presente trabalho foi o único com tal comportamento entre 230 amostras analisadas por nós desde 1979. A relevância de existência de rotavirus não relacionados antigenicamente a outros membros do grupo é discutida.
Feng, N; Burns, J W; Bracy, L; Greenberg, H B
Rotaviruses are the single most important cause of severe diarrhea in young children worldwide, and vaccination is probably the most effective way to control the disease. Most current live virus vaccine candidates are based on the host range-restricted attenuation of heterologous animal rotaviruses in humans. The protective efficacy of these vaccine candidates has been variable. To better understand the nature of the heterologous rotavirus-induced active immune response, we compared the diffe...
Full Text Available This study sought the characterization of rotaviruses in a trial with a tetravalent rhesus-human rotavirus vaccine in Belém, Brazil in children who received three doses of vaccine or placebo in the 1st, 3rd and 5th months of life. Rotavirus electropherotypes, subgroups, G serotypes, G, [P] and [P],G genotypes were determined in 93.3%, 95.9%, 93.3%, 73.3%, 95.5% and 92.2% of isolates, respectively. Serotypes G1, G2 and G4 were detected in 58.9%, 30% and 4.4% of the cases, respectively. Rotavirus genotype G5 was detected for the first time in Northern region in 4.4% of the infections. Rotavirus genotypes P, P, P and P[8+6] were detected in 54.5%, 26.7%, 12.2%, and 2.2% of the cases, respectively. The predominant genotypes were P,G1 and P,G2 with 53% and 26.6% of the infections, respectively. Unusual strains accounted for 20.5% including P,G1, P,G1, P,G4, P,G5, P,G2, P,G5. Mixed infections involving P[8+6],G2 and P[8+6],G1 were also noted. The neonatal P strains associated with diarrhea were detected among children aged 9-24 months. To our knowledge, this study represents the first in Brazil to analyse, on molecular basis, rotavirus genotypes from children participating in a rotavirus vaccine trial. These results are of potential importance regarding future rotavirus vaccination strategies in Brazil.
Hull, Jennifer J; Cunliffe, Nigel; Jere, Khuzwayo C; Moon, Sung-Sil; Wang, Yuhuan; Parashar, Umesh; Jiang, Baoming
Rotavirus and HIV infection are major causes of death among children in sub-Saharan Africa. A previous study reported no association between concomitant HIV infection and rotavirus disease severity among hospitalised children in Malawi. This study examined rotavirus antigenaemia and broader immune responses among HIV-infected and uninfected children. Stored (-80°C), paired sera from acute and convalescent phases of Malawian children less than 5 years old, hospitalised for acute gastroenteritis in the primary study, collected from July 1997 to June 1999, were utilised. Among children older than 15 months, HIV infection was defined as the presence of HIV antibody in the blood, when confirmed by at least 2 established methods. For those younger than 15 months, nested polymerase chain reaction (PCR) amplification of proviral DNA was used for verification. All were followed for up to 4 weeks after hospital discharge. Rotavirus antigen levels in sera were measured with Premier™ Rotaclone® rotavirus enzyme immunoassay (EIA) kit. Acute-phase sera were examined for 17 cytokines, using Luminex fluorescent bead human cytokine immunoassay kit. Rotavirus-specific IgA and neutralising activity were determined by EIA and microneutralisation (MN) assay, respectively. Human strains and bovine-human reassortants were propagated in MA104 cells with serum-free Iscove's Modified Dulbecco's Medium (IMDM). Differences in results, from specimens with and without HIV infection, were analysed for statistical significance using the chi-square test. We detected rotavirus antigen in 30% of the HIV-infected and 21% HIV-uninfected, in the acute-phase sera. HIV-infected children developed slightly prolonged rotavirus antigenaemia compared to HIV-uninfected children. Rotavirus-specific IgA seroconversion rates and neutralising titres were similar in HIV-infected and HIV-uninfected children, thus, HIV infection had no major effect on immune responses to rotavirus infection.
Kiulia, N M; Peenze, I; Dewar, J; Nyachieo, A; Galo, M; Omolo, E; Steele, A D; Mwenda, J M
Rotavirus is the most common cause of severe infantile diarrhoea disease in infants and young children below five years worldwide. Rotavirus is associated with high cases of morbidity and mortality and it is estimated that up to 650,000 deaths in young children occur annually in the less developed countries and approximately 150,000-200,000 deaths occur in Africa alone. To characterise the circulating rotavirus strains in Maua, Meru North district, Kenya. A prospective study to investigate and characterise rotavirus serotypes/genotypes and electropherotypes in infants and children with severe diarrhoea hospitalised and/or attending the outpatient department of Maua Methodist Hospital during the period April 2004 to September 2005. Maua Methodist Hospital, Meru North, Kenya. Faecal samples were collected from 135 infants and children with acute diarrhoea and were screened first for the presence of human Group A rotavirus antigen using commercially available enzyme linked immunosorbent assay kit (ELISA). The positive samples were evaluated by sodium dodecyl polycrylamide gel electrophoresis (SDS-PAGE) to determine the viral RNA electropherotype profile. Rotavirus strains were also genotyped using reverse transcriptase polymerase chain reaction (RT-PCR) of the VP7 gene. Assay of these samples with commercial ELISA showed that 17.8% (24/135) were positive for group A rotavirus antigen. Twenty of these ELISA positive samples were also analysed by SDS-PAGE of which 75% (15/20) gave detectable electropherotype pattern with the long electropherotype being predominant 80.0% (12/15) followed by the short RNA profile 20.0% (2/ 15). Seventeen of the ELISA positive samples were genotyped for VP7 and the results showed that G9 was the most predominant genotype comprising 47.1% (8/17) followed by G8 29.4% (5/17), GI 17.4% (3/17) and the mixed genotype was G8/G9 5.9% (1/17). Most patients with rotavirus infection were of the age of 3 - 60 months, with 79% being less than 18 months
Mohammed, Anaam; Immergluck, Lilly; Parker, Trisha Chan; Jain, Shabnam; Leong, Traci; Anderson, Evan J.; Jerris, Robert C.
Introduction Rotavirus remains the leading cause of severe diarrhea in children under 5 years worldwide. In the US, Rotarix® (RV1) and RotaTeq® (RV5), have been associated with reductions in and severity of rotavirus disease. Studies have evaluated the impact of RV1 or RV5 but little is known about the impact of incomplete or mixed vaccination upon vaccine effectiveness. Methods Case control study to examine association of combined RV1 and RV5 and rotavirus acute gastroenteritis, factoring severity of diarrheal disease. Children born after March 1, 2009 with acute gastroenteritis from three pediatric hospitals in Atlanta, Georgia were approached for enrollment. Survey was administered, stool specimen was collected, and vaccination records were obtained. Results 891 of 1127 children with acute gastroenteritis were enrolled. Stool specimens were collected from 708 for rotavirus testing; 215 stool samples tested positively for rotavirus. Children >12 months of age were more likely to have rotavirus. Children categorized with Vesikari score of >11 were almost twice as likely to be rotavirus positive. Prior rotavirus vaccination decreased the mean Vesikari score, p vaccination were protected against rotavirus (OR 0.21, 95% CI: 0.14–0.31, p rotavirus vaccination with a single vaccine type resulted in protection against rotavirus diarrhea and decrease in severity of rotavirus gastroenteritis. Incomplete rotavirus vaccination either with a single vaccine or mixed vaccination types also provided some protection. PMID:26322843
Oishi, I; Kimura, T; Murakami, T; Haruki, K; Yamazaki, K; Seto, Y; Minekawa, Y; Funamoto, H
Chronic rotavirus infection of an infant with severe combined immunodeficiency (SCID) was studied by virological examinations in association with long-term observation of his symptoms and immune status. During eleven months of hospitalization, the patient was suffering from incurable severe diarrhea with persisting excretion of rotaviruses detected by electron microscopy and the reversed-passive hemagglutination (R-PHA) test and had transient hepatitis symptom despite multiple administrations of human gammaglobulin and high calorie fluids. The detected viruses were morphologically recognized as rotavirus with double capsid structure. Polyacrylamide gel electrophoretic (PAGE) analysis of their genomic RNAs showed the long electropherotype of group A virus with abnormal migration profiles changing considerably from the early to the late phase of illness: (1) The 11th segment became undetectable; (2) the molecular weight of the 6th segment slightly increased; (3) seven to fourteen extra segments appeared; and (4) PAGE patterns of viral genomic RNAs changed every three or four months. These findings suggest that chronic infection with rotavirus accompanied the generation of extra viral genomic segments and their unusual assortments in an immunodeficient host.
Haffejee, I E
Rotavirus (RV) infections in newborns differ from those in older infants; the majority of RV infections that occur in neonates are mild or asymptomatic. Generally, fewer than one-third of RV-infected neonates have diarrhea, although rates have reached 77% in some hospital nursery populations. Cases with severe diarrhea, necrotizing enterocolitis, bowel perforation, and death have been reported, but such cases are very rare. Infection usually occurs during the first week of life and generally invokes a mucosal antibody response without a concomitant serologic antibody response. Neonatal RV infections appear to incite an immune response that affords significant protection against severe RV-associated diarrhea, although not necessarily against a symptomatic RV infection later in life. Strains that cause neonatal infections differ from those that infect older infants; the outer-capsid protein VP4 is highly conserved in "nursery" RV strains, a property that probably plays a key role in their attenuated virulence. Immaturity of proteolytic enzymes in the neonatal gut and presence of secretory anti-RV IgA and trypsin inhibitors in breast milk are other factors that could account for the asymptomatic nature of RV infections in newborns. Natural "nursery" strains of RV are currently being evaluated as vaccine candidates.
Full Text Available Obesity is associated with cardiovascular mortality. Linear methods, including time domain and frequency domain analysis, are normally applied on the heart rate variability (HRV signal to investigate autonomic cardiovascular control, whose imbalance might promote cardiovascular disease in these patients. However, given the cardiac activity non-linearities, non-linear methods might provide better insight. HRV complexity was hereby analyzed during wakefulness and different sleep stages in healthy and obese subjects. Given the short duration of each sleep stage, complexity measures, normally extracted from long-period signals, needed be calculated on short-term signals. Sample entropy, Lempel-Ziv complexity and detrended fluctuation analysis were evaluated and results showed no significant differences among the values calculated over ten-minute signals and longer durations, confirming the reliability of such analysis when performed on short-term signals. Complexity parameters were extracted from ten-minute signal portions selected during wakefulness and different sleep stages on HRV signals obtained from eighteen obese patients and twenty controls. The obese group presented significantly reduced complexity during light and deep sleep, suggesting a deficiency in the control mechanisms integration during these sleep stages. To our knowledge, this study reports for the first time on how the HRV complexity changes in obesity during wakefulness and sleep. Further investigation is needed to quantify altered HRV impact on cardiovascular mortality in obesity.
SUMMARYCommunity and hospital-acquired cases of human rotavirus are responsible for millions of gastroenteritis cases in children worldwide, chiefly in developing countries, and vaccines are now available. During surveillance activity for human rotavirus infections in Ireland, between 2006 and 2009, a total of 420 rotavirus strains were collected and analysed. Upon either PCR genotyping and sequence analysis, a variety of VP7 (G1-G4 and G9) and VP4 (P, P, P and P) genotypes were detected. Strains G1P were found to be predominant throughout the period 2006-2008, with slight fluctuations seen in the very limited samples available in 2008-2009. Upon either PCR genotyping and sequence analysis of selected strains, the G1, G3 and G9 viruses were found to contain E1 (Wa-like) NSP4 and I1 VP6 genotypes, while the analysed G2 strains possessed E2 NSP4 and I2 VP6 genotypes, a genetic make-up which is highly conserved in the major human rotavirus genogroups Wa- and Kun-like, respectively. Upon sequence analysis of the most common VP4 genotype, P, at least two distinct lineages were identified, both unrelated to P Irish rotaviruses circulating in previous years, and more closely related to recent European humans rotaviruses. Moreover, sequence analysis of the VP7 of G1 rotaviruses revealed the onset of a G1 variant, previously unseen in the Irish population.
Vizzi, Esmeralda; Piñeros, Oscar A; Oropeza, M Daniela; Naranjo, Laura; Suárez, José A; Fernández, Rixio; Zambrano, José L; Celis, Argelia; Liprandi, Ferdinando
Rotavirus (RV) is the most common cause of severe childhood diarrhea worldwide. Despite Venezuela was among the first developing countries to introduce RV vaccines into their national immunization schedules, RV is still contributing to the burden of diarrhea. Concerns exist about the selective pressure that RV vaccines could exert on the predominant types and/or emergence of new strains. To assess the impact of RV vaccines on the genotype distribution 1 year after the vaccination was implemented, a total of 912 fecal specimens, collected from children with acute gastroenteritis in Caracas from February 2007 to April 2008, were screened, of which 169 (18.5%) were confirmed to be RV positive by PAGE. Rotavirus-associated diarrhea occurred all year-round, although prevailed during the coolest and driest months among unvaccinated children under 24 months old. Of 165 RV strains genotyped for G (VP7) and P (VP4) by seminested multiplex RT-PCR, 77 (46.7%) were G2P and 63 (38.2%) G1P. G9P, G3P and G2P were found in a lower proportion (7.3%). Remarkable was also the detection of <5% of uncommon combinations (G8P, G8P, G1P and G4P) and 3.6% of mixed infections. A changing pattern of G/P-type distribution was observed during the season studied, with complete predominance of G2P from February to June 2007 followed by its gradual decline and the reemergence of G1P, predominant since January 2008. Phylogenetic analysis of VP7 and VP4 genes revealed a high similarity among G2P and global strains belonging to G2-II and P-V lineages. The amino acid substitution 96D → N, related with reemergence of the G2 genotype elsewhere, was observed. The G1P strains from Caracas were grouped into the lineages G1-I and P-III, along with geographically remote G1P rotaviruses, but they were rather distant from Rotarix ® vaccine and pre-vaccine strains. Unique amino acid substitutions observed on neutralization domains of the VP7 sequence from
Vonderfecht, S L; Osburn, B I
The local and systemic humoral immune responses to rotavirus were studied in six conventional neonatal calves. Attenuated bovine rotavirus was administered either orally or directly into an isolated intestinal loop. The parameters monitored were neutralizing rotavirus antibody in serum, immunofluorescent and neutralizing rotavirus antibody in intestinal loop washings, and rotavirus antibody-producing cells in intestinal mucosa. An antibody response was observed in the serum and intestinal secretions from one calf only. Viral replication was not detected in the isolated intestinal loop. Rotavirus antibody-producing cells were found in the intestinal mucosa of five calves. Double staining revealed that most of these cells produced antibody of the immunoglobulin A class. The conclusions were: (i) a previously described system to detect rotavirus antibody-producing cells can be used to study immune responses in neonatal calves, (ii) the class or subclass of antibody in rotavirus antibody-producing cells can be determined by double immunofluorescent staining, (iii) neonatal calves respond to rotavirus inoculation with a local immunoglobulin A response, and (iv) most of the rotavirus antibody-producing cells are located in the mucosa of the proximal small intestine.
Yeung, Karene Hoi Ting; Tate, Jacqueline E; Chan, Ching Ching; Chan, Martin C W; Chan, Paul K S; Poon, Kin Hung; Siu, Sylvia Luen Yee; Fung, Genevieve Po Gee; Ng, Kwok Leung; Chan, Iris Mei Ching; Yu, Pui Tak; Ng, Chi Hang; Lau, Yu Lung; Nelson, E Anthony S
Rotavirus is a common infectious cause of childhood hospitalisation in Hong Kong. Rotavirus vaccines have been used in the private sector since licensure in 2006 but have not been incorporated in the government's universal Childhood Immunisation Programme. This study aimed to evaluate rotavirus vaccine effectiveness against hospitalisation. This case-control study was conducted in the 2014/2015 rotavirus season in six public hospitals. Hospitalised acute gastroenteritis patients meeting inclusion criteria were recruited and copies of their immunisation records were collected. Case-patients were defined as enrolled subjects with stool specimens obtained in the first 48h of hospitalisation that tested positive for rotavirus, whereas control-patients were those with stool specimens obtained in the first 48h of hospitalisation testing negative for rotavirus. Vaccine effectiveness for administration of at least one dose of either Rotarix(®) (GlaxoSmithKline Biologicals) or RotaTeq(®) (Merck Research Laboratories) was calculated as 1 minus the odds ratio for rotavirus vaccination history for case-patients versus control-patients. Among the 525 eligible subjects recruited, immunisation records were seen in 404 (77%) subjects. 31% (162/525 and 126/404) tested positive for rotavirus. In the 404 subjects assessed for vaccine effectiveness, 2.4% and 24% received at least 1 dose of either rotavirus vaccine in case- and control-patients respectively. The unmatched vaccine effectiveness against hospitalisation for administration of at least one dose of either rotavirus vaccines was 92% (95% confidence interval [CI]: 75%, 98%). The matched analyses by age only and both age and admission date showed 96% (95% CI: 72%, 100%) and 89% (95% CI: 51%, 97%) protection against rotavirus hospitalisation respectively. Rotavirus vaccine is highly effective in preventing hospitalisation from rotavirus disease in young Hong Kong children. Copyright © 2016 The Authors. Published by Elsevier
Full Text Available Interaction with cellular glycans is a critical initial step in the pathogenesis of many infectious agents. Technological advances in glycobiology have expanded the repertoire of studies delineating host glycanâpathogen interactions. For rotavirus, the VP8* domain of the outer capsid spike protein VP4 is known to interact with cellular glycans. Sialic acid was considered the key cellular attachment factor for rotaviruses for decades. Although this is true for many rotavirus strains causing infections in animals, glycan array screens show that many human rotavirus strains bind nonsialylated glycoconjugates, called histo-blood group antigens, in a strain-specific manner. The expression of histo-blood group antigens is determined genetically and is regulated developmentally. Variations in glycan binding between different rotavirus strains are biologically relevant and provide new insights into multiple aspects of virus pathogenesis such as interspecies transmission, host range restriction, and tissue tropism. The genetics of glycan expression may affect susceptibility to different rotavirus strains and vaccine viruses, and impact the efficacy of rotavirus vaccination in different populations. A multidisciplinary approach to understanding rotavirusâhost glycan interactions provides molecular insights into the interaction between microbial pathogens and glycans, and opens up new avenues to translate findings from the bench to the human population. Keywords: Rotavirus, VP8*, Glycans, Sia, Histo-Blood Group Antigens
Behbahani, Soroor; Dabanloo, Nader Jafarnia; Nasrabadi, Ali Motie; Dourado, Antonio
Epileptic onsets often affect the autonomic function of the body during a seizure, whether it is in ictal, interictal or post-ictal periods. The different effects of localization and lateralization of seizures on heart rate variability (HRV) emphasize the importance of autonomic function changes in epileptic patients. On the other hand, the detection of seizures is of primary interests in evaluating the epileptic patients. In the current paper, we analyzed the HRV signal to develop a reliable offline seizure-detection algorithm to focus on the effects of lateralization on HRV. We assessed the HRV during 5-min segments of continuous electrocardiogram (ECG) recording with a total number of 170 seizures occurred in 16 patients, composed of 86 left-sided and 84 right-sided focus seizures. Relatively high and low-frequency components of the HRV were computed using spectral analysis. Poincaré parameters of each heart rate time series considered as non-linear features. We fed these features to the Support Vector Machines (SVMs) to find a robust classification method to classify epileptic and non-epileptic signals. Leave One Out Cross-Validation (LOOCV) approach was used to demonstrate the consistency of the classification results. Our obtained classification accuracy confirms that the proposed scheme has a potential in classifying HRV signals to epileptic and non-epileptic classes. The accuracy rates for right-sided and left-sided focus seizures were obtained as 86.74% and 79.41%, respectively. The main finding of our study is that the patients with right-sided focus epilepsy showed more reduction in parasympathetic activity and more increase in sympathetic activity. It can be a marker of impaired vagal activity associated with increased cardiovascular risk and arrhythmias. Our results suggest that lateralization of the seizure onset zone could exert different influences on heart rate changes. A right-sided seizure would cause an ictal tachycardia whereas a left
Full Text Available Exposure to polycyclic aromatic hydrocarbons (PAHs is associated with reduced heart rate variability (HRV, a strong predictor of cardiovascular diseases, but the mechanism is not well understood.We hypothesized that PAHs might induce systemic inflammation and stress response, contributing to altered cardiac autonomic function.HRV indices were measured using a 3-channel digital Holter monitor in 800 coke oven workers. Plasma levels of interleukin-6 (IL-6 and heat shock protein 70 (Hsp70 were determined using ELISA. Twelve urinary PAHs metabolites (OH-PAHs were measured by gas chromatography-mass spectrometry.We found that significant dose-dependent relationships between four urinary OH-PAHs and IL-6 (all Ptrend<0.05; and an increase in quartiles of IL-6 was significantly associated with a decrease in total power (TP and low frequency (LF (Ptrend = 0.014 and 0.006, respectively. In particular, elevated IL-6 was associated in a dose-dependent manner with decreased TP and LF in the high-PAHs metabolites groups (all Ptrend<0.05, but not in the low-PAHs metabolites groups. No significant association between Hsp70 and HRV in total population was found after multivariate adjustment. However, increased Hsp70 was significantly associated with elevated standard deviation of NN intervals (SDNN, TP and LF in the low-PAHs metabolites groups (all Ptrend<0.05. We also observed that both IL-6 and Hsp70 significantly interacted with multiple PAHs metabolites in relation to HRV.In coke oven workers, increased IL-6 was associated with a dose-response decreased HRV in the high-PAHs metabolites groups, whereas increase of Hsp70 can result in significant dose-related increase in HRV in the low-PAHs metabolites groups.
Guerrero, C A; Zárate, S; Corkidi, G; López, S; Arias, C F
We have tested the effect of metabolic inhibitors, membrane cholesterol depletion, and detergent extraction of cell surface molecules on the susceptibility of MA104 cells to infection by rotaviruses. Treatment of cells with tunicamycin, an inhibitor of protein N glycosylation, blocked the infectivity of the SA-dependent rotavirus RRV and its SA-independent variant nar3 by about 50%, while the inhibition of O glycosylation had no effect. The inhibitor of glycolipid biosynthesis d, l-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) blocked the infectivity of RRV, nar3, and the human rotavirus strain Wa by about 70%. Sequestration of cholesterol from the cell membrane with beta-cyclodextrin reduced the infectivity of the three viruses by more than 90%. The involvement of N-glycoproteins, glycolipids, and cholesterol in rotavirus infection suggests that the virus receptor(s) might be forming part of lipid microdomains in the cell membrane. MA104 cells incubated with the nonionic detergent octyl-beta-glucoside (OG) showed a ca. 60% reduction in their ability to bind rotaviruses, the same degree to which they became refractory to infection, suggesting that OG extracts the potential virus receptor(s) from the cell surface. Accordingly, when preincubated with the viruses, the OG extract inhibited the virus infectivity by more than 95%. This inhibition was abolished when the extract was treated with either proteases or heat but not when it was treated with neuraminidase, indicating the protein nature of the inhibitor. Two protein fractions of around 57 and 75 kDa were isolated from the extract, and these fractions were shown to have rotavirus-blocking activity. Also, antibodies to these fractions efficiently inhibited the infectivity of the viruses in untreated as well as in neuraminidase-treated cells. Five individual protein bands of 30, 45, 57, 75, and 110 kDa, which exhibited virus-blocking activity, were finally isolated from the OG extract. These proteins
Full Text Available ... thimerosal vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles media room Flu's Gonna Lose M.O.V.E. newsfeeds PSAs publications infectious disease workshop pediatric hepatitis report someone you know has hbv/hcv standard ...
Full Text Available ... immunizations about immunizations current news Flu's Gonna Lose hepatitis a & b vaccines im/sq how to do kids infect kids ... not vaccinating the abcs of mmr & dtp thimerosal vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles ...
Martinón-Torres, Federico; Aramburo, Angela; Martinón-Torres, Nazareth; Cebey, Miriam; Seoane-Pillado, María Teresa; Redondo-Collazo, Lorenzo; Martinón-Sánchez, Jose Maria
In 2010, and due to a quality problem identified in the vaccine manufacture, the rotavirus (RV) vaccination was withheld in Spain during 5 months. Our study aimed to evaluate the impact that this sudden cease had on rotavirus acute gastroenteritis (RAGE) hospitalizations. An increase in RAGE hospitalization was observed in parallel to the drop in vaccine coverage. Here, we report the first reverse evidence of rotavirus vaccine impact.
Kharchenko, Y; Lavrukova, S; Yurchenko, I; Movlyanova, N; Eremenko, S
The aim of the research was to develop the method for predicting the course of rotavirus gastroenteritis in children.Under the supervision were 3607 children aged from 9 days to 5 years with the diagnosis of "Acute gastroenteritis" and "Acute gastroenterocolitis". The diagnosis of rotavirus infection was on the basis of a set of clinical, epidemiological data and the results of para-clinical and bacteriological studies and data of detection of rotavirus antigen strain. Genotyping of rotavirus group A was performed by PCR 269 faecal samples. For rotavirus infection is characterized by the following clinical symptoms: intestinal disorders, symptoms of intoxication, signs of dehydration. Clinical manifestation of rotavirus infection is closely correlated with indicators of leukogram, erythrocyte sedimentation rate and the degree of metabolic acidosis. The presence of concomitant bacterial infection burden for rotavirus, but the presence of conditionally pathogenic flora practically did not influence on the clinical manifestation of the disease. The longest duration of diarrhea was observed in patients with rotavirus gastroenteritis was caused by a strain with genotype PCR they often occurred in children older than 2 years (t=3,4; p<0.01)). Special scheme has been developed for predicting the course of rotavirus gastroenteritis, including the availability of mix infection, to determine the severity of the pathological process a specially designed scale.
Manuel A. Franco
. In Clinical virology. D. D. Richman, F. G. Hayden and R. J. Whitley (Ed., pp. 743-762. Washington DC, ASM Press.
2. JAIMES, M. C., O. L. ROJAS, A. M. GONZALEZ, I. CAJIAO, A. CHARPILIENNE, P. POTHIER, E. KHOLI, H. B. GREENBERG, M. A. FRANCO AND J. ANGEL. Frequencies of virus specific cd4+ and cd8+ t lymphocytes secreting interferon gamma after acute natural rotavirus infection in children and adults. J Virology 2002; 76: 4741–4749.
3. ROJAS, O. L., A. M. GONZÁLEZ, R. GONZÁLEZ, I. PÉREZSCHAEL, H. B. GREENBERG, M. A. FRANCO AND J. ANGEL. Human rotavirus specific t cells: Quantification by elispot and expression of homing receptors on cd4+ t cells. Virology 2003; 314: 671–679.
4. GONZALEZ, A. M., M. C. JAIMES, I. CAJIAO, O. L. ROJAS, J. COHEN, P. POTHIER, E. KOHLI, E. C. BUTCHER, H. B. GREENBERG, J. ANGEL AND M. A. FRANCO. Rotavirusspecific B cells induced by recent infection in adults and children predominantly express the intestinal homing receptor alpha4beta7. Virology 2003; 305: 93-105.
Kapikian, A Z; Flores, J; Hoshino, Y; Midthun, K; Gorziglia, M; Green, K Y; Chanock, R M; Potash, L; Sears, S D; Clements, M L
Major advances have been made in elucidating the etiologic agents of severe infantile diarrhea, and it is clear that rotaviruses are the single most important etiologic agents. Progress in the development of rotavirus vaccine candidates has also moved swiftly with the "Jennerian" approach, in which a related live, attenuated rotavirus strain from a nonhuman host is used as the immunizing antigen. If this strategy is not effective against all rotavirus serotypes, reassortant rotaviruses hold great promise for the development of a multivalent vaccine. Field trials with the "Jennerian" approach vaccines are under way, and phase 1 trials with the reassortants have been initiated.
Full Text Available Positive associations have been found between reading and emotions. Various techniques, including traditional as well as modern, have been used to measure emotions in the previous studies. However, emotional measurement of the readers of a literary piece through HRV Biofeedback has never been investigated. A study was undertaken to assess whether Heart Rate Variability (HRV biofeedback regarding measurement of emotions in the readers of English Literature is likely to be effective or not for the first time at University Malaysia Pahang. In this study two scripts of the plays “Dr. Faustus” and “Waiting for Godot” were used. The Scripts were prepared from the Original Texts of these two plays, which might convey the overall message of the plays to the readers and resultantly produce the desired effect on the readers’ emotions. The total words of these two scripts were around 1050 each, allowing the students to complete one script in 7-8 minutes. Six subjects were selected randomly. While they were sitting calm and quiet at the desk, photoplethysmograph sensor was attached to their one of the earlobes which was connected to the emWave Desktop-PC software to record their Baseline HRV. The subjects, one at a time, read the Script 1 “Waiting for Godot” silently. After completion of the reading of Script 1, the emWave software was stopped and the HRV of the subject was recorded and saved automatically in the computer. The same process was repeated with Script 2 “Dr. Faustus”. In this way, emWave software recorded three HRV data for every subject. Results show obvious changes and significant correlations in the HRV of the participants while reading both the scripts. VLF increased for Script 1 while it decreased for Script 2. On the other hand, HF increased for Script 1 and further increased for Script 2. LF decreased for Script 1 and increased for Script 2. These results point out the tendency that the stress level of the
Ukae, S; Nakata, S; Adachi, N; Kogawa, K; Chiba, S
We conducted a clinical trial of rhesus rotavirus vaccine MMU-18006 (RRV, serotype 3) to assess the immunogenicity, transmissibility and booster effect of this vaccine in a welfare nursery in Sapporo, from September 1986 to October 1988. After the trial, in March 1989, an outbreak of gastroenteritis due to a wild strain of serotype 1 rotavirus (RV-1) occurred in the study population. Infants were divided into three groups based on vaccination history: five booster vaccinees, 18 one-dose vaccinees and 18 control infants who did not receive vaccine. There was a significant relationship between asymptomatic infection and higher levels of preoutbreak antibody titres against KU (serotype 1) but not RRV. Significant protection from rotavirus illness was observed both in the booster vaccine group and in the one-dose vaccine group but not in the control group. Rotavirus-specific serum IgA immune response was considered to be one of the indicators of recent rotavirus infection, and did not correlate with resistance to rotavirus illness. Our results revealed that protection from rotavirus illness was serotype-specific and that previous rotavirus infection, including vaccination, was important to induce the heterotypic immune response, and that ageing or booster inoculation of RRV might play a role in the protection against serotype 1 rotavirus infection. From our findings, a booster administration was thought to be important to induce effective heterotypic immunity and should be included in a future rotavirus vaccine trial to obtain sufficient protection against four major serotypes of rotavirus.
Boon, K H; Khalil-Hani, M; Malarvili, M B
This paper presents a method that able to predict the paroxysmal atrial fibrillation (PAF). The method uses shorter heart rate variability (HRV) signals when compared to existing methods, and achieves good prediction accuracy. PAF is a common cardiac arrhythmia that increases the health risk of a patient, and the development of an accurate predictor of the onset of PAF is clinical important because it increases the possibility to electrically stabilize and prevent the onset of atrial arrhythmias with different pacing techniques. We propose a multi-objective optimization algorithm based on the non-dominated sorting genetic algorithm III for optimizing the baseline PAF prediction system, that consists of the stages of pre-processing, HRV feature extraction, and support vector machine (SVM) model. The pre-processing stage comprises of heart rate correction, interpolation, and signal detrending. After that, time-domain, frequency-domain, non-linear HRV features are extracted from the pre-processed data in feature extraction stage. Then, these features are used as input to the SVM for predicting the PAF event. The proposed optimization algorithm is used to optimize the parameters and settings of various HRV feature extraction algorithms, select the best feature subsets, and tune the SVM parameters simultaneously for maximum prediction performance. The proposed method achieves an accuracy rate of 87.7%, which significantly outperforms most of the previous works. This accuracy rate is achieved even with the HRV signal length being reduced from the typical 30 min to just 5 min (a reduction of 83%). Furthermore, another significant result is the sensitivity rate, which is considered more important that other performance metrics in this paper, can be improved with the trade-off of lower specificity. Copyright © 2017 Elsevier B.V. All rights reserved.
Cassirame, Johan; Vanhaesebrouck, Romain; Chevrolat, Simon; Mourot, Laurent
Heart rate variability (HRV) analysis is widely used to investigate autonomous cardiac drive. This method requires periodogram measurement, which can be obtained by an electrocardiogram (ECG) or from a heart rate monitor (HRM), e.g. the Garmin 920 XT device. The purpose of this investigation was to assess the accuracy of RR time series measurements from a Garmin 920 XT HRM as compared to a standard ECG, and to verify whether the measurements thus obtained are suitable for HRV analysis. RR time series were collected simultaneously with an ECG (Powerlab system, AD Instruments, Castell Hill, Australia) and a Garmin XT 920 in 11 healthy subjects during three conditions, namely in the supine position, the standing position and during moderate exercise. In a first step, we compared RR time series obtained with both tools using the Bland and Altman method to obtain the limits of agreement in all three conditions. In a second step, we compared the results of HRV analysis between the ECG RR time series and Garmin 920 XT series. Results show that the accuracy of this system is in accordance with the literature in terms of the limits of agreement. In the supine position, bias was 0.01, - 2.24, + 2.26 ms; in the standing position, - 0.01, - 3.12, + 3.11 ms respectively, and during exercise, - 0.01, - 4.43 and + 4.40 ms. Regarding HRV analysis, we did not find any difference for HRV analysis in the supine position, but the standing and exercise conditions both showed small modifications.
Fernanda Dornelas Florentino Silva
Full Text Available Rotavirus is the causative pathogen of diarrhea in humans and in several animal species. Eight pairs of primers were developed and used for Sanger sequencing of the coding region of the NSP1, NSP3, and VP6 genes based on the conserved regions of the genome of the group A porcine rotavirus. Three samples previously screened as positive for group A rotaviruses were subjected to gene amplification and sequencing to characterize the pathogen. The information generated from this study is crucial for the understanding of the epidemiology of the disease.
Christopher C. Stobart
Full Text Available Human rhinovirus (HRV remains a leading cause of several human diseases including the common cold. Despite considerable research over the last 60 years, development of an effective vaccine to HRV has been viewed by many as unfeasible due, in part, to the antigenic diversity of circulating HRVs in nature. Over 150 antigenically distinct types of HRV are currently known which span three species: HRV A, HRV B, and HRV C. Early attempts to develop a rhinovirus vaccine have shown that inactivated HRV is capable of serving as a strong immunogen and inducing neutralizing antibodies. Yet, limitations to virus preparation and recovery, continued identification of antigenic variants of HRV, and logistical challenges pertaining to preparing a polyvalent preparation of the magnitude required for true efficacy against circulating rhinoviruses continue to prove a daunting challenge. In this review, we describe HRV biology, antigenic diversity, and past and present advances in HRV vaccine design.
Weinberg, Geoffrey A.; Teel, Elizabeth N.; Mijatovic-Rustempasic, Slavica; Payne, Daniel C.; Roy, Sunando; Foytich, Kimberly; Parashar, Umesh D.; Gentsch, Jon R.; Bowen, Michael D.
Surveillance for rotavirus-associated diarrhea after implementation of rotavirus vaccination can assess vaccine effectiveness and identify disease-associated genotypes. During active vaccine postlicensure surveillance in the United States, we found a novel rotavirus genotype, G14P, in a stool sample from a child who had diarrhea. Unusual rotavirus strains may become more prevalent after vaccine implementation.
Ianiro, G; Delogu, R; Bonomo, P; Castiglia, P; Ruggeri, F M; Fiore, L
In 2011, two children with acute rotavirus gastroenteritis were hospitalized in Sardinia, Italy. Two RVA strains with G8P genotype were detected in their stools, and were named SS56/2011 and SS65/2011. The aim of the study was to characterize these two rare strains, collected within a national RVA gastroenteritis surveillance program. Eight of the 11 RVA genes were sequenced and phylogenetic analysis performed. VP7 amino acid sequence was also analyzed. Sequencing of genes encoding the VP4, VP6, VP7, and NSP1-5 proteins classified both strains as G8-P-I2-A2-N2-T2-E2-H2, not detected previously in Italy. Phylogenetic analysis revealed that most genes of Italian RVA strains were closely similar to typical DS-1 like strains circulating worldwide, whereas the VP7 gene was strictly related to G8 strains firstly reported in Africa. This finding of G8P RVA strains with a DS-1 like genomic constellation also in a southern European country further confirms the wide circulation of this uncommon genotype in the world. Comparison of the deduced amino acid sequence of the VP7 capsid protein of the Italian G8P RVA strains with sequences reported previously suggests that the G8 genotype should be divided into three major lineages. Copyright © 2013 Elsevier B.V. All rights reserved.
I. V. Dukhovlinov
Full Text Available Rotavirus infection is among leading causes of severe diarrhea which often leads to severe dehydration, especially, in children under 5 years old. In Russia, the incidence of rotavirus infection is constantly increased, due to higher rates of actual rotavirus infection cases and improved diagnostics of the disease. Immunity to rotavirus is unstable, thus causing repeated infections intra vitam. Anti-infectious resistance in reconvalescents is explained by induction of specific IgM, IgG, and, notably, IgA antibodies. Due to absence of market drugs with direct action against rotavirus, a rational vaccination is considered the most effective way to control the disease. Currently available vaccines for prevention of rotavirus infection are based on live attenuated rotavirus strains, human and/or animal origin, which replicate in human gut. Their implementation may result into different complications. Meanwhile, usage of vaccines based on recombinant proteins is aimed to avoid risks associated with introduction of a complete virus into humans. In this paper, we studied protective activity of candidate vaccines against rotavirus.In this work we studied protective activity of a candidate vaccine against rotavirus infection based on recombinant FliCVP6VP8 protein which includes VP6 and VP8, as well as components of Salmonella typhimurium flagellin (FliC as an adjuvant. Different components are joined by flexible bridges. Efficiency of the candidate vaccine was studied in animal model using Balb/c mice. We have shown high level of protection which occurs when the candidate vaccine is administered twice intramuscularly. Complete protection of animals against mouse rotavirus EDC after intramuscular immunization with a candidate vaccine was associated with arising rotavirus-specific IgA and IgG antibodies in serum and intestine of immunized animals. The efficacy of candidate vaccine based on recombinant protein FliCVP6VP8 against rotavirus infection was
Jia, Lianzhi; Li, Tingdong; Ge, Shengxiang
Rotaviruses are leading causes of worldwide acute diarrhea in children younger than 5 years old, with severe consequence of social and economic burden. Vaccination is the most effective way to control rotavirus infection, however, the licensed rotavirus vaccines are ineffective in some low-income countries of Africa and Asia, where the mortality caused by rotavirus is higher than other areas. In addition, there are also safety concerns such as increased risk of intussusception. Therefore, it is urgent to improve the efficiency and safety of rotavirus vaccine to reduce the morbidity and mortality caused by rotavirus. Till now, many efforts are made to improve the effectiveness of rotavirus vaccines, and the inactive vaccine becomes the main trend in the research of rotavirus vaccine. The developments in recombinant rotavirus vaccines, especially in VP4 subunit vaccines are summarized in this review, and it could be helpful to develop effective recombinant rotavirus vaccines in further studies.
The New England journal of medicine.2006;354:23-33. 6. Patel M, Pedreira C, De Oliveira LH, Tate J, Orozco M, Mercado J, et al. Association between pentavalent rotavirus vaccine and severe rotavirus diarrhoea among children in Nicaragua. Jama.2009;301:2243-2251. 7. Moon SS, Wang Y, Shane AL, Nguyen T, Ray P, ...
Jul 10, 2017 ... were inoculated with 1 X 106 cfu/ml of Salmonella pullorum, group C chicks were inoculated with 1 X 106 pfu/ml of rotavirus and ... Significant growth retardation was observed in chicks given either rotavirus or Salmonella pullorum, but this effect was more ... feed and water were provided ad libitum. All the.
EPIDEMIOLOGY OF ROTAVIRUS AND ASTROVIRUS INFECTIONS IN CHILDREN IN NORTHWESTERN NIGERIA. M Aminu, MD Esona, A Geyer, AD Steele. Abstract. Background: Recent estimates attribute 527 000 deaths in children less than five years of age to rotavirus diarrhea annually, with 145 000 occurring in ...
Jeremy D Driskell
Full Text Available Human enteric virus infections range from gastroenteritis to life threatening diseases such as myocarditis and aseptic meningitis. Rotavirus is one of the most common enteric agents and mortality associated with infection can be very significant in developing countries. Most enteric viruses produce diseases that are not distinct from other pathogens, and current diagnostics is limited in breadth and sensitivity required to advance virus detection schemes for disease intervention strategies. A spectroscopic assay based on surface enhanced Raman scattering (SERS has been developed for rapid and sensitive detection of rotavirus. The SERS method relies on the fabrication of silver nanorod array substrates that are extremely SERS-active allowing for direct structural characterization of viruses. SERS spectra for eight rotavirus strains were analyzed to qualitatively identify rotaviruses and to classify each according to G and P genotype and strain with >96% accuracy, and a quantitative model based on partial least squares regression analysis was evaluated. This novel SERS-based virus detection method shows that SERS can be used to identify spectral fingerprints of human rotaviruses, and suggests that this detection method can be used for pathogen detection central to human health care.
Flem, Elmira T; Kasymbekova, Kaliya T; Vainio, Kirsti; Gentsch, Jon; Abdikarimov, Sabirjan T; Glass, Roger I; Bresee, Joseph S
To estimate the rotavirus-associated burden in Kyrgyzstan, we conducted hospital surveillance among children Kyrgyzstan may be attributable to rotavirus. Rotavirus vaccination could be an important health intervention to reduce the burden of rotavirus gastroenteritis.
McAtee, Casey L.; Webman, Rachel; Gilman, Robert H.; Mejia, Carolina; Bern, Caryn; Apaza, Sonia; Espetia, Susan; Pajuelo, Mónica; Saito, Mayuko; Challappa, Roxanna; Soria, Richard; Ribera, Jose P.; Lozano, Daniel; Torrico, Faustino
The effectiveness of rotavirus vaccine in the field may set the stage for a changing landscape of diarrheal illness affecting children worldwide. Norovirus and rotavirus are the two major viral enteropathogens of childhood. This study describes the prevalence of norovirus and rotavirus 2 years after widespread rotavirus vaccination in Cochabamba, Bolivia. Stool samples from hospitalized children with acute gastroenteritis (AGE) and outpatients aged 5–24 months without AGE were recruited from an urban hospital serving Bolivia's third largest city. Both viruses were genotyped, and norovirus GII.4 was further sequenced. Norovirus was found much more frequently than rotavirus. Norovirus was detected in 69/201 (34.3%) of specimens from children with AGE and 13/71 (18.3%) of those without diarrhea. Rotavirus was detected in 38/201 (18.9%) of diarrheal specimens and 3/71 (4.2%) of non-diarrheal specimens. Norovirus GII was identified in 97.8% of norovirus-positive samples; GII.4 was the most common genotype (71.4% of typed specimens). Rotavirus G3P was the most prevalent rotavirus genotype (44.0% of typed specimens) and G2P was second most prevalent (16.0% of typed specimens). This community is likely part of a trend toward norovirus predominance over rotavirus in children after widespread vaccination against rotavirus. PMID:26598569
McAtee, Casey L; Webman, Rachel; Gilman, Robert H; Mejia, Carolina; Bern, Caryn; Apaza, Sonia; Espetia, Susan; Pajuelo, Mónica; Saito, Mayuko; Challappa, Roxanna; Soria, Richard; Ribera, Jose P; Lozano, Daniel; Torrico, Faustino
The effectiveness of rotavirus vaccine in the field may set the stage for a changing landscape of diarrheal illness affecting children worldwide. Norovirus and rotavirus are the two major viral enteropathogens of childhood. This study describes the prevalence of norovirus and rotavirus 2 years after widespread rotavirus vaccination in Cochabamba, Bolivia. Stool samples from hospitalized children with acute gastroenteritis (AGE) and outpatients aged 5-24 months without AGE were recruited from an urban hospital serving Bolivia's third largest city. Both viruses were genotyped, and norovirus GII.4 was further sequenced. Norovirus was found much more frequently than rotavirus. Norovirus was detected in 69/201 (34.3%) of specimens from children with AGE and 13/71 (18.3%) of those without diarrhea. Rotavirus was detected in 38/201 (18.9%) of diarrheal specimens and 3/71 (4.2%) of non-diarrheal specimens. Norovirus GII was identified in 97.8% of norovirus-positive samples; GII.4 was the most common genotype (71.4% of typed specimens). Rotavirus G3P was the most prevalent rotavirus genotype (44.0% of typed specimens) and G2P was second most prevalent (16.0% of typed specimens). This community is likely part of a trend toward norovirus predominance over rotavirus in children after widespread vaccination against rotavirus. © The American Society of Tropical Medicine and Hygiene.
Feng, N; Burns, J W; Bracy, L; Greenberg, H B
Rotaviruses are the single most important cause of severe diarrhea in young children worldwide, and vaccination is probably the most effective way to control the disease. Most current live virus vaccine candidates are based on the host range-restricted attenuation of heterologous animal rotaviruses in humans. The protective efficacy of these vaccine candidates has been variable. To better understand the nature of the heterologous rotavirus-induced active immune response, we compared the differences in the mucosal and systemic immune responses generated by heterologous (nonmurine) and homologous (murine) rotaviruses as well as the ability of these infections to produce subsequent protective immunity in a mouse model. Sucking mice were orally inoculated with a heterologous simian or bovine rotavirus (strain RRV or NCDV) or a homologous murine rotavirus (wild-type or tissue culture-adapted) strain EHP at various doses. Six weeks later, mice were challenged with a virulent murine rotavirus (wild-type strain ECW) and the shedding of viral antigen in feces was quantitated. Levels of rotavirus-specific serum immunoglobulin G (IgG) and fecal IgA prior to challenge were measured and correlated with subsequent viral shedding or protection. Heterologous rotavirus-induced active protection was highly dependent on the strain and dose of the virus tested. Mice inoculated with a high dose (10(7) PFU per mouse) of RRV were completely protected, while the protection was diminished in animals inoculated with NCDV or lower doses of RRV. The ability of a heterologous rotavirus to stimulate a detectable intestinal IgA response correlated with the ability of the virus to generate protective immunity. Serum IgG titer did not correlate with protection. Homologous rotavirus infection, on the other hand, was much more efficient at inducing both mucosal and systemic immune responses as well as protection regardless of the virulence of the virus strain or the size of the immunizing dose.
Full Text Available Group A rotaviruses are the most significant cause of acute gastroenteritis in children worldwide. Rotaviruses are shed in high numbers and dispersed widely throughout bodies of water in the environment. This represents a significant health hazard for humans, mainly due to the stability of the viruses during wastewater treatment processes. This study was conducted to evaluate the prevalence of rotaviruses, to determine G genotypes of circulating rotaviruses and to assess the efficiency of rotavirus removal in urban and hospital sewage treatment plants in Shiraz, Iran.Materials and methods: During the period from October 2010 to June 2011, a total of sixty sewage samples from urban and hospital sewage disposal systems were collected by Grab Sampling in Shiraz, Iran. All the samples were concentrated in pellet form and two-phase methods and then group A rotaviruses were investigated with enzyme immunoassays (EIA. Rotavirus-positive specimens were genotyped by the nested RT-PCR and by using different types of specific primers.Results:In total, rotaviruses were identified in 25% (15 cases of sewage samples, representing 73.33% (11 cases of influent and 26.67% (4 cases of effluent systems. The frequency of rotavirus detection in autumn, winter and spring was 46.67%, 33.33% and 20%, respectively (P= 0.004. The most common circulating genotype was G1 (73.33%, followed by G1G4 (20% and non-typeable (6.67%, respectively.Conclusions:The high prevalence of rotaviruses in urban and hospital sewage systems highlights the importance of environmental surveillance as a tool to detect new genotypes and to investigate the epidemiology of rotaviruses circulating in the community.
Zeller, Mark; Donato, Celeste; Trovão, Nídia Sequeira; Cowley, Daniel; Heylen, Elisabeth; Donker, Nicole C; McAllen, John K; Akopov, Asmik; Kirkness, Ewen F; Lemey, Philippe; Van Ranst, Marc; Matthijnssens, Jelle; Kirkwood, Carl D
Rotaviruses are the most important etiological agent of acute gastroenteritis in young children worldwide. Among the first countries to introduce rotavirus vaccines into their national immunization programs were Belgium (November 2006) and Australia (July 2007). Surveillance programs in Belgium (since 1999) and Australia (since 1989) offer the opportunity to perform a detailed comparison of rotavirus strains circulating pre- and postvaccine introduction. G1P rotaviruses are the most prominent genotype in humans, and a total of 157 G1P rotaviruses isolated between 1999 and 2011 were selected from Belgium and Australia and their complete genomes were sequenced. Phylogenetic analysis showed evidence of frequent reassortment among Belgian and Australian G1P rotaviruses. Although many different phylogenetic subclusters were present before and after vaccine introduction, some unique clusters were only identified after vaccine introduction, which could be due to natural fluctuation or the first signs of vaccine-driven evolution. The times to the most recent common ancestors for the Belgian and Australian G1P rotaviruses ranged from 1846 to 1955 depending on the gene segment, with VP7 and NSP4 resulting in the most recent estimates. We found no evidence that rotavirus population size was affected after vaccine introduction and only six amino acid sites in VP2, VP3, VP7, and NSP1 were identified to be under positive selective pressure. Continued surveillance of G1P strains is needed to determine long-term effects of vaccine introductions, particularly now rotavirus vaccines are implemented in the national immunization programs of an increasing number of countries worldwide. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
Zeller, Mark; Donato, Celeste; Trovão, Nídia Sequeira; Cowley, Daniel; Heylen, Elisabeth; Donker, Nicole C.; McAllen, John K.; Akopov, Asmik; Kirkness, Ewen F.; Lemey, Philippe; Van Ranst, Marc; Matthijnssens, Jelle; Kirkwood, Carl D.
Rotaviruses are the most important etiological agent of acute gastroenteritis in young children worldwide. Among the first countries to introduce rotavirus vaccines into their national immunization programs were Belgium (November 2006) and Australia (July 2007). Surveillance programs in Belgium (since 1999) and Australia (since 1989) offer the opportunity to perform a detailed comparison of rotavirus strains circulating pre- and postvaccine introduction. G1P rotaviruses are the most prominent genotype in humans, and a total of 157 G1P rotaviruses isolated between 1999 and 2011 were selected from Belgium and Australia and their complete genomes were sequenced. Phylogenetic analysis showed evidence of frequent reassortment among Belgian and Australian G1P rotaviruses. Although many different phylogenetic subclusters were present before and after vaccine introduction, some unique clusters were only identified after vaccine introduction, which could be due to natural fluctuation or the first signs of vaccine-driven evolution. The times to the most recent common ancestors for the Belgian and Australian G1P rotaviruses ranged from 1846 to 1955 depending on the gene segment, with VP7 and NSP4 resulting in the most recent estimates. We found no evidence that rotavirus population size was affected after vaccine introduction and only six amino acid sites in VP2, VP3, VP7, and NSP1 were identified to be under positive selective pressure. Continued surveillance of G1P strains is needed to determine long-term effects of vaccine introductions, particularly now rotavirus vaccines are implemented in the national immunization programs of an increasing number of countries worldwide. PMID:26254487
Dang, Duc Anh; Nguyen, Van Trang; Vu, Dinh Thiem; Nguyen, Thi Hien Anh; Nguyen, Duc Mao; Yuhuan, Wang; Baoming, Jiang; Nguyen, Dang Hien; Le, Thi Luan
We tested a candidate live, oral, rotavirus vaccine (Rotavin-M1™) derived from an attenuated G1P  strain (KH0118-2003) isolated from a child in Vietnam. The vaccine was tested first for safety in 29 healthy adults. When deemed safe, it was further tested for safety and immunogenicity in 160 infants (4 groups) aged 6-12 weeks in a dose and schedule ranging study. The vaccine was administered in low titer (10(6.0)FFU/dose) on a 2-dose schedule given 2 months apart (Group 2L) and on a 3-dose schedule given 1 month apart (Group 3L) and in high titer (10(6.3)FFU/dose) in 2 doses 2 months apart (Group 2H) and in 3 doses 1 month apart (Group 3H). For comparison, 40 children (group Rotarix™) were given 2 doses of the lyophilized Rotarix™ vaccine (10(6.5)CCID(50)/dose) 1 month apart. All infants were followed for 30 days after each dose for clinical adverse events including diarrhea, vomiting, fever, abdominal pain, irritability and intussusception. Immunogenicity was assessed by IgA seroconversion and viral shedding was monitored for 7 days after administration of each dose. Two doses of Rotavin-M1 (10(6.3)FFU/dose) were well tolerated in adults. Among infants (average 8 weeks of age at enrollment), administration of Rotavin-M1 was safe and did not lead to an increased rate of fever, diarrhea, vomiting or irritability compared to Rotarix™, indicating that the candidate vaccine virus had been fully attenuated by serial passages. No elevation of levels of serum transaminase, blood urea, or blood cell counts were observed. The highest rotavirus IgA seroconversion rate (73%, 95%CI (58-88%)) was achieved in group 2H (2 doses--10(6.3)FFU/dose, 2 months apart). The 2 dose schedules performed slightly better than the 3 dose schedules and the higher titer doses performed slightly better than the lower titer doses. These rates of seroconversion were similar to that of the Rotarix™ group (58%, 95%CI (42-73%)). However more infants who received Rotarix™ (65%) shed virus
Kaufhold, Robin M; Field, Jodie A; Caulfield, Michael J; Wang, Su; Joseph, Heather; Wooters, Melissa A; Green, Tina; Clark, H Fred; Krah, David; Smith, Jeffrey G
Measurements of serum-neutralizing antibody and anti-rotavirus immunoglobulin A (IgA) are the current standard for assessing immune responses following rotavirus vaccination. However, there is ongoing debate as to whether antibody titers correlate with protection against rotavirus gastroenteritis. Children recovering from rotavirus gastroenteritis have increased gamma interferon release from cultured peripheral blood mononuclear cells (PBMCs), suggesting that cell-mediated immunity (CMI) may play a role in viral clearance and protection from subsequent gastroenteritis. We have developed a gamma interferon enzyme-linked immunospot (ELISPOT) assay for evaluation of CMI responses to rotavirus using frozen PBMCs obtained from healthy adults. Responses to three different rotavirus antigen types were analyzed-a peptide pool based on the human VP6 sequence; reassortant human:bovine vaccine strains; and cell culture-adapted (CCA) human G1, G2, G3, G4, and bovine (WC3) G6 strains. The reassortant strains consist of a bovine WC3 genome background expressing the human rotavirus surface proteins VP7 (G1, G2, G3, or G4) or VP4 (P1). Responses to titrations of the peptide pool as well as CCA and reassortant strains were assessed. Gamma interferon ELISPOT responses were similar for CCA and reassortant strains, whether live or UV inactivated, and when tested either individually or pooled. For most subjects, responses to the VP6 peptide pool positively correlated with responses to CCA and reassortant strains. Cell depletion studies indicate the memory responses detected with these frozen adult PBMCs were primarily due to the CD4+ T-cell population. This gamma interferon ELISPOT assay provides a new tool to apply in clinical studies for the characterization of natural or vaccine-induced CMI to rotavirus.
Jere, Khuzwayo Chidiwa
Despite the global licensure of two live-attenuated rotavirus vaccines, Rotarix® and RotaTeq®, rotavirus remains the major cause of severe dehydrating diarrhoea in young mammals and the need for further development of additional rotavirus vaccines, especially vaccines effective against regional strains in developing country settings, is increasing. The design and formulation of new effective multivalent rotavirus vaccines is complicated by the wide rotavirus strain diversity. N...
Coulson, B S
Rotavirus-neutralizing antibody responses in sera and stools of children hospitalized with rotavirus gastroenteritis and then monitored longitudinally were optimally detected by using local rotavirus strains. Stool responses were highest on days 5 to 8 after the onset of diarrhea. Longitudinal monitoring suggested that serum neutralizing antibody responses were a more useful measure of severely symptomatic rotavirus infection than stool responses but that stool antibody responses may be a useful measure of rotavirus immunity.
Full Text Available Purpose: The aim of the research was the evaluation of the selected HRV factors of the training volleyball players in two training periods and non-training people. Materials and methods : The study involved 8 leading volleyball players aged 20-23 and 13 non-training persons aged 19-26. The study of the training players was conducted twice: in the pre-competition and in the competition period. The study for the non-training persons was conducted once. The selected factors of the spectral analysis have been evaluated: TP [ms 2], share of LF and HF power [n.u], LF/HF indicator and time analysis factors: RR [ms], HR [1/min], RMSSD [ms]. Results : Statistically significant differences appeared only in the selected time analysis factors (RR, HR, between the group of the training and non-training persons. Other differences in the evaluated parameters were not statistically significant. Conclusions : Physical activity influences on the HRV growth. HRV measurement may serve for the control of the changes taking place in the AUN under the influence of the physical activity.
Cilla, G; Montes, M; Gomariz, M; Alkorta, M; Iturzaeta, A; Perez-Yarza, E G; Perez-Trallero, E
Between July 2009 and June 2011, rotavirus was detected in 507 of 4597 episodes of acute gastroenteritis in children aged G-type was determined in 458 (90·3%). During the annual seasonal epidemic of 2010-2011, the unusual G-type 12 was predominant, causing 65% (145/223) of cases of rotavirus gastroenteritis. All the G12 strains were clustered in lineage III and were preferentially associated with P-type 8. This epidemic was characterized by broad geographical distribution (rural and urban) and, over 7 months, affected both infants and children, the most frequently affected being children between 4 and 24 months. Of children with rotavirus G12, 16% required hospital admission, the admission rate in children aged G12 rotaviruses documented in this winter outbreak suggest that they may soon become a major human rotavirus genotype.
Yeom, Jung Sook; Kim, Young-Soo; Kim, Rock Bum; Park, Ji Sook; Seo, Ji-Hyun; Park, Eunsil; Lim, Jae-Young; Park, Chan-Hoo; Woo, Hyang-Ok; Youn, Hee-Shang
To determine whether clinical features of rotavirus-associated seizures have been altered by rotavirus vaccination, we compared clinical and laboratory data of 2 groups of patients with rotavirus-associated seizures: pre- and post-vaccine introduction groups. The seizure characteristics differed significantly between the groups, with a lower incidence of fever at seizure onset, longer interval between the onset of gastroenteritis and seizures, and more frequent seizures in the postintroduction group. These characteristics may suggest that seizure susceptibility was increased in the postintroduction group. Based on the lower serum Cl(-) (102.1 ± 4.1 vs 98.2 ± 3.2 mg/dL; P rotavirus enterotoxin may have played a role in increasing the seizure susceptibility in this group. Our results suggest that a rotavirus vaccination program may modulate the manifestations of rotavirus-associated seizures. © The Author(s) 2014.
Inchauste, Lucia; Patzi, Maritza; Halvorsen, Kjetil; Solano, Susana; Montesano, Raul; Iñiguez, Volga
The public health impact of rotavirus vaccination in countries with high child mortality rates remains to be established. The RV1 rotavirus vaccine was introduced in Bolivia in August 2008. This study describes the trends in deaths, hospitalizations, and healthcare visits due to acute gastroenteritis (AGE) and in rotavirus-related hospitalizations, among children Bolivia, as a measure for protecting children against AGE. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Malik, Jyoti; Bhan, Maharaj K; Ray, Pratima
Annual deaths in infants and young children due to rotavirus (RV) infection are around 100,000 in India and about 600,000 globally. Development of a vaccine for this disease is a high priority. The protective mechanisms for RV diarrhea in human are not fully understood, but it is known that children develop natural immunity against RV. Early exposure to RV results in most severe episode of diarrhea and subsequent infections are milder or asymptomatic. Of the immune responses measured during natural infection, RV-specific antibodies have been well documented, whereas data on cellular immunity in humans are sparse. It is generally thought that two outer capsid proteins VP4 and VP7 play a critical role in protective immunity by stimulating production of neutralizing antibodies. While serotype- specific protection mediated by antibodies directed against the outer capsid proteins may be a mechanism of protection, such a correlate for protection has been difficult to demonstrate in humans during clinical trials. Increasing evidences suggest that viral proteins that lack a capacity of eliciting neutralizing antibody response also induce protective immunity. Limited efforts have focused on the role of non-structural proteins in protective immunity. This review describes current understanding of antibody responses in children with focus on responses specific to viral antigens with their possible role in protective immunity. We have also briefly reviewed the responses elicited to non-antibody effectors during RV infection in human subjects.
Wang, Yuan-Hong; Pang, Bei-Bei; Zhou, Xuan; Ghosh, Souvik; Tang, Wei-Feng; Peng, Jin-Song; Hu, Quan; Zhou, Dun-Jin; Kobayashi, Nobumichi
The group A rotavirus (RVA) G3P is a rare VP7-VP4 genotype combination, detected occasionally in humans and cats. Other than the prototype G3P strain, RVA/Human- tc/JPN/AU-l/1982/G3P3, the whole genomes of only two human G3P RVA strains and two feline G3P RVA strains have been analyzed so far, revealing complex evolutionary patterns, distinct from that of AU-1. We report here the whole genomic analyses of two human G3P RVA strains, RVA/Human-tc/CHN/L621/2006/G3P and RVA/Human-wt/CHN/E2451/2011/G3P, detected in patients with diarrhea in China. Strains L621 and E2451 possessed a H6 NSP5 genotype on an AU-1-like genotype constellation, not reported previously. However, not all the genes of L621 and E2451 were closely related to those of AU-1, or to each other, revealing different evolutionary patterns among the AU-1-like RVAs. The VP7, VP4, VP6 and NSP4 genes of E2451 and L621 were found to cluster together with human G3P RVA strains believed to be of possible feline/canine origin, and feline or raccoon dog RVA strains. The VP1, VP3, NSP2 and NSP5 genes of E2451 and L621 formed distinct clusters in genotypes typically found in feline/canine RVA strains or RVA strains from other host species which are believed to be of feline/canine RVA origin. The VP2 genes of E2451 and L621, and NSP3 gene of L621 clustered among RVA strains from different host species which are believed to have a complete or partial feline/canine RVA origin. The NSP1 genes of E2451 and L621, and NSP3 gene of E2451 clustered with AU-1 and several other strains possessing a complete or partial feline RVA strain BA222-05-like genotype constellation. Taken together, these observations suggest that nearly all the eleven gene segments of G3P RVA strains L621 and E2451 might have originated from feline/canine RVAs, and that reassortments may have occurred among these feline/canine RVA strains, before being transmitted to humans. Copyright © 2013 Elsevier B.V. All rights
María Mercedes Martínez
Full Text Available Rotavirus presence in a waste composting process. Organic fertilizers as vehicles for viral contamination. Objective. To show thepresence of rotavirus in different stages of a composting process: matrices used as raw material, mixture to be composted and the finalproduct. Materials and methods. Immunochromatography, ELISA and RT-PCR were used for viral detection. Results. Rotavirus wasfound in the first composting step, no virus was found in the second step, and some inhibitory substances were found in the third step thatposed difficulties in interpreting the PCR results and therefore providing a concluding result on rotavirus presence in the final product.Conclusions. Organic fertilizers can be vectors of human pathogenic viruses; therefore quality control tests must be implemented to avoidfurther viral dissemination. There are inhibitory substances present in organic fertilizers capable of interfering with the detection tests.
Coria-Galindo, Elsa; Rangel-Huerta, Emma; Verdugo-Rodríguez, Antonio; Brousset, Dulce; Salazar, Sandie; Padilla-Noriega, Luis
Group A rotaviruses infect and cause diarrhea in the young of a broad range of terrestrial mammals, but it is unknown, to our knowledge, whether they infect marine mammals. During February and March of 2002 and 2003, we collected 125 serum samples and 18 rectal swab samples from Galapagos sea lion pups (GSL, Zalophus wollebaeki), and 22 serum samples from Galapagos fur seal pups (GFS, Arctocephalus galapagoensis) from nine islands of the Galapagos archipelago, Ecuador. Sera were tested for antibodies (immunoglobulin G [IgG]) to rotavirus by an enzyme immunoassay using rhesus rotavirus as the capture antigen. In addition, rectal swabs were analyzed for the presence of rotavirus genomic double-stranded RNA by silver-stained polyacrylamide gel electrophoresis. Antibodies to rotavirus were detected in 27 GSL pups (22%) and five GFS pups (23%), and rotavirus RNA was detected in the fecal sample from one GSL pup (6%). These results provide the first evidence that rotavirus infections are prevalent at an early age in Galapagos sea lions and Galapagos fur seals.
conclusions After the vaccine introduction in Slovenia in 2007, no specific changes in molecular epidemiology of rotaviruses was observed. This finding was expected since rotavirus vaccine coverage in 2007 in Slovenia was very low. Genotype G1P remains the most prevalent genotype. The rotavirus strain surveillance in Slovenia should be carried on to allow monitoring the spread of some unusual rotavirus genotypes, like G10. The G10 strains should be tracked especially in vaccinated children as no data on vaccine efficiency against infection with G10 strains was presented till now.
Albright, Catherine J.; Hall, David J.
Human rhinovirus (HRV) is one of the most common human respiratory pathogens and is responsible for the majority of upper respiratory illnesses. Recently, a phylogeny was constructed from all known American Type Culture Collection (ATCC) HRV sequences. From this study, three HRV classifications (HRVA, HRVB, and HRVC) were determined and techniques…
Feng, N; Franco, M A; Greenberg, H B
The murine model of homologous rotavirus infection has been used to study the determinants of protection. The local IgA immune response appears to be the critical factor in generating protective immunity after natural infection. A series of knockout mice were used to evaluate the contribution of T cells and B cells to immunity and resolution from primary infection. Both arms of immune system played a role in the resolution of primary infection but antibody was much more important for prevention of reinfection.
Mita, Valentin; Capanna, Alessandra; Gervasi, Giuseppe; Zaratti, Laura; Franco, Elisabetta
Rotaviruses are the most common etiological cause for pediatric acute gastroenteritis, particularly in children under 5 years of age or immunocompromised. Since 2008, vaccination program has determined a decrease in Rotavirus-related hospitalization, outpatient's visits, emergency department visits and mortality. These indicators of illness for Rotaviruses diseases remain high in those countries where there is no access to rehydrating therapies. In Italy vaccine coverage is very low, even if the burden of RV disease is well known, and at present vaccination is offered free of charge in a single region.
Deng, Li; Jia, Li-ying; Qian, Yuan; Chen, Dong-mei; Zhang, You; Zhang, Yan-ling
To compare the clinical manifestations of gastroenteritis caused by norovirus and rotavirus in infants and young children in Beijing. Stool specimens were collected from infants and young children with acute diarrhea who visited the Affiliated Children's Hospital to Capital Institute of Pediatrics from January 2002 to December 2006. Registration form was designed for clinical data collection for each patient from whom specimen was collected. Poly-acrylamide gel electrophoresis (PAGE) and enzyme immunoassay (EIA) were used to detect rotavirus and Human norovirus, respectively. Among 779 stool specimens tested for rotavirus, 263 were positive (33.8%), and norovirus positive specimens were 79 out of 318 (24.8%) specimens tested. Most of the clinical manifestations of gastroenteritis caused by these two viruses were quite similar with no significant difference, except for fever. The seasonal distribution of these two viruses were different with the peak of rotavirus infection was in cold weather between October and January, as indicated by the peak of the positive rates of the virus detection. The infection of norovirus seemed no obvious peak in the year. Rotavirus is the most important pathogen for acute diarrhea among infants and young children while. Norovirus is also an important pathogen for acute gastroenteritis in infants and young children. No significant difference was found out for clinical manifestations for the gastroenteritis caused by these two viruses.
Rivera, Rosario; Forney, Kristen; Castro, Maria René; Rebolledo, Paulina A.; Mamani, Nataniel; Patzi, Maritza; Halkyer, Percy; Leon, Juan S.; Iñiguez, Volga
Summary Objectives Rotavirus is the most important etiology of severe diarrhea in Bolivia. The monovalent attenuated human oral rotavirus vaccine Rotarix® was introduced in Bolivia in 2008. We describe the molecular epidemiology of circulating rotavirus strains before vaccine introduction. Methods Two thousand one hundred thirty-five diarrheal samples were collected from hospitals in four Bolivian cities during 2007–2008. Forty-three percent (445 of 1030 rotavirus-positive samples) were analyzed for G and P genotypes. Among those, 331 were electropherotyped by polyacrylamide gel electrophoresis. Disease severity was quantified using a modified Vesikari scale. Results Among the 445 samples, five genotypes were found to be prevalent: G9P (33%), G1P (17%), G2P (13%), G9P (12%), and G1P (4%). Co-infections with two or more strains accounted for 14% of samples. The most prevalent strain, G9, showed greater electropherotype diversity compared to other serogroups. Strain G1P generally infected younger children and peaked later in the year than other strains. No particular genotype was associated with a higher severity score, though there was a significant difference in the duration of diarrhea between genotypes. Conclusions During the 2-year pre-vaccine period, substantial diversity of rotavirus co-circulating strains was observed. These data constitute a baseline against which changes in circulating strains post-vaccine introduction can be monitored. PMID:23688547
Rivera, Rosario; Forney, Kristen; Castro, Maria René; Rebolledo, Paulina A; Mamani, Nataniel; Patzi, Maritza; Halkyer, Percy; Leon, Juan S; Iñiguez, Volga
Rotavirus is the most important etiology of severe diarrhea in Bolivia. The monovalent attenuated human oral rotavirus vaccine Rotarix(®) was introduced in Bolivia in 2008. We describe the molecular epidemiology of circulating rotavirus strains before vaccine introduction. Two thousand one hundred thirty-five diarrheal samples were collected from hospitals in four Bolivian cities during 2007-2008. Forty-three percent (445 of 1030 rotavirus-positive samples) were analyzed for G and P genotypes. Among those, 331 were electropherotyped by polyacrylamide gel electrophoresis. Disease severity was quantified using a modified Vesikari scale. Among the 445 samples, five genotypes were found to be prevalent: G9P (33%), G1P (17%), G2P (13%), G9P (12%), and G1P (4%). Co-infections with two or more strains accounted for 14% of samples. The most prevalent strain, G9, showed greater electropherotype diversity compared to other serogroups. Strain G1P generally infected younger children and peaked later in the year than other strains. No particular genotype was associated with a higher severity score, though there was a significant difference in the duration of diarrhea between genotypes. During the 2-year pre-vaccine period, substantial diversity of rotavirus co-circulating strains was observed. These data constitute a baseline against which changes in circulating strains post-vaccine introduction can be monitored. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Zeng, Sai-Zhen; Xiao, Ni-Guang; Xie, Zhi-Ping; Xie, Guang-Cheng; Zhong, Li-Li; Wang, Juan; Huang, Han; Zhang, Bing; Duan, Zhao-Jun
Human rhinovirus (HRV) is a causative agent of acute respiratory tract infections. This study analyzed the prevalence and clinical characteristics of three HRV groups (HRV-A, -B, and -C) among 1,165 children aged 14 years or younger who were hospitalized with acute lower respiratory tract infection in China. PCR or reverse transcription-PCR was performed to detect 14 respiratory viruses in nasopharyngeal aspirates collected from September 2007 to August 2008 in Changsha, China. HRV was detected in 202 (17.3%) of the 1,165 children; 25.3% of the HRV-positive children were 13-36 months of age (χ(2) = 22.803, P = 0.000). HRV was detected year round and peaked between September and December. Fifty-three percent of the HRV-positive samples were also positive for other respiratory viruses; respiratory syncytial virus (RSV) was the most common secondary virus. Phylogenetic analysis using the VP4/VP2 region grouped the HRV-positive strains as follows: 101 HRV-A (50.0%), 21 HRV-B (10.4%), and 80 HRV-C (39.6%). HRV-A infections occurred predominantly in spring and autumn, and the peak prevalence of HRV-C was in early winter and late autumn. HRV-B infections were less common in spring (χ(2) = 31.914, P = 0.000). No significant difference in clinical severity or presentation was found between patients with HRV single infection and HRV co-detections. Furthermore, the clinical characterizations did not differ among the three HRV species. These results suggest that HRV-C is an important viral agent along with HRV-A and HRV-B and that among hospitalized children with acute lower respiratory tract infection in China, the three HRV genotypes have similar clinical characteristics. © 2014 Wiley Periodicals, Inc.
Gamazo, Pablo; Schijven, Jack; Victoria, Matias; Alvareda, Elena; López Tort, Fernando; Ramos, Julián; Lizasoain, Andrés; Sapriza, Gonzalo; Castells, Matias; Colina, Rodney
In Uruguay, as in many developed and developing countries, rotavirus and norovirus are major causes of diarrhea and others symptoms of acute gastroenteritis. In some areas of Uruguay, groundwater is the only source of water for human consumption. In the rural area of the Salto district, virus contamination has been detected in several groundwater wells. Because sewer coverage is low, the most probable sources of contamination are nearby septic systems. This work aims to evaluate the transport of rotavirus and norovirus from clinic samples in two sets of column experiments under saturated conditions: 6.7-cm columns with quartz sand (ionic strength 1mM, pH 7.0) and with sand from the Salto aquifer (Uruguay) (9,2% coarse sand, 47,8% medium sand, 40,5% fine sand, magnesium/calcium bicarbonate water, Ionic strength 15.1 mM, pH 7.2). Both viruses were seeded for 2 pore volumes onto the columns. Samples were collected at the column outlet and viruses were enumerated by Q-PRCR. Breakthrough curves were constructed and fitted to a two-site kinetic attachment/detachment model, including blocking using Hydrus-1D. In the quartz sand column, both rotavirus and norovirus were removed two orders in magnitude. In the Salto sand column, rotavirus was removed 2 log10 as well, but norovirus was removed 4 log10. The fitting of the breakthrough curves indicated that blocking played a role for rotavirus in the Salto sand column. These results are consistent with the field observation where only rotavirus was detected in the Salto aquifer, while similar concentrations in Salto sewer effluent were measured for both viruses. This work, besides reporting actual parameters values for human virus transport modelling, shows the significant differences in transport that human viruses can have in standardised and natural soil-water systems.
Tzipori, S; Unicomb, L; Bishop, R; Montenaro, J; Vaelioja, L M
The development of rotavirus vaccines against acute gastroenteritis for human infants has been accorded a very high priority. Several vaccine candidates all of which are live cultivated strains of animal origin have been tested in humans. However the nature of attenuation of these viruses for humans is unknown. In this study we have attenuated a pig rotavirus by 15 sequential passages in cell culture after which the virus no longer causes diarrhoea in piglets. The pathogenesis of infection of the attenuated rotavirus strain (AT/76 P15) in gnotobiotic piglets was compared with that of the virulent parent strain (AT/76). The pattern of virus replication in the small intestine was judged by histology, disaccharidase assay, immunoperoxidase labelling of gut sections using group A specific rotavirus antibody, and rotavirus antigen assay of gut contents. The parent strain caused variable but extensive infection that resulted in the complete destruction of mature small intestinal enterocytes and villous contraction within 3 days. Membrane bound digestive enzymes were lost, and profound watery diarrhoea and dehydration resulted in causing piglets to become moribund. In contrast attenuated virus appeared to propagate at a much slower pace. Fewer infected epithelial cells were detected at any one time. Destruction of enterocytes was never extensive enough to cause marked mucosal changes in histology. Membrane bound digestive enzymes remained near normal levels and there was little or no diarrhoea. Virus replication ceased after 6 days. It is concluded that attenuation of the porcine rotavirus strain studied was associated with its decreased ability to propagate in enterocytes after adaption to culture.
Full Text Available Human rhinovirus (HRV is a leading cause of acute respiratory infection (ARI in young children and infants worldwide and has a high impact on morbidity and mortality in this population. Initially, HRV was classified into two species: HRV-A and HRV-B. Recently, a species called HRV-C and possibly another species, HRV-D, were identified. In Mexico, there is little information about the role of HRV as a cause of ARI, and the presence and importance of species such as HRV-C are not known. The aim of this study was to determine the clinical characteristics and genetic variability of HRV in Mexican children. Genetic characterization was carried out by phylogenetic analysis of the 5′-nontranslated region (5′-NTR of the HRV genome. The results show that the newly identified HRV-C is circulating in Mexican children more frequently than HRV-B but not as frequently as HRV-A, which was the most frequent species. Most of the cases of the three species of HRV were in children under 2 years of age, and all species were associated with very mild and moderate ARI.
This doctoral thesis makes an in-depth analysis of HRV (Heart Rate Variability) as calculated from an ECG (Electro Cardio Gram) and how it varies related to the attention span shown by individuals when driving land vehicles. The aim is to use this knowledge in applications where this attention span needs to be estimated, and to focus primarily on measuring the influence that the new HMIs (Human Machine Interfaces) being tried out in the latest generation of vehicles may have on road safety. ...
Asada, Kazutoyo; Kamiya, Hajime; Suga, Shigeru; Nagao, Mizuho; Ichimi, Ryoji; Fujisawa, Takao; Umemoto, Masakazu; Tanaka, Takaaki; Ito, Hiroaki; Tanaka, Shigeki; Ido, Masaru; Taniguchi, Koki; Ihara, Toshiaki; Nakano, Takashi
Rotavirus vaccines were introduced in Japan in November 2011. We evaluated the subsequent reduction of the health-care burden of rotavirus gastroenteritis. We conducted active surveillance for rotavirus gastroenteritis among children under 5 years old before and after the vaccine introduction. We surveyed hospitalization rates for rotavirus gastroenteritis in children in Tsu City, Mie Prefecture, Japan, from 2007 to 2015 and surveyed the number of outpatient visits at a Tsu City clinic from 2010 to 2015. Stool samples were obtained for rotavirus testing and genotype investigation. We assessed rotavirus vaccine coverage for infants living in Tsu City. In the pre-vaccine years (2007-2011), hospitalization rates for rotavirus gastroenteritis in children under 5 years old were 5.5, 4.3, 3.1 and 3.9 cases per 1000 person-years, respectively. In the post-vaccine years (2011-2015), the rates were 3.0, 3.5, 0.8 and 0.6 cases per 1000 person-years, respectively. The hospitalization rate decreased significantly in the 2013-2014 and 2014-2015 seasons compared to the average of the seasons before vaccine introduction (P vaccine year (2010-2011), the number of outpatient visits due to the rotavirus infection was 66. In the post-vaccine years (2011-2015), the numbers for each season was 23, 23, 7 and 5, respectively. The most dominant rotavirus genotype shifted from G3P to G1P and to G2P. The coverage of one dose of rotavirus vaccine in Tsu City was 56.5% in 2014. After the vaccine introduction, the hospitalization rates and outpatient visits for rotavirus gastroenteritis greatly decreased.
Chang, Ji-Tao; Li, Xin; Liu, Hai-Jun; Yu, Li
Group A bovine rotaviruses (BRVs) are the most important cause of diarrheal diseases in neonatal calves and cause significant morbidity and mortality in the young animals, and epidemiologic surveillance of bovine rotavirus G genotypes conducted in various cattle populations throughout the world has shown that approximately 90% of the bovine rotavirus isolates belong to G6 and G10. Based on the modified Jennerian approach to immunization, we constructed and characterized a reassortant rotavirus stain, which bears a single bovine rotavirus VP7 gene encoding G genotype 6 specificity while the remaining 10 genes are derived from the ovine attenuated rotavirus LLR-85. The reassortant rotavirus strain, named as R191, and its parental virus strain LLR-85 were combined as bivalent vaccine candidates to inoculate the colostrums-deprived neonatal calves for evaluation of the immunogenicity. The calves were orally inoculated with the reassortant R191 (group 1), the parental rotavirus LLR-85 (group 2), or combined the R191 and LLR-85 (group 3), and serum specimens were detected to determine the immune response of IgG and IgA antibodies. Results showed that seroconversion to positivity for IgG and IgA antibodies occurred at postinoculation day (PID) 10 in all of the inoculated calves, and the highest titers of the serum IgG (range 1:800 to 1:6400) and IgA (range 1:800 to 1:3200) antibodies were obtained at PID 21 for all calves. Meanwhile, virus shedding was detected after inoculation, showing that the inoculated virus was positive in 2 of 77 fecal specimens (2.6%) collected from the inoculated calves during the first 7 days of oral inoculation with the rotavirus vaccine candidates. The results suggested that the rotavirus strains R191 and LLR-85 are promising bivalent vaccine candidates for the prevention of bovine G6 and G10 rotavirus infection. Copyright © 2010 Elsevier B.V. All rights reserved.
Kamiya, Hajime; Suga, Shigeru; Nagao, Mizuho; Ichimi, Ryoji; Fujisawa, Takao; Umemoto, Masakazu; Tanaka, Takaaki; Ito, Hiroaki; Tanaka, Shigeki; Ido, Masaru; Taniguchi, Koki; Ihara, Toshiaki; Nakano, Takashi
Background Rotavirus vaccines were introduced in Japan in November 2011. We evaluated the subsequent reduction of the health-care burden of rotavirus gastroenteritis. Methods We conducted active surveillance for rotavirus gastroenteritis among children under 5 years old before and after the vaccine introduction. We surveyed hospitalization rates for rotavirus gastroenteritis in children in Tsu City, Mie Prefecture, Japan, from 2007 to 2015 and surveyed the number of outpatient visits at a Tsu City clinic from 2010 to 2015. Stool samples were obtained for rotavirus testing and genotype investigation. We assessed rotavirus vaccine coverage for infants living in Tsu City. Results In the pre-vaccine years (2007–2011), hospitalization rates for rotavirus gastroenteritis in children under 5 years old were 5.5, 4.3, 3.1 and 3.9 cases per 1000 person-years, respectively. In the post-vaccine years (2011–2015), the rates were 3.0, 3.5, 0.8 and 0.6 cases per 1000 person-years, respectively. The hospitalization rate decreased significantly in the 2013–2014 and 2014–2015 seasons compared to the average of the seasons before vaccine introduction (P rotavirus infection was 66. In the post-vaccine years (2011–2015), the numbers for each season was 23, 23, 7 and 5, respectively. The most dominant rotavirus genotype shifted from G3P to G1P and to G2P. The coverage of one dose of rotavirus vaccine in Tsu City was 56.5% in 2014. Conclusion After the vaccine introduction, the hospitalization rates and outpatient visits for rotavirus gastroenteritis greatly decreased. PMID:28246579
Papp, Hajnalka; Malik, Yashpal S; Farkas, Szilvia L; Jakab, Ferenc; Martella, Vito; Bányai, Krisztián
Surveillance of rotavirus infections and circulating strains in small ruminants (i.e. lambs, goats and camelids) has been a neglected research area in the past. However, recent years that have seen an intensification of surveillance in humans and livestock animals, where vaccines to reduce disease burden caused by Rotavirus A (RVA) are available, led to the efforts to better understand the epidemiology, ecology and evolution of RVA strains in other hosts, including lambs, goats and camelids. The aim of this review is to provide an update of the epidemiology and strain diversity of RV strains in these species through searching for relevant information in public data bases.
Feb 2, 1991 ... Estes MK, Graham DY, Dimitrov DH. The molecular epidemiology of rotavirus gastroenteritis. Prog Med Virol 1984; 29: 1-22. 2. Sanders RC. Molecular epidemiology of human rotavirus infections. Eur J. Epidemiol 1985; 1: 19-32. 3. Albert MJ, Bishop RF, Shann FA. Epidemiology of rotavirus diarrhoea in.
Benhafid, Mohammed; Elomari, Nezha; Azzouzi Idrissi, Meryem; Rguig, Ahmed; Gentsch, Jon R; Parashar, Umesh; Elaouad, Rajae
Rotarix(TM) vaccine was introduced into the National Program of Immunization of Morocco in October 2010, reaching quickly 87% of the target population of children nationally. The incidence of rotavirus gastroenteritis and the prevalence of circulating rotavirus strains has been monitored in three sentinel hospitals since June 2006. The average percentage of rotavirus positive cases among all children under 5 years old hospitalized for gastroenteritis during the pre-vaccine period (2006-2010) was 44%. This percentage dropped to 29%, 15% and 24% in the 3 years post vaccine introduction (2011, 2012 and 2013), which is a decline of 34%, 66%, and 45%, respectively. Declines in prevalence were greatest among children 0-1 years of age (53%) and were most prominent during the winter and autumn rotavirus season. The prevalence of the G2P and G9P genotype sharply increased in the post vaccine period (2011-2013) compared to the previous seasons (2006-2010). Rotavirus vaccines have reduced greatly the number of children hospitalized due to rotavirus infection at the three sentinel hospitals; it is however unclear if the predominance of G2P and G9P genotypes is related to the vaccine introduction, or if this is attributable to normal genotype fluctuations. Continued surveillance will be pivotal to answer this question in the future. © 2015 Wiley Periodicals, Inc.
L'Huillier, Arnaud G; Kaiser, Laurent; Petty, Tom J; Kilowoko, Mary; Kyungu, Esther; Hongoa, Philipina; Vieille, Gaël; Turin, Lara; Genton, Blaise; D'Acremont, Valérie; Tapparel, Caroline
Human rhinoviruses (HRVs) and enteroviruses (HEVs) belong to the Enterovirus genus and are the most frequent cause of infection worldwide, but data on their molecular epidemiology in Africa are scarce. To understand HRV and HEV molecular epidemiology in this setting, we enrolled febrile pediatric patients participating in a large prospective cohort assessing the causes of fever in Tanzanian children. Naso/oropharyngeal swabs were systematically collected and tested by real-time RT-PCR for HRV and HEV. Viruses from positive samples were sequenced and phylogenetic analyses were then applied to highlight the HRV and HEV types as well as recombinant or divergent strains. Thirty-eight percent (378/1005) of the enrolled children harboured an HRV or HEV infection. Although some types were predominant, many distinct types were co-circulating, including a vaccinal poliovirus, HEV-A71 and HEV-D68. Three HRV-A recombinants were identified: HRV-A36/HRV-A67, HRV-A12/HRV-A67 and HRV-A96/HRV-A61. Four divergent HRV strains were also identified: one HRV-B strain and three HRV-C strains. This is the first prospective study focused on HRV and HEV molecular epidemiology in sub-Saharan Africa. This systematic and thorough large screening with careful clinical data management confirms the wide genomic diversity of these viruses, brings new insights about their evolution and provides data about associated symptoms.
Full Text Available Bucharest, capital of Romania, deals with serious difficulties as a result of urban politics: influx of people due to industrialization and development of dormitory areas, lack of a modern infrastructure, absence of coherent and long term urban development politics, continuous depletion of environment. This paper presents a multisensor study relying on multiple data sets, both analogical and digital: satellite images (Corona – 1964 panchromatic, SPOT HRV – 1994 multispctral and panchromatic, IKONOS – 2007 multispectral, aerial photographs – 1994, complementary products (topographic and thematic maps. Georeferenced basis needs to be generated to highlight changes detection. The digital elevation model is generated from aerial photography 1:5,000 scaled, acquired in 1994. First a height correction is required followed by an affine transformation to the ground control points identified both in aerial photographs and IKONOS image. SPOT-HRV pansharpened satellite image has been rectified on georeferenced IKONOS image, by an affine transformation method. The Corona panoramic negative film was scanned and rubber sheeting method is used for rectification. The first 25 years of the study period (1964–1989 are characterized by growth of industrial areas, high density apartment buildings residential areas and leisure green areas by demolition of cultural heritage areas (hundred years old churches and architectural monuments. Changes between the imagery were determined partially through visual interpretation, using elements such as location, size, shape, shadow, tone, texture, and pattern (Corona image, partially using unsupervised classification (SPOT HRV and IKONOS. The second period of 18 years (1989–2007 highlighted considerable growth of residential areas in the city neighborhood, simultaneously with the diminish of green areas and massive deforestation in confiscated areas before and returned to the original owners.
Andrêssa S.F. Assis
Conclusions: The study evidenced a significant decrease in the prevalence of rotavirus, mainly in children aged between 0 and 36 months in the 2007-2011 period, as well as a reduction in G1 genotype circulation.
... winter and spring (December through June). Protect Your Child with Rotavirus Vaccine The best way to protect your child from ... insurance or if your insurance does not cover vaccines for your child, the Vaccines for Children (VFC) Program may be ...
Angel, Juana; Franco, Manuel A; Greenberg, Harry B
Selected topics in the field of rotavirus immunity are reviewed focusing on recent developments that may improve efficacy and safety of current and future vaccines. Rotaviruses (RVs) have developed multiple mechanisms to evade interferon (IFN)-mediated innate immunity. Compared to more developed regions of the world, protection induced by natural infection and vaccination is reduced in developing countries where, among other factors, high viral challenge loads are common and where infants are infected at an early age. Studies in developing countries indicate that rotavirus-specific serum IgA levels are not an optimal correlate of protection following vaccination, and better correlates need to be identified. Protection against rotavirus following vaccination is substantially heterotypic; nonetheless, a role for homotypic immunity in selection of circulating postvaccination strains needs further study. Copyright © 2012 Elsevier B.V. All rights reserved.
Jéssica Wildgrube Bertol
Full Text Available Group A human rotaviruses (HuRVA are causative agents of acute gastroenteritis. Six viral structural proteins (VPs and six nonstructural proteins (NSPs are produced in RV-infected cells. NSP4 is a diarrhoea-inducing viral enterotoxin and NSP4 gene analysis revealed at least 15 (E1-E15 genotypes. This study analysed the NSP4 genetic diversity of HuRVA G2P strains collected in the state of São Paulo (SP from 1994 and 2006-2010 using reverse transcription-polymerase chain reaction, sequencing and phylogenetic analysis. Forty (97.6% G2P strains displayed genotype E2; one strain (2.4% displayed genotype E1. These results are consistent with the proposed linkage between VP4/VP7 (G2P and the NSP4 (E2 genotype of HuRVA. NSP4 phylogenetic analysis showed distinct clusters, with grouping of most strains by their genotype and collection year, and most strains from SP were clustered together with strains from other Brazilian states. A deduced amino acid sequence alignment for E2 showed many variations in the C-terminal region, including the VP4-binding domain. Considering the ability of NSP4 to generate host immunity, monitoring NSP4 variations, along with those in the VP4 or VP7 protein, is important for evaluating the circulation and pathogenesis of RV. Finally, the presence of one G2PE1 strain reinforces the idea that new genotype combinations emerge through reassortment and independent segregation.
Bertol, Jéssica Wildgrube; Fregolente, Maria Clara Duarte; Caruzo, Thabata Alessandra Ramos; Silva, Márcio José da; Munford, Veridiana; Sáfadi, Marco Aurélio Palazzi; Rácz, Maria Lucia; Gatti, Maria Silvia Viccari
Group A human rotaviruses (HuRVA) are causative agents of acute gastroenteritis. Six viral structural proteins (VPs) and six nonstructural proteins (NSPs) are produced in RV-infected cells. NSP4 is a diarrhoea-inducing viral enterotoxin and NSP4 gene analysis revealed at least 15 (E1-E15) genotypes. This study analysed the NSP4 genetic diversity of HuRVA G2P strains collected in the state of São Paulo (SP) from 1994 and 2006-2010 using reverse transcription-polymerase chain reaction, sequencing and phylogenetic analysis. Forty (97.6%) G2P strains displayed genotype E2; one strain (2.4%) displayed genotype E1. These results are consistent with the proposed linkage between VP4/VP7 (G2P) and the NSP4 (E2) genotype of HuRVA. NSP4 phylogenetic analysis showed distinct clusters, with grouping of most strains by their genotype and collection year, and most strains from SP were clustered together with strains from other Brazilian states. A deduced amino acid sequence alignment for E2 showed many variations in the C-terminal region, including the VP4-binding domain. Considering the ability of NSP4 to generate host immunity, monitoring NSP4 variations, along with those in the VP4 or VP7 protein, is important for evaluating the circulation and pathogenesis of RV. Finally, the presence of one G2PE1 strain reinforces the idea that new genotype combinations emerge through reassortment and independent segregation.
Mortalidad por enfermedad diarreica en menores, antes y después de la introducción de la vacuna contra el rotavirus Analysis of the mortality due to diarrhea in younger children, before and after the introduction of rotavirus vaccine
Full Text Available OBJETIVO: Analizar la mortalidad por diarrea en menores de cinco años en México, antes y después de la vacunación contra el rotavirus. MATERIAL Y MÉTODOS: Se compararon defunciones y mortalidad por diarrea mediante diferencias porcentuales anuales por grupo etario, antes (2000-2005 y después (2006-2007 de la vacunación. RESULTADOS: Entre 2000 y 2007 la mortalidad por diarrea disminuyó 42%. En los estados con vacunación, la mortalidad se redujo 15.8 y 27.7% en menores de uno y de uno a cuatro años, respectivamente, en el periodo de 2006 a 2007. DISCUSIÓN: La reducción observada en la mortalidad por diarrea en menores de cinco años después de 2005 puede atribuirse en parte a la vacunación contra el rotavirus.OBJECTIVE: To analyze the mortality due to acute diarrhea in children younger than five years old, before and after the introduction of rotavirus vaccine in Mexico. MATERIAL AND METHODS: Number of deaths and mortality rates due to acute diarrhea were compared by children's age and states' vaccine status using annual percentage differences before (2000-2005 and after (2006-2007 the introduction of the HRV. RESULTS: From 2000-2007, deaths due to acute diarrhea in children under five years of age dropped 42%. In those states that received the HRV early in 2006, diarrhea mortality decreased between 2006-2007 15.8% in children younger than one year old and 22.7% in children 1-4 years old. DISCUSSION: The observed reduction in mortality due to acute diarrhea in children under five years of age after 2005 can be, in part, attributed to the HRV.
Group A chicks were inoculated with 1 X 106 pfu/ml of rotavirus, group B chicks were inoculated with 1 X 106 cfu/ml of Salmonella pullorum, group C chicks were inoculated with 1 X 106 pfu/ml of rotavirus and 1 X 106 cfu/ml of Salmonella pullorum, while group D birds were given 1ml of PBS alone. Birds in all groups were ...
Angel, Juana; Franco, Manuel A.; Greenberg, Harry B.
Selected topics in the field of rotavirus immunity are reviewed focusing on recent developments that may improve efficacy and safety of current and future vaccines. Rotaviruses have developed multiple mechanisms to evade interferon-mediated innate immunity. Compared to more developed regions of the world, protection induced by natural infection and vaccination is reduced in developing countries where, among other factors, high viral challenge loads are common and where infants are infected at...
Full Text Available The purpose of this study is to characterize and attenuate the influence of mean heart rate (HR on nonlinear heart rate variability (HRV indices (correlation dimension, sample and approximate entropy as a consequence of being the HR the intrinsic sampling rate of HRV signal. This influence can notably alter nonlinear HRV indices and lead to biased information regarding autonomic nervous system (ANS modulation.First, a simulation study was carried out to characterize the dependence of nonlinear HRV indices on HR assuming similar ANS modulation. Second, two HR-correction approaches were proposed: one based on regression formulas and another one based on interpolating RR time series. Finally, standard and HR-corrected HRV indices were studied in a body position change database.The simulation study showed the HR-dependence of non-linear indices as a sampling rate effect, as well as the ability of the proposed HR-corrections to attenuate mean HR influence. Analysis in a body position changes database shows that correlation dimension was reduced around 21% in median values in standing with respect to supine position (p < 0.05, concomitant with a 28% increase in mean HR (p < 0.05. After HR-correction, correlation dimension decreased around 18% in standing with respect to supine position, being the decrease still significant. Sample and approximate entropy showed similar trends.HR-corrected nonlinear HRV indices could represent an improvement in their applicability as markers of ANS modulation when mean HR changes.
de Blasio, Birgitte Freiesleben; Kasymbekova, Kaliya; Flem, Elmira
New rotavirus vaccines show promise to reduce the burden of severe diarrhea among children in developing countries. We present an age-specific dynamic rotavirus model to assess the effect of rotavirus vaccination in Kyrgyzstan, a country in Central Asia that is eligible for funds from the GAVI Alliance. A routine rotavirus vaccination program at 95% coverage and 54% effectiveness against severe infection is estimated to lead to a 56% reduction in rotavirus-associated deaths and a 50% reduction in hospital admissions, while outpatient visits and homecare episodes would decrease by 52% compared to baseline levels after 5 years of intervention. A 10% reduction in vaccine efficacy due to incomplete 3-dose regimen is estimated to increase the numbers of severe cases by 6-8%. Herd immunity was found to account for 1% or less of averted cases of severe gastroenteritis, while an extra 7-8% of all rotavirus infections would be avoided due to reduced transmission. Rotavirus vaccines would reduce the burden of rotavirus disease substantially, but the results are sensitive to delay in age-appropriate vaccination. Copyright © 2010 Elsevier Ltd. All rights reserved.
Conclusions: The significant decrease in main AGE-related health indicators in children <5 years of age after the introduction of rotavirus vaccine provides evidence of a substantial public health impact of rotavirus vaccination in Bolivia, as a measure for protecting children against AGE.
Kirkwood, Carl D; Roczo-Farkas, Susie; Bishop, Ruth F; Barnes, Graeme L
This report from the Australian Rotavirus Surveillance Program, together with collaborating laboratories Australia-wide, describes the rotavirus genotypes responsible for the hospitalisation of children with acute gastroenteritis during the period 1 January to 31 December 2012. During the survey period, 1,300 faecal samples were referred to the centre for rotavirus G and P genotype analysis, and of these 748 were confirmed as rotavirus positive. A total of 491 specimens were collected from children under 5 years of age, while 257 were from older children and adults. Genotype analysis revealed that G1P was the dominant type in this reporting period, identified in 35% of strains nationally. Genotype G2P was the second most common strain nationally, representing 28% of samples, followed by genotype G12P (23%). This represents the first report where G12P strains are a major cause of disease in this community. Fluctuations in genotype distribution were also observed based on the vaccine type in use. Genotype G2P was more common in states and territories using Rotarix while G1P was more common in states using RotaTeq. This survey of rotavirus strains circulating in 2012 highlights the continued fluctuations in rotavirus genotypes, with an annual change in dominant genotypes as well as emergence of a previously rare genotype, suggesting a dynamic wild-type population. firstname.lastname@example.org
Rotavirus infections cause diarrhea and vomiting that can lead to severe dehydration. Despite extensive tissue damage and cell death, the inflammatory response is very limited. The focus of this thesis was to study pathophysiological mechanisms behind diarrhea and vomiting during rotavirus infection and also to investigate the mechanism behind the limited inflammatory response. An important discovery in this thesis was that rotavirus infection and the rotavirus toxin NSP4 stimulate release of...
Busi, Chiara; Martella, Vito; Papetti, Alice; Sabelli, Cristiano; Lelli, Davide; Alborali, G Loris; Gibelli, Lucia; Gelmetti, Daniela; Lavazza, Antonio; Cordioli, Paolo; Boniotti, M Beatrice
In 2011, a group A rotavirus was isolated from the brain of a fox with encephalitis and neurologic signs, detected by rabies surveillance in Italy. Intracerebral inoculation of fox brain homogenates into mice was fatal. Genome sequencing revealed a heterologous rotavirus of avian origin, which could provide a model for investigating rotavirus neurovirulence.
These results show that rotavirus plays an important role in severe viral diarrhoea in young children in Maua, Meru North district, Kenya. Furthermore, this high G9 rotavirus prevalence in Kenya may require vaccine trials to be held in Kenya so as to determine the efficacy of new rotavirus vaccine candidates that do not ...
Conclusion: Rotavirus frequency was 25% among children less than 5 years. Rotavirus vaccine, routine and proper diagnosis of rotavirus infection in children with acute diarrhea help to determine appropriate treatment, prevents the unnecessary use of antibiotics and minimizes the spread of the disease among susceptible ...
control strategies. However, development and application of appropriate rotavirus vaccines requires an understanding of the magnitude of diarrhoea associated with rotavirus infection, the age group most affected, the severity of diarrhoea associated with rotavirus infections and the strain types circulating in an area.
We aimed to determine the prevalence of group A rotavirus (RVA) in children below 5 years with diarrhea in two regions of Northern Cameroon (North West and Far North Regions) so as to improve our knowledge on the burden of rotavirus disease for imminent introduction of a rotavirus vaccine. Methods: Stool samples ...
Coulson, Barbara S.
Rotavirus-neutralizing antibody responses in sera and stools of children hospitalized with rotavirus gastroenteritis and then monitored longitudinally were optimally detected by using local rotavirus strains. Stool responses were highest on days 5 to 8 after the onset of diarrhea. Longitudinal monitoring suggested that serum neutralizing antibody responses were a more useful measure of severely symptomatic rotavirus infection than stool responses but that stool antibody responses may be a use...
Kirkwood, Carl D; Roczo-Farkas, Suzie
The Australian Rotavirus Surveillance Program, together with collaborating laboratories Australia-wide, reports the rotavirus genotypes responsible for the hospitalisation of children with acute gastroenteritis. During the survey period of 1 January to 31 December 2014, 1,022 faecal samples were referred for rotavirus G and P genotype analysis, and of these 733 were confirmed as rotavirus positive. A total of 480 specimens were collected from children under 5 years of age, while 253 were from older children and adults. Genotype analysis of the 733 rotavirus samples collected from both children and adults revealed that G12P was the dominant genotype in this reporting period, identified in 29.6% of strains nationally. Genotype G1P was the 2nd most common strain nationally, representing 22.9% of samples, followed by genotype G3P (14.9%). This report highlights the continued significance of G12P strains as the major cause of disease in this population. The genotype distribution was slightly altered when the analysis was restricted to samples collected from children under 5 years of age, with G1P being the dominant genotype (29%) followed by G12P as the 2nd most common genotype (26%). Fluctuations in genotype distribution were also observed based on the vaccine type in use. Genotype G12P was more common in states and territories using RotaTeq, while G1P was more common in the locations using Rotarix. This survey highlights the yearly fluctuations in rotavirus genotypes observed since vaccine introduction. The continuation of G12P as the dominant genotype further illustrates the dynamic and diversity present in the wild-type rotavirus population evident in the Australian population since vaccine introduction.
Kang, Joo Yeon; Lee, Do Kyung; Ha, Nam Joo; Shin, Hea Soon
Rotavirus is worldwide cause of severe gastroenteritis including severe diarrhea and fatal dehydration in infants and young children. There is an available vaccination program for preventing rotavirus infection, but it has limits and restrictions. Probiotics therapy could be an alternative method of antiviral prevention and modulation against rotavirus infection. In this study, we screened the antiviral activity of probiotic bacteria such as 3 Lactobacillus spp. and 14 Bifidobacterium spp. isolated from young Korean. Three of the bacteria, Lactobacillus ruminis SPM0211, Bifidobacterium longum SPM1205, and SPM1206, inhibited human strain Wa rotavirus infection in Caco-2 cells. Furthermore, these bacterial strains inhibited rotavirus replication in a rotavirus-infected neonatal mouse model. To clarify the mechanism of inhibition, we investigated gene expression of Interferon (IFN)-signaling components and IFN-inducible antiviral effectors. All 3 probiotics increased IFN-α and IFN-β levels compared with the control. Gene expression of IFNsignaling components and IFN-inducible antiviral effectors also increased. Overall, these results indicate that L. ruminis SPM0211, B. longum SPM1205 and 1206 efficiently inhibit rotavirus replication in vitro and in vivo. Especially, the antiviral effect of Lactobacillus ruminis SPM0211 is worthy of notice. This is the first report of L. ruminis with antiviral activity. Anti-rotaviral effects of the 3 probiotics are likely due to their modulation of the immune response through promoting type I IFNs, which are key regulators in IFN signaling pathway.
Garmendia, Antonio E; Lopez, Wellington; Ortega, Nastassja; Chamorro, Marycris J
Alpacas (Vicugna pacos), a species of South American camelids (SAC), suffer high morbidity and mortality from infectious diseases. Diarrhea is one of the leading causes of alpaca cria mortality in Peru and elsewhere. In order to develop appropriate control and/or treatment, it is necessary to identify infectious pathogens that cause diarrhea in crias. Rotavirus was isolated in cell culture from feces collected from crias with acute diarrhea that tested positive to rotaviral antigen by rapid immunochromatographic methods in an earlier study. The isolates were identified as rotaviruses by RT-PCR run with specific primers for human rotavirus VP7 coding sequences using total RNA extracted from cells displaying cytopathic effects as template. These alpaca isolates were further identified as group A rotaviruses by means of a VP6-specific PCR and were designated as ALRVA-K'ayra/Perú/3368-10 and ALRVA-K'ayra/Perú/3386-10. Molecular G and P typing, placed the former as G3/P11 and the latter as G3/P?. Sequence analysis of two genome segments (coding for VP4 and VP7) from the alpaca isolates revealed partial homologies to swine and human rotaviruses, respectively. These results demonstrate that rotaviruses are associated with a proportion of cases of diarrhea in crias, although prevalence and impact remain to be determined. The isolation of rotaviruses from alpaca crias with diarrhea will contribute positively to further understand the pathogen and its role in the diarrhea complex. Copyright © 2015 Elsevier B.V. All rights reserved.
Full Text Available Live-attenuated oral rotavirus (RV vaccines have lower efficacy in low income countries, and additionally are associated with a rare but severe adverse event, intussusception. We have been pursuing the development of an inactivated rotavirus vaccine (IRV using the human rotavirus strain CDC-9 (G1P through parenteral immunization and previously demonstrated dose sparing and enhanced immunogenicity of intradermal (ID unadjuvanted IRV using a coated microneedle patch in comparison with intramuscular (IM administration in mice. The aim of this study was to evaluate the immune response and protection against RV infection and diarrhea conferred by the administration of the ID unadjuvanted IRV using the microneedle device MicronJet600® in neonatal gnotobiotic (Gn piglets challenged with virulent Wa G1P human RV. Three doses of 5 μg IRV when administered intradermally and 5 μg IRV formulated with aluminum hydroxide [Al(OH3] when administered intramuscularly induced comparable rotavirus-specific antibody titers of IgA, IgG, IgG avidity index and neutralizing activity in sera of neonatal piglets. Both IRV vaccination regimens protected against RV antigen shedding in stools, and reduced the cumulative diarrhea scores in the piglets. This study demonstrated that the ID and IM administrations of IRV are immunogenic and protective against RV-induced diarrhea in neonatal piglets. Our findings highlight the potential value of an adjuvant sparing effect of the IRV ID delivery route.
Gastañaduy, Paul A; Sánchez-Uribe, Edgar; Esparza-Aguilar, Marcelino; Desai, Rishi; Parashar, Umesh D; Patel, Manish; Richardson, Vesta
In Mexico, declines in childhood diarrhea deaths have been documented during 2008-2010 after rotavirus vaccine introduction in 2007. Because of concerns about variation in rotavirus vaccine efficacy by socioeconomic status, we compared reductions in diarrhea mortality in the lesser developed southern region versus the more developed northern and central regions of Mexico. We obtained data from national vital statistics on diarrhea deaths among children aged diarrhea mortality before (2003-2006) and after (2009-2011) vaccine introduction. Regional vaccine coverage was estimated from administrative data, and socioeconomic status was assessed by using the Human Development Index. In northern, central, and southern Mexico, the 2007 Human Development Index was 0.84, 0.82, and 0.77, respectively, and by 2010 an estimated 99%, 84%, and 89% of children aged Diarrhea mortality among children .8). After introduction of rotavirus vaccination, marked and sustained declines in diarrhea deaths were seen among children in all regions of Mexico, including in the least developed southern region with the highest baseline diarrhea mortality. This finding indicates equitable vaccine delivery to children with varying risk of mortality and reaffirms the beneficial effects of rotavirus vaccination against fatal diarrheal disease.
Sugata, Ken; Taniguchi, Koki; Yui, Akiko; Miyake, Fumi; Suga, Sadao; Asano, Yoshizo; Ohashi, Masahiro; Suzuki, Kyoko; Nishimura, Naoko; Ozaki, Takao; Yoshikawa, Tetsushi
This study was conducted to examine the association between rotavirus antigenemia and clinical features, particularly extraintestinal manifestations, and the association between serum cytokine levels and rotavirus antigen quantity. Sixty hospitalized children who received a diagnosis of acute rotavirus gastroenteritis were enrolled in this study. Paired serum samples were collected from the 60 children when admitted to and discharged from the hospital. Associations among viral antigen levels and fever, elevated transaminase levels, and seizures were evaluated to determine whether antigenemia correlated with disease severity. Viral antigen was measured by using an in-house enzyme-linked immunosorbent assay that detected VP6 antigen. A flow-cytometric bead array was used to measure serum cytokine levels. Rotavirus antigen levels were significantly higher in serum collected at the time of hospital admission than at the time of discharge. Serum rotavirus antigen levels peaked on day 2 of the illness (2.02 +/- 0.73), followed by a gradual decrease in antigen levels to nearly undetectable levels by day 6. The quantity of rotavirus antigen was significantly higher in serum collected from patients with fever than those without fever. The presence or absence of elevated transaminase levels and seizures was not associated with serum rotavirus antigen levels. A weak but significantly positive association was observed between interleukin 8 levels and antigenemia. A weak but significantly negative association was observed between interleukin 10 levels and antigenemia. Rotavirus antigenemia is frequently observed in a patient's serum during the acute phase, and viral antigen levels change dramatically during the acute phase of the illness. Because patients with fever had higher rotavirus antigen levels, antigenemia severity might contribute to fever. The host immune response plays an important role in controlling antigenemia levels.
Bortkiewicz, Alicja; Gadzicka, Elżbieta; Szymczak, Wiesław; Zmyślony, Marek
The aim of the study was to assess the mechanism of cardiovascular impairments in workers exposed to UHF-VHF radio frequency electromagnetic fields (EMF). Heart rate variability (HRV) was analysed using 512 normal heart beats registered at rest. The analysis concerned time-domain (STD R-R) and frequency-domain (VLF, LF, HF) parameters of HRV. Fifty nine workers (group I) with low-level and 12 workers (group II) with high-level exposure were examined. The mean age of the subjects was 47 ± 9 years and 41 ± 14 years, and mean exposure duration 19.1 ± 8.8 years and 13 ± 4 years, in groups I and II, respectively. The groups were divided according to: E(max), E(dose), E(mean) for frequencies UHF, VHF and UHF+VHF: The control group consisted of 42 non-exposed subjects, aged 49 ± 8 years. Statistical analysis comprised one-way analysis of variance, covariance analysis and logistic regression models. In the exposed groups, the heart rate was higher than in the control one. Standard deviation of R-R intervals (STD R-R) was found to be significantly (p = 0.0285) lower in group I (42.5 ± 24.7 ms) compared to the control group (62.9 ± 53.5 ms). The risk of lowered STD R-R was significantly increased (OR = 2.37, p = 0.023) in group II. Both exposed groups presented significantly higher VLF and LF values than the control group (p = 0.005 and p = 0.0025, respectively). The EMF-exposed groups were characterised by the dominance of the sympathetic system (LF/HF 1.3 ± 0.35). The results indicate that exposure to radiofrequency EMF may affect the neurovegetative regulation.
Full Text Available Background Distinguishing rotavirus from non-rotavirus diarrhea is helpful for managing the illness. However, definitively diagnosing rotavirus diarrhea from serology is difficult and expensive. Objectives To distinguish between the clinical manifestations of rotavirus and non-rotavirus diarrhea, and to assess the accuracy of using such clinical manifestations to predict the type of diarrhea in children. Methods A cross-sectional study was performed from April to October 2015 in all children less than five years of age who presented with acute diarrhea at the Pediatric Outpatient Clinic of the Department of Child Health and Emergency Department, Dr. Mohammad Hoesin and Bari Hospitals, Palembang, South Sumatera. Clinical manifestations were collected from history and physical examinations; stool specimens were examined by immunochromatography. Clinical parameters were analyzed by multivariate analysis, and scores given to each significant parameter. The accuracy of the scoring system based in these parameters was analyzed by means of receiver-operating characteristic (ROC area under the curve (AUC. Results Of 184 children, 92 had rotavirus and 92 had non-rotavirus diarrhea. Multivariate analysis showed 3 clinical parameters commonly seen in the rotavirus diarrhea cases: male sex (OR 2.718; 95%CI 1.373 to 5.382, cough (OR 3.500; 95%CI 1.788 to 6.582, and yellow-greenish stool (OR 4.009; 95%CI 2.061 to 7.797. A scoring system was constructed based on the parameters: male (score of 1, cough (score of 2, and yellow-greenish stool (score of 3. From ROC analysis, the AUC was 0.755. Using a cut-off score of > 3, the sensitivity was 81.5%, specificity 51.1%, and PPV 62.5%. Conclusion Cough, yellow-greenish stool, and male are significant parameters for differentiating rotavirus from non-rotavirus diarrhea. A scoring system from these parameters is sensitive for predicting rotavirus vs. non-rotavirus diarrhea in children less than five years of age.
Seheri, L Mapaseka; Page, Nicola A; Mawela, Mothahadini P B; Mphahlele, M Jeffrey; Steele, A Duncan
Diarrhoeal diseases are ranked the third major cause of childhood mortality in South African children less than 5 years, where the majority of deaths are among black children. Acute severe dehydrating rotavirus diarrhoea remains an important contributor towards childhood mortality and morbidity and has been well documented in South Africa. As the preventive strategy to control rotavirus diarrhoea, South Africa became the first country in the WHO African Region to adopt the rotavirus vaccine in the national childhood immunisation programme in August 2009. The rotavirus vaccine in use, Rotarix, GSK Biologicals, is given at 6 and 14 weeks of age, along with other vaccines as part of Expanded Programme on Immunisation (EPI). Studies which facilitated the introduction of rotavirus vaccine in South Africa included the burden of rotavirus disease and strain surveillance, economic burden of rotavirus infection and clinical trials to assess the safety and efficacy of vaccine candidates. This paper reviews the epidemiology of rotavirus in South Africa, outlines some of the steps followed to introduce rotavirus vaccine in the EPI, and highlights the early positive impact of vaccination in reducing the rotavirus burden of disease based on the post-marketing surveillance studies at Dr George Mukhari hospital, a sentinel site at University of Limpopo teaching hospital in Pretoria, South Africa, which has conducted rotavirus surveillance for >20 years. Copyright © 2012 Elsevier Ltd. All rights reserved.
Lee, Way Seah; Lim, Benjamin Tze Ying; Chai, Pei Fan; Kirkwood, Carl D.; Lee, Jimmy Kok Foo
Group A rotavirus (RV-A) genotypes isolated in Malaysia was studied to estimate the effectiveness of a universal RV-A vaccination in Malaysia. A simple mathematical model was used, with input from a two-year, two-center, prospective study on hospitalization of RV-A gastroenteritis (RVGE) in young children, published data on RV-A hospitalizations and genotypes, mortality on childhood GE and published genotype-specific efficacy data on two RV-A vaccines. Assuming a 95% vaccine coverage, the overall projected effectiveness was 75.7 to 88.1% for Rotateq® and 78.7 to 90.6% for Rotarix® against RVGE-related hospitalizations. The projected annual reduction in RVGE-related deaths was 27 to 32 deaths (from 34 deaths) for Rotateq® and 28 to 32 deaths annually forRotarix®. A universal RV-A vaccine is efficacious in reducing RVGE-related hospitalizations and mortality in Malaysia. PMID:23022710
Martel-Paradis, Olivier; Laurin, Marc-André; Martella, Vito; Sohal, Jagdip Singh; L'Homme, Yvan
Group A rotaviruses with G2 and G9 VP7 specificity are common in humans, while G11 strains have been detected only sporadically. G2, G9 and G11 rotaviruses also circulate in pigs and swine rotaviruses have been suspected of interspecies and zoonotic transmissions in numerous studies. However, the complete gene constellation of G2 and G9 porcine rotaviruses has not yet been determined. In order to start filling this gap, the genomic make up of two G2, one G9 and one G11 porcine rotavirus strains, detected in Canada in 2005-2007, was determined. With the exception of a G2P strain, with E9 NSP4 type and mixed I5+I14 VP6 type, the constellation of genomic segments was rather conserved and were closely related to prototype porcine strains in the four viruses characterized (I5-R1-C1-M1-A8-N1-T7-E1-H1). Most notably, all the viruses displayed a rare NSP3 genotype, T7, which has also been identified in rare human reassortant strains and in the reference strain RVA/Cow-tc/GBR/UK/1973/G6P. This study provides crucial genetic data on these complex viruses and will help understand the origin and ecological niche of gene segments and the role played by pigs in their evolution. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.
Monaco, Annalisa; Cattaneo, Ruggero; Ortu, Eleonora; Constantinescu, Marian Vladimir; Pietropaoli, Davide
Ultra Low Frequency Transcutaneous Electric Nervous Stimulation (ULF-TENS) is extensively used for pain relief and for the diagnosis and treatment of temporomandibular disorders (TMD). In addition to its local effects, ULF-TENS acts on the autonomic nervous system (ANS), with particular reference to the periaqueductal gray (PAG), promoting the release of endogenous opioids and modulating descending pain systems. It has been suggested that the PAG participates in the coupling between the emotional stimulus and the appropriate behavioral autonomic response. This function is successfully investigated by HRV. Therefore, our goal is to investigate the effects of trigeminal ULF-TENS stimulation on autonomic behavior in terms of HRV and respiratory parameters during an experimentally-induced arithmetic stress test in healthy subjects. Thirty healthy women between 25 and 35years of age were enrolled and randomly assigned to either the control (TENS stimulation off) or test group (TENS stimulation on). Heart (HR, LF, HF, LF/HF ratio, DET, RMSSD, PNN50, RR) and respiratory (BR) rate were evaluated under basal, T1 (TENS off/on), and stress (mathematical task) conditions. Results showed that HRV parameters and BR significantly changed during the arithmetic stress paradigm (pTENS and control group could be discriminated only by non-linear HRV data, namely RR and DET (p=0.038 and p=0.027, respectively). During the arithmetic task, LF/HF ratio was the most sensitive parameter to discriminate between groups (p=0.019). Our data suggest that trigeminal sensory ULF-TENS reduces the autonomic response in terms of HRV and BR during acute mental stress in healthy subjects. Future directions of our work aim at applying the HRV and BR analysis, with and without TENS stimulation, to individuals with dysfunctional ANS among those with TMD. Copyright © 2017 Elsevier Inc. All rights reserved.
Aladin, Farah; Nawaz, Sameena; Iturriza-Gómara, Miren; Gray, Jim
Rotaviruses are classified into G- and P-types, which are determined by the reactivity with antibodies to the outer viral proteins, VP7 and VP4, respectively, or sequence variation in the genes encoding these proteins. There are presently a number of different rotavirus strains co-circulating within the UK, with the common human strains G1P, G2P and G9P being the most prevalent. As part of strain surveillance for the European Rotavirus Network (EuroRotaNet) a cluster (n=29) of G8 strains was detected in the UK between February and May 2009. G8 strains were initially mistyped as G12 through multiplex RT-PCR, therefore further investigation was performed to ascertain the reasons behind this mistyping. The genes encoding the VP7 of these G8 strains were sequenced and aligned with the existing G8- and G12-specific oligonucleotide primers. Multiple alignment of sequences derived from these strains and the G8- and G12-specific oligonucleotide primers revealed a series of point mutations which resulted in mismatches at the 3' end of the G8-specific primer binding site that prevented amplification with the G8-specific primer, whilst a close homology with the G12-specific primer allowed mis-priming. Both the G8 and G12 primers were redesigned and their ability to correctly identify G8 and G12 strains was evaluated and confirmed. These findings highlight the importance of monitoring the specificity and sensitivity of the genotyping methods in order to detect changes in the genotype distribution and changes associated with genetic drift of common or uncommon genotypes. Copyright 2010 Elsevier B.V. All rights reserved.
Ianiro, Giovanni; Delogu, Roberto; Bonomo, Paolo; Fiore, Lucia; Ruggeri, Franco M
Hospital-based surveillance of acute gastroenteritis caused by rotavirus has produced ample knowledge on the infection in children, whereas little is known on rotavirus infection among adults. The Italian surveillance program RotaNet-Italia collected 1,595 samples from patients admitted to hospital with gastroenteritis in 2012. All patients presented with vomiting, diarrhea, fever, and/or abdominal pain. Forty-two samples obtained by the RotaNet-Italia (2.6%) were from adolescents or adults (10-89 years). The study compared the genotypes and gene sequences of the rotavirus strains identified in adults with strains obtained from children worldwide. All 42 Italian strains were genotyped by the EuroRotaNet RT-nested-PCR protocols, and 12 rotaviruses from patients >13-year-old were subjected to nucleotide sequencing of their VP7 and/or VP4 genes. All strains analyzed belonged to the common human genotypes G1P, G2P, G4P, and G9P, except an uncommon G3P genotype detected in a single patient. Phylogenetic analysis of the 12 strains showed that within each genotype they clustered in RVA lineages reported worldwide. The amino acid sequences of the VP7 and the VP8* hypervariable regions were highly conserved between the RVA strains collected from adults and children, in each lineage. Genotyping, phylogenetic analysis, and the study of viral epitopes revealed that rotaviruses circulating in adults in Italy are closely similar to the strains circulating in children, with high nucleotide identity particularly with strains reported in Europe and Asia. The circulation of the same rotavirus strains in both children and adults suggests that adults may contribute to sustain the circulation of rotaviruses through the population. © 2014 Wiley Periodicals, Inc.
Jain, Swapnil; Thakur, Nutan; Grover, Neelam; Vashistt, Jitendraa; Changotra, Harish
Diarrheal diseases are responsible for a significant proportion of mortality and morbidity all around the globe. The contribution of viruses to gastroenteritis incidences in humans is well established. In the present study, we have studied the prevalence of rotavirus, norovirus and enterovirus in Himachal Pradesh, a north Indian state. A total of 287 (111 children and 176 adults) stool samples of gastroenteritis patients were screened for the viruses using RT-PCR method. 34.5 % samples were positive for the viral pathogens of gastroenteritis. Rotavirus was the predominant virus detected in the study with 49.5 and 14.8 % positivity in children and adults, respectively. Enterovirus was present in 5.6 % cases whereas norovirus had least prevalence (1.4 %). Co infection (rotavirus and enterovirus) was witnessed at the prevalence rate of 0.6 %. Among different age groups, the prevalence of studied viruses was highest in the children belonging to the age groups of Rotavirus infections were found to be significantly associated with vomiting and trend of higher rates of fever and dehydration was seen in children along with diarrhea. Seasonal distribution shows circulation of diarrheagenic viruses throughout the year. This is the first report of prevalence of various diarrheagenic viruses circulating in this region. The outcome of the study from this cohort provides a baseline data which can be used to design the preventive strategies in the otherwise unexplored state of Himachal Pradesh.
Koroglu, Mehmet; Yakupogullari, Yusuf; Otlu, Baris; Ozturk, Serhat; Ozden, Mehmet; Ozer, Ali; Sener, Kemal; Durmaz, Riza
We characterized an outbreak of acute diarrheal disease caused by group A rotavirus that occurred during the Autumn of 2005 in Malatya City, Turkey. A total 9907 patients between 0 to 91 years old (mean age: 25.05�19.67) were included in the epidemic. The patients� data were prospectively collected and statistically analyzed. Microbiologic analyses were performed to determine the etiologic agent. Rapid onset diarrhea (98.36%), abdominal cramps (69%), fever (44.4%) and vomiting (69.6%) were the most common symptoms observed in patients. Rotavirus antigen was detected in 52.7% of the studied patients. RT-PCR analysis led to identification of Group A rotavirus as the causative agent of this epidemic. Simultaneous measurements of the drinking water samples yielded very low chlorine levels; as low as 0 to 0.05 mg/L. The outbreak investigation team indicated possible contamination of a large water depository from a water well, which supplies drinking water to two major districts of the city. Effective chlorination and blockage of the passage between the well and the water depository stopped the outbreak. This outbreak shows the high epidemic potency of rotavirus in large human populations, including all age groups, and underlines the importance of water safety in pipeline systems.
Full Text Available Rotavirus is a major cause of infectious diarrhea in infants and young children. The objective of this study was to characterize the genotypes of Human Rotavirus found in children hospitalized with acute diarrhea in the Pediatric Hospital Prof. Hosannah de Oliveira of the UFBA in Salvador, Bahia, Brazil, during the years of 1999, 2000 and 2002. Fecal samples were analyzed (n=358 by methods EIARA and SDS-PAGE for detection of Rotavirus. Positive samples of one or two of these methods (n=168 were submitted to RT-PCR and Multiplex-Nested PCR to determine genotypes G and P. A hundred sixty-eight (46.9% samples were positive and 190 (53.1% negative. Only 17 (4.7% samples had divergent results. The distribution of genotypes G during the first year, showed that the genotype G9 was present in 96,8% of the analyzed samples, in the second year, it was responsible for 96% and in the third year, 88,1%. The characterization of genotypes P demonstrated that the genotype P1A was the most outstanding in all years. In this study we discuss the benefit to control the genotypes of Rotavirus through the molecular characterization for the development of potential vaccines.
Ricardo Q Gurgel
Full Text Available BACKGROUND AND AIMS: Rotavirus causes severe diarrhoea and Brazil introduced the Rotarix G1P vaccine in 2006. We aimed to describe changes in rotavirus incidence and diarrhoea epidemiology before and after vaccine introduction. METHODS: DESIGN: (i hospital-based survey of children with diarrhoea (2006-2012; (ii diarrhea-mortality and hospitalization surveillance (1999-2012. SETTING: (i Aracaju and (ii state and national level. RESULTS: 1841 children were enrolled and 231 (12.5% had rotavirus. Rotavirus was less frequent from January-June than from July-December (9.4% versus 20.9%, p<0.01, but the seasonal variation was less defined after 2009. Very few rotavirus cases (8-3.9% were detected in 2011, with an increase in 2012 (13-18.5%. In 2006, unvaccinated children were more likely to have rotavirus, but thereafter unvaccinated and vaccinated children had equally low incidence. Older children and those with rotavirus were more likely to have severe diarrhea episodes. The most frequent genotype from 2006 to 2010 was G2P; except in 2009, when most cases were G1P. Very few G2P were detected from 2011 and 50% cases in 2012 were G8P. Diarrhoea-hospitalizations decreased nationally from 89,934 (2003 to 53,705 (2012; 40.3% reduction and in the state from 1729 to 748 (56.7% reduction. Diarrhoea-deaths decreased nationally from 4368 in 1999 to 697 in 2012 (84% reduction, p<0.001 and in the state from 132 to 18 (86% reduction. These changes were much larger after vaccine introduction. CONCLUSIONS: The vaccine was associated with substantial reductions in rotavirus incidence and diarrhoea-hospitalizations and deaths. The G2P genotype predominance disappeared over time and may be replaced by other heterotypic genotypes.
Full Text Available BACKGROUND: Human rhinoviruses (HRV are associated with upper and lower respiratory illnesses, including severe infections causing hospitalization in both children and adults. Although the clinical significance of HRV infections is now well established, no detailed investigation of the immune response against HRV has been performed. The purpose of this study was to assess the IgG1 antibody response to the three known HRV species, HRV-A, -B and -C in healthy subjects. METHODS: Recombinant polypeptides of viral capsid protein 1 (VP1 from two genotypes of HRV-A, -B and -C were expressed as glutathione S-transferase (GST fusion proteins and purified by affinity and then size exclusion chromatography. The presence of secondary structures similar to the natural antigens was verified by circular dichroism analysis. Total and species-specific IgG1 measurements were quantitated by immunoassays and immunoabsorption using sera from 63 healthy adults. RESULTS: Most adult sera reacted with the HRV VP1 antigens, at high titres. As expected, strong cross-reactivity between HRV genotypes of the same species was found. A high degree of cross-reactivity between different HRV species was also evident, particularly between HRV-A and HRV-C. Immunoabsorption studies revealed HRV-C specific titres were markedly and significantly lower than the HRV-A and HRV-B specific titres (P<0.0001. A truncated construct of HRV-C VP1 showed greater specificity in detecting anti-HRV-C antibodies. CONCLUSIONS: High titres of IgG1 antibody were bound by the VP1 capsid proteins of HRV-A, -B and -C, but for the majority of people, a large proportion of the antibody to HRV-C was cross-reactive, especially to HRV-A. The improved specificity found for the truncated HRV-C VP1 indicates species-specific and cross-reactive regions could be defined.
Full Text Available Abstract Background We report the first multi-site rotavirus genotype analysis in Canada. Prior to this study, there was a dearth of rotavirus G and P genotyping data in Canada. Publically funded universal rotavirus vaccination in Canada started in 2011 and has been introduced by four provinces to date. Uptake of rotavirus vaccines in Canada prior to 2012 has been very limited. The aim of this study was to describe the genotypes of rotavirus strains circulating in Canada prior to widespread implementation of rotavirus vaccine by genotyping samples collected from selected paediatric hospitals. Secondly we identified rotavirus strains that differed genetically from those included in the vaccines and which could affect vaccine effectiveness. Methods Stool specimens were collected by opportunity sampling of children with gastroenteritis who presented to emergency departments. Samples were genotyped for G (VP7 genotypes and P (VP4 genotypes by hemi-nested multiplex PCR methods. Phylogenetic analysis was carried out on Canadian G9 strains to investigate their relationship to G9 strains that have circulated in other regions of the world. Results 348 samples were collected, of which 259 samples were rotavirus positive and genotyped. There were 34 rotavirus antigen immunoassay negative samples genotyped using PCR-based methods. Over the four rotavirus seasons, 174 samples were G1P, 45 were G3P, 22 were G2P, 13 were G9P, 3 were G4P and 2 were G9P. Sequence analysis showed that all Canadian G9 isolates are within lineage III. Conclusions Although a limited number of samples were obtained from a median of 4 centres during the 4 years of the study, it appears that currently approved rotavirus vaccines are well matched to the rotavirus genotypes identified at these hospitals. Further surveillance to monitor the emergence of rotavirus genotypes in Canada is warranted.
Background We report the first multi-site rotavirus genotype analysis in Canada. Prior to this study, there was a dearth of rotavirus G and P genotyping data in Canada. Publically funded universal rotavirus vaccination in Canada started in 2011 and has been introduced by four provinces to date. Uptake of rotavirus vaccines in Canada prior to 2012 has been very limited. The aim of this study was to describe the genotypes of rotavirus strains circulating in Canada prior to widespread implementation of rotavirus vaccine by genotyping samples collected from selected paediatric hospitals. Secondly we identified rotavirus strains that differed genetically from those included in the vaccines and which could affect vaccine effectiveness. Methods Stool specimens were collected by opportunity sampling of children with gastroenteritis who presented to emergency departments. Samples were genotyped for G (VP7) genotypes and P (VP4) genotypes by hemi-nested multiplex PCR methods. Phylogenetic analysis was carried out on Canadian G9 strains to investigate their relationship to G9 strains that have circulated in other regions of the world. Results 348 samples were collected, of which 259 samples were rotavirus positive and genotyped. There were 34 rotavirus antigen immunoassay negative samples genotyped using PCR-based methods. Over the four rotavirus seasons, 174 samples were G1P, 45 were G3P, 22 were G2P, 13 were G9P, 3 were G4P and 2 were G9P. Sequence analysis showed that all Canadian G9 isolates are within lineage III. Conclusions Although a limited number of samples were obtained from a median of 4 centres during the 4 years of the study, it appears that currently approved rotavirus vaccines are well matched to the rotavirus genotypes identified at these hospitals. Further surveillance to monitor the emergence of rotavirus genotypes in Canada is warranted. PMID:23153184
Sultan Kocaman Aksakal
Full Text Available GCOS (Global Climate Observing System is a long-term program for monitoring the climate, detecting the changes, and assessing their impacts. Remote sensing techniques are being increasingly used for climate-related measurements. Imagery of the SEVIRI instrument on board of the European geostationary satellites Meteosat-8 and Meteosat-9 are often used for the estimation of essential climate variables. In a joint project between the Swiss GCOS Office and ETH Zurich, geometric accuracy and temporal stability of 1-km resolution HRV channel imagery of SEVIRI have been evaluated over Switzerland. A set of tools and algorithms has been developed for the investigations. Statistical analysis and blunder detection have been integrated in the process for robust evaluation. The relative accuracy is evaluated by tracking large numbers of feature points in consecutive HRV images taken at 15-minute intervals. For the absolute accuracy evaluation, lakes in Switzerland and surroundings are used as reference. 20 lakes digitized from Landsat orthophotos are transformed into HRV images and matched via 2D translation terms at sub-pixel level. The algorithms are tested using HRV images taken on 24 days in 2008 (2 days per month. The results show that 2D shifts that are up to 8 pixels are present both in relative and absolute terms.
Etemadi, Mohammad Reza; Othman, Norlijah; Savolainen-Kopra, Carita; Sekawi, Zamberi; Wahab, NoraAbd; Sann, Lye Munn
There is accumulating evidence that human rhinovirus (HRV) causes acute lower respiratory tract infections (ALRTI). Recently, HRV-C was identified as a new species of HRV, but its spectrum of clinical disease is not well understood. We investigated the molecular epidemiology, demographic and clinical characteristics of HRVs among hospitalized children with ALRIs. One hundred and sixty-five nasopharangeal aspirates taken from children respiratory viruses were also investigated using semi-nested multiplex RT-PCR assay. Clinical parameters were analyzed between HRV, RSV and IFV-A mono-infections and between HRV species. HRV was detected in 54 (33%) patients for both single (36 samples) and multiple (18 samples) infections, 61.1% (22/36) represents HRV-A strains while the remaining 14 HRV-C. Strain P51 was the first reported representative of HRV98. The majority of the single HRV cases were in the second half of infancy; HRV-C occurred among older children compared with HRV-A. HRV children were admitted significantly earlier and less febrile than RSV and IFV-A infection. HRV-C infected children were more likely to have rhonchi and vomiting as compared to HRV-A. Pneumonia was the most common discharge diagnosis followed by bronchiolitis and post-viral wheeze in HRV patients. Our study showed high prevalence of HRVs and detection of HRV-C among hospitalized children with ALRTIs in Malaysia. Analysis of clinical parameters suggested specific features associated with HRVs infections and specific HRV groups. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.
AVANT Immunotherapeutics (formerly Virus Research Institute) and GlaxoSmithKline are developing a live oral rotavirus vaccine with potential to elicit a broadly-protective immune response against the most prevalent strains of rotavirus. Following successful completion of a phase II clinical efficacy trial in June 1999, SmithKline Beecham (now GlaxoSmithKline) assumed responsibility for all subsequent clinical and other development activities , . Following a licensing agreement, the vaccine was refined and renamed RIX-4414 . In May 2000, AVANT reported the results of a second-year surveillance extension of the phase II study. The results suggested that AVANT's two-dose oral rotavirus vaccine should be helpful in preventing rotavirus gastroenteritis (RGE) disease in young children for at least two years following administration . In March 2000, SmithKline Beecham reported that it had initiated phase I/II bridging studies in Europe and the company planned to start phase III safety and efficacy studies in 2001 after review with the health authorities . In October 2000, Dain Rauscher Wessels stated that an estimated market penetration of 30 to 40% suggested potential sales in excess of US $500 million pa. As a result, the analysts also estimated that incremental revenues to AVANT could be over US $50 million pa .
Singh, Butta; Singh, Dilbag; Jaryal, A. K.; Deepak, K. K.
Approximate entropy (ApEn) and sample entropy (SampEn) are the promising techniques for extracting complex characteristics of cardiovascular variability. Ectopic beats, originating from other than the normal site, are the artefacts contributing a serious limitation to heart rate variability (HRV) analysis. The approaches like deletion and interpolation are currently in use to eliminate the bias produced by ectopic beats. In this study, normal R-R interval time series of 10 healthy and 10 acute myocardial infarction (AMI) patients were analysed by inserting artificial ectopic beats. Then the effects of ectopic beats editing by deletion, degree-zero and degree-one interpolation on ApEn and SampEn have been assessed. Ectopic beats addition (even 2%) led to reduced complexity, resulting in decreased ApEn and SampEn of both healthy and AMI patient data. This reduction has been found to be dependent on level of ectopic beats. Editing of ectopic beats by interpolation degree-one method is found to be superior to other methods.
Shim, Jung Ok; Thai Than, Van; Ryoo, Eell; Lim, Inseok; Yoon, Yoosik; Kim, Kijeong; Chung, Sang-In; Kim, Wonyong
Genotyping of human rotaviruses was performed on 299 (40.1%) rotavirus-positive samples obtained from 745 children with acute diarrhea in three provinces in South Korea between March 2008 and February 2010, approximately 2 years following the introduction of the RotaTeq (September 2007) and Rotarix (July 2008). The most prevalent G genotypes were G1 (51.5%), followed by G3 (24.0%), G4 (15.4%), G9 (6.4%), and G2 (4.7%). The predominant types of P genotypes were P (72.6%), followed by P (19.1%) and P (6.0%). The phylogenetic analyses of the VP7 genes of G9 strains revealed they were highly identical and belonged in lineage III. This study highlights the consistency of the predominant G1 genotype and slightly higher predominance of the identical G9 strains over the G2 genotype. Copyright © 2013 Wiley Periodicals, Inc.
Ichihara, Maria Y T; Rodrigues, Laura C; Teles Santos, Carlos A S; Teixeira, Maria da Gloria L C; De Jesus, Sandra R; Alvim De Matos, Sheila M; Gagliardi Leite, Jose P; Barreto, Mauricio L
Rotavirus is one of the leading cause of hospitalization and outpatients visits among children under five years. This study evaluated overall and genotype-specific vaccine effectiveness of oral monovalent rotavirus vaccine (G1P strain) in preventing hospital admission of Brazilian children with rotavirus acute diarrhea. A hospital based case-control study was conducted in five Regions of Brazil using the National Rotavirus Acute Diarrhea Surveillance System from July 2008 to August 2011. A total of 215 cases (aged 4-24 months) admitted with confirmed rotavirus diarrhea were recruited and 1961 controls hospitalized without diarrhea were frequency matched by sex and age group to cases. Two-dose adjusted vaccine effectiveness (adjusted by year of birth and the frequency matching variables) was 76% (95%CI: 58-86) lasting for two years. Effectiveness controlled by the available potential confounders was 72% (95%CI: 44-85), suggesting no appreciable confounding by those factors for which adjustment was made. In a half of the cases the rotavirus genotype was G2P and in 15% G1P. Genotype-specific VE (two doses) was 89% (95%CI: 78-95), for G1P and 76% (95%CI: 64-84) for G2P. For all G1, it was 74% (95%CI: 35-90), for all G2, 76% (95%CI: 63-84), and for all non G1/G2 genotypes, 63% (95%CI: -27-99). Effectiveness for one dose was 62% (95%CI: 39-97). Effectiveness of two-dose monovalent rotavirus vaccine in preventing hospital admission with rotavirus diarrhea was high, lasted for two years and it was similar against both G1P and G2P. Based on the findings of the study we recommend the continued use of rotavirus in the Brazilian National Immunization Program and the monitoring of the early emergence of unusual and novel rotavirus genotypes. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Full Text Available Objetivo. Comparar la gravedad de la diarrea por rotavirus (RV y por no rotavirus. Material y métodos. Estudio transversal en 520 lactantes con diarrea aguda, efectuado entre octubre de 1994 y marzo de 1995 en siete centros del primer nivel de atención en cinco estados de México. El diagnóstico de RV se realizó con ensayo inmunoenzimático o por electroforesis. El análisis se hizo a través de medidas de tendencia central. Los resultados se presentan como promedio y desviación estándar o mediana o variación. Resultados. Se aisló RV en 264 lactantes (50.7% con predominio en varones de 6 meses a un año. Las manifestaciones clínicas fueron significativamente diferentes entre el grupo rotavirus positivo y el grupo rotavirus negativo en mediana de evacuaciones por 24 horas, frecuencia de vómitos, temperatura > 38° C, deshidratación y calificación de gravedad, respectivamente. Conclusiones. Estos resultados mostraron peor pronóstico por mayor gravedad de la diarrea por RV en lactantes, con relación a otra etiología. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.htmlObjective. To compare the severity of rotavirus diarrhea (RV and non-rotavirus diarrhea. Material and Methods. Between October 1994 and March 1995, a cross-sectional study was performed in 520 infants with acute diarrhea, at seven primary care level centers in five states of Mexico. Diagnosis of RV was done through immunoenzymatic assay or electrophoresis. Central tendency measures were used for data analysis. Results were presented as means and standard deviations, or median and variation. Results. RV was isolated from 264 children; most of them were males aged 6 months to 1 year. Differences in clinical manifestations were statistically significant between the rotavirus-positive group and the rotavirus-negative group, in the following variables: median number of stools/24 hours; frequency of vomiting; temperature > 38
Maheshkumar, K; Dilara, K; Maruthy, K N; Sundareswaren, L
Heart rate variability (HRV) analysis is a simple and noninvasive technique capable of assessing autonomic nervous system modulation on heart rate (HR) in healthy as well as disease conditions. The aim of the present study was to compare (validate) the HRV using a temporal series of electrocardiograms (ECG) obtained by simple analog amplifier with PC-based sound card (audacity) and Biopac MP36 module. Based on the inclusion criteria, 120 healthy participants, including 72 males and 48 females, participated in the present study. Following standard protocol, 5-min ECG was recorded after 10 min of supine rest by Portable simple analog amplifier PC-based sound card as well as by Biopac module with surface electrodes in Leads II position simultaneously. All the ECG data was visually screened and was found to be free of ectopic beats and noise. RR intervals from both ECG recordings were analyzed separately in Kubios software. Short-term HRV indexes in both time and frequency domain were used. The unpaired Student's t-test and Pearson correlation coefficient test were used for the analysis using the R statistical software. No statistically significant differences were observed when comparing the values analyzed by means of the two devices for HRV. Correlation analysis revealed perfect positive correlation (r = 0.99, P < 0.001) between the values in time and frequency domain obtained by the devices. On the basis of the results of the present study, we suggest that the calculation of HRV values in the time and frequency domains by RR series obtained from the PC-based sound card is probably as reliable as those obtained by the gold standard Biopac MP36.
Full Text Available Objective: To observe the HRV changes before and after the radiofrequency current catheter ablationventricular premature beats originated from different site of right ventricular outflow tract. Methods: A total of 102 patients with frequent RVOT-VPC admitted to our hospital were accepted radiofrequency current catheter ablation (RF. According to the origin of RVOT-VPC, it was divided into 2 groups, one is from ventricular septum, and the other one is from free wall, and in each group, male and female are observed separately. Results: (1 HRV before RF ablation: 1 rMSSD in the female patients with RVOT-VPC from free wall was significantly lower than those from septum; 2 frequency domain index (W, LF were higher than normal range, and in male patients, LF/HF1. (2 HRV after RF ablation: 1 Significant changes were found in female patients with RVOT-VPC from septum, rMSSD, PNN50, HF and LF decreased; 2 In female patients with RVOT-VPC from free wall, rMSSD decreased; 3 In male patients, there were no significant HRV changes found before and after RF ablation. (3 Heart rate changes: 1 In female patients with RVOT-VPC from septum, heart rate decreased significantly [(76.47±9.47 bpm vs (69.29±14.59 bpm]. 2 No significant changes were found in male patients. Conclusion: In patients with RVOT-PVC sympathetic and vagus excitability increased, and after catheter ablation, in female patients with RVOT-PVC originated from septum, the HRV index relating to sympathetic and vagus excitability significantly decreased.
Fischer, Thea Kølsen; Nielsen, Nete Munk; Wohlfahrt, Jan
In anticipation of licensure and introduction of rotavirus vaccine into the western market, we used modeling of national hospital registry data to determine the incidence and direct medical costs of annual rotavirus-associated admissions over >11 years in Denmark. Diarrhea-associated hospitalizat......In anticipation of licensure and introduction of rotavirus vaccine into the western market, we used modeling of national hospital registry data to determine the incidence and direct medical costs of annual rotavirus-associated admissions over >11 years in Denmark. Diarrhea......-associated hospitalizations coded as nonspecified viral or presumed infectious have demonstrated a marked winter peak similar to that of rotavirus-associated hospitalizations, which suggests that the registered rotavirus-coded admissions are grossly underestimated. We therefore obtained more realistic estimates by 2...... models to analyze readily available hospital discharge data resulted in more consistent and reliable estimates....
Cowley, Daniel; Bogdanovic-Sakran, Nada; Hutton, Melanie L.; Lyras, Dena; Kirkwood, Carl D.; Buttery, Jim P.
ABSTRACT Rotavirus gastroenteritis is a leading global cause of mortality and morbidity in young children due to diarrhea and dehydration. Over 85% of deaths occur in developing countries. In industrialised countries, 2 live oral rotavirus vaccines licensed in 2006 quickly demonstrated high effectiveness, dramatically reducing severe rotavirus gastroenteritis admissions in many settings by more than 90%. In contrast, the same vaccines reduced severe rotavirus gastroenteritis by only 30–60% in developing countries, but have been proven life-saving. Bridging this “efficacy gap” offers the possibility to save many more lives of children under the age of 5. The reduced efficacy of rotavirus vaccines in developing settings may be related to differences in transmission dynamics, as well as host luminal, mucosal and immune factors. This review will examine strategies currently under study to target the issue of reduced efficacy and effectiveness of oral rotavirus vaccines in developing settings. PMID:27835052
Jacobs, Samantha E; Lamson, Daryl M; Soave, Rosemary; Guzman, Brigitte Huertas; Shore, Tsiporah B; Ritchie, Ellen K; Zappetti, Dana; Satlin, Michael J; Leonard, John P; van Besien, Koen; Schuetz, Audrey N; Jenkins, Stephen G; George, Kirsten St; Walsh, Thomas J
Human rhinoviruses (HRVs) are common causes of upper respiratory tract infection (URTI) in hematologic malignancy (HM) patients. Predictors of lower respiratory tract infection (LRTI) including the impact of HRV species and types are poorly understood. This study aims to describe the clinical and molecular epidemiology of HRV infections among HM patients. From April 2012-March 2013, HRV-positive respiratory specimens from symptomatic HM patients were molecularly characterized by analysis of partial viral protein 1 (VP1) or VP4 gene sequence. HRV LRTI risk-factors and outcomes were analyzed using multivariable logistic regression. One hundred and ten HM patients presented with HRV URTI (n=78) and HRV LRTI (n=32). Hypoalbuminemia (OR 3.0; 95% CI, 1.0-9.2; p=0.05) was independently associated with LRTI, but other clinical and laboratory markers of host immunity did not differ between patients with URTI versus LRTI. Detection of bacterial co-pathogens was common in LRTI cases (25%). Among 92 typeable respiratory specimens, there were 58 (64%) HRV-As, 12 (13%) HRV-Bs, and 21 (23%) HRV-Cs, and one Enterovirus 68. LRTI rates among HRV-A (29%), HRV-B (17%), and HRV-C (29%) were similar. HRV-A infections occurred year-round while HRV-B and HRV-C infections clustered in the late fall and winter. HRVs are associated with LRTI in HM patients. Illness severity is not attributable to specific HRV species or types. The frequent detection of bacterial co-pathogens in HRV LRTIs further substantiates the hypothesis that HRVs predispose to bacterial superinfection of the lower airways, similar to that of other community-acquired respiratory viruses. Copyright © 2015 Elsevier B.V. All rights reserved.
Azim, Tasnim; Zaki, M Hasan; Podder, Goutam; Sultana, Novera; Salam, M Abdus; Rahman, S Moshfiqur; Sefat-e-Khuda; Sack, David A
Rotavirus-specific subclass antibody responses and cytokines, tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-8 (IL-8), and IL-10, were measured in children 7-24 months of age with rotavirus diarrhoea (n = 29); the responses were compared with children with watery diarrhoea from whom no enteric pathogens were isolated (controls; n = 11). All children had diarrhoea for or = 4-fold rise in antibody titre between the acute and convalescent stages were considered to have a response. The numbers of children with rotavirus-specific IgA and IgA1 responses in stool were similar in the two groups of children. In the plasma, more children with rotavirus diarrhoea had rotavirus-specific IgA, IgA1, IgG, IgG1, and IgG3 responses than did control children (P = 0.049, 0.007, 0.001, 0.002, and 0.012, respectively). IgA2 was not detectable. Among cytokines measured in supernatants from peripheral blood mononuclear cells (PBMCs) cultured for 6 and 24 hr, IFN-gamma was the only cytokine that was higher in children with rotavirus diarrhoea compared with controls (P = 0.013). Severity of illness did not correlate with nutritional status or antibody titres, but severity did correlate with TNF-alpha during the acute stage of illness. IFN-gamma correlated positively with IgG1 titres. These findings suggest a role for IFN-gamma in the pathogenesis of rotavirus infection, but this needs confirmation by other studies. The immune responses described are relevant to future vaccine trials, as immune responses in vaccinees should mimic those in natural infection.
Kordasti, S; Sjövall, H; Lundgren, O; Svensson, L
Background and aims: The mechanisms underlying intestinal secretion in rotavirus diarrhoea remain to be established. We previously reported that rotavirus evokes intestinal fluid and electrolyte secretion by activation of the enteric nervous system. We now report that antagonists for the 5-hydroxytryptamine 3 receptor (5-HT3) and vasoactive intestinal peptide (VIP) receptor, but not antagonists for 5-hydroxytryptamine 4 receptor or the muscarinic receptor, attenuate rotavirus induced diarrhoea.
Uchiyama, Robin; Chassaing, Benoit; Zhang, Benyue; Gewirtz, Andrew T.
Background. Rotavirus causes 500 000 deaths and millions of physician visits and hospitalizations per year, with worse outcomes and reduced vaccine efficacy in developing countries. We hypothesized that the gut microbiota might modulate rotavirus infection and/or antibody response and thus potentially play a role in such regional differences. Methods. The microbiota was ablated via germ-free or antibiotic approaches. Enhanced exposure to microbiota was achieved via low-dose dextran sodium sulfate (DSS) treatment. Rotavirus infection and replication was assessed by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse-transcription polymerase chain reaction. Diarrhea was scored visually. Humoral responses to rotavirus were measured by ELISA and enzyme-linked immunosorbent spot assay. Results. Microbiota elimination delayed infection and reduced infectivity by 42%. Antibiotics did not alter ratios of positive-sense to negative-sense strands, suggesting that entry rather than replication was influenced. Antibiotics reduced the diarrhea incidence and duration, indicating that the reduction in the level of rotavirus antigen was biologically significant. Despite lowered antigen level, antibiotics resulted in a more durable rotavirus mucosal/systemic humoral response. Increased rotavirus antibody response durability correlated with increased small intestinal rotavirus-specific, immunoglobulin A–producing antibody-secreting cell concentration in antibiotic-treated mice. Conversely, DSS treatment impaired generation of rotavirus-specific antibodies. Conclusions. Microbiota ablation resulted in reduced rotavirus infection/diarrhea and a more durable rotavirus antibody response, suggesting that antibiotic administration before rotavirus vaccination could raise low seroconversion rates that correlate with the vaccine's inefficacy in developing regions. PMID:24436449
Verberk, J.D.M.; Bruijning, P.C.; de Melker, Hester
Rotavirus can cause a gastrointestinal infection and is common in young children. There are two vaccines available; both have to be administered via the mouth. The Dutch Health Council will advise the Ministry of Health, Welfare and Sport on how childhood vaccination against rotavirus will be made available. The Minister makes a decision on the basis of this advice. To support the Health Council, the RIVM has put together background information on rotavirus disease. The information includes t...
Verkerk JDM; Bruijning-Verhagen P; Melker H de; RVP; I. V.,
Rotavirus can cause a gastrointestinal infection and is common in young children. There are two vaccines available; both have to be administered via the mouth. The Dutch Health Council will advise the Ministry of Health, Welfare and Sport on how childhood vaccination against rotavirus will be made available. The Minister makes a decision on the basis of this advice. To support the Health Council, the RIVM has put together background information on rotavirus disease. The information includes ...
Kim, Sun-Young; Goldie, Sue J; Salomon, Joshua A
Abstract Background Rotavirus is the most common cause of severe diarrhea leading to hospitalization or disease-specific death among young children. New rotavirus vaccines have recently been approved. Some previous studies have provided broad qualitative insights into the health and economic consequences of introducing the vaccines into low-income countries, representing several features of rotavirus infection, such as varying degrees of severity and age-dependency of clinical manifestation, ...
Zhao, Wei; Xia, Mingjing; Bridges-Malveo, Tamika; Cantú, Mayra; McNeal, Monica M; Choi, Anthony H; Ward, Richard L; Sestak, Karol
We recently established a non-human primate model of rotavirus infection that is characterized by consistent and high levels of virus antigen shedding in stools. Here, we report that starting from post challenge day (PCD) 2, 6 x 10(3) to 1.5 x 10(6) copies of rotavirus double-stranded RNA per nanogram of total RNA were detected by real-time PCR in MA104 cells that were 48 h pre-incubated with filtered stool suspensions of three experimentally infected juvenile macaques. The peak of virus load was detected at PCD 4-5, followed by decreased load at PCD 6-11, and very low levels at PCD 12. Such a pattern corresponded to virus shedding in stools as reported recently based on enzyme-linked immunosorbent assay (ELISA) results. In addition, plasma and cerebrospinal fluids (CSF) from six infected animals were tested for the presence of rotavirus. Rotavirus extraintestinal escape was revealed in three out of six animals by a combination of real-time and nested PCR. However, very low quantities of detected viral RNA (approximately 20 copies/ng of total RNA) were not suggestive of viremia. Thus, the rhesus model of rotavirus infection can be exploited further in studies with vaccine candidates designed to prevent or abrogate rotavirus infection.
Zar Heather J
Full Text Available Abstract Background Infections caused by human rhinoviruses (HRVs are important triggers of wheezing in young children. Wheezy illness has increasingly been recognised as an important cause of morbidity in African children, but there is little information on the contribution of HRV to this. The aim of this study was to determine the role of HRV as a cause of acute wheezing in South African children. Methods Two hundred and twenty children presenting consecutively at a tertiary children's hospital with a wheezing illness from May 2004 to November 2005 were prospectively enrolled. A nasal swab was taken and reverse transcription PCR used to screen the samples for HRV. The presence of human metapneumovirus, human bocavirus and human coronavirus-NL63 was assessed in all samples using PCR-based assays. A general shell vial culture using a pool of monoclonal antibodies was used to detect other common respiratory viruses on 26% of samples. Phylogenetic analysis to determine circulating HRV species was performed on a portion of HRV-positive samples. Categorical characteristics were analysed using Fisher's Exact test. Results HRV was detected in 128 (58.2% of children, most (72% of whom were under 2 years of age. Presenting symptoms between the HRV-positive and negative groups were similar. Most illness was managed with ambulatory therapy, but 45 (35% were hospitalized for treatment and 3 (2% were admitted to intensive care. There were no in-hospital deaths. All 3 species of HRV were detected with HRV-C being the most common (52% followed by HRV-A (37% and HRV-B (11%. Infection with other respiratory viruses occurred in 20/128 (16% of HRV-positive children and in 26/92 (28% of HRV-negative samples. Conclusion HRV may be the commonest viral infection in young South African children with acute wheezing. Infection is associated with mild or moderate clinical disease.
Conclusions. 1. In the mixed form of rotavirus infection, in all cases we observed the lesions of the small intestine, which is often combined with lesions of the stomach, less often — of the large intestine. 2. Follow-up of children who suffered a mixed rotavirus infection should be carried out within three months, as in this period there are both common complaints and complaints from the gastrointestinal tract, not only in children in whom rotavirus antigen is still detectable, but also in children without isolation of rotavirus antigen.
Full Text Available The diarrhea morbidity in Indonesia has increased, however, all the reports had not been done carefully, so that accurate surveillance are essential for improving quality of morbidity data. To determine the prevalence and clinical manifestations of rotavirus diarrhea and to characterize the circulating rotavirus strains, children below 5 years old who were admitted to Hasan Sadikin Hospital, Bandung because of diarrhea, from January 2006 through March 2007 were enrolled in a surveillance study and had stool specimens tested for the presence of rotavirus using enzyme immunoassay (EIA. The strains of rotavirus were determined using reverse transcriptase-polymerase chain reaction (RT-PCR. Rotavirus were detected in 47.8% analyzed samples (87/184, G and P-genotype of rotavirus were G (37.5% and P (53.5%. Most subjects were males (56%, 6–11 months of age (35%. Most common clinical manifestations besides diarrhea were dehydration (72.7% and vomiting (50%. Subjects with positive rotavirus more common had dehydration (72% vs 28% and vomiting (61% vs 39%. In conclusion, vomiting and dehydration are the prominent clinical manifestations of diarrhea with positive rotavirus infection. G1 and P6 are the most common genotype of rotavirus.
lymphocytes secreting interferon gamma after acute natural rotavirus infection in children and adults. J Virology 2002; 76: 4741–4749.
5. ROJAS, O. L., A. M. GONZÁLEZ, R. GONZÁLEZ, I. PÉREZSCHAEL, H. B. GREENBERG, M. A. FRANCO AND J. ANGEL. Human rotavirus specific t cells: Quantification by elispot and expression of homing receptors on cd4+ t cells. Virology 2003; 314: 671–679.
Gamazo, P. A.; Schijven, J. F.; Victoria, M.; Alvareda, E.; Lopez, F.; Ramos, J.; Lizasoain, A.; Sapriza-Azuri, G.; Castells, M.; Colina, R.
Rotavirus and Norovirus are waterborne viruses that are major causes of diarrhea and others symptoms of acute gastroenteritis. An important pathway of these viruses is groundwater. In Uruguay, as in many developed and developing countries, there are areas where the only source of water for human consumption is groundwater. In the rural area of the Salto district, groundwater is commonly used without any treatment, as it is traditionally considered as a safe source. However, virus contamination have been detected in several wells in the area. The most probable source of contamination are nearby septic systems, since the sewer coverage is scarce. This work aims to evaluate and compare the virus transport processes for a standardised soil-water systems and for the Salto aquifer system. For this, the transport of Rotavirus and Norovirus from clinic samples was studied in two sets of column experiments: 6.7 cm columns with quartz sand under saturated conditions (ionic strength 1mM, pH 7.0) and with sand from the Salto aquifer (Uruguay) (9,2% coarse sand, 47,8% medium sand, 40,5% fine sand, magnesium/calcium bicarbonate water, Ionic strength 15.1 mM, pH 7.2). Both viruses were seeded for 2 pore volumes on the columns. Samples were collected at the column outlet and viruses were enumerated by Q-PRCR. Breakthrough curves were constructed and fitted to a two-site kinetic attachment/detachment model, including blocking using Hydrus-1D. In the quartz sand column, both Rotavirus and Norovirus were removed two orders in magnitude. In the Salto sand column, Rotavirus was removed 2 log10 as well, but Norovirus was removed 4 log10. The fitting of the breakthrough curves indicated that blocking played a role for Rotavirus in the Salto sand column. These results are consistent with field observation where only Rotavirus was detected in the Salto aquifer, while similar concentrations in Salto sewer effluent was measured for these two viruses. This work, besides reporting actual
Perez-Schael, I; Blanco, M; Garcia, D; White, L; Alfonzo, E; Crespo, I; Cunto, W; Pittman, A L; Kapikian, A Z; Flores, J
Three phase I trials of the rhesus rotavirus (RRV)-based quadrivalent vaccine [composed of serotype 3 (RRV), and serotypes 1 (D x RRV), 2 (DS1 x RRV), and 4 (ST3 x RRV) human rotavirus x RRV reassortants] and the M37 (nursery strain) rotavirus vaccine candidates were conducted in an attempt to find a safe and optimally antigenic formulation. Infants 10-20 weeks old received, in trial I, 1) the quadrivalent vaccine as two separate bivalent doses (1 x 10(4) PFU each of D x RRV and RRV, followed 4 weeks later by 1 x 10(4) PFU each of DS1 x RRV and ST3 x RRV) or 2) placebo; in trial II, 1) one dose of quadrivalent vaccine (10(4) PFU of each component), or 2) two doses of quadrivalent vaccine, or 3) a 10(4) PFU dose of M37 vaccine, or 4) M37 vaccine followed by the quadrivalent vaccine, or 5) placebo; in trial III, 1) a dose of a higher-titered quadrivalent vaccine (10(5) PFU of each component), or 2) two doses of higher titered quadrivalent vaccine, or 3) a dose of higher titered M37 vaccine (10(5) PFU) or 4) two doses of M37 vaccine (10(5) PFU), or 5) M37 vaccine (10(5) PFU) followed by the higher titered quadrivalent vaccine, or 6) placebo. A mild, transient fever during the first week postvaccination was associated with the bivalent or quadrivalent vaccines but not with the M37 vaccine. Fourfold or greater serum IgA ELISA responses to rotavirus were observed in 48-92% of the infants receiving quadrivalent vaccine and in 32-50% of those receiving M37 vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)
Sahakyan, Gayane; Grigoryan, Svetlana; Wasley, Annemarie; Mosina, Liudmila; Sargsyan, Shushan; Asoyan, Ara; Gevorgyan, Zaruhi; Kocharyan, Karine; Avagyan, Tigran; Lopman, Benjamin; Vanyan, Artavazd; Khactatryan, Sergey; Parashar, Umesh D; Cortese, Margaret M
The Republic of Armenia was 1 of the 2 earliest countries in the Newly Independent States to introduce rotavirus vaccine into its national immunization program to reduce the burden of rotavirus disease (documented to cause 38% of acute gastroenteritis hospitalizations [AGE] among children aged rotavirus antigen, was used to assess trends in rotavirus hospitalizations. Immunization records on children enrolled after vaccine introduction were obtained from clinics, and vaccine effectiveness (VE) was estimated using children with AGE who test negative for rotavirus as controls for the rotavirus-positive cases. Among infants, rotavirus hospitalizations were reduced by 48% within the first year after introduction, and by ≥75% in years 2 and 3 following introduction. Reductions of ≥30% in other young children too old to have been vaccinated suggest additional benefit through indirect protection; overall in year 3, rotavirus hospitalizations were reduced by 69% among children aged rotavirus hospitalization (any severity) was 62% (95% confidence interval [CI], 36%-77%) among children aged 6-23 months; 68% (95% CI, 24%-86%) among those aged 6-11 months, and 60% (95% CI, 20%-80%) in children aged 12-23 months. Against more severe rotavirus disease, VE was 79% (95% CI, 55%-90%) and similarly high in both age groups. RV1 is effective in young Armenian children and substantially reduced rotavirus hospitalizations shortly after introduction. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Silva Maria Luzia da Rosa e
Full Text Available In order to develop good polices regarding public health measures and vaccine use to prevent rotavirus induced gastroenteritis, the epidemiology of the illness in various regions of Brazil is necessary. Accordingly, this study was to detect the frequency and types of rotavirus in one city in a tropical part of Brazil. This is an epidemiological survey of pediatric gastroenteritis caused by rotavirus conducted in Juiz de Fora, Minas Gerais State, Brazil. We analyzed 656 in-patient (190 and out-patient (466 stool samples from children ages 0 to 5 years during 1998. Rotavirus detection was performed using polyacrylamide gel electrophoresis (PAGE. Rotavirus was isolated from 62/190 stool samples (32.6% from hospitalized children and 16/466 (3.4% from out-patients. The overall rotavirus frequency in this population was 11.9%. The highest rotavirus detection was found in hospitalized children ages 6 to 24 months. Rotaviruses were detected from March to September, with a peak incidence in June (33.3%, the coldest and driest month in the region. Electrophoretic analysis identified 10 different profiles, all long and compatible with group A rotavirus, termed L A through LJ. The L B and L D profiles circulated throughout most of the study period. However, in June, when the highest detection rate occurred, the vast majority (92.5% of the positive samples displayed the L B profile, thus suggesting an outbreak caused by this rotavirus profile. Rotavirus induced gastroenteritis is common in one tropical region of Brazil, it is an important cause of diarrhea in hospitalized children ages 6 to 24 months, it is most common during dry, cold months of the year, and it may occur in electrophoretype restricted epidemics. Such analyses throughout Brazil will assist in developing sound guidelines regarding its prevention.
Chen, Wei-Ju; Arnold, John C; Fairchok, Mary P; Danaher, Patrick J; McDonough, Erin A; Blair, Patrick J; Garcia, Josefina; Halsey, Eric S; Schofield, Christina; Ottolini, Martin; Mor, Deepika; Ridoré, Michelande; Burgess, Timothy H; Millar, Eugene V
human rhinovirus (HRV) is a major cause of influenza-like illness (ILI) in adults and children. Differences in disease severity by HRV species have been described among hospitalized patients with underlying illness. Less is known about the clinical and virologic characteristics of HRV infection among otherwise healthy populations, particularly adults. to characterize molecular epidemiology of HRV and association between HRV species and clinical presentation and viral shedding. observational, prospective, facility-based study of ILI was conducted from February 2010 to April 2012. Collection of nasopharyngeal specimens, patient symptoms, and clinical information occurred on days 0, 3, 7, and 28. Patients recorded symptom severity daily for the first 7 days of illness in a symptom diary. HRV was identified by RT-PCR and genotyped for species determination. Cases who were co-infected with other viral respiratory pathogens were excluded from the analysis. We evaluated the associations between HRV species, clinical severity, and patterns of viral shedding. eighty-four HRV cases were identified and their isolates genotyped. Of these, 62 (74%) were >18 years. Fifty-four were HRV-A, 11HRV-B, and 19HRV-C. HRV-C infection was more common among children than adults (59% vs. 10%, P<0.001). Among adults, HRV-A was associated with higher severity of upper respiratory symptoms compared to HRV-B (P=0.02), but no such association was found in children. In addition, adults shed HRV-A significantly longer than HRV-C (P trend=0.01). among otherwise healthy adults with HRV infection, we observed species-specific differences in respiratory symptom severity and duration of viral shedding. Copyright © 2015 Elsevier B.V. All rights reserved.
Jensen, Marie Aarrebo; Garde, Anne Helene; Kristiansen, Jesper
PURPOSE: The purpose of this review is to summarize the current knowledge from field studies on how many consecutive night shifts are required for adaptation of diurnal rhythms in cortisol, melatonin and heart rate variability (HRV) to night work. METHODS: A systematic search of the databases Pub......Med and Web of Science resulted in 18 studies selected for review. RESULTS: Cortisol was measured in five studies, melatonin in 11 studies and HRV in four studies. Diurnal rhythms were assessed by use of several different measures based on three to eight samples per day for cortisol and melatonin and 24-h...... to night work had not occurred after two consecutive night shifts, whereas a small number found evidence for full adaptation after seven consecutive night shifts based on diurnal rhythms in cortisol and melatonin. CONCLUSION: There are methodological differences in the field studies analyzing diurnal...
Sharma, Sumit; Paul, Vinod K; Bhan, Maharaj K; Ray, Pratima
In the present investigation we molecularly characterized nontypeable rotavirus strains previously identified during surveillance in New Delhi, India. The majority of strains were demonstrated to belong to genotype G1 (54.5%) or P (77.8%) on the basis of nucleotide sequencing of fragments from their VP7 and VP4 genes. The other genotypes detected included G2, G8, G9, G12, and P. A G8P strain, strain DS108, was detected for the first time in northern India. The VP7 gene of DS108 was most homologous with the VP7 gene of a bovine G8 strain, strain A5 (98.9%), indicating its bovine parentage. In contrast, the VP4 gene had a high degree of nucleotide sequence homology (92.9% to 99.1%) with the VP4 genes of human P strains. The VP6 gene and nonstructural genes (NSP1 to NSP3 and NSP5) were most homologous with the VP6 gene and nonstructural genes of human rotaviruses belonging to the DS1 genogroup. Interestingly, the NSP4 gene of DS108 clustered within genotype E6 that until now had only two representative strains, both with G12P specificity (strains RV176-00 and N26-02). Together, these results indicate that G8 strain DS108 belongs to the DS1 genogroup and could be the result of the acquisition of the VP7, VP4, and NSP4 genes by a human G2P strain from more than one donor, similar to the evolution of G12P strain RV176-00. The present study highlights the importance of characterizing multiple genes of nontypeable rotavirus strains to detect novel strains and get a more complete picture of rotavirus evolution.
Kuate Defo, Zenas; Lee, Byong
Rotavirus is the leading cause of severe dehydrating diarrhea worldwide, and affects primarily developing nations, in large part because of the inaccessibility of vaccines and high rates of mortality present therein. At present, there exist two oral rotaviral vaccines, Rotarix™ and RotaTeq™. These vaccines are generally effective in their actions: however, associated costs often stymie their effectiveness, and they continue to be associated with a slight risk of intussusception. While different programs are being implemented worldwide to enhance vaccine distribution and monitor vaccine administration for possible intussusception in light of recent WHO recommendation, another major problem persists: that of the reduced efficacy of the existing rotaviral vaccines in developing countries over time. The development of new oral rotavirus vaccine classes - live-attenuated vaccines, virus-like particles, lactic acid bacteria-containing vaccines, combination therapy with immunoglobulins, and biodegradable polymer-encapsulated vaccines - could potentially circumvent these problems.
Dash, Nabaneeta; Verma, Sanjay
Pertussis and rotavirus vaccines have been the subject of several controversies over the years. In this paper the authors discuss facts and myths behind these controversies and also suggest solutions to overcome some limitations of these vaccines. The whole-cell pertussis vaccine (wPV) came into disrepute due to the associated adverse reactions, resulting in its replacement by acellular pertussis vaccine (aPV) in industrialized nations in 1990s. Although wPV is known to have more side effects; but they are usually minor. Whole-cell pertussis containing vaccine is being used safely in the National Immunization programme in India from many years. Another controversy erupted during 2009-2010, when there were reports of resurgence of pertussis cases among adolescents and adults, from developed nations. Present literature review raises doubts about long term protection offered by aPV, when compared with wPV. In spite of prevailing controversy, acellular pertussis containing vaccines should be acceptable, if timely delivery of primary and booster doses is ensured; including vaccination of adolescents and pregnant women. Initial rotavirus vaccine was withdrawn from the market because of increased risk of intussusception. Although three new generation rotavirus vaccines are currently available for use in India, but doubts about their efficacy, long term protection and safety still exists. Present literature review found them to be safe and moderately efficacious because of reasonable good cross protection. Even a moderately efficacious vaccine like rotavirus vaccine could significantly improve the outcome if disease burden is high. Therefore, it is being included in National Immunization Programme of India.
Full Text Available Human rhinoviruses (HRV are known to cause common cold as well as more complicated respiratory infections. HRV species -A, -B and -C have all been associated with lower respiratory infections and exacerbations of asthma. However, the type distribution of strains connected to different kinds of lower respiratory conditions is not clearly known. We have analysed the presence of HRV in sputum specimens derived from military recruits with and without pre-diagnosed asthma at times of acute respiratory infection (CIAS Study, 2004-2005. The analysis was performed with HRV and HEV real-time RT-PCR assays. Subsequently we studied type distribution of HRV strains by genetic typing in the VP4/VP2 genomic region. In total 146 (38.8% specimens were HRV-positive and 36 (9.3% HEV-positive. No difference was found in HRV detection between the asthmatic vs. non-asthmatic patients. Most of the genetically typed strains, 18 (62.1%, belonged to HRV-A, while HRV-B strains constituted five (17.2% of the HRV-positive strains. HRV-C strain was typed four times from the HRV-positive cases and a HEV-D strain twice. We further typed six HEV positive strains in the partial VP1 region. Three of these belonged to HRV-A and three to HEV-D. HRV-A strains were discovered throughout the study period, while HRV-C strains originated from winter and spring specimens. Interestingly, four out of five typed HRV-B strains originated from the summer season specimens.
Martin, Emily K; Kuypers, Jane; Chu, Helen Y; Lacombe, Kirsten; Qin, Xuan; Strelitz, Bonnie; Bradford, Miranda; Jones, Charla; Klein, Eileen J; Englund, Janet A
Human rhinovirus (HRV) infections are highly prevalent, genetically diverse, and associated with both mild upper respiratory tract and more severe lower tract illnesses (LRTI). To characterize the molecular epidemiology of HRV infections in young children seeking acute medical care. Nasal swabs collected from symptomatic children FilmArray(®)) for multiple viruses including HRV/enterovirus. HRV-positive results were confirmed by laboratory-developed real-time reverse transcription PCR (LD-PCR). Clinical data were collected by chart review. A subset of samples was selected for sequencing using the 5' noncoding region. Associations between LRTI and HRV species and genotypes were estimated using logistic regression analysis. Of 595 samples with HRV/enterovirus detected by FilmArray, 474 (80%) were confirmed as HRV by LD-PCR. 211 (96%) of 218 selected samples were sequenced; HRV species A, B, and C were identified in 133 (63%), 6 (3%), and 72 (34%), respectively. LRTI was more common in HRV-C than HRV-A illness episodes (adjusted OR [95% CI] 2.35[1.03-5.35). Specific HRV-A and HRV-C genotypes detected in multiple patients were associated with a greater proportion of LRTI episodes. In 18 patients with >1 HRV-positive illness episodes, a distinct genotype was detected in each. Diverse HRV genotypes circulated among symptomatic children during the study period. We found an association between HRV-C infections and LRTI in this patient population and evidence of association between specific HRV genotypes and LRTI. Copyright © 2014 Elsevier B.V. All rights reserved.
Santos, Victor S; Marques, Daniella P; Martins-Filho, Paulo R S; Cuevas, Luis E; Gurgel, Ricardo Q
Rotavirus was the leading cause of childhood diarrhoea-related hospitalisations and death before the introduction of rotavirus vaccines. We describe the effectiveness of rotavirus vaccines to prevent rotavirus infections and hospitalizations and the main rotavirus strains circulating before and after vaccine introduction through a systematic review and meta-analysis of studies published between 1990 and 2014. 203 studies were included to estimate the proportion of infections due to rotavirus and 10 to assess the impact of the vaccines. 41 of 46 studies in the post-vaccination period were used for meta-analysis of genotypes, 20 to calculate VE against infection, eight for VE against hospitalisation and seven for VE against severe rotavirus-diarrhoea. 24.3 % (95 % CI 22.1-26.5) and 16.1 % (95 % CI 13.2-19.3) of cases of diarrhoea were due to rotavirus before and after vaccine introduction, respectively. The most prevalent G types after vaccine introduction were G2 (51.6 %, 95 % CI 38-65), G9 (14.5 %, 95 % CI 7-23) and G1 (14.2 %, 95 % CI 7-23); while the most prevalent P types were P (54.1 %, 95 % CI 41-67) and P (33 %, 95 % CI 22-46). G2P was the most frequent genotype combination after vaccine introduction. Effectiveness was 53 % (95 % CI 46-60) against infection, 73 % (95 % CI, 66-78) against hospitalisation and 74 % (95 % CI, 68.0-78.0) against severe diarrhoea. Reductions in hospitalisations and mortality due to diarrhoea were observed in countries that adopted universal rotavirus vaccination. Rotavirus vaccines are effective in preventing rotavirus-diarrhoea in children in Latin America. The vaccines were associated with changes in genotype distribution.
Full Text Available Objective. To assess the disease burden of rotavirus diarrhea in Peru as well the need for and the potential cost savings with a rotavirus vaccine in that country. Methods. To assess the burden of rotavirus diarrhea in Peru, we reviewed published and unpublished reports where rotavirus was sought as the etiologic agent of diarrhea in children. Rotavirus detection rates obtained from these studies were combined with diarrhea incidence rates from a number of national surveys in order to estimate both the burden of rotavirus diarrhea in the country and its associated medical costs. Results. Rotavirus is a significant cause of morbidity and mortality in Peruvian children. In their first 5 years of life, an estimated 1 in 1.6 children will experience an episode of rotavirus diarrhea, 1 in 9.4 will seek medical care, 1 in 19.7 will require hospitalization, and 1 in 375 will die of the disease. Per year, this represents approximately 384 000 cases, 64 000 clinic visits, 30 000 hospitalizations, and 1 600 deaths. The annual cost of medical care alone for these children is approximately US$ 2.6 million--and that does not take into account the indirect or societal costs of the illness and the deaths. Conclusions. Rotavirus immunization provides the prospect of decreasing the morbidity and mortality from diarrhea in Peru, but a vaccine regimen would have to be relatively inexpensive, a few dollars or less per child. Future cost-effectiveness analyses should explore the total costs (medical as well as indirect or societal associated with rotavirus diarrhea. Newly licensed vaccines should be tested according to both their ability to avert deaths and their efficacy with fewer than three doses. All three of these factors could increase the cost savings associated with a rotavirus vaccine.
Full Text Available Objective. To assess the disease burden of rotavirus diarrhea in Peru as well the need for and the potential cost savings with a rotavirus vaccine in that country. Methods. To assess the burden of rotavirus diarrhea in Peru, we reviewed published and unpublished reports where rotavirus was sought as the etiologic agent of diarrhea in children. Rotavirus detection rates obtained from these studies were combined with diarrhea incidence rates from a number of national surveys in order to estimate both the burden of rotavirus diarrhea in the country and its associated medical costs. Results. Rotavirus is a significant cause of morbidity and mortality in Peruvian children. In their first 5 years of life, an estimated 1 in 1.6 children will experience an episode of rotavirus diarrhea, 1 in 9.4 will seek medical care, 1 in 19.7 will require hospitalization, and 1 in 375 will die of the disease. Per year, this represents approximately 384 000 cases, 64 000 clinic visits, 30 000 hospitalizations, and 1 600 deaths. The annual cost of medical care alone for these children is approximately US$ 2.6 million--and that does not take into account the indirect or societal costs of the illness and the deaths. Conclusions. Rotavirus immunization provides the prospect of decreasing the morbidity and mortality from diarrhea in Peru, but a vaccine regimen would have to be relatively inexpensive, a few dollars or less per child. Future cost-effectiveness analyses should explore the total costs (medical as well as indirect or societal associated with rotavirus diarrhea. Newly licensed vaccines should be tested according to both their ability to avert deaths and their efficacy with fewer than three doses. All three of these factors could increase the cost savings associated with a rotavirus vaccine.
Mackow, E R; Vo, P T; Broome, R; Bass, D; Greenberg, H B
A baculovirus-expressed VP4 protein derived from the simian rhesus rotavirus (RRV) was used to parenterally immunize murine dams. VP4-immunized dams developed high levels of neutralizing antibodies against RRV and low levels of cross-reactive neutralizing antibodies against human strains Wa, ST3, and S2 and animal strains SA-11, NCDV, and Eb. Newborn mice suckled on VP4-immunized dams were protected against a virulent challenge dose of the simian strain RRV and against murine rotavirus Eb. The cross-reactive nature of the serum-neutralizing response generated by VP4 immunization and the protective efficacy of the immunization suggest that recombinant-expressed VP4 proteins should be considered as viable vaccine candidates.
Ihara, T; Samejima, T; Kuwahara, H; Tajima, M
Two cytopathogenic bovine rotavirus strains were isolated. The infectivity of both isolates was relatively stable at pH 3.0 and resistant to ether. Their replication was not affected by 5-iodo-2'-deoxyuridine. The new isolates shared immunofluorescent antigen with the Lincoln strain of bovine rotavirus. By neutralization test, however, these strains were clearly distinguished from one another.
Estes MK. Rotaviruses and their replication In: Fields BN, Knippe DM, Howley PM et al. (Eds). Virology. Vol. 2, 4th edition. Lippincott Williams and Wilkins, Philadelphia. 2001 Pp 1747-1785. 12. Gorziglia. MI,. Collins PL. Intracellular amplification and expression of a synthetic analogue of rotavirus genomic RNA bearing a.
In August 1998, the sun was shining on the rotavirus world as the first rotavirus vaccine candidate was licensed in the United States. RotaShield® was licensed by the Food and Drag. Administration (FDA) in the United States  and was soon recommended for routine use in. American Children and inclusion in the.
Verberk, J D M; Bruijning, P.C.|info:eu-repo/dai/nl/353785652; de Melker, Hester
Rotavirus can cause a gastrointestinal infection and is common in young children. There are two vaccines available; both have to be administered via the mouth. The Dutch Health Council will advise the Ministry of Health, Welfare and Sport on how childhood vaccination against rotavirus will be made
Objectives. An effective vaccine is needed to protect against severe rotavirus disease, an important cause of gastroenteritis. Since there are no data on the incidence and antigenic diversity of rotavirus infection in Sierra Leone, we studied its epidemiology to enable an effective vaccine strategy to be designed. Methods.
Although this study suggests a decline when compared with previous studies in this center, variations are well reported in incidence of rotaviruses both seasonally and periodically even in the same geographical area. However, it is recommended that rotavirus vaccine be introduced as a means of protecting children from ...
The massive impact of rotavirus-associated diarrhoea on the children of South Africa and Africa has long been acknowledged. Effective properly administered rotavirus vaccine could potentially prevent 170 000 – 210 000 childhood deaths per year or about one in 20 deaths in children under five years of age. While the ...
Background: Rotavirus is the leading etiological agent among the causes of acute diarrhea in infants and young children. However, there is no attempt to indicate its significance in other regions of Ethiopia, out of the capital, Addis Ababa. Objective: This study is aimed at revealing the prevalence of rotavirus infection among ...
Full Text Available INTRODUCTION: Rotavirus is the main cause of gastroenteritis in Canadian children younger than five years of age, resulting in significant morbidity and cost. The present study provides evidence on the cost effectiveness of two alternative rotavirus vaccinations (RotaTeq [Merck Frosst Canada Ltd, Canada] and Rotarix [GlaxoSmithKline, Canada] available in Canada.
Background Rotavirus is the leading cause of severe diarrhea in infants and young children worldwide including Bangladesh. Unlike what was seen in high-income countries, the licensed rotavirus vaccines did not show high efficacy in Bangladeshi trials. We assessed rotavirus prevalence and genotypes in Bangladesh over six-year period to provide baseline information on the rotavirus burden and changing profile in the country. Methods This study was conducted from June 2006 to May 2012 in Matlab, Bangladesh. Group A rotaviruses were detected in stools collected from diarrhea patients by ELISA and genotyped using multiplex reverse transcription PCR followed by nucleotide sequencing. Results Of the 9678 stool samples, 20.3% were positive for rotavirus. The most predominant genotype was G1P (22.4%), followed by G9P (20.8%), G2P (16.9%) and G12P (10.4%). Mixed infections were detected in 14.2% of the samples. Emergence of an unusual strain, G9P was documented during 2011–12. Several amino acid mismatches in the antigenic epitopes of VP7 and VP4 between Bangladeshi and the vaccine strains were identified. Conclusions Our study provides important information on rotavirus genotypes that should be considered for the selection and introduction of rotavirus vaccines in Bangladesh. PMID:23855423
The study was carried out to determine the molecular characteristics of the rotavirus strains associated with diarrhea among children in Kwara state, Nigeria. A total of 150 stool samples were collected from diarrheic children. The stool samples were screened for rotavirus,using Enzyme linked Immunosorbent assay (ELISA).
children above 12 months of age, with the rotavirus infection peaking among children 25-36 months. It could also be due to development of immunity at this age group leading to sub clinical manifestation. CONCLUSION. The study has revealed rotavirus remains an important cause of acute diarrhoea in children under five.
di Somma, C; Fiore, L; Di Lonardo, A; Ridolfi, B; Garzillo, C; Chersi, A; Buono, C; Menna, T; Ruffilli, A
The present study investigates immunological cross-reactivity between Par o 1, the major pollen allergen of Parietaria, and the VP4 protein of rotavirus, a microorganism that is world-wide the main etiological agent of gastroenteritis in children. IgG and IgE cross-reactivity was assessed by direct binding and competitive inhibition assays (ELISA and DARIA), using recombinant VP4 from rhesus infectious rotavirus (RR), synthetic peptides and Par o 1-specific antibodies affinity purified from pooled and individual human sera. Antibodies specifically binding Par o 1, affinity purified from the sera of 35 individuals with skin test positivity to Parietaria and from 14 pools, were extensively cross-reactive with RRVP4. Cross-reactive binding was specifically inhibited by synthetic peptides derived from the C-terminal sequences of the VP4 proteins from human and rhesus infectious rotavirus. This study reports the first evidence of cross-reactivity between an allergen and a viral antigen.
Flem, Elmira T; Musabaev, Erkin; Juraev, Rivojiddin; Kerin, Tara; Gentsch, Jon; Glass, Roger I; Bresee, Joseph S
To determine the value of rotavirus vaccines in Central Asia, we conducted surveillance of rotavirus in Uzbekistan, the country with the largest birth cohort in the region. Uzbekistan is eligible for international funds to introduce new vaccines. We screened stool samples for rotavirus that were collected from children aged Uzbekistan may be attributable to rotavirus. Introduction of rotavirus vaccines into the national immunization program at the current subsidized prices could be cost-effective.
Ndze, Valentine Ngum; Akum, Achidi Eric; Kamga, Gonsu Hortense; Enjema, Lyonga Emilia; Esona, Mathew Dioh; Banyai, Krisztian; Therese, Obama Abena Marie
Background Rotavirus still remains the major cause of diarrhea in children below 5 years. No data on rotavirus epidemiology is available in the Northern regions of Cameroon. We aimed to determine the prevalence of group A rotavirus (RVA) in children below 5 years with diarrhea in two regions of Northern Cameroon (North West and Far North Regions) so as to improve our knowledge on the burden of rotavirus disease for imminent introduction of a rotavirus vaccine. Methods Stool samples were colle...
Piekarska, Anna; Kacerka, Anna; Majda-Stanis?awska, Ewa; J??wiak, Barbara; Sidorkiewicz, Ma?gorzata
Introduction Rotavirus (RV) infection is the most common cause of gastroenteritis in children. This paper identifies the most common genotypes of rotaviruses isolated from children hospitalized with gastroenteritis and attempts to determine any relationship between infection with a certain rotavirus genotype. Material and methods The investigated group consisted of 68 consecutive children with rotavirus gastroenteritis (confirmed by an agglutination test). Rotavirus genotype was determined in...
Kelly Claudia M
Full Text Available Abstract Background Rotavirus is the leading cause of severe diarrhea in young children and causes substantial morbidity and mortality. Although the clinical aspects have been well described, little information is available regarding the emotional, social, and economic impact of rotavirus gastroenteritis on the family of a sick child. The objectives of this study were to: 1 assess the family impact of rotavirus gastroenteritis through qualitative interviews with parents; 2 compare the clinical severity of rotavirus-positive and negative gastroenteritis; 3 test a questionnaire asking parents to rank the importance of various factors associated with a case of rotavirus gastroenteritis. Methods The study enrolled parents and children (2–36 months of age brought to one of the study sites (outpatient clinic or ER if the child experienced ≥ 3 watery or looser-than normal stools and/or forceful vomiting within any 24-hour period within the prior 3 days. The clinical severity of each child's illness was rated using a clinical scoring system and stool samples were tested for rotavirus antigen. Parents of rotavirus-positive children were invited to participate in focus group or individual interviews and subsequently completed a questionnaire regarding the impact of their child's illness. Results Of 62 enrolled children, 43 stool samples were collected and 63% tested positive for rotavirus. Illness was more severe in children with rotavirus-positive compared to rotavirus-negative gastroenteritis (92% vs. 37.5% rated as moderate/severe. Seventeen parents of rotavirus-positive children participated in the interviews and completed the written questionnaire. Parents were frightened by the severity of vomiting and diarrhea associated with rotavirus gastroenteritis, and noted that family life was impacted in several ways including loss of sleep, missed work, and an inability to complete normal household tasks. They expressed frustration at the lack of a
Ndze, Valentine Ngum; Esona, Mathew Dioh; Achidi, Eric Akum; Gonsu, Kamga Hortense; Dóró, Renáta; Marton, Szilvia; Farkas, Szilvia; Ngeng, Marxcel Bong; Ngu, Akum Felix; Obama-Abena, Marie Therese; Bányai, Krisztián
Over the past few years whole genome sequencing of rotaviruses has become a routine laboratory method in many strain surveillance studies. To study the molecular evolutionary pattern of representative Cameroonian Rotavirus A (RVA) strains, the semiconductor sequencing approach was used following random amplification of genomic RNA. In total, 31 RVA strains collected during 2010-2011 in three Cameroonian study sites located 120 to 1240 km from each other were sequenced and analyzed. Sequence analysis of the randomly selected representative strains showed that 18 RVAs were Wa-like, expressing G1P, G12P, or G12P neutralization antigens on the genotype 1 genomic constellation (I1-R1-C1-M1-A1-N1-T1-E1-H1), whereas 13 other strains were DS-1-like, expressing G2P, G2P, G3P, and G6P on the genotype 2 genomic constellation (I2-R2-C2-M2-A2-N2-T2-E2-H2). No inter-genogroup reassortment in the backbone genes was observed. Phylogenetic analysis of the Cameroonian G6P strains indicated the separation of the strains identified in the Far North region (Maroua) and the Northwest region (Bamenda and Esu) into two branches that is consistent with multiple introductions of G6P strains into this country. The present whole genome based molecular characterization study indicates that the emerging G6P strain is fully heterotypic to Rotarix, the vaccine introduced during 2014 in childhood immunization program in Cameroon. Continuous strain monitoring is therefore needed in this area and elsewhere to see if G6s, besides genotype G1 to G4, G8, G9 and G12, may become a new, regionally important genotype in the post vaccine licensure era in Africa. Copyright © 2014 Elsevier B.V. All rights reserved.
Martinón-Torres, Federico; Greenberg, David; Varman, Meera; Killar, John A; Hille, Darcy; Strable, Erica L; Stek, Jon E; Kaplan, Susan S
Rotavirus is the leading cause of severe diarrhea in infants and young children. The current formulation of pentavalent rotavirus vaccine (RV5) must be stored refrigerated at 2-8°C. A modified formulation of RV5 (RV5mp) has been developed with stability at 37°C for 7 days and an expiry extended to 36 months when stored at 2-8°C. This study (ClinicalTrials.gov identifier: NCT01600092; EudraCT number: 2012-001611-23) evaluated the safety, tolerability and immunogenicity of RV5mp versus the currently marketed RV5 in infants. To maintain blinding, both vaccine formulations were stored refrigerated at 2-8°C for the duration of the study. Immunogenicity endpoints were (1) serum neutralizing antibody titers to human rotavirus serotypes G1, G2, G3, G4 and P1A and (2) proportion of subjects with a ≥3-fold rise from baseline for serum neutralizing antibody to human rotavirus serotypes G1, G2, G3, G4 and P1A and serum antirotavirus immunoglobulin A. The RV5mp group (n = 505) and RV5 group (n = 509) had comparable safety profiles. There were no deaths and no vaccine-related serious adverse events in this study. With respect to immunogenicity, RV5mp was noninferior compared with RV5. Serum neutralizing antibody responses by country and breast-feeding status were generally consistent with the overall results. RV5mp enhances storage requirements while maintaining the immunogenicity and safety profile of the currently licensed RV5. A vaccine that is stable at room temperature may be more convenient for vaccinators, particularly in places where the cold chain is unreliable, and ultimately will permit more widespread use.
Fischer, Thea Kølsen; Nielsen, Nete Munk; Wohlfahrt, Jan
In anticipation of licensure and introduction of rotavirus vaccine into the western market, we used modeling of national hospital registry data to determine the incidence and direct medical costs of annual rotavirus-associated admissions over >11 years in Denmark. Diarrhea......-associated hospitalizations coded as nonspecified viral or presumed infectious have demonstrated a marked winter peak similar to that of rotavirus-associated hospitalizations, which suggests that the registered rotavirus-coded admissions are grossly underestimated. We therefore obtained more realistic estimates by 2...... different models, which indicated 2.4 and 2.5 (for children rotavirus-associated admissions per 1,000 children per year, respectively. These admissions amount to associated direct medical costs of US $1.7-1.8 million per year. Using 2 simple...
Approximately 40 years have passed since the discovery of the rotavirus and 10 years since the introduction and progressive dissemination of rotavirus vaccines worldwide. Currently, 92 countries have introduced rotavirus vaccines into national or subnational programs with evident impact in disease reduction. Two vaccines have been widely used, and four additional vaccines have been licensed and are being used in defined regions. In this context, one main issue that remains unsolved is the lower vaccine efficacy/effectiveness in low-income countries. An additional partially answered issue relates to rotavirus strain circulation in vaccinated populations. These issues are discussed in this review. The most imperative challenge ahead is to fulfill the WHO’s recommendation to introduce rotavirus vaccines in all countries. PMID:28928954
Elnady, Hala Gouda; Abdel Samie, Ola M; Saleh, Maysa Tawhid; Sherif, Lobna S; Abdalmoneam, Naglaa; Kholoussi, Naglaa M; Kholoussi, Shams M; El-Taweel, Ahmed N
Rotavirus gastroenteritis is an important public health problem all over the world, causing a notable economic burden in both developing and developed countries. To explore the relationship between blood group typing, rotavirus gastroenteritis, and its severity in Egyptian children. A cross sectional case control study was conducted on 231 cases of acute gastroenteritis attending the outpatient clinic of Al-Zahraa University Hospital. Full history taking, clinical examination, and clinical data collection were done. Blood samples were collected for an ABO grouping. Stool samples were tested for viral gastroenteritis agents. Rota positive cases of GE were significantly more prevalent among cases with blood group A (p fever (p rotavirus gastroenteritis. This could highlight an important risk factor, which could play a significant role for the pathogenesis of rotavirus gastroenteritis and severity as well. Furthermore, more intervention care could be needed for blood group A paediatric patients, if gastroenteritis especially rotavirus affect this group to avoid comorbidities.
Jianwu Bai; Smock, Steven L.; Jackson, George R.; MacIsaac, Kenzie D.; Yongsheng Huang; Courtney Mankus; Jonathan Oldach; Brian Roberts; Yu-Lu Ma; Klappenbach, Joel A.; Crackower, Michael A.; Alves, Stephen E.; Patrick J. Hayden
Objectives Human airway epithelial cells are the principal target of human rhinovirus (HRV), a common cold pathogen that triggers the majority of asthma exacerbations. The objectives of this study were 1) to evaluate an in vitro air liquid interface cultured human airway epithelial cell model for HRV infection, and 2) to identify gene expression patterns associated with asthma intrinsically and/or after HRV infection using this model. Methods Air-liquid interface (ALI) human airway epithelial...
Tu, Hong Anh T.; Rozenbaum, Mark H.; de Boer, Pieter T.; Noort, Albert C.; Postma, Maarten J.
Background: To update a cost-effectiveness analysis of rotavirus vaccination in the Netherlands previously published in 2011.Methods: The rotavirus burden of disease and the indirect protection of older children and young adults (herd protection) were updated.Results: When updated data was used,
Sow, Samba O; Steele, A Duncan; Mwenda, Jason M; Armah, George E; Neuzil, Kathleen M
The Center for Vaccine Development - Mali (CVD - Mali), the World Health Organization's regional office in Africa (WHO/AFRO), and the CVD at the University of Maryland School of Medicine hosted the 10th African Rotavirus Symposium in Bamako, Mali on 1-2 June 2016. The symposium is coordinated by WHO/AFRO, the Regional Rotavirus Reference Laboratories, and the African Rotavirus Network (ARN), with support from the Bill & Melinda Gates Foundation. The event brings together leading rotavirus researchers, scientists, and policy-makers from across Africa and the world. Over 150 participants, from 31 countries, including 27 in Africa, joined forces to address the theme "Reaching Every Child in Africa with Rotavirus Vaccines." This symposium, the first in francophone Africa, occurred at an unprecedented time when 33 African countries had introduced rotavirus vaccines into their national immunization programs. The symposium concluded with a Call to Action to introduce rotavirus vaccines in the 21 remaining African countries, to increase access in countries with existing vaccination programs, and to continue surveillance and research on rotavirus and other diarrheal diseases. Copyright © 2017.
van Amerongen Geert
Full Text Available Abstract Background Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The current study was conducted to assess whether colostrum containing rotavirus-specific antibodies (Gastrogard-R® could protect against rotavirus infection. In addition, this illness model was used to study modulatory effects of intervention on several immune parameters after re-infection. Methods BALB/c mice were treated by gavage once daily with Gastrogard-R® from the age of 4 to 10 days, and were inoculated with rhesus rotavirus (RRV at 7 days of age. A secondary inoculation with epizootic-diarrhea infant-mouse (EDIM virus was administered at 17 days of age. Disease symptoms were scored daily and viral shedding was measured in fecal samples during the post-inoculation periods. Rotavirus-specific IgM, IgG and IgG subclasses in serum, T cell proliferation and rotavirus-specific delayed-type hypersensitivity (DTH responses were also measured. Results Primary inoculation with RRV induced a mild but consistent level of diarrhea during 3-4 days post-inoculation. All mice receiving Gastrogard-R® were 100% protected against rotavirus-induced diarrhea. Mice receiving both RRV and EDIM inoculation had a lower faecal-viral load following EDIM inoculation then mice receiving EDIM alone or Gastrogard-R®. Mice receiving Gastrogard-R® however displayed an enhanced rotavirus-specific T-cell proliferation whereas rotavirus-specific antibody subtypes were not affected. Conclusions Preventing RRV-induced diarrhea by Gastrogard-R® early in life showed a diminished protection against EDIM re-infection, but a rotavirus-specific immune response was developed including both B cell and T cell responses. In general, this intervention model can be used for studying clinical symptoms as well as the immune responses required for protection against viral re-infection.
Mohammed Amood AL-Kamarany
Full Text Available The study aims to assess the impact of rotavirus vaccine introduction on diarrheal diseases hospitalization and to identify the rotavirus genotypes most prevalent before and after vaccine introduction among children ≤ 5 years of age. Rotarix™ ® rotavirus vaccine is currently licensed for infants in Yemen and was introduced in 2012. The vaccination course consists of two doses. The first dose is administrated at 6 weeks of age and the second dose is completed by 10 weeks. Based on a longitudinal observational study, we assessed the impact of vaccination on rotavirus hospitalization before and after vaccination among children ≤ 5 years of age at the Yemeni-Swedish Hospital (YSH in Taiz, Yemen. Prevaccination covered January 2009–July 2012 during which 2335 fecal samples were collected from children ≤ 5 years old. Postvaccination covered January 2013–December 2014 during which 1114 fecal samples were collected. Rotavirus was detected by Enzyme Linkage Immunosorbent Assay (ELISA. The incidence of rotavirus hospitalization decreased from 43.79% in 2009 to 10.54% in 2014. Hospitalization due to rotavirus diarrhea was reduced by 75.93%. Vaccine coverage increased from 23% in 2012 to 72% in 2014. Also, the results showed that the most predominant genotypes in prevaccination period were G2P (55.0%, followed by G1P (15.0%, while in postvaccination period G1P (31% was the predominant genotype, followed by G9P (27.5%. In conclusion, rotavirus vaccination in Yemen resulted in sharp reduction in diarrheal hospitalization. A successful rotavirus vaccination program in Yemen will rely upon efficient vaccine delivery systems and sustained vaccine efficacy against diverse and evolving rotavirus strains.
Kirkwood, Carl D; Roczo-Farkas, Susie
This report from the Australian Rotavirus Surveillance Program, together with collaborating laboratories Australia-wide, describes the rotavirus genotypes responsible for the hospitalisation of children with acute gastroenteritis during the period 1 January to 31 December 2013. During the survey period, 1,035 faecal samples were referred for rotavirus G and P genotype analysis. Of these 828 were confirmed as rotavirus positive. A total of 503 specimens were collected from children under 5 years of age, while 325 were from older children and adults. Genotype analysis of the 828 rotavirus samples collected from both children and adults revealed that G12P was the dominant genotype in this reporting period, identified in 33% of strains nationally. Genotype G3P was the second most common strain nationally, representing 31% of samples, followed by genotype G2P (14%). This represents the first report where G12P strains are the major cause of disease in this population. The genotype distribution was slightly altered when the analysis was restricted to samples collected from children under 5 years of age, with G3P being the dominant genotype (39.2%) followed by G12P as the second most common genotype (31%). Fluctuations in genotype distribution were also observed based on the vaccine type in use. Genotype G12P was more common in states and territories using RotaTeq, while G3P was more common in the locations using Rotarix. This survey highlights the yearly fluctuations in rotavirus genotypes observed since vaccine introduction, with changes in dominant genotypes an annual event. The emergence of G12P as the dominant genotype further illustrates the ongoing changes in the wild type rotavirus population evident in the Australian population since vaccine introduction. This work is copyright. You may download, display, print and reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation
González Chávez, Rosabel
In general, it has been reported that rotavirus infection was detected year round in tropical countries. However, studies in Venezuela and Brazil suggest a seasonal behavior of the infection. On the other hand, some studies link infection with climatic variables such as rainfall. This study analyzes the pattern of behavior of the rotavirus infection in Carabobo-Venezuela (2001-2005), associates the seasonality of the infection with rainfall, and according to the seasonal pattern, estimates the age of greatest risk for infection. The analysis of the rotavirus temporal series and accumulated precipitation was performed with the software SPSS. The infection showed two periods: high incidence (November-April) and low incidence (May-October). Accumulated precipitation presents an opposite behavior. The highest frequency of events (73.8% 573/779) for those born in the period with a low incidence of the virus was recorded at an earlier age (mean age 6.5 +/- 2.0 months) when compared with those born in the station of high incidence (63.5% 568/870, mean age 11.7 +/- 2.2 months). Seasonality of the infection and the inverse relationship between virus incidence and rainfall was demonstrated. In addition, it was found that the period of birth determines the age and risk of infection. This information generated during the preaccine period will be helpful to measure the impact of the vaccine against the rotavirus.
Lanata, C F; Midthun, K; Black, R E; Butron, B; Huapaya, A; Penny, M E; Ventura, G; Gil, A; Jett-Goheen, M; Davidson, B L
An oral rhesus-human rotavirus tetravalent (RRV-TV) vaccine (10(4) pfu of rhesus rotavirus [type G3] and of 3 human-rhesus reassortants [G1, G2, and G4]) was evaluated in a field trial in Lima, Peru. At 2, 3, and 4 months of age, infants received either a dose of RRV-TV, an initial dose of vaccine followed by a dose of placebo at 3 and 4 months, or a dose of placebo. Rotavirus-specific IgA responses were detected by ELISA in 75% of the three-dose vaccine group, 59% of the one-dose vaccine group (P = .05), and 24% of the placebo group (P < .001): 64%, 48%, and 12% of each group, respectively, had a neutralizing antibody response to at least 1 serotype. Both one and three doses of vaccine failed to induce a significant level of protection against rotavirus diarrhea; however, they did provide some protection (range, 35%-66%) against more severe rotavirus diarrhea, especially for episodes caused by type G1.
Thabata Alessandra Ramos Caruzo
Full Text Available In this study, 331 samples from calves less than one month old from a dairy herd in the district of Piracanjuba, state of Goiás, Brazil were tested for rotavirus. Thirty-three samples (9.9% tested positive for rotavirus. Out of those, 31 were submitted to G and P characterization by reverse transcription followed by semi-nested polymerase chain reaction. Two samples were characterized as G6P, three as G10P and five as G6P. The majority of the samples (51.6% displayed multiple P genotypes (P-genotype mixtures, including typical human genotypes P and P[6M], suggesting the occurrence of co-infections and genetic reassortment. Also, the detection of human genotypes in bovine samples may be considered evidence of the zoonotic potential of rotaviruses. To our knowledge, this is the first report of such a high frequency of P genotype mixtures in bovine rotavirus samples. It also increases data on G and P rotavirus genotypes circulating in dairy herds in Brazil and can help in the development of more efficient immunization approaches, thereby controlling infection and reducing economical losses.
Pietsch, C; Petersen, L; Patzer, L; Liebert, U G
A rare G8P rotavirus, designated GER1H-09, was detected in a stool sample from an infant suffering from repeated episodes of emesis for 2 days without diarrhea. Sequencing of all genomic RNA segments was performed, and complete coding sequences were determined. The VP7 amino acid sequence revealed a close phylogenetic relationship to human G8P and G8P isolates from Slovenia and Africa. GER1H-09 shared typical amino acid residues within variable regions VR3 to VR7 with those strains, and their subclassification as lineage G8-II rotaviruses is proposed. The variability in VR3 was identified as the likely reason for the failure in genotyping G8-II rotaviruses by commonly used multiplex PCR. Furthermore, the sequences of associated structural and nonstructural proteins showed high amino acid identities to DS-1-like rotaviruses. The genotype composition of GER1H-09 (G8-P-I2-R2-C2-M2-A2-N2-T2-E2-H2) suggests the occurrence of reassortment events between G8 genotypes and human DS-1-like G2P rotaviruses.
Ana Marli Christovam Sartori
Full Text Available OBJECTIVE: To study the epidemiology of rotavirus and estimate rotavirus-associated morbidity and mortality in children OBJETIVOS: Analizar la epidemiología del rotavirus y estimar la morbilidad y la mortalidad asociadas con las infecciones por rotavirus en niños < 5 años de edad en Brasil en 2004, antes de incluir la vacuna contra el rotavirus en el Programa Nacional de Inmunizaciones (PNI. MÉTODOS: Para estimar la morbilidad por rotavirus se revisaron los estudios publicados (1999-2006 que abordaban la incidencia de diarrea aguda en niños < 5 años de edad y la frecuencia de las infecciones por rotavirus en niños con diarrea en Brasil. Los casos de diarrea se dividieron en tres categorías de gravedad según el nivel de atención que requirieron: casos leves que solo requirieron atención domiciliaria, casos moderados que requirieron la visita a un servicio ambulatorio de salud y casos graves que requirieron hospitalización. Para estimar la mortalidad por rotavirus se utilizó el número de muertes registradas por diarrea en niños de < 5 años, según el Sistema de Información sobre Mortalidad (SIM del Sistema Único de Salud (SUS de Brasil, y se calculó la proporción de muertes causadas por este virus. RESULTADOS: Se estimó que las infecciones por rotavirus causan anualmente 3 525 053 casos de diarrea, 655 853 visitas a servicios ambulatorios de salud, 92 453 hospitalizaciones y 850 muertes en niños < 5 años de edad en Brasil. CONCLUSIONES: Las infecciones por rotavirus constituyen una importante causa de morbilidad y mortalidad en Brasil.
Full Text Available Rotavirus is an important pediatric pathogen, causing severe diarrhea and being associated with a high mortality rate causing approximately 500 000 deaths annually worldwide. Even though some vaccines are currently available, their efficacy is lower in the developing world, as compared to developed countries. Therefore, alternative or complementary treatment options are needed in the developing countries where the disease burden is the largest. The effect of Lactobacillus in promoting health and its use as a vehicle for delivery of protein and antibody fragments was previously shown. In this study, we have developed co-expression vectors enabling Lactobacillus paracasei BL23 to produce two VHH fragments against rotavirus (referred to as anti-rotavirus proteins 1 and 3, ARP1 and ARP3 as secreted and/or surface displayed products. ARP1 and ARP3 fragments were successfully co-expressed as shown by Western blot and flow cytometry. In addition, engineered Lactobacillus produced VHH antibody fragments were shown to bind to a broad range of rotavirus serotypes (including the human rotavirus strains 69M, Va70, F45, DS1, Wa and ST3 and simian rotavirus strains including RRV and SA11, by flow cytometry and ELISA. Hereby, we have demonstrated for the first time that when RRV was captured by one VHH displayed on the surface of co-expressor Lactobacillus, targeting other epitope was possible with another VHH secreted from the same bacterium. Therefore, Lactobacillus producing two VHH antibody fragments may potentially serve as treatment against rotavirus with a reduced risk of development of escape mutants. This co-expression and delivery platform can also be used for delivery of VHH fragments against a variety of mucosal pathogens or production of other therapeutic molecules.
Full Text Available G1P rotaviruses are responsible for the majority of human rotavirus infections worldwide. The effect of universal mass vaccination with rotavirus vaccines on circulating G1P rotaviruses is still poorly understood. Therefore we analyzed the complete genomes of the Rotarix™ vaccine strain, and 70 G1P rotaviruses, detected between 1999 and 2010 in Belgium (36 before and 34 after vaccine introduction to investigate the impact of rotavirus vaccine introduction on circulating G1P strains. All rotaviruses possessed a complete Wa-like genotype constellation, but frequent intra-genogroup reassortments were observed as well as multiple different cluster constellations circulating in a single season. In addition, identical cluster constellations were found to circulate persistently over multiple seasons. The Rotarix™ vaccine strain possessed a unique cluster constellation that was not present in currently circulating G1P strains. At the nucleotide level, the VP6, VP2 and NSP2 gene segments of Rotarix™ were relatively distantly related to any Belgian G1P strain, but other gene segments of Rotarix™ were found in clusters also containing circulating Belgian strains. At the amino acid level, the genetic distance between Rotarix™ and circulating Belgian strains was considerably lower, except for NSP1. When we compared the Belgian G1P strains collected before and after vaccine introduction a reduction in the proportion of strains that were found in the same cluster as the Rotarix™ vaccine strain was observed for most gene segments. The reduction in the proportion of strains belonging to the same cluster may be the result of the vaccine introduction, although natural fluctuations cannot be ruled out.
Reimerink, Johan H J; Boshuizen, Jos A; Einerhand, Alexandra W C; Duizer, Erwin; van Amerongen, Geert; Schmidt, Nico; Koopmans, Marion P G
Rotavirus is an important cause of morbidity and mortality worldwide and vaccines are currently under development, with clinical trails conducted in humans worldwide. The immune responses in infant BALB/c mice were examined following oral inoculation with murine rotavirus EDIM (2 x 10(4) focus-forming units) and with three CsCl gradient-purified fractions of heterologous simian rotavirus SA11 (standardized at 2 x 10(6) CCID(50)) that differed in antigen composition: fraction 1 was enriched for double-layered rotavirus particles, fraction 2 for triple-layered particles and fraction 3 consisted mainly of cell components. Diarrhoea and high IgG responses, but marginal IgA responses, were observed after inoculation with all three SA11 fractions. Virus shedding was observed in all EDIM-inoculated mice, but in none of the SA11-inoculated mice. Rotavirus-specific IgG1 : 2a ratios were similar in mice inoculated with EDIM and SA11 fraction 1, but higher for SA11 fraction 3- and lower for SA11 fraction 2-inoculated mice. A higher IgG1 : 2a ratio indicates a more Th2-like immune response. This undesirable response is apparently mostly induced by inoculation with heterologous rotavirus in the presence of abundant cell-associated and soluble rotavirus proteins, compared with infection with a more purified preparation or with homologous virus. These data show that, following inoculation with a standardized amount of infectious virus, the composition of the fraction influences the outcome of the immune responses significantly.
Zeller, Mark; Heylen, Elisabeth; Tamim, Sana; McAllen, John K; Kirkness, Ewen F; Akopov, Asmik; De Coster, Sarah; Van Ranst, Marc; Matthijnssens, Jelle
G1P rotaviruses are responsible for the majority of human rotavirus infections worldwide. The effect of universal mass vaccination with rotavirus vaccines on circulating G1P rotaviruses is still poorly understood. Therefore we analyzed the complete genomes of the Rotarix™ vaccine strain, and 70 G1P rotaviruses, detected between 1999 and 2010 in Belgium (36 before and 34 after vaccine introduction) to investigate the impact of rotavirus vaccine introduction on circulating G1P strains. All rotaviruses possessed a complete Wa-like genotype constellation, but frequent intra-genogroup reassortments were observed as well as multiple different cluster constellations circulating in a single season. In addition, identical cluster constellations were found to circulate persistently over multiple seasons. The Rotarix™ vaccine strain possessed a unique cluster constellation that was not present in currently circulating G1P strains. At the nucleotide level, the VP6, VP2 and NSP2 gene segments of Rotarix™ were relatively distantly related to any Belgian G1P strain, but other gene segments of Rotarix™ were found in clusters also containing circulating Belgian strains. At the amino acid level, the genetic distance between Rotarix™ and circulating Belgian strains was considerably lower, except for NSP1. When we compared the Belgian G1P strains collected before and after vaccine introduction a reduction in the proportion of strains that were found in the same cluster as the Rotarix™ vaccine strain was observed for most gene segments. The reduction in the proportion of strains belonging to the same cluster may be the result of the vaccine introduction, although natural fluctuations cannot be ruled out.
Borade, Ashwin; Bais, Ajit Singh; Bapat, Vaijayanti; Dhongade, Ram
Diarrheal diseases affect millions of people around the world and have the greatest impact on children, especially those in developing countries. Rotavirus is now known to contribute significantly to the etiology of diarrheal diseases in both developing and developed countries. To study demographic, clinical, and laboratory characteristics of rotavirus infection in cases of acute diarrhea admitted in the hospital who were below the age 5 years. It was a prospective study conducted from June 2009 to June 2011 to determine characteristics, clinical profile, and antigenemia of rotavirus. The study group included patients up to 5 years of age hospitalized with a diagnosis of acute gastroenteritis. Statistical analysis was done using the chi-square test. Data were analyzed using SPSS (Statistical Package for Social Sciences) version 17.0. From the 246 cases studied in the hospitalized patients of acute gastroenteritis, 88 cases (35.77%) were found to be positive for rotavirus infection. The occurrence of infection was found to be most common in the age group of 11-20 months (38.63%) followed by the age group of 0-10 months (23.86%). There was no association with the sex of the child. In rotavirus-positive patients, associated features were fever in 48.86%, vomiting in 29.54%, and pain in abdomen in 53.4% of cases. Seasonal variation of rotavirus infection was observed in the present study with peak in the winter season. It was found that 5.68% cases which were positive for rotavirus in their stool samples were positive for rotavirus present in their urine sample, suggesting extraintestinal manifestation of rotavirus. It is concluded that in spite of clean hygienic condition and vaccination rotavirus is still an important cause of infantile diarrhea in urban area like Pune. There is association between the occurrence of rotavirus and degree of dehydration, fever, vomiting, and pain in abdomen. Peak incidence was found in the months of December and January. There is
Goldie Sue J
Full Text Available Abstract Background Rotavirus is the most common cause of severe diarrhea leading to hospitalization or disease-specific death among young children. New rotavirus vaccines have recently been approved. Some previous studies have provided broad qualitative insights into the health and economic consequences of introducing the vaccines into low-income countries, representing several features of rotavirus infection, such as varying degrees of severity and age-dependency of clinical manifestation, in their model-based analyses. We extend this work to reflect additional features of rotavirus (e.g., the possibility of reinfection and varying degrees of partial immunity conferred by natural infection, and assess the influence of the features on the cost-effectiveness of rotavirus vaccination. Methods We developed a Markov model that reflects key features of rotavirus infection, using the most recent data available. We applied the model to the 2004 Vietnamese birth cohort and re-evaluated the cost-effectiveness (2004 US dollars per disability-adjusted life year [DALY] of rotavirus vaccination (Rotarix® compared to no vaccination, from both societal and health care system perspectives. We conducted univariate sensitivity analyses and also performed a probabilistic sensitivity analysis, based on Monte Carlo simulations drawing parameter values from the distributions assigned to key uncertain parameters. Results Rotavirus vaccination would not completely protect young children against rotavirus infection due to the partial nature of vaccine immunity, but would effectively reduce severe cases of rotavirus gastroenteritis (outpatient visits, hospitalizations, or deaths by about 67% over the first 5 years of life. Under base-case assumptions (94% coverage and $5 per dose, the incremental cost per DALY averted from vaccination compared to no vaccination would be $540 from the societal perspective and $550 from the health care system perspective. Conclusion
Kim, Sun-Young; Goldie, Sue J; Salomon, Joshua A
Rotavirus is the most common cause of severe diarrhea leading to hospitalization or disease-specific death among young children. New rotavirus vaccines have recently been approved. Some previous studies have provided broad qualitative insights into the health and economic consequences of introducing the vaccines into low-income countries, representing several features of rotavirus infection, such as varying degrees of severity and age-dependency of clinical manifestation, in their model-based analyses. We extend this work to reflect additional features of rotavirus (e.g., the possibility of reinfection and varying degrees of partial immunity conferred by natural infection), and assess the influence of the features on the cost-effectiveness of rotavirus vaccination. We developed a Markov model that reflects key features of rotavirus infection, using the most recent data available. We applied the model to the 2004 Vietnamese birth cohort and re-evaluat