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Sample records for attenuated human rotavirus

  1. Rotavirus specific plasma secretory immunoglobulin in children with acute gastroenteritis and children vaccinated with an attenuated human rotavirus vaccine

    OpenAIRE

    Herrera Daniel; Vásquez Camilo; Corthésy Blaise E.; Franco M. A.; Angel Juana

    2013-01-01

    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...

  2. Rotavirus specific plasma secretory immunoglobulin in children with acute gastroenteritis and children vaccinated with an attenuated human rotavirus vaccine.

    Science.gov (United States)

    Herrera, Daniel; Vásquez, Camilo; Corthésy, Blaise; Franco, Manuel A; Angel, Juana

    2013-11-01

    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.

  3. Vitamin A deficiency impairs adaptive B and T cell responses to a prototype monovalent attenuated human rotavirus vaccine and virulent human rotavirus challenge in a gnotobiotic piglet model.

    Directory of Open Access Journals (Sweden)

    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

  4. 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.

    Science.gov (United States)

    Paul, Anu; Babji, Sudhir; Sowmyanarayanan, T V; Dhingra, Mandeep Singh; Ramani, Sasirekha; Kattula, Deepthi; Kang, Gagandeep

    2014-05-23

    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[8] rotavirus strain as the antigen were consistently higher than with the bovine G6P[5] WC3 strain and the human G2P[4] 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.

  5. Human immunity to rotavirus.

    Science.gov (United States)

    Molyneaux, P J

    1995-12-01

    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.

  6. Studies on attenuation of rotavirus. A comparison in piglets between virulent virus and its attenuated derivative.

    Science.gov (United States)

    Tzipori, S; Unicomb, L; Bishop, R; Montenaro, J; Vaelioja, L M

    1989-01-01

    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.

  7. Serotonin and vasoactive intestinal peptide antagonists attenuate rotavirus diarrhoea

    OpenAIRE

    Kordasti, S; Sjövall, H; Lundgren, O; Svensson, L

    2004-01-01

    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.

  8. Safety and immunogenicity of two live attenuated human rotavirus vaccine candidates, 116E and I321, in infants: results of a randomised controlled trial.

    Science.gov (United States)

    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

    2006-07-26

    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.

  9. Towards a human rotavirus disease model.

    Science.gov (United States)

    Hagbom, Marie; Sharma, Sumit; Lundgren, Ove; Svensson, Lennart

    2012-08-01

    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.

  10. Safety and immunogenicity of live attenuated human-bovine (UK) reassortant rotavirus vaccines with VP7-specificity for serotypes 1, 2, 3 or 4 in adults, children and infants.

    Science.gov (United States)

    Clements-Mann, M L; Makhene, M K; Mrukowicz, J; Wright, P F; Hoshino, Y; Midthun, K; Sperber, E; Karron, R; Kapikian, A Z

    1999-06-04

    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.

  11. Serotonin and vasoactive intestinal peptide antagonists attenuate rotavirus diarrhoea.

    Science.gov (United States)

    Kordasti, S; Sjövall, H; Lundgren, O; Svensson, L

    2004-07-01

    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-HT(3)) and vasoactive intestinal peptide (VIP) receptor, but not antagonists for 5-hydroxytryptamine 4 receptor or the muscarinic receptor, attenuate rotavirus induced diarrhoea. Neurotransmitter antagonists were administered to wild-type or neurokinin 1 receptor knockout mice infected with homologous (EDIM) or heterologous (RRV) rotavirus. While RRV infected mice had diarrhoea for 3.3 (0.2) days (95% confidence interval (CI) 3.04-3.56), the 5-HT(3) receptor antagonist (granisetron) and the VIP receptor antagonist (4Cl-D-Phe(6),Leu(17))-VIP both reduced the total number of days of RRV induced diarrhoea to 2.1 (0.3) (95% CI 1.31-2.9) (protavirus. On the other hand, rotavirus diarrhoea was not attenuated in the neurokinin 1 receptor knockout mice. Our results suggest that the neurotransmitters serotonin and VIP are involved in rotavirus diarrhoea; observations that could imply new principles for treatment of this disease with significant global impact.

  12. Effect of breastfeeding on immunogenicity of oral live-attenuated human rotavirus vaccine: a randomized trial in HIV-uninfected infants in Soweto, South Africa

    Science.gov (United States)

    Moon, Sung-Sil; Velasquez, Daniel; Jones, Stephanie; Koen, Anthonet; van Niekerk, Nadia; Jiang, Baoming; Parashar, Umesh D; Madhi, Shabir A

    2014-01-01

    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

  13. Porcine rotavirus strain Gottfried-based human rotavirus candidate vaccines: construction and characterization.

    Science.gov (United States)

    Hoshino, Yasutaka; Jones, Ronald W; Ross, Jerri; Kapikian, Albert Z

    2005-05-31

    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[6]) closely related to human rotavirus P serotype 2A[6] 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[8], 1B[4] and 2A[6]. In addition, following immunization of guinea pigs with Gottfried VP4, we found low but consistent levels of neutralizing antibodies to VP4 with P1A[8] or P1B[4] 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[8], P1B[4] or P2A[6] VP4.

  14. Evaluation of safety and immunogenicity of a live attenuated tetravalent (G1-G4) Bovine-Human Reassortant Rotavirus vaccine (BRV-TV) in healthy Indian adults and infants.

    Science.gov (United States)

    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

    2014-08-11

    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

  15. The gnotobiotic piglet as a model for studies of disease pathogenesis and immunity to human rotaviruses.

    Science.gov (United States)

    Saif, L J; Ward, L A; Yuan, L; Rosen, B I; To, T L

    1996-01-01

    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

  16. Human group C rotaviruses identified in Kenya | Mwenda | East ...

    African Journals Online (AJOL)

    ... 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.

  17. Live attenuated tetravalent (G1-G4) bovine-human reassortant rotavirus vaccine (BRV-TV): Randomized, controlled phase III study in Indian infants.

    Science.gov (United States)

    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

    2017-06-16

    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

  18. Genomic characterization of human rotavirus G8 strains from the African rotavirus network: relationship to animal rotaviruses.

    Science.gov (United States)

    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

    2009-05-01

    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[8],G8 and two P[6],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[8] and P[6]. 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.

  19. Rotarix (RIX4414): an oral human rotavirus vaccine.

    Science.gov (United States)

    O'Ryan, Miguel

    2007-02-01

    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.

  20. A dose-escalation safety and immunogenicity study of a new live attenuated human rotavirus vaccine (Rotavin-M1) in Vietnamese children.

    Science.gov (United States)

    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

    2012-04-27

    We tested a candidate live, oral, rotavirus vaccine (Rotavin-M1™) derived from an attenuated G1P [8] 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

  1. Serotype diversity and reassortment between human and animal rotavirus strains: implications for rotavirus vaccine programs.

    Science.gov (United States)

    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

    2005-09-01

    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[6]) 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.

  2. Comparison of the efficacy of rotavirus VLP vaccines to a live homologous rotavirus vaccine in a pig model of rotavirus disease.

    Science.gov (United States)

    El-Attar, L; Oliver, S L; Mackie, A; Charpilienne, A; Poncet, D; Cohen, J; Bridger, J C

    2009-05-21

    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.

  3. Rotavirus vaccines: an overview.

    Science.gov (United States)

    Midthun, K; Kapikian, A Z

    1996-07-01

    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.

  4. Molecular characterization of rotavirus strains detected during a clinical trial of a human rotavirus vaccine in Blantyre, Malawi

    Science.gov (United States)

    Nakagomi, Toyoko; Nakagomi, Osamu; Dove, Winifred; Doan, Yen Hai; Witte, Desiree; Ngwira, Bagrey; Todd, Stacy; Steele, A Duncan; Neuzil, Kathleen M; Cunliffe, Nigel A

    2014-01-01

    The human, G1P[8] 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[6], G1P[8], G9P[8], and G8P[4] 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

  5. Mechanisms of protection against rotavirus in humans and mice.

    Science.gov (United States)

    Ward, R L

    1996-09-01

    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.

  6. Rotaviruses

    Centers for Disease Control (CDC) Podcasts

    2009-01-06

    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.

  7. Stability of heat stable, live attenuated Rotavirus vaccine (ROTASIIL®).

    Science.gov (United States)

    Naik, Sameer P; Zade, Jagdish K; Sabale, Rajendra N; Pisal, Sambhaji S; Menon, Ravi; Bankar, Subhash G; Gairola, Sunil; Dhere, Rajeev M

    2017-05-19

    Vaccines currently available across the globe are stored and transported in a continuous cold-chain at 2-8°C or below -20°C. A temperature excursion outside this range affects the potency of the vaccines. Such vaccines need to be discarded leading wastage. The Rotavirus disease burden is predominantly reported in developing and low-income countries and therefore, has entered or poised to enter their national immunization programs. These countries already have several limitations for effective storage, maintenance and distribution of vaccines in a cold-chain and this introduction is expected to further stress this fragile ecosystem. To help mitigate the cold chain related issues, SIIPL has developed a thermostable rotavirus vaccine ROTASIIL® which can be stored at a temperature below 25°C for 36months, completely by-passing the standard 2-8°C cold storages. In addition it has the capability to withstand temperatures of 37°C and 40°C for 18months and short term exposure to 55°C. It can also tolerate a temperature shock of being thawed from an extreme cold temperature of -20°C to a high temperature of 42°C. The vaccine contains serotypes G1, G2, G3, G4 and G9 (UK-Bovine reassortant strains procured from National Institute of Health-USA). The vaccine is recently licensed in India. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Systematic and intestinal antibody-secreting cell responses and correlates of protective immunity to human rotavirus in a gnotobiotic pig model of disease.

    OpenAIRE

    Yuan, L; Ward, L A; Rosen, B I; To, T L; Saif, L J

    1996-01-01

    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...

  9. Phase I trial of RV3-BB rotavirus vaccine: a human neonatal rotavirus vaccine.

    Science.gov (United States)

    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

    2013-05-28

    RV3 is a human neonatal rotavirus strain (G3P[6]) 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.

  10. Novel Human Rotavirus Genotype G5P[7] from Child with Diarrhea, Cameroon

    Science.gov (United States)

    Geyer, Annelise; Banyai, Krisztian; Page, Nicola; Aminu, Maryam; Armah, George E.; Hull, Jennifer; Steele, Duncan A.; Glass, Roger I.; Gentsch, Jon R.

    2009-01-01

    We report characterization of a genotype G5P[7] 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[7] strain exemplifies the importance of heterologous animal rotaviruses in generating HRV genetic diversity through reassortment. PMID:19116059

  11. Stability of live attenuated rotavirus vaccine with selected preservatives and primary containers.

    Science.gov (United States)

    Lal, Manjari; Jarrahian, Courtney; Zhu, Changcheng; Hosken, Nancy A; McClurkan, Chris L; Koelle, David M; Saxon, Eugene; Roehrig, Andrew; Zehrung, Darin; Chen, Dexiang

    2016-05-11

    Rotavirus infection, which can be prevented by vaccination, is responsible for a high burden of acute gastroenteritis disease in children, especially in low-income countries. An appropriate formulation, packaging, and delivery device for oral rotavirus vaccine has the potential to reduce the manufacturing cost of the vaccine and the logistical impact associated with introduction of a new vaccine, simplify the vaccination procedure, and ensure that the vaccine is safely and accurately delivered to children. Single-dose prefilled presentations can be easy to use; however, they are typically more expensive, can be a bottleneck during production, and occupy a greater volume per dose vis-à-vis supply chain storage and medical waste disposal, which is a challenge in low-resource settings. Multi-dose presentations used thus far have other issues, including increased wastage of vaccine and the need for separate delivery devices. In this study, the goals were to evaluate both the technical feasibility of using preservatives to develop a liquid multi-dose formulation and the primary packaging alternatives for orally delivered, liquid rotavirus vaccines. The feasibility evaluation included evaluation of commonly used preservatives for compatibility with rotavirus vaccines and stability testing of rotavirus vaccine in various primary containers, including Lameplast's plastic tubes, BD's oral dispenser version of Uniject™ (Uniject DP), rommelag's blow-fill-seal containers, and MEDInstill's multi-dose vial and pouch. These presentations were compared to a standard glass vial. The results showed that none of the preservatives tested were compatible with a live attenuated rotavirus vaccine because they had a detrimental effect on the viability of the virus. In the presence of preservatives, vaccine virus titers declined to undetectable levels within 1 month. The vaccine formulation without preservatives maintained a stability profile over 12 months in all primary containers

  12. Rotavirus shedding following administration of RV3-BB human neonatal rotavirus vaccine.

    Science.gov (United States)

    Cowley, Daniel; Boniface, Karen; Bogdanovic-Sakran, Nada; Kirkwood, Carl D; Bines, Julie E

    2017-08-03

    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.

  13. Systematic and intestinal antibody-secreting cell responses and correlates of protective immunity to human rotavirus in a gnotobiotic pig model of disease.

    Science.gov (United States)

    Yuan, L; Ward, L A; Rosen, B I; To, T L; Saif, L J

    1996-05-01

    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.

  14. Milk Oligosaccharides Inhibit Human Rotavirus Infectivity in MA104 Cells.

    Science.gov (United States)

    Laucirica, Daniel R; Triantis, Vassilis; Schoemaker, Ruud; Estes, Mary K; Ramani, Sasirekha

    2017-09-01

    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[8] and G2P[4] 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[8] infectivity was seen with 2'FL when added after the onset of infection (62% reduction, P < 0.01), whereas the maximum reduction in G2P[4] 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[4] 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

  15. Jennerian and modified Jennerian approach to vaccination against rotavirus diarrhea using a quadrivalent rhesus rotavirus (RRV) and human-RRV reassortant vaccine.

    Science.gov (United States)

    Kapikian, A Z; Hoshino, Y; Chanock, R M; Perez-Schael, I

    1996-01-01

    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.

  16. Rotavirus vaccines: an overview.

    OpenAIRE

    Midthun, K; Kapikian, A Z

    1996-01-01

    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...

  17. Definition of human rotavirus serotypes by plaque reduction assay.

    Science.gov (United States)

    Wyatt, R G; Greenberg, H B; James, W D; Pittman, A L; Kalica, A R; Flores, J; Chanock, R M; Kapikian, A Z

    1982-07-01

    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.

  18. Reassortant rotaviruses as potential live rotavirus vaccine candidates.

    Science.gov (United States)

    Midthun, K; Greenberg, H B; Hoshino, Y; Kapikian, A Z; Wyatt, R G; Chanock, R M

    1985-03-01

    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.

  19. Impact of high coverage of monovalent human rotavirus vaccine on Emergency Department presentations for rotavirus gastroenteritis.

    Science.gov (United States)

    Davey, Heather M; Muscatello, David J; Wood, James G; Snelling, Thomas L; Ferson, Mark J; Macartney, Kristine K

    2015-03-30

    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.

  20. 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.

    Science.gov (United States)

    Hoshino, Y; Jones, R W; Chanock, R M; Kapikian, A Z

    1997-04-01

    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.

  1. WHO informal consultation on quality, safety and efficacy specifications for live attenuated rotavirus vaccines Mexico City, Mexico, 8-9 February 2005.

    Science.gov (United States)

    Wood, David

    2005-12-01

    Rotavirus vaccines are at an advanced stage of development but there are as yet no WHO recommendations on production and quality control to provide regulatory guidance. A meeting of experts was convened by WHO and PAHO/AMRO to review the scientific basis for production and quality control of rotavirus vaccines, and to discuss specific measures to assure the safety and efficacy of rotavirus vaccines. The meeting was attended by 25 experts from 14 countries, drawn from academia, public health, national regulatory authorities and vaccine producers. It was agreed that existing guidance for other live virus vaccines provides a very good basis for product characterization, especially for source materials and control of production. The basis for attenuation of current vaccines or vaccine candidates is not known but, at least for the vaccines based on the Jennerian approach of using animal (bovine) rotaviruses, is likely to be multigenic. The risk of intussusception in humans is influenced by genetic background and age. Recent analyzes of large vaccine safety trials found that certain strains of vaccine virus were not associated with intussusception, although in these trials the first dose of vaccine was not administered to children over 3 months of age. Since age is a risk factor for intussusception, this may suggest that early delivery of the first dose of vaccine is desirable. However, maternal antibodies may mitigate against early delivery of the first vaccine dose. Factors which could affect vaccine efficacy or safety include strain diversity, malnutrition, other enteric infections, parasitic infection or immune suppression. It was concluded that data from clinical trials conducted in one part of the world would not necessarily be predictive of vaccine efficacy in other places. It was agreed that in nonclinical evaluations there was a need to use oral dosing for toxicity studies and, because rotavirus is non-neurovirulent, that there was no need for an animal

  2. Rotavirus vaccines--an update.

    Science.gov (United States)

    Kirkwood, Carl D; Buttery, Jim

    2003-02-01

    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.

  3. RNA polymerase associated with human rotaviruses in diarrhea stools.

    Science.gov (United States)

    Hruska, J F; Notter, M F; Menegus, M A; Steinhoff, M C

    1978-01-01

    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

  4. The human rotavirus vaccine RIX4414 in infants: a review of safety and tolerability.

    Science.gov (United States)

    Cheuvart, Brigitte; Friedland, Leonard R; Abu-Elyazeed, Remon; Han, Htay Htay; Guerra, Yolanda; Verstraeten, Thomas

    2009-03-01

    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.

  5. Inactivation of human and simian rotaviruses by chlorine dioxide.

    Science.gov (United States)

    Chen, Y S; Vaughn, J M

    1990-01-01

    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

  6. Reassortant rotaviruses as potential live rotavirus vaccine candidates.

    OpenAIRE

    Midthun, K; Greenberg, H B; Hoshino, Y; Kapikian, A Z; Wyatt, R G; Chanock, R M

    1985-01-01

    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...

  7. Whole genotype constellation of prototype feline rotavirus strains FRV-1 and FRV64 and their phylogenetic relationships with feline-like human rotavirus strains.

    Science.gov (United States)

    Gauchan, Punita; Sasaki, Eriko; Nakagomi, Toyoko; Do, Loan Phuong; Doan, Yen Hai; Mochizuki, Masami; Nakagomi, Osamu

    2015-02-01

    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[9]-I3-R3-C3-M3-A3-N3-T3-E3-H3 and G3-P[3]-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.

  8. Immunogenicity, safety and protective efficacy of one dose of the rhesus rotavirus vaccine and serotype 1 and 2 human-rhesus rotavirus reassortants in children from Lima, Peru.

    Science.gov (United States)

    Lanata, C F; Black, R E; Flores, J; Lazo, F; Butron, B; Linares, A; Huapaya, A; Ventura, G; Gil, A; Kapikian, A Z

    1996-02-01

    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

  9. Sunlight-induced inactivation of human Wa and porcine OSU rotaviruses in the presence of exogenous photosensitizers

    KAUST Repository

    Romero-Maraccini, Ofelia C.

    2013-10-01

    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.

  10. Development of candidate rotavirus vaccines.

    Science.gov (United States)

    Bishop, R F

    1993-01-01

    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.

  11. [The sorption of human and animal rotaviruses by Enterosgel].

    Science.gov (United States)

    Barbova, A I

    1995-01-01

    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.

  12. Human rotavirus genotypes causing acute watery diarrhea among ...

    African Journals Online (AJOL)

    2014-06-17

    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.

  13. Human rotavirus genotypes causing acute watery diarrhea among ...

    African Journals Online (AJOL)

    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.

  14. Human rotavirus group a serotypes causing gastroenteritis in ...

    African Journals Online (AJOL)

    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 ...

  15. Reassortment of Human and Animal Rotavirus Gene Segments in Emerging DS-1-Like G1P[8] Rotavirus Strains.

    Science.gov (United States)

    Komoto, Satoshi; Tacharoenmuang, Ratana; Guntapong, Ratigorn; Ide, Tomihiko; Tsuji, Takao; Yoshikawa, Tetsushi; Tharmaphornpilas, Piyanit; Sangkitporn, Somchai; Taniguchi, Koki

    2016-01-01

    The emergence and rapid spread of novel DS-1-like G1P[8] 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[8] (RVA/Human-wt/THA/SKT-281/2013/G3P[8] and RVA/Human-wt/THA/SKT-289/2013/G3P[8]) and G2P[8] (RVA/Human-wt/THA/LS-04/2013/G2P[8]) 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[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2 for strains SKT-281 and SKT-289, and G2-P[8]-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[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2) is commonly shared with DS-1-like G1P[8] 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[8] 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[8], 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[4] human rotaviruses, while three genes (VP4, VP2, and NSP1) were assumed to be derived from DS-1-like G1P[8] 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[8], locally circulating

  16. Reassortment of Human and Animal Rotavirus Gene Segments in Emerging DS-1-Like G1P[8] Rotavirus Strains.

    Directory of Open Access Journals (Sweden)

    Satoshi Komoto

    Full Text Available The emergence and rapid spread of novel DS-1-like G1P[8] 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[8] (RVA/Human-wt/THA/SKT-281/2013/G3P[8] and RVA/Human-wt/THA/SKT-289/2013/G3P[8] and G2P[8] (RVA/Human-wt/THA/LS-04/2013/G2P[8] 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[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2 for strains SKT-281 and SKT-289, and G2-P[8]-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[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2 is commonly shared with DS-1-like G1P[8] 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[8] 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[8], 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[4] human rotaviruses, while three genes (VP4, VP2, and NSP1 were assumed to be derived from DS-1-like G1P[8] 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[8], locally

  17. Engineering and expression of a human rotavirus candidate vaccine in Nicotiana benthamiana.

    Science.gov (United States)

    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

    2015-12-02

    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[8], and the other a G1-G4 P[8] 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[6] (RVA/Human-wt/ZAF/GR10924/1999/G9P[6]) 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[6] rotavirus strain. This could be more effective in developing countries, thereby possibly providing a higher

  18. Rotavirus Vaccine

    Science.gov (United States)

    ... 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 ...

  19. Rotavirus vaccines: current prospects and future challenges.

    Science.gov (United States)

    Glass, Roger I; Parashar, Umesh D; Bresee, Joseph S; Turcios, Reina; Fischer, Thea K; Widdowson, Marc-Alain; Jiang, Baoming; Gentsch, Jon R

    2006-07-22

    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.

  20. Developing an Inactivated Rotavirus Vaccine and Evaluating the Immunogenicity Against a Commercially Available Attenuated Rotavirus Vaccine Using a Mice Animal Model.

    Science.gov (United States)

    Hashim, Ayaa S M; Aboshanab, Khaled M A; El-Sayed, Aly F M

    2016-12-01

    There is a high demand for public immunization against Rotavirus (RV), especially in Africa. In Africa, the attenuated RV vaccination is contraindicated in patients with immune diseases and nutrition deficiency. Therefore, the inactivated RV vaccine (IRVV) could be an alternative. In this study, we aimed to develop a pentavalent-IRVV using the most circulating RV strains in Egypt and evaluate it against the commercially available Rotarix® vaccine. Trial-IRVV was developed with 5% sucrose, 2% polysorbate-80, and adsorbed on Alum to potentiate the vaccine immune response. Then, it was injected subcutaneously into mice groups at 0-, 21-, and 35-time intervals. In parallel, Rotarix was administered twice on 0 and 28th day. The success of the pentavalent-IRVV/monovalent-Rotarix vaccine immunity rested on achieving immunoglobulin G (IgG) exceeding 1:6,400 that implies less susceptibility to RV infection (RVI). IRVV stimulating IgG >1:6,400 could be an alternative vaccination approach to reach a reasonable protective immunization level against RVI. In addition, Alum adjuvant incorporation effectively provoked a triple elevation of the immunization pattern.

  1. Identification of Rotavirus VP6-Specific CD4+ T Cell Epitopes in a G1P[8] Human Rotavirus-Infected Rhesus Macaque

    Directory of Open Access Journals (Sweden)

    Wei Zhao

    2008-01-01

    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[8] and G9P[8] of human rotaviruses. Infection accompanied by G1P[8] 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.

  2. Molecular characterizations of human and animal group a Rotaviruses in the Netherlands

    NARCIS (Netherlands)

    Heide, van der R.; Koopmans, M.P.G.; Shekary, N.; Houwers, D.J.; Duynhoven, van Y.; Poel, van der W.H.M.

    2005-01-01

    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

  3. Molecular epidemiology of group A human rotaviruses in North West ...

    African Journals Online (AJOL)

    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 ...

  4. Shift in genomic RNA patterns of human rotaviruses isolated from ...

    African Journals Online (AJOL)

    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 ...

  5. Construction and Characterization of Human Rotavirus Recombinant VP8* Subunit Parenteral Vaccine Candidates

    Science.gov (United States)

    Wen, Xiaobo; Cao, Dianjun; Jones, Ronald W.; Li, Jianping; Szu, Shousun; Hoshino, Yasutaka

    2012-01-01

    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[8], DS-1 P[4] or 1076 P[6] 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[8], P[4] or P[6]) 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

  6. Construction and characterization of human rotavirus recombinant VP8* subunit parenteral vaccine candidates.

    Science.gov (United States)

    Wen, Xiaobo; Cao, Dianjun; Jones, Ronald W; Li, Jianping; Szu, Shousun; Hoshino, Yasutaka

    2012-09-21

    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[8], DS-1 P[4] or 1076 P[6] 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[8], P[4] or P[6]) 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.

  7. A rare G1P[6] super-short human rotavirus strain carrying an H2 genotype on the genetic background of a porcine rotavirus.

    Science.gov (United States)

    Do, Loan Phuong; Nakagomi, Toyoko; Nakagomi, Osamu

    2014-01-01

    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[6] 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[6]-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.

  8. Association of serum anti-rotavirus immunoglobulin A antibody seropositivity and protection against severe rotavirus gastroenteritis: analysis of clinical trials of human rotavirus vaccine.

    Science.gov (United States)

    Cheuvart, Brigitte; Neuzil, Kathleen M; Steele, A Duncan; Cunliffe, Nigel; Madhi, Shabir A; Karkada, Naveen; Han, Htay Htay; Vinals, Carla

    2014-01-01

    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.

  9. Effect of human rotavirus vaccine on severe diarrhea in African infants.

    Science.gov (United States)

    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

    2016-09-01

    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

  10. Rotavirus vaccines: is the second time the charm?

    Science.gov (United States)

    Ward, Richard L

    2005-08-01

    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.

  11. Immunity to rotavirus in conventional neonatal calves.

    OpenAIRE

    Vonderfecht, S L; Osburn, B I

    1982-01-01

    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...

  12. Full genomic characterization of a novel genotype combination, G4P[14], of a human rotavirus strain from Barbados.

    Science.gov (United States)

    Tam, Ka Ian; Roy, Sunando; Esona, Mathew D; Jones, Starlene; Sobers, Stephanie; Morris-Glasgow, Victoria; Rey-Benito, Gloria; Gentsch, Jon R; Bowen, Michael D

    2014-12-01

    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[14], detected through PAHO surveillance in Barbados. Full genome sequencing of strain RVA/Human-wt/BRB/CDC1133/2012/G4P[14] revealed that its genotype is G4-P[14]-I1-R1-C1-M1-A8-N1-T1-E1-H1. The possession of a Genogroup 1 (Wa-like) backbone distinguishes this strain from other P[14] 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[14] 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[14] rotavirus genotype. Published by Elsevier B.V.

  13. Safety and efficacy of the pentavalent human-bovine (WC3) reassortant rotavirus vaccine in healthy premature infants.

    Science.gov (United States)

    Goveia, Michelle G; Rodriguez, Zoe M; Dallas, Michael J; Itzler, Robbin F; Boslego, John W; Heaton, Penny M; DiNubile, Mark J

    2007-12-01

    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

  14. Human rotavirus vaccine Rotarix™ provides protection against diverse circulating rotavirus strains in African infants: a randomized controlled trial

    Science.gov (United States)

    2012-01-01

    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[8] 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[4] (20 [1.4%] in placebo) and P[6] (13 [0.9%] in placebo). Vaccine efficacy against P[8] was 59.1% (95% CI: 32.8%; 75.3%), P[4] was 70.9% (95% CI: 37

  15. Comparison of virus shedding after lived attenuated and pentavalent reassortant rotavirus vaccine.

    Science.gov (United States)

    Hsieh, Yu-Chia; Wu, Fang-Tzy; Hsiung, Chao A; Wu, Ho-Sheng; Chang, Kuang-Yi; Huang, Yhu-Chering

    2014-02-26

    Transmission of rotavirus vaccine or vaccine-reassortant strains to unvaccinated contacts has been reported. Therefore, it is essential to evaluate and characterize the nature of vaccine-virus shedding among rotavirus vaccine recipients. Two groups of healthy infants who received a complete course of RotaTeq (RV5) or Rotarix (RV2) were enrolled (between March 2010 and June 2011) to compare fecal shedding for one month after each vaccine dose. Shedding was assessed using both enzyme immunoassay (EIA) and real-time reverse transcription-polymerase chain reaction (RT-PCR). Eighty-seven infants (34 girls and 53 boys) were enrolled in the study. After the first vaccine dose, the peak time of virus shedding occurred between day 4 and day 7, with positive detection rates of 80-90% by real-time RT-PCR and 20-30% by EIA. In both groups, vaccine shedding occurred as early as one day and as late as 25-28 days. Mixed effects logistic regression analysis of real-time RT-PCR data showed no significant differences between two groups when shedding rates were compared after the first vaccine dose (odds ratio [OR] 1.26; P=0.71) or after the second vaccine dose (odds ratio [OR] 1.26; P=0.99). However, infants receiving RV2 shed significantly higher viral loads than those receiving RV5 when compared after the first vaccine dose (P=0.001) and after the second dose (P=0.039). In terms of shedding rates detected by real-time RT-PCR, vaccine uptake of RV5 or RV2 among infants in Taiwan was comparable. Clinical significance of higher shedding viral loads in RV2 should be further observed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Full genomic analysis of a human rotavirus G1P[8] strain isolated in South Korea.

    Science.gov (United States)

    Cho, Min-Kyu; Jheong, Weon-Hwa; Lee, Sung-Geun; Park, Chul Jong; Jung, Kum Hee; Paik, Soon-Young

    2013-01-01

    A rotavirus G1P[8] 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[8]-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[8] (Thai-1604 and Dhaka8-02), respectively. This is the first report that group A rotavirus was analyzed with G1P[8] 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.

  17. Human rotavirus vaccine Rotarix™ provides protection against diverse circulating rotavirus strains in African infants: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Steele Andrew

    2012-09-01

    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[8] 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[4] (20 [1.4%] in placebo and P[6] (13 [0.9%] in placebo. Vaccine efficacy against P[8] was 59.1% (95% CI: 32.8%; 75.3%, P[4] was 70.9% (95% CI: 37.5%; 87

  18. Vacinas contra rotavírus e papilomavírus humano (HPV Vaccines against rotavirus and human papillomavirus (HPV

    Directory of Open Access Journals (Sweden)

    Alexandre C. Linhares

    2006-07-01

    -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.

  19. Human rotavirus in an adult population with travelers' diarrhea and its relationship to the location of food consumption.

    Science.gov (United States)

    Vollet, J J; Ericsson, C D; Gibson, G; Pickering, L K; DuPont, H L; Kohl, S; Conklin, R H

    1979-01-01

    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.

  20. 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[8] or 1B[4] and the remaining 10 genes of rhesus monkey rotavirus MMU18006 or bovine rotavirus UK.

    Science.gov (United States)

    Hoshino, Yasutaka; Jones, Ronald W; Chanock, Robert M; Kapikian, Albert Z

    2002-10-04

    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[8] or 1B[4] 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[8] or 1B[4], thus possibly augmenting its immunogenicity. Similarly, three single VP4 gene (P1A[8] or P1B[4]) 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.

  1. Comparison of mucosal and systemic humoral immune responses and subsequent protection in mice orally inoculated with a homologous or a heterologous rotavirus.

    OpenAIRE

    Feng, N; Burns, J W; Bracy, L; Greenberg, H B

    1994-01-01

    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...

  2. Molecular Characterization of Human Rotavirus from Children with Diarrhoeal Disease in Sokoto State, Nigeria

    Directory of Open Access Journals (Sweden)

    B. R. Alkali

    2016-01-01

    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[6] 3 (13%, P[8] 11 (47.8%, and the rare human P genotype (P[9], found in 9 patients (39.1%. Nine strains identified with the common G and P combinations were G4 P[8] 5 (56%, G4 P[6] 1 (11%, G1 P[8] 2 (22%, and G3 P[8] 1 (11%, while seven strains with unusual combinations or rare G or P genotypes identified were G12 P[8] 1 (14%, G2 P[8] 2 (29%, and G4 P[9] 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.

  3. Molecular characterization of genotype G6 human rotavirus strains detected in Italy from 1986 to 2009.

    Science.gov (United States)

    De Grazia, Simona; Martella, Vito; Rotolo, Valentina; Bonura, Floriana; Matthijnssens, Jelle; Bányai, Krisztián; Ciarlet, Max; Giammanco, Giovanni M

    2011-08-01

    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[9] or P[14] 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[9]/[14]-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[9] 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.

  4. Genetic Analyses Reveal Differences in the VP7 and VP4 Antigenic Epitopes between Human Rotaviruses Circulating in Belgium and Rotaviruses in Rotarix and RotaTeq

    Science.gov (United States)

    Zeller, Mark; Patton, John T.; Heylen, Elisabeth; De Coster, Sarah; Ciarlet, Max; Van Ranst, Marc

    2012-01-01

    Two live-attenuated rotavirus group A (RVA) vaccines, Rotarix (G1P[8]) and RotaTeq (G1-G4, P[8]), 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[8], G2P[4], G3P[8], G4P[8], G9P[8], and G12P[8] 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[8] RVA strains and the G1 and P[8] components of both RVA vaccines. In particular, RVA strains of the P[8] lineage 4 (OP354-like) showed a significant number of amino acid differences with the P[8] 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

  5. Evidence of VP7 and VP4 intra-lineage diversification in G4P[8] Italian human rotaviruses.

    Science.gov (United States)

    Medici, Maria Cristina; Tummolo, Fabio; Guerra, Paola; Arcangeletti, Maria Cristina; Chezzi, Carlo; De Conto, Flora; Calderaro, Adriana

    2014-04-01

    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[8] strains identified in Parma, Northern Italy, during 2004-2005 and 2008-2012. All the strains clustered into lineages Ic (VP7) and P[8]-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.

  6. CD4+ CD25− FoxP3+ regulatory cells are the predominant responding regulatory T cells after human rotavirus infection or vaccination in gnotobiotic pigs

    Science.gov (United States)

    Wen, Ke; Li, Guohua; Yang, Xingdong; Bui, Tammy; Bai, Muqun; Liu, Fangning; Kocher, Jacob; Yuan, Lijuan

    2012-01-01

    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

  7. Whole genome detection of rotavirus mixed infections in human, porcine and bovine samples co-infected with various rotavirus strains collected from sub-Saharan Africa.

    Science.gov (United States)

    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

    2015-04-01

    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

  8. Rotavirus structural proteins and dsRNA are required for the human primary plasmacytoid dendritic cell IFNalpha response

    National Research Council Canada - National Science Library

    Deal, Emily M; Jaimes, Maria C; Crawford, Sue E; Estes, Mary K; Greenberg, Harry B

    2010-01-01

    .... 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...

  9. Glycan-modifying bacteria-derived soluble factors from Bacteroides thetaiotaomicron and Lactobacillus casei inhibit rotavirus infection in human intestinal cells.

    Science.gov (United States)

    Varyukhina, Svetlana; Freitas, Miguel; Bardin, Sabine; Robillard, Emilie; Tavan, Emmanuelle; Sapin, Catherine; Grill, Jean-Pierre; Trugnan, Germain

    2012-03-01

    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.

  10. Analysis of complete genome sequences of G9P[19] rotavirus strains from human and piglet with diarrhea provides evidence for whole-genome interspecies transmission of nonreassorted porcine rotavirus.

    Science.gov (United States)

    Yodmeeklin, Arpaporn; Khamrin, Pattara; Chuchaona, Watchaporn; Kumthip, Kattareeya; Kongkaew, Aphisek; Vachirachewin, Ratchaya; Okitsu, Shoko; Ushijima, Hiroshi; Maneekarn, Niwat

    2017-01-01

    Whole genomes of G9P[19] human (RVA/Human-wt/THA/CMH-S070-13/2013/G9P[19]) and porcine (RVA/Pig-wt/THA/CMP-015-12/2012/G9P[19]) 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[19] was most closely related to those of porcine rotavirus RVA/Pig-wt/THA/CMP-015-12/2012/G9P[19] 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[19] detected in human and piglet were identical and displayed as the G9-P[19]-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[19] 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[19] porcine RVA to human occurring in nature in northern Thailand. Copyright © 2016. Published by Elsevier B.V.

  11. Full Genomic Characterization of a Novel Genotype Combination, G4P[14], of a Human Rotavirus Strain from Barbados

    OpenAIRE

    Tam, Ka Ian; Roy, Sunando; Esona, Mathew D.; Jones, Starlene; Sobers, Stephanie; Morris-Glasgow, Victoria; Rey-Benito, Gloria; Gentsch, Jon R.; Bowen, Michael D.

    2014-01-01

    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[14], detected through PAHO surveillance in Barbados. Full genome sequencing of strain RVA/Human-wt/BRB/CDC1133/2012/G4P[14] revealed that its genotype is G4-P[14]-I1-R1-C1-M1-A8-N1-T1-E1-H1. The possession of a Genogroup 1 (Wa-like) backbone distinguishes this strain from ...

  12. Rotavirus vaccines.

    Science.gov (United States)

    Lynch, Maureen; Bresee, Joseph S.; Gentsch, Jon R.; Glass, Roger I.

    2000-10-01

    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.

  13. Complete genome sequence analysis of candidate human rotavirus vaccine strains RV3 and 116E.

    Science.gov (United States)

    Rippinger, Christine M; Patton, John T; McDonald, Sarah M

    2010-09-15

    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[6]) and 116E (G9P[11]), 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[6] 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.

  14. Whole genome characterisation and engineering of chimaeric rotavirus-like particles using African rotavirus field strains / Khuzwayo Chidiwa Jere

    OpenAIRE

    Jere, Khuzwayo Chidiwa

    2012-01-01

    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...

  15. Rotavirus structural proteins and dsRNA are required for the human primary plasmacytoid dendritic cell IFNalpha response.

    Directory of Open Access Journals (Sweden)

    Emily M Deal

    2010-06-01

    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

  16. Rotavirus structural proteins and dsRNA are required for the human primary plasmacytoid dendritic cell IFNalpha response.

    Science.gov (United States)

    Deal, Emily M; Jaimes, Maria C; Crawford, Sue E; Estes, Mary K; Greenberg, Harry B

    2010-06-03

    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

  17. Characterisation of G8 human rotaviruses in Australian children with gastroenteritis.

    Science.gov (United States)

    Swiatek, Dayna L; Palombo, Enzo A; Lee, Alvin; Coventry, Michael J; Britz, Margaret L; Kirkwood, Carl D

    2010-03-01

    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[14] strains, one was G8P[8]+[14] 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[11] bovine rotavirus strain detected in Japan. VP4 sequence data of one G8P[14] strain revealed that the closest identity was to another human-bovine-like strain detected in Australia, MG6, a G6P[14] strain. The identification of G8 strains causing disease further extends the number of G8P[14] 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.

  18. Whole genomic analysis of G2P[4] human Rotaviruses in Mymensingh, north-central Bangladesh

    Directory of Open Access Journals (Sweden)

    Satoru Aida

    2016-09-01

    Full Text Available Rotavirus A (RVA is a dominant causative agent of acute gastroenteritis in children worldwide. G2P[4] 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[4] 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[4] 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[4] 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[4] 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[4] rotavirus strains in Bangladesh.

  19. Approaches to immunization of infants and young children against gastroenteritis due to rotaviruses.

    Science.gov (United States)

    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

    1980-01-01

    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.

  20. Rotaviruses and rotavirus vaccines.

    Science.gov (United States)

    Desselberger, Ulrich; Manktelow, Emily; Li, Wilson; Cheung, Winsome; Iturriza-Gómara, Miren; Gray, Jim

    2009-01-01

    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

  1. Sequence analysis of the VP7 gene of human rotavirus G1 isolated in Japan, China, Thailand, and Vietnam in the context of changing distribution of rotavirus G-types.

    Science.gov (United States)

    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

    2007-07-01

    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.

  2. Characterization of 2 human genotype G10 rotavirus strains, 3008CM and 1784/CI/1999, isolated in Cameroon and Cote d'Ivoire during the 1999-2000 rotavirus season.

    Science.gov (United States)

    Esona, Mathew D; Page, Nicola A; Akran, Veronique A; Armah, George E; Steele, A Duncan

    2010-09-01

    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[8] by reverse-transcription polymerase chain reaction. Further investigation of the polymerase chain reaction G-typing results with a second set of primers revealed that the specimens were not genotype G3, and both samples were sequenced to elucidate the problem. Both strains were found to be genotype 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.

  3. Rotavirus Treatment

    Science.gov (United States)

    ... 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 ...

  4. Analysis of the full genome of human group C rotaviruses reveals lineage diversification and reassortment.

    Science.gov (United States)

    Medici, Maria Cristina; Tummolo, Fabio; Martella, Vito; Arcangeletti, Maria Cristina; De Conto, Flora; Chezzi, Carlo; Fehér, Enikő; Marton, Szilvia; Calderaro, Adriana; Bányai, Krisztián

    2016-08-01

    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.

  5. Complete Genome Analysis of a Rabbit Rotavirus Causing Gastroenteritis in a Human Infant

    Directory of Open Access Journals (Sweden)

    Melisa Berenice Bonica

    2015-02-01

    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[14] and G3P[22] were found to be the most common G/P-genotypes. During the 2012-2013 rotavirus season in Belgium, a G3P[14] RVA strain was isolated from stool collected from a two-year-old boy. We investigated whether RVA/Human-wt/BEL/BE5028/2012/G3P[14] 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[14]-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[14], 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.

  6. Rotavirus in various animal species in Ouagadougou, Burkina Faso ...

    African Journals Online (AJOL)

    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.

  7. A first report on the characterization of rotavirus strains in Sierra Leone.

    Science.gov (United States)

    Jere, K C; Sawyerr, T; Seheri, L M; Peenze, I; Page, N A; Geyer, A; Steele, A D

    2011-03-01

    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[4] (30.23%), G2P[6] (13.95%), G8P[6] (11.63%), G2P[8] (4.65%), G8P[4] (4.65%), and G8P[8] (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.

  8. Molecular characterization of the NSP4 gene of human group A rotavirus samples from the West Central region of Brazil

    Directory of Open Access Journals (Sweden)

    Talissa de Moraes Tavares

    2008-05-01

    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.

  9. Antibody-secreting cell responses and protective immunity assessed in gnotobiotic pigs inoculated orally or intramuscularly with inactivated human rotavirus.

    Science.gov (United States)

    Yuan, L; Kang, S Y; Ward, L A; To, T L; Saif, L J

    1998-01-01

    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.

  10. Construction and Characterization of Human Rotavirus Recombinant VP8* Subunit Parenteral Vaccine Candidates

    OpenAIRE

    Wen, Xiaobo; Cao, Dianjun; Jones, Ronald W.; Li, Jianping; Szu, Shousun; Hoshino, Yasutaka

    2012-01-01

    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...

  11. A systematic review of genetic diversity of human rotavirus circulating in South Korea.

    Science.gov (United States)

    Than, Van Thai; Jeong, Sunyoung; Kim, Wonyong

    2014-12-01

    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[8], followed by G3P[8], G4P[6], and G2P[4], accounted for approximately 76.7% of the total identified strains, and more recently, rotavirus G9P[8] 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.

  12. Prospects for development of a rotavirus vaccine against rotavirus diarrhea in infants and young children.

    Science.gov (United States)

    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

    1989-01-01

    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.

  13. Rotavirus Structural Proteins and dsRNA Are Required for the Human Primary Plasmacytoid Dendritic Cell IFN? Response

    OpenAIRE

    Deal, Emily M.; Jaimes, Maria C.; Crawford, Sue E.; Estes, Mary K.; Greenberg, Harry B.

    2010-01-01

    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...

  14. Ovine rotaviruses | Gazal | Open Veterinary Journal

    African Journals Online (AJOL)

    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 ...

  15. Experimental reproduction of rotavirus and Salmonella pullorum ...

    African Journals Online (AJOL)

    ADEYEYE

    2017-07-10

    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).

  16. A cost comparison of introducing and delivering pneumococcal, rotavirus and human papillomavirus vaccines in Rwanda.

    Science.gov (United States)

    Ngabo, Fidèle; Levin, Ann; Wang, Susan A; Gatera, Maurice; Rugambwa, Celse; Kayonga, Celestin; Donnen, Philippe; Lepage, Philippe; Hutubessy, Raymond

    2015-12-16

    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

  17. Novel rotaviruses in animals and man.

    Science.gov (United States)

    Bridger, J C

    1987-01-01

    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.

  18. Human group A rotavirus infections in children in Denmark: detection of reassortant G9 strains and zoonotic P[14] strains.

    Science.gov (United States)

    Midgley, S; Böttiger, B; Jensen, T G; Friis-Møller, A; Person, L K; Nielsen, L; Barzinci, S; Fischer, T K

    2014-10-01

    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[8] 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[8] and G2P[4]) were detected in the majority of samples (n=733, 88.2%). Rare genotype combinations such as G6P[14] 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[4] 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.

  19. Influence of potential protective mechanisms on the development of live rotavirus vaccines.

    Science.gov (United States)

    Ward, Richard L; Clark, H Fred; Offit, Paul A

    2010-09-01

    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.

  20. Human milk oligosaccharides shorten rotavirus-induced diarrhea and modulate piglet mucosal immunity and colonic microbiota.

    Science.gov (United States)

    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

    2014-08-01

    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.

  1. Efficacy, Immunogenicity and Safety of a Human Rotavirus Vaccine RIX4414 in Singaporean Infants.

    Science.gov (United States)

    Phua, Kong Boo; Lim, Fong Seng; Quak, Seng Hock; Lee, Bee Wah; Teoh, Yee Leong; Suryakiran, Pemmaraju V; Han, Htay Htay; Bock, Hans L

    2016-02-01

    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.

  2. Simultaneous administration of two human-rhesus rotavirus reassortant strains of VP7 serotype 1 and 2 specificity to infants and young children.

    Science.gov (United States)

    Wright, P F; King, J; Araki, K; Kondo, Y; Thompson, J; Tollefson, S J; Kobayashi, M; Kapikian, A Z

    1991-08-01

    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.

  3. [Phylogenetic analysis indicates human origin of rotavirus and hepatitis A virus strains found in the drinking water of western Colombia].

    Science.gov (United States)

    Moreno, Sandra; Alvarado, Mónica Viviana; Bermúdez, Andrea; Gutiérrez, María Fernanda

    2009-06-01

    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.

  4. Sequential administration of two human-rhesus rotavirus reassortant strains of VP7 serotype 1 and 2 specificity to infants and young children.

    Science.gov (United States)

    Kobayashi, M; Araki, K; Thompson, J; Tollefson, S J; Wright, P F

    1993-03-01

    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.

  5. Comparative In Vitro and In Vivo Studies of Porcine Rotavirus G9P[13] and Human Rotavirus Wa G1P[8].

    Science.gov (United States)

    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

    2015-10-14

    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[13] and evaluated the short-term cross-protection between this strain and human RV (HRV) Wa G1P[8] in gnotobiotic pigs. Complete genome sequencing demonstrated that PRV G9P[13] possessed a human-like G9 VP7 genotype but shared higher overall nucleotide identity with historic PRV strains. PRV G9P[13] induced longer rectal virus shedding and RV RNAemia in pigs than HRV Wa G1P[8] and generated complete short-term cross-protection in pigs challenged with HRV or PRV, whereas HRV Wa G1P[8] induced only partial protection against PRV challenge. Moreover, PRV G9P[13] replicated more extensively in porcine monocyte-derived dendritic cells (MoDCs) than did HRV Wa G1P[8]. Cross-protection was likely not dependent on serum virus-neutralizing (VN) antibodies, as the heterologous VN antibody titers in the sera of G9P[13]-inoculated pigs were low. Thus, our results suggest that heterologous protection by the current monovalent G1P[8] 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

  6. Serum and intestinal isotype antibody responses to Wa human rotavirus in gnotobiotic pigs are modulated by maternal antibodies.

    Science.gov (United States)

    Parreño, V; Hodgins, D C; de Arriba, L; Kang, S Y; Yuan, L; Ward, L A; Tô, T L; Saif, L J

    1999-06-01

    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.

  7. Rotavirus gastroenteritis.

    Science.gov (United States)

    Leung, A K; Pai, C H

    1988-01-01

    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.

  8. Emergence of unusual human rotavirus strains in Salento, Italy, during 2006–2007

    Directory of Open Access Journals (Sweden)

    De Donno Antonella

    2009-04-01

    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[8], G1P[8], G2P[4] and G9P[8] amongst 59.8% of the typeable rotavirus positives. Rotavirus G2P[8] 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[10], G4P[10], G8P[4], G9P[11] and G10P[8] is noteworthy. Furthermore, a significant number of mixed infections were observed during the survey period but G3P[8] 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.

  9. Complete genotype constellation of human rotavirus group A circulating in Thailand, 2008-2011.

    Science.gov (United States)

    Theamboonlers, A; Maiklang, O; Thongmee, T; Chieochansin, T; Vuthitanachot, V; Poovorawan, Y

    2014-01-01

    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[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 22.7% (5/22); G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2 27.3% (6/22); G3-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 18.2% (4/22); G3-P[9]-I3-R3-C3-M3-A3-N3-T3-E3-H6 4.6% (1/22); G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 9.1% (2/22); G12-P[6]-I1-R1-C1-M1-A1-N1-T1-E1-H1 4.6% (1/22) and G12-P[8]-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[6] 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.

  10. Immunity to rotavirus in conventional neonatal calves.

    Science.gov (United States)

    Vonderfecht, S L; Osburn, B I

    1982-11-01

    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.

  11. Whole genome sequencing of a rare rotavirus from archived stool sample demonstrates independent zoonotic origin of human G8P[14] strains in Hungary.

    Science.gov (United States)

    Marton, Szilvia; Dóró, Renáta; Fehér, Enikő; Forró, Barbara; Ihász, Katalin; Varga-Kugler, Renáta; Farkas, Szilvia L; Bányai, Krisztián

    2017-01-02

    Genotype P[14] 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[14] 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[14] strain, RVA/Human-wt/HUN/182-02/2001/G8P[14]. The whole genome constellation (G8-P[14]-I2-R2-C2-M2-A11-N2-T6-E2-H3) of this strain was shared with another Hungarian zoonotic G8P[14] strain, RVA/Human-wt/HUN/BP1062/2004/G8P[14], although phylogenetic analyses revealed the two rotaviruses likely had different progenitors. Overall, our findings indicate that human G8P[14] 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 © 2016. Published by Elsevier B.V.

  12. No evidence of murine leukemia virus-related viruses in live attenuated human vaccines.

    Directory of Open Access Journals (Sweden)

    William M Switzer

    Full Text Available The association of xenotropic murine leukemia virus (MLV-related virus (XMRV in prostate cancer and chronic fatigue syndrome reported in previous studies remains controversial as these results have been questioned by recent data. Nonetheless, concerns have been raised regarding contamination of human vaccines as a possible source of introduction of XMRV and MLV into human populations. To address this possibility, we tested eight live attenuated human vaccines using generic PCR for XMRV and MLV sequences. Viral metagenomics using deep sequencing was also done to identify the possibility of other adventitious agents.All eight live attenuated vaccines, including Japanese encephalitis virus (JEV (SA-14-14-2, varicella (Varivax, measles, mumps, and rubella (MMR-II, measles (Attenuvax, rubella (Meruvax-II, rotavirus (Rotateq and Rotarix, and yellow fever virus were negative for XMRV and highly related MLV sequences. However, residual hamster DNA, but not RNA, containing novel endogenous gammaretrovirus sequences was detected in the JEV vaccine using PCR. Metagenomics analysis did not detect any adventitious viral sequences of public health concern. Intracisternal A particle sequences closest to those present in Syrian hamsters and not mice were also detected in the JEV SA-14-14-2 vaccine. Combined, these results are consistent with the production of the JEV vaccine in Syrian hamster cells.We found no evidence of XMRV and MLV in eight live attenuated human vaccines further supporting the safety of these vaccines. Our findings suggest that vaccines are an unlikely source of XMRV and MLV exposure in humans and are consistent with the mounting evidence on the absence of these viruses in humans.

  13. Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian children in the second year of life.

    Science.gov (United States)

    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

    2014-08-11

    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.

  14. Effects of chlorine and chlorine dioxide on human rotavirus infectivity and genome stability.

    Science.gov (United States)

    Xue, Bin; Jin, Min; Yang, Dong; Guo, Xuan; Chen, Zhaoli; Shen, Zhiqiang; Wang, Xinwei; Qiu, Zhigang; Wang, Jingfeng; Zhang, Bin; Li, Junwen

    2013-06-15

    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.

  15. Evaluation of unintended effects in the composition of tomatoes expressing a human immunoglobulin A against rotavirus.

    Science.gov (United States)

    Juarez, Paloma; Fernandez-del-Carmen, Asun; Rambla, Jose L; Presa, Silvia; Mico, Amparo; Granell, Antonio; Orzaez, Diego

    2014-08-13

    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.

  16. Antigenic and Genomic Diversity of Human Rotavirus VP4 in Two Consecutive Epidemic Seasons in Mexico

    Science.gov (United States)

    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.

    1998-01-01

    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[4] and P[8] 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

  17. Effectiveness of a live oral human rotavirus vaccine after programmatic introduction in Bangladesh: A cluster-randomized trial.

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    K Zaman

    2017-04-01

    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

  18. Human Milk Contains Novel Glycans That Are Potential Decoy Receptors for Neonatal Rotaviruses*

    Science.gov (United States)

    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.

    2014-01-01

    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[11]) and RV3(G3P[6]) and a bovine strain, B223(G10P[11]). 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

  19. Whole genomic constellation of the first human G8 rotavirus strain detected in Japan.

    Science.gov (United States)

    Agbemabiese, Chantal Ama; Nakagomi, Toyoko; Doan, Yen Hai; Nakagomi, Osamu

    2015-10-01

    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[4]-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[14] 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[4] 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[4] 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.

  20. Chimaeric virus-like particles derived from consensus genome sequences of human rotavirus strains co-circulating in Africa.

    Directory of Open Access Journals (Sweden)

    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[4], P[6] or P[8] 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

  1. Chimaeric virus-like particles derived from consensus genome sequences of human rotavirus strains co-circulating in Africa.

    Science.gov (United States)

    Jere, Khuzwayo C; O'Neill, Hester G; Potgieter, A Christiaan; van Dijk, Alberdina A

    2014-01-01

    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[4], P[6] or P[8] 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

  2. Chimaeric Virus-Like Particles Derived from Consensus Genome Sequences of Human Rotavirus Strains Co-Circulating in Africa

    Science.gov (United States)

    Jere, Khuzwayo C.; O'Neill, Hester G.; Potgieter, A. Christiaan; van Dijk, Alberdina A.

    2014-01-01

    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[4], P[6] or P[8] 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

  3. Segurança, imunogenicidade e eficácia protetora de duas doses da vacina RIX4414 contendo rotavírus atenuado de origem humana Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy Brazilian infants

    Directory of Open Access Journals (Sweden)

    Eliete C. Araujo

    2007-06-01

    efficacy of two doses of rotavirus vaccine in healthy Brazilian infants. METHODS: A randomized, multicenter, double-blind, placebo-controlled trial was conducted in Brazil, Mexico and Venezuela. Infants received two oral doses of vaccine or placebo at 2 and 4 months of age, concurrently with routine immunizations, except for oral poliomyelitis vaccine (OPV. This paper reports results from Belém, Brazil, where the number of subjects per group and the viral vaccine titers were: 194 (10(4.7 focus forming units - FFU, 196 (10(5.2 FFU, 194 (10(5.8 FFU and 194 (placebo. Anti-rotavirus (anti-RV antibody response was assessed in 307 subjects. Clinical severity of gastroenteritis episodes was measured using a 20-point scoring system with a score of > 11 defined as severe GE. RESULTS: The rates of solicited general symptoms were similar in vaccine and placebo recipients. At 2 months after the second dose, a serum IgA response to RV occurred in 54.7 to 74.4% of vaccinees. No interference was seen in the immunogenicity of routine vaccines. Vaccine efficacy against any rotavirus gastroenteritis (RVGE was 63.5% (95%CI 20.8-84.4 for the highest concentration (10(5.8 FFU. Efficacy was 81.5% (95%CI 44.5-95.4 against severe RVGE. At its highest concentration (10(5.8 FFU, RIX4414 provided 79.8% (95%CI 26.4-96.3 protection against severe RVGE by G9 strain. CONCLUSIONS: RIX4414 was highly immunogenic with a low reactogenicity profile and did not interfere with seroresponse to diptheria, tetanus, pertussis, hepatitis B and Hib antigens. Two doses of RIX4414 provided significant protection against severe GE caused by RV.

  4. Characterization and Transferring of Human Rotavirus Double-Layered Particles in MA104 Cells.

    Science.gov (United States)

    Teimoori, Ali; Soleimanjahi, Hoorieh; Makvandi, Manoochehr

    2014-06-01

    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.

  5. MicroRNA profile analysis of host cells before and after wild human rotavirus infection.

    Science.gov (United States)

    Zhou, Yan; Wu, Jinyuan; Geng, Panpan; Kui, Xiang; Xie, Yuping; Zhang, Lei; Liu, Yaling; Yin, Na; Zhang, Guangming; Yi, Shan; Li, Hongjun; Sun, Maosheng

    2016-09-01

    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 [8] 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.

  6. Comparison of mucosal and systemic humoral immune responses and subsequent protection in mice orally inoculated with a homologous or a heterologous rotavirus.

    Science.gov (United States)

    Feng, N; Burns, J W; Bracy, L; Greenberg, H B

    1994-12-01

    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.

  7. Rotavirus Infections

    Science.gov (United States)

    ... 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 ...

  8. Rotavirus Symptoms

    Science.gov (United States)

    ... 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 ...

  9. Reactions to and antigenicity of two human-rhesus rotavirus reassortant vaccine candidates of serotypes 1 and 2 in Venezuelan infants.

    Science.gov (United States)

    Flores, J; Perez-Schael, I; Blanco, M; Vilar, M; Garcia, D; Perez, M; Daoud, N; Midthun, K; Kapikian, A Z

    1989-03-01

    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.

  10. Evolution of human G4P[8] group A rotavirus strains circulating in Italy in 2013.

    Science.gov (United States)

    Ianiro, Giovanni; Delogu, Roberto; Fiore, Lucia; Ruggeri, Franco M

    2015-06-02

    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[8], G2P[4], G3P[8], G4P[8] and G9P[8]. 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[8] 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[8]-III for VP4, in line with the modern G4P[8] 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[8] 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[8] RVA strains presented amino acid substitutions near known neutralizing epitopes. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Analyses of homologous rotavirus infection in the mouse model.

    Science.gov (United States)

    Burns, J W; Krishnaney, A A; Vo, P T; Rouse, R V; Anderson, L J; Greenberg, H B

    1995-02-20

    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.

  12. Characterization and Transferring of Human Rotavirus Double-Layered Particles in MA104 Cells

    OpenAIRE

    Teimoori, Ali; Soleimanjahi, Hoorieh; Makvandi, Manoochehr

    2014-01-01

    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...

  13. Quantitative reverse transcription PCR to determine the inactivation of Human Rotavirus by chlorine.

    Science.gov (United States)

    Xue, Bin; Li, Chenyu; Zhang, Bin; Zhao, Tianyu; Shen, Zhiqiang; Qiu, Zhigang; Jin, Min; Wang, Jingfeng; Li, Junwen

    2017-06-01

    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.

  14. Analysis of rotavirus species diversity and evolution including the newly determined full-length genome sequences of rotavirus F and G.

    Science.gov (United States)

    Kindler, Eveline; Trojnar, Eva; Heckel, Gerald; Otto, Peter H; Johne, Reimar

    2013-03-01

    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.

  15. Emergence of G9 P[6] human rotaviruses in Argentina: phylogenetic relationships among G9 strains.

    Science.gov (United States)

    Bok, K; Palacios, G; Sijvarger, K; Matson, D; Gomez, J

    2001-11-01

    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.

  16. Distribution of human rotavirus G and P genotypes in a hospital setting from Northern India.

    Science.gov (United States)

    Chakravarti, Anita; Chauhan, Mayank Singh; Sharma, Anju; Verma, Vikas

    2010-09-01

    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[8] (40%) followed by P[4] (26%) and P[6] (17%). The most common G-P combinations were G1P[8] (26%), followed by G1P[4] and G1P[6]. Mixed infection involved 28% of strains. In this study the G1 and P[8] genotypes were the leading G and P types. Two cases with G12 genotype were also observed during the study.

  17. LAS PROTEÍNAS β3 Y PDI AISLADAS DE PLAQUETAS HUMANAS SE UNEN CON EL ROTAVIRUS ECwt IN VITRO β3 and PDI proteins isolated from human platelets bind with ECwt rotavirus in vitro

    Directory of Open Access Journals (Sweden)

    Diana Mayorga

    2010-01-01

    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

  18. PROTECTIVE ACTIVITY STUDY OF A CANDIDATE VACCINE AGAINST ROTAVIRUS INFECTION BASED ON RECOMBINANT PROTEIN FliCVP6VP8

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    I. V. Dukhovlinov

    2016-01-01

    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

  19. Identification and characterization of a human G9P[23] rotavirus strain from a child with diarrhoea in Thailand: evidence for porcine-to-human interspecies transmission.

    Science.gov (United States)

    Komoto, Satoshi; Tacharoenmuang, Ratana; Guntapong, Ratigorn; Ide, Tomihiko; Sinchai, Phakapun; Upachai, Sompong; Fukuda, Saori; Yoshikawa, Tetsushi; Tharmaphornpilas, Piyanit; Sangkitporn, Somchai; Taniguchi, Koki

    2017-04-01

    An unusual rotavirus strain with the G9P[23] genotype (RVA/Human-wt/THA/KKL-117/2014/G9P[23]) 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[23]-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.

  20. Efficacy of a Monovalent Human-Bovine (116E) Rotavirus Vaccine in Indian Infants: A Randomised Double Blind Placebo Controlled Trial

    Science.gov (United States)

    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

    2015-01-01

    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

  1. Clinical and epidemiological features of acute infantile gastroenteritis associated with human rotavirus subgroups 1 and 2.

    OpenAIRE

    Uhnoo, I; Svensson, L

    1986-01-01

    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...

  2. Diarrheal response of gnotobiotic pigs after fetal infection and neonatal challenge with homologous and heterologous human rotavirus strains.

    Science.gov (United States)

    Torres, A; Ji-Huang, L

    1986-12-01

    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.

  3. The Impact of Socio-Economic Determinants on the Vaccination Rates with Rotavirus and Human Papiloma Virus Vaccine.

    Science.gov (United States)

    Grdadolnik, Urška; Sočan, Maja

    2016-03-01

    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.

  4. Detection and molecular characterization of human rotaviruses isolated in Italy and Albania.

    Science.gov (United States)

    Annarita, Petrinca; Grassi, Tiziana; Donia, Domenica; De Donno, Antonella; Idolo, Adele; Alfio, Cristaldi; Alessandri, Claudia; Alberto, Spanò; Divizia, Maurizio

    2010-03-01

    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[8] (54.5%), G1 P[8] (27.3%), and G2 P[4] (18.2%); in Albania they were G9 P[8] (72.1%), G4 P[8] (8.8%), G1 P[8] (5.9%), and G2 P[4] (2.9%). The prevalence in Albania of atypical combinations was 7.4% for G4 P[4] and 2.9% for G9 P[4]. 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.

  5. Whole genome analysis of selected human and animal rotaviruses identified in Uganda from 2012 to 2014 reveals complex genome reassortment events between human, bovine, caprine and porcine strains.

    Science.gov (United States)

    Bwogi, Josephine; Jere, Khuzwayo C; Karamagi, Charles; Byarugaba, Denis K; Namuwulya, Prossy; Baliraine, Frederick N; Desselberger, Ulrich; Iturriza-Gomara, Miren

    2017-01-01

    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.

  6. Extraintestinal rotavirus infections in children with immunodeficiency.

    Science.gov (United States)

    Gilger, M A; Matson, D O; Conner, M E; Rosenblatt, H M; Finegold, M J; Estes, M K

    1992-06-01

    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.

  7. Ondansetron treatment reduces rotavirus symptoms—A randomized double-blinded placebo-controlled trial

    National Research Council Canada - National Science Library

    Marie Hagbom; Daniel Novak; Malin Ekström; Younis Khalid; Maria Andersson; Magnus Lindh; Johan Nordgren; Lennart Svensson

    2017-01-01

    .... The objective of this randomized double-blinded placebo-controlled study was to investigate whether ondansetron, a serotonin receptor antagonist could attenuate rotavirus- and norovirus-induced...

  8. Safety, reactogenicity and immunogenicity of the human rotavirus vaccine in preterm European Infants: a randomized phase IIIb study.

    Science.gov (United States)

    Omenaca, Felix; Sarlangue, Jean; Szenborn, Leszek; Nogueira, Marta; Suryakiran, Pemmaraju V; Smolenov, Igor V; Han, Htay H

    2012-05-01

    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

  9. Rotavirus genotype distribution during the pre-vaccine period in Bolivia: 2007–2008

    Science.gov (United States)

    Rivera, Rosario; Forney, Kristen; Castro, Maria René; Rebolledo, Paulina A.; Mamani, Nataniel; Patzi, Maritza; Halkyer, Percy; Leon, Juan S.; Iñiguez, Volga

    2013-01-01

    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[8] (33%), G1P[6] (17%), G2P[4] (13%), G9P[6] (12%), and G1P[8] (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[6] 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

  10. Rotavirus genotype distribution during the pre-vaccine period in Bolivia: 2007-2008.

    Science.gov (United States)

    Rivera, Rosario; Forney, Kristen; Castro, Maria René; Rebolledo, Paulina A; Mamani, Nataniel; Patzi, Maritza; Halkyer, Percy; Leon, Juan S; Iñiguez, Volga

    2013-09-01

    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[8] (33%), G1P[6] (17%), G2P[4] (13%), G9P[6] (12%), and G1P[8] (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[6] 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.

  11. IgY antibodies protect against human Rotavirus induced diarrhea in the neonatal gnotobiotic piglet disease model.

    Directory of Open Access Journals (Sweden)

    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[8] 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.

  12. G8 rotaviruses with conserved genotype constellations detected in Malawi over 10 years (1997–2007) display frequent gene reassortment among strains co-circulating in humans

    Science.gov (United States)

    Nakagomi, Toyoko; Doan, Yen Hai; Dove, Winifred; Ngwira, Bagrey; Iturriza-Gómara, Miren; Nakagomi, Osamu

    2013-01-01

    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[8], G2P[4], G3P[8], G4P[8] and G9P[8]. 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[6] to P[4] and P[8] 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[6] 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

  13. G8 rotaviruses with conserved genotype constellations detected in Malawi over 10 years (1997-2007) display frequent gene reassortment among strains co-circulating in humans.

    Science.gov (United States)

    Nakagomi, Toyoko; Doan, Yen Hai; Dove, Winifred; Ngwira, Bagrey; Iturriza-Gómara, Miren; Nakagomi, Osamu; Cunliffe, Nigel A

    2013-06-01

    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[8], G2P[4], G3P[8], G4P[8] and G9P[8]. 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[6] to P[4] and P[8] 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[6] 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.

  14. Ovine rotavirus strain LLR-85-based bovine rotavirus candidate vaccines: construction, characterization and immunogenicity evaluation.

    Science.gov (United States)

    Chang, Ji-Tao; Li, Xin; Liu, Hai-Jun; Yu, Li

    2010-11-20

    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.

  15. Full Genome Characterization of Novel DS-1-Like G8P[8] Rotavirus Strains that Have Emerged in Thailand: Reassortment of Bovine and Human Rotavirus Gene Segments in Emerging DS-1-Like Intergenogroup Reassortant Strains.

    Directory of Open Access Journals (Sweden)

    Ratana Tacharoenmuang

    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[8] 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[8]-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[8]-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

  16. Rotavirus overview.

    Science.gov (United States)

    Bernstein, David I

    2009-03-01

    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.

  17. Molecular epidemiology of the human group A rotavirus in the Paraná State, Brazil

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    Jucélia Stadinicki dos Santos

    2008-04-01

    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

  18. Study of the Ability of Bifidobacteria of Human Origin to Prevent and Treat Rotavirus Infection Using Colonic Cell and Mouse Models

    Science.gov (United States)

    Darveau, André; Fliss, Ismaïl

    2016-01-01

    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

  19. Attenuation Coefficient Estimation of the Healthy Human Thyroid In Vivo

    Science.gov (United States)

    Rouyer, J.; Cueva, T.; Portal, A.; Yamamoto, T.; Lavarello, R.

    Previous studies have demonstrated that attenuation coefficients can be useful towards characterizing thyroid tissues. In this work, ultrasonic attenuation coefficients were estimated from healthy human thyroids in vivo using a clinical scanner. The selected subjects were five young, healthy volunteers (age: 26 ± 6 years old, gender: three females, two males) with no reported history of thyroid diseases, no palpable thyroid nodules, no smoking habits, and body mass index less than 30 kg/m2. Echographic examinations were conducted by a trained sonographer using a SonixTouch system (Ultrasonix Medical Corporation, Richmond, BC) equipped with an L14-5 linear transducer array (nominal center frequency of 10 MHz, transducer footprint of 3.8 cm). Radiofrequency data corresponding to the collected echographic images in both transverse and longitudinal views were digitized at a sampling rate of 40 MHz and processed with Matlab codes (MathWorks, Natick, MA) to estimate attenuation coefficients using the spectral log difference method. The estimation was performed using an analysis bandwidth spanning from 4.0 to 9.0 MHz. The average value of the estimated ultrasonic attenuation coefficients was equal to 1.34 ± 0.15 dB/(cm.MHz). The standard deviation of the estimated average attenuation coefficient across different volunteers suggests a non-negligible inter-subject variability in the ultrasonic attenuation coefficient of the human thyroid.

  20. Efficacy of human rotavirus vaccine against severe gastroenteritis in Malawian children in the first two years of life: a randomised, double-blind, placebo controlled trial

    Science.gov (United States)

    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

    2014-01-01

    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[8] 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

  1. One year survey of human rotavirus strains suggests the emergence of genotype G12 in Cameroon.

    Science.gov (United States)

    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

    2013-08-01

    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[4], P[6] and P[8] VP4 genotypes. Genotype G12 predominated in combination with P[8] (54.1%) and P[6] (10.4%) genotypes followed by G1P[6] (8.2%), G3P[6] (6.7%), G2P[4] (5.9%), G8P[6] (3.7%), G2P[6] (0.7%), G3P[8] (0.7%), and G9P[8] (0.7%). Genotype P[6] 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[6] (1.5%); and G(NT)P[8] (0.7%). Mixed infections were found in five specimens (3.7%) in several combinations including G1+ G12P[6], G2+ G3P[6] + P[8], G3+ G8P[6], G3 + G12P[6] + P[8], and G12P[6] +P[8]. The approximately 10% relative frequency of G12P[6] 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[6] strains. Copyright © 2013 Wiley Periodicals, Inc.

  2. Whole-genome sequence analysis of a Korean G11P[25] rotavirus strain identifies several porcine-human reassortant events.

    Science.gov (United States)

    Than, Van Thai; Park, Jong-Hwa; Chung, In Sik; Kim, Jong Bum; Kim, Wonyong

    2013-11-01

    A rare rotavirus, RVA/Human-wt/KOR/CAU12-2/2012/G11P[25], 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[25]-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[25] viruses (Dhaka6, KTM368, and N-38 strains) identified in South Asia, whereas the VP1 gene originated from a porcine G11P[7] 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[25]-I12 genotype was introduced into the South Korean population by interspecies transmissions of human and animal rotaviruses, followed by multiple reassortment events.

  3. Molecular epidemiology and genetic evolution of the whole genome of G3P[8] human rotavirus in Wuhan, China, from 2000 through 2013.

    Directory of Open Access Journals (Sweden)

    Yuan-Hong Wang

    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[8] 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[8]-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[8] strains were assigned to Cluster 2 containing only one clade of G3P[8] strains in the US detected in the 1970s, which was distinct from Cluster 1 comprising most of old G3P[8] 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[8] 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[8] in an Asian country.

  4. Molecular Epidemiology and Genetic Evolution of the Whole Genome of G3P[8] Human Rotavirus in Wuhan, China, from 2000 through 2013

    Science.gov (United States)

    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

    2014-01-01

    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[8] 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[8]-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[8] strains were assigned to Cluster 2 containing only one clade of G3P[8] strains in the US detected in the 1970s, which was distinct from Cluster 1 comprising most of old G3P[8] 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[8] 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[8]) in an Asian country. PMID:24676363

  5. Robustness of the healthcare utilization results from the Rotavirus Efficacy and Safety Trial (REST evaluating the human-bovine (WC3 reassortant pentavalent rotavirus vaccine (RV5

    Directory of Open Access Journals (Sweden)

    Van Damme Pierre

    2010-06-01

    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

  6. Continuous detection and genetic diversity of human rotavirus A in sewage in eastern China, 2013-2014.

    Science.gov (United States)

    Zhou, Nan; Lv, Dong; Wang, Suting; Lin, Xiaojuan; Bi, Zhenwang; Wang, Haiyan; Wang, Pei; Zhang, Huaning; Tao, Zexin; Hou, Peibin; Song, Yanyan; Xu, Aiqiang

    2016-09-13

    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[8] (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.

  7. [Rotavirus: an ubiquitous infection?].

    Science.gov (United States)

    Bellaiche, M; Viala, J; Degas, V; Cézard, J-P

    2007-10-01

    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.

  8. Rotavirus vaccines: an update.

    Science.gov (United States)

    Dennehy, Penelope H

    2005-02-01

    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.

  9. Asiatic acid attenuates malignancy of human metastatic ovarian ...

    African Journals Online (AJOL)

    Conclusion: Asiatic acid attenuates the malignancy of human metastatic ovarian cancer cells via epithelial-to-mesenchymal ... Keywords: Asiatic acid, Ovarian cancer, Metastasis, Epithelial-to-mesenchymal transition, Vometin. Tropical Journal of ... Ovarian cancer is a deadly disease accounting for 3 % of cancer while 5 ...

  10. The role of human adenoviruses type 41 in acute diarrheal disease in Minas Gerais after rotavirus vaccination

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    Thaís Aparecida Vieira Reis

    2016-03-01

    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

  11. The engineering and optimization of expression of rotavirus-like particles in insect cells using a South African G9P[6] rotavirus strain / by Maria J. van der Westhuizen.

    OpenAIRE

    Van der Westhuizen, Maria Jacoba

    2012-01-01

    Rotavirus infection causes gastroenteritis, specifically severe gastroenteritis, affecting children younger than five globally, regardless of hygiene and water quality. Current licensed, live, attenuated vaccines do not contain the G9 genotype, which is a prevalent rotavirus strain circulating in sub-Saharan Africa, a region that carries a high rotavirus disease burden. Rotavirus-like particles (RV-VLPs) is an attractive non-live vaccine candidate, which has shown promising results in animal ...

  12. Typing of human rotaviruses: Nucleotide mismatches between the VP7 gene and primer are associated with genotyping failure

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    Zaman Khalequz

    2005-03-01

    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.

  13. Skin Vaccination against Rotavirus Using Microneedles: Proof of Concept in Gnotobiotic Piglets.

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    Yuhuan Wang

    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[8] 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[8] 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.

  14. Sequence analysis of Vietnamese P[6] rotavirus strains suggests evidence of interspecies transmission.

    Science.gov (United States)

    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

    2007-12-01

    Nucleotide and amino acid sequences of the VP8* gene of five Vietnamese P[6] rotavirus strains detected from hospitalized patients with acute gastroenteritis were analyzed and compared with other human and porcine P[6] 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[6] rotavirus strains belonging to lineage I that cluster into sublineage Ic with porcine rotaviruses, and not into sublineage Ia, as other human P[6] rotaviruses have done so far. Sequence analysis of the VP7 gene of these P[6] rotavirus strains was also performed. The results showed that the Vietnamese G9P[6] strain had high similarity with other human G9 rotaviruses, confirming a human-animal reassortant virus, whereas other three G4P[6] 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.

  15. Low cytotoxicity effect of dendrosome as an efficient carrier for rotavirus VP2 gene transferring into a human lung cell line : dendrosome, as a novel intranasally gene porter.

    Science.gov (United States)

    Pourasgari, Farzaneh; Ahmadian, Shahin; Salmanian, Ali Hatef; Sarbolouki, Mohammad Nabi; Massumi, Mohammad

    2009-01-01

    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.

  16. Bovine rotavirus pentavalent vaccine development in India.

    Science.gov (United States)

    Zade, Jagdish K; Kulkarni, Prasad S; Desai, Sajjad A; Sabale, Rajendra N; Naik, Sameer P; Dhere, Rajeev M

    2014-08-11

    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.

  17. Genomic characterization of uncommon human G3P[6] rotavirus strains causing diarrhea in children in Italy in 2009.

    Science.gov (United States)

    Ianiro, Giovanni; Delogu, Roberto; Fiore, Lucia; Ruggeri, Franco M

    2015-07-01

    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[8], G2P[4], G3P[8], G4P[8] and G9P[8]. During the surveillance activity of RotaNet-Italy, three uncommon G3P[6] RVA strains, designated as RVA/Human-wt/ITA/NA01/2009/G3P[6], RVA/Human-wt/ITA/NA06/2009/G3P[6], and RVA/Human-wt/ITA/NA19/2009/G3P[6], 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[6]. 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[6]-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[6] 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[6] RVA strains involved in this study. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Sequence analysis of the VP7 gene of human rotaviruses G2 and G4 isolated in Japan, China, Thailand, and Vietnam during 2001-2003.

    Science.gov (United States)

    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

    2010-05-01

    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.

  19. Rice Bran and Probiotics Alter the Porcine Large Intestine and Serum Metabolomes for Protection against Human Rotavirus Diarrhea

    Directory of Open Access Journals (Sweden)

    Elizabeth P. Ryan

    2017-04-01

    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

  20. Rice Bran and Probiotics Alter the Porcine Large Intestine and Serum Metabolomes for Protection against Human Rotavirus Diarrhea.

    Science.gov (United States)

    Nealon, Nora Jean; Yuan, Lijuan; Yang, Xingdong; Ryan, Elizabeth P

    2017-01-01

    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

  1. Effects of Racecadotril on Weight Loss and Diarrhea Due to Human Rotavirus in Neonatal Gnotobiotic Pigs (Sus scrofa domesticus).

    Science.gov (United States)

    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

    2017-03-01

    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.

  2. Clinical evaluation of a single oral dose of human-bovine (UK) reassortant rotavirus vaccines Wa x UK (P1A[8],G6) and Wa x (DS-1 x UK) (P1A[8],G2).

    Science.gov (United States)

    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

    2002-03-01

    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.

  3. Emergence of human rotavirus genotype G9 in metropolitan Detroit between 2007 and 2009.

    Science.gov (United States)

    Abdel-Haq, Nahed; Amjad, Muhammad; McGrath, Eric; Chearskul, Pimpanada; Amer, Ahdi; Salimnia, Hossein; Asmar, Basim I

    2011-06-01

    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[6] 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[8] was the most prevalent P genotype (66.5 %), followed by P[4] (21.9 %) and P[6] (11.2 %). The gene combinations G1P[8] and G9P[8] were the most prevalent (21.4 % and 20.6 %, respectively), followed by G4P[8] (13 %) and G9P[6] (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[8] 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[8], P[6] and P[4] specificity circulating in the metropolitan Detroit area. While the protective efficacy of the RV vaccines has been demonstrated against G9P[8] strains, the level of cross-protection offered by the vaccines against G9 strains with P[6] and P[4] genotypes in the Detroit paediatric population remains to be determined.

  4. Detection and characterization of a human G9P[4] rotavirus strain in Japan.

    Science.gov (United States)

    Yamamoto, Seiji P; Kaida, Atsushi; Ono, Atsushi; Kubo, Hideyuki; Iritani, Nobuhiro

    2015-08-01

    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[8], G2P[4], G3P[8], G9P[4], and G9P[8]. Although G9P[4] is a rare genotype that had not been reported in Japan, it was the second most prevalent genotype, following G1P[8], and accounted for 35.3% of RVA cases in the 2011/2012 season. Further genotyping revealed that the G9P[4] strain had genotype 2 internal protein genes except for NSP3: G9-P[4]-I2-R2-C2-M2-A2-N2-T1-E2-H2. Among detected RVA strains, G9P[4] and some G9P[8] strains shared high nucleotide identity in VP7 and NSP3 genes. Phylogenetic and BLAST search analyses showed that the G9P[4] strain in Japan shared high nucleotide identity in genotype 2 genes with common G2P[4] strains circulating globally, but was distinct from other G9P[4] strains circulating worldwide. These results suggest that the G9P[4] strain in Japan may have emerged through an independent reassortment between G9P[8] and G2P[4]. 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.

  5. Lactobacillus rhamnosus GG modulates innate signaling pathway and cytokine responses to rotavirus vaccine in intestinal mononuclear cells of gnotobiotic pigs transplanted with human gut microbiota.

    Science.gov (United States)

    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

    2016-06-14

    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

  6. Suspected zoonotic transmission of rotavirus group A in Danish adults

    DEFF Research Database (Denmark)

    Midgley, S. E.; Hjulsager, Charlotte Kristiane; Larsen, Lars Erik

    2012-01-01

    Group A rotaviruses infect humans and a variety of animals. In July 2006 a rare rotavirus strain with G8P[14] 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[14] 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...

  7. Rotavirus stimulates release of serotonin (5-HT) from human enterochromaffin cells and activates brain structures involved in nausea and vomiting.

    Science.gov (United States)

    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

    2011-07-01

    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.

  8. Rotavirus stimulates release of serotonin (5-HT from human enterochromaffin cells and activates brain structures involved in nausea and vomiting.

    Directory of Open Access Journals (Sweden)

    Marie Hagbom

    2011-07-01

    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.

  9. Septicemia following rotavirus gastroenteritis.

    Science.gov (United States)

    Scheier, Eric; Aviner, Shraga

    2013-03-01

    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.

  10. Prevaccination Rotavirus Serum IgG and IgA Are Associated With Lower Immunogenicity of Live, Oral Human Rotavirus Vaccine in South African Infants.

    Science.gov (United States)

    Moon, Sung-Sil; Groome, Michelle J; Velasquez, Daniel E; Parashar, Umesh D; Jones, Stephanie; Koen, Antoinette; van Niekerk, Nadia; Jiang, Baoming; Madhi, Shabir A

    2016-01-15

    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.

  11. MASA DEPAN VAKSIN ROTAVIRUS DI INDONESIA

    Directory of Open Access Journals (Sweden)

    Krisna Nur Andriana Pangesti

    2015-01-01

    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[8] 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[8] 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

  12. Molecular epidemiology of rotaviruses in India.

    Science.gov (United States)

    Broor, Shobha; Ghosh, Dhrubaa; Mathur, Purva

    2003-08-01

    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[4] and P[8]. 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[11] strain B223 and VP7 was closely related to the human serotype G9 strain. Another neonatal strain G10P[11] was reported from Bangalore. G10P[11] strains also have a high

  13. Whole Genomic Analysis of an Unusual Human G6P[14] Rotavirus Strain Isolated from a Child with Diarrhea in Thailand: Evidence for Bovine-To-Human Interspecies Transmission and Reassortment Events.

    Science.gov (United States)

    Tacharoenmuang, Ratana; Komoto, Satoshi; Guntapong, Ratigorn; Ide, Tomihiko; Haga, Kei; Katayama, Kazuhiko; Kato, Takema; Ouchi, Yuya; Kurahashi, Hiroki; Tsuji, Takao; Sangkitporn, Somchai; Taniguchi, Koki

    2015-01-01

    An unusual rotavirus strain, SKT-27, with the G6P[14] genotypes (RVA/Human-wt/THA/SKT-27/2012/G6P[14]), 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[14]-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[14] 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[14] strains that have emerged in Southeast Asia. Our observations will provide important insights into the origin of G6P[14] strains, and into dynamic interactions between human and bovine rotavirus strains.

  14. Whole Genomic Analysis of an Unusual Human G6P[14] Rotavirus Strain Isolated from a Child with Diarrhea in Thailand: Evidence for Bovine-To-Human Interspecies Transmission and Reassortment Events.

    Directory of Open Access Journals (Sweden)

    Ratana Tacharoenmuang

    Full Text Available An unusual rotavirus strain, SKT-27, with the G6P[14] genotypes (RVA/Human-wt/THA/SKT-27/2012/G6P[14], 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[14]-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[14] 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[14] strains that have emerged in Southeast Asia. Our observations will provide important insights into the origin of G6P[14] strains, and into dynamic interactions between human and bovine rotavirus strains.

  15. History of rotavirus research in children in Malawi: the pursuit of a killer

    African Journals Online (AJOL)

    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.

  16. Crystallization and preliminary X-ray diffraction analysis of the carbohydrate-recognizing domain (VP8*) of bovine rotavirus strain NCDV.

    Science.gov (United States)

    Yu, Xing; Guillon, Annabel; Szyczew, Alex J; Kiefel, Milton J; Coulson, Barbara S; von Itzstein, Mark; Blanchard, Helen

    2008-06-01

    The infectivity of rotavirus is dramatically enhanced by proteolytic cleavage of its outer layer VP4 spike protein into two functional domains, VP8* and VP5*. The carbohydrate-recognizing domain VP8* is proposed to bind sialic acid-containing host cell-surface glycans and this is followed by a series of subsequent virus-cell interactions. Live attenuated human and bovine rotavirus vaccine candidates for the prevention of gastroenteritis have been derived from bovine rotavirus strain NCDV. The NCDV VP8*(64-224) was overexpressed, purified to homogeneity and crystallized in the presence of an N-acetylneuraminic acid derivative. X-ray diffraction data were collected to a resolution of 2.0 A and the crystallographic structure of NCDV VP8*(64-224) was determined by molecular replacement.

  17. VP6: A candidate rotavirus vaccine.

    Science.gov (United States)

    Ward, Richard L; McNeal, Monica M

    2010-09-01

    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.

  18. Advances in molecular biology: impact on rotavirus vaccine development.

    Science.gov (United States)

    Estes, M K

    1996-09-01

    The first candidate rotavirus vaccine was a live attenuated oral vaccine made by the classical empirical method of serial passage of virus in tissue culture cells. Current tetravalent vaccine candidates that are in the final stages of efficacy testing in the United States were made by genetic reassortment. This article briefly highlights how advances in the basic understanding of the molecular biology of rotaviruses have facilitated vaccine development. New approaches for second-generation vaccines and improvements in vaccine efficacy based on further exploitation of the tools and knowledge of rotavirus molecular biology and pathogenesis are discussed.

  19. Epidemiological aspects of human rotavirus infection in children hospitalized with acute gastroenteritis in an area of northern Italy.

    Science.gov (United States)

    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

    2004-08-01

    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.

  20. epidemiology of rotavirus and astrovirus infections in children

    African Journals Online (AJOL)

    Emmanuel Ameh

    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.

  1. Zoonotic Transmission of Rotavirus in Denmark; a Case Report

    DEFF Research Database (Denmark)

    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...

  2. Association of serum anti-rotavirus immunoglobulin A antibody seropositivity and protection against severe rotavirus gastroenteritis

    OpenAIRE

    Cheuvart, Brigitte; Neuzil, Kathleen M; Steele, A Duncan; Cunliffe, Nigel; Madhi, Shabir A; Karkada, Naveen; Han, Htay Htay; Vinals, Carla

    2013-01-01

    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...

  3. Mechanical compression attenuates normal human bronchial epithelial wound healing

    Directory of Open Access Journals (Sweden)

    Malavia Nikita

    2009-02-01

    Full Text Available Abstract Background Airway narrowing associated with chronic asthma results in the transmission of injurious compressive forces to the bronchial epithelium and promotes the release of pro-inflammatory mediators and the denudation of the bronchial epithelium. While the individual effects of compression or denudation are well characterized, there is no data to elucidate how these cells respond to the application of mechanical compression in the presence of a compromised epithelial layer. Methods Accordingly, differentiated normal human bronchial epithelial cells were exposed to one of four conditions: 1 unperturbed control cells, 2 single scrape wound only, 3 static compression (6 hours of 30 cmH2O, and 4 6 hours of static compression after a scrape wound. Following treatment, wound closure rate was recorded, media was assayed for mediator content and the cytoskeletal network was fluorescently labeled. Results We found that mechanical compression and scrape injury increase TGF-β2 and endothelin-1 secretion, while EGF content in the media is attenuated with both injury modes. The application of compression after a pre-existing scrape wound augmented these observations, and also decreased PGE2 media content. Compression stimulated depolymerization of the actin cytoskeleton and significantly attenuated wound healing. Closure rate was partially restored with the addition of exogenous PGE2, but not EGF. Conclusion Our results suggest that mechanical compression reduces the capacity of the bronchial epithelium to close wounds, and is, in part, mediated by PGE2 and a compromised cytoskeleton.

  4. Neonatal rotavirus infections.

    Science.gov (United States)

    Haffejee, I E

    1991-01-01

    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.

  5. Characterization of human rotaviruses circulating in Iraq in 2008: atypical G8 and high prevalence of P[6] strains.

    Science.gov (United States)

    Ahmed, Salwa; Klena, John; Albana, Antun; Alhamdani, Faisal; Oskoff, John; Soliman, Mireille; Heylen, Elisabeth; Teleb, Nadia; Husain, Tupur; Matthijnssens, Jelle

    2013-06-01

    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[6]. G1 was the second most common genotype (16%, 16/98) mainly associated with P[8] and P[UT]. G3, G4 and G9 were detected at a lower prevalence (3%, 11%, 3%, respectively), mainly associated with P[6]. Surprisingly, five G8P[6], and seven G12 RVA strains in combination with P[6] and P[8] were also detected for the first time in Iraq. Overall, a striking high prevalence of 47% of the analyzed samples possessed the P[6] genotype (65% of the P-typed RVA strains). Atypical genotype combinations such as G1P[4], G1P[6], G2P[8] or strains with mixed G-types were detected sporadically. The detection of unusual G8P[6] RVA strains prompted us to further analyze the NSP2, NSP3, NSP4 and NSP5 gene segments of three selected G8P[6] 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[6] 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.

  6. Rotavirus (For Parents)

    Science.gov (United States)

    ... 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 ...

  7. Rotavirus vaccine - what you need to know

    Science.gov (United States)

    ... 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 ...

  8. Diversity and zoonotic potential of rotaviruses in swine and cattle across Europe

    DEFF Research Database (Denmark)

    Midgley, Sofie E.; Bányai, Krisztián; Buesa, Javier

    2012-01-01

    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[27] and P[32], 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...

  9. Why does the world need another rotavirus vaccine?

    Science.gov (United States)

    Ward, Richard L; McNeal, Monica M; Steele, A Duncan

    2008-02-01

    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.

  10. Burden of Rotavirus Diarrhea in Under five Indian Children.

    Science.gov (United States)

    Kumar, Ashok; Basu, Sriparna; Vashishtha, Vipin; Choudhury, Panna

    2016-07-08

    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.

  11. Current status of rotavirus vaccines.

    Science.gov (United States)

    Wang, Ching-Min; Chen, Shou-Chien; Chen, Kow-Tong

    2015-11-01

    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.

  12. United States rotavirus strain surveillance from 2005 to 2008: genotype prevalence before and after vaccine introduction.

    Science.gov (United States)

    Hull, Jennifer J; Teel, Elizabeth N; Kerin, Tara K; Freeman, Molly M; Esona, Mathew D; Gentsch, Jon R; Cortese, Margaret M; Parashar, Umesh D; Glass, Roger I; Bowen, Michael D

    2011-01-01

    A live, attenuated rotavirus vaccine, RotaTeq®, was approved in 2006 for immunization of infants in the United States. To monitor the distribution of rotavirus genotypes before and after vaccine introduction, the Centers for Disease Control and Prevention conducted strain surveillance with the National Rotavirus Strain Surveillance System. Over 3 rotavirus seasons, 2005-2006, 2006-2007, and 2007-2008, National Rotavirus Strain Surveillance System laboratories collected rotavirus-positive stool specimens and submitted them to the Centers for Disease Control and Prevention. Rotavirus strains were G- and P-genotyped by multiplex reverse transcription-polymerase chain reaction or nucleotide sequencing. During 2005-2006 and 2006-2007 seasons, G1 was the dominant G-type but in the 2007-2008 season, G3 replaced G1 as the most frequently detected strain. Four genotypes, G1P[8], G2P[4], G3P[8], and G9P[8] were detected in every season. Uncommon strains observed during the study period were G2P[8], G1P[6], G2P[6], G4P[6], G1P[4], G3P[9], G12P [6], and G12P[8]. The mean age of rotavirus cases in the 2007-2008 season increased significantly in patients less than 3 years old compared with the 2 previous seasons. : The increased overall prevalence of G3P [8] strains in 2007-2008, the first rotavirus season with reasonable rotavirus vaccine coverage, was consistent with Australian reports of G3 dominance following RotaTeq introduction. However, these strain changes in both countries have occurred in the context of large declines in severe rotavirus disease and we cannot rule out that they are simply the result of naturally occurring changes in rotavirus strain prevalence. These findings underscore the need for careful monitoring of strains to assess possible vaccine pressure-induced changes and vaccine effectiveness against various rotavirus genotypes.

  13. Uniformity of serotype and electropherotype in local human rotavirus isolates during each of three successive cold seasons.

    Science.gov (United States)

    Shif, I; Silberstein, I; Aboudy, Y; Mendelson, E; Mates, A; Gotlieb-Stematsky, T

    1992-04-01

    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.

  14. Lack of correlation between serum rotavirus antibody titers and protection following vaccination with reassortant RRV vaccines. US Rotavirus Vaccine Efficacy Group.

    Science.gov (United States)

    Ward, R L; Bernstein, D I

    1995-09-01

    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)

  15. Why does the world need another rotavirus vaccine?

    Directory of Open Access Journals (Sweden)

    Richard L Ward

    2008-03-01

    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

  16. [Annual incidence of human group A rotavirus G-serotypes detected in a Japanese University Hospital between 2003 and 2007].

    Science.gov (United States)

    Nakamura, Hisako; Marumo, Kenji; Iwasawa, Atsuo; Tazawa, Setsuko; Kawano, Rumiko; Kikuchi, Toshiki; Nagashima, Goro; Taguchi, Kazumi; Isoyama, Keiichi

    2011-01-01

    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.

  17. First Detection of G12 Rotaviruses in Newborns with Neonatal Rotavirus Infection at All India Institute of Medical Sciences, New Delhi, India▿

    OpenAIRE

    Ray, Pratima; Sharma, S.; Agarwal, R. K.; Longmei, K.; Gentsch, J. R.; Paul, V. K.; Glass, R. I.; Bhan, M. K.

    2007-01-01

    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...

  18. One Family's Struggles with Rotavirus

    Medline Plus

    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 ...

  19. One Family's Struggles with Rotavirus

    Medline Plus

    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 ...

  20. Implementing rotavirus vaccination in Asia.

    Science.gov (United States)

    Santosham, Mathuram; Nelson, E Anthony S; Bresee, Joseph S

    2007-11-01

    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.

  1. Zoonotic transmission of rotavirus in Denmark; a case report

    DEFF Research Database (Denmark)

    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 ([4], [6], and [8]). Two samples contained a G8 P[goat] rotavirus (G8 98% identical to bovine G8, 96% identical to goat...

  2. Genetic diversity of porcine group A rotavirus strains in the UK.

    Science.gov (United States)

    Chandler-Bostock, Rebecca; Hancox, Laura R; Nawaz, Sameena; Watts, Oliver; Iturriza-Gomara, Miren; Mellits, Kenneth H; Mellits, Kenneth M

    2014-09-17

    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[6], P[7], P[8], P[13], P[23], and P[32]. With the exception of a single P[8] isolate, there was less than 95% nucleotide identity between sequences from this study and any available rotavirus sequences. The G9 and P[6] 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[8] genotype in one isolate, this genotype is almost exclusively found in humans. The P[8] was linked to a human Irish rotavirus isolate in the same year. The discovery of human genotype P[8] 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.

  3. New approaches in oral rotavirus vaccines.

    Science.gov (United States)

    Kuate Defo, Zenas; Lee, Byong

    2016-05-01

    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.

  4. Detection of rotavirus in dogs with diarrhea in Brazil

    Directory of Open Access Journals (Sweden)

    Gabbay Yvone B.

    2003-01-01

    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.

  5. Frequently Asked Questions about Rotavirus

    Science.gov (United States)

    ... 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 ...

  6. Rotavirus infections and vaccines: burden of illness and potential impact of vaccination.

    Science.gov (United States)

    Grimwood, Keith; Lambert, Stephen B; Milne, Richard J

    2010-08-01

    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

  7. 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

    Directory of Open Access Journals (Sweden)

    A. C. Linhares

    1998-05-01

    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.

  8. Rotavirus and the Vaccine (Drops) to Prevent It

    Science.gov (United States)

    ... 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 ...

  9. Development of a human live attenuated West Nile infectious DNA vaccine: Suitability of attenuating mutations found in SA14-14-2 for WN vaccine design

    Energy Technology Data Exchange (ETDEWEB)

    Yamshchikov, Vladimir, E-mail: yaximik@gmail.com; Manuvakhova, Marina; Rodriguez, Efrain

    2016-01-15

    Direct attenuation of West Nile (WN) virus strain NY99 for the purpose of vaccine development is not feasible due to its high virulence and pathogenicity. Instead, we created highly attenuated chimeric virus W1806 with the serological identity of NY99. To further attenuate W1806, we investigated effects of mutations found in Japanese encephalitis virus vaccine SA14-14-2. WN viruses carrying all attenuating mutations lost infectivity in mammalian, but not in mosquito cells. No single reversion restored infectivity in mammalian cells, although increased infectivity in mosquito cells was observed. To identify a subset of mutations suitable for further attenuation of W1806, we analyzed effects of E{sub 138}K and K{sub 279}M changes on virulence, growth properties, and immunogenicity of derivatized W956, from which chimeric W1806 inherited its biological properties and attenuation profile. Despite strong dominant attenuating effect, introduction of only two mutations was not sufficient for attenuating W1806 to the safety level acceptable for human use. - Highlights: • Further attenuation of a WN vaccine precursor is outlined. • Effect of SA14-14-2 attenuating mutations is tested. • Mechanism of attenuation is proposed and illustrated. • The need for additional attenuating mutations is justified.

  10. Detection of human adenovirus, rotavirus and enterovirus in water samples collected on dairy farms from Tenente Portela, Northwest of Rio Grande do Sul, Brazil

    Directory of Open Access Journals (Sweden)

    Fernando Rosado Spilki

    2013-09-01

    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.

  11. Detection of human adenovirus, rotavirus and enterovirus in water samples collected on dairy farms from Tenente Portela, Northwest of Rio Grande do Sul, Brazil.

    Science.gov (United States)

    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

    2013-01-01

    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.

  12. Bicarbonate attenuates arterial desaturation during maximal exercise in humans

    DEFF Research Database (Denmark)

    Nielsen, Henning B; Bredmose, Per P; Strømstad, Morten

    2002-01-01

    in the difference between the end-tidal O2 pressure and arterial PO2 was similar in the two trials. Also, pulmonary O2 uptake and changes in muscle oxygenation as determined by near-infrared spectrophotometry during exercise were similar. The enlarged blood-buffering capacity after infusion of Bic attenuated...

  13. Molecular epidemiology of human rotaviruses. Analysis of outbreaks of acute gastroenteritis in Glasgow and the west of Scotland 1981/82 and 1982/83.

    Science.gov (United States)

    Follett, E. A.; Sanders, R. C.; Beards, G. M.; Hundley, F.; Desselberger, U.

    1984-01-01

    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

  14. Systemic and mucosal immune responses to rhesus rotavirus vaccine MMU 18006.

    Science.gov (United States)

    Losonsky, G A; Rennels, M B; Lim, Y; Krall, G; Kapikian, A Z; Levine, M M

    1988-06-01

    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.

  15. Introduktion. Om rotavirus. Teknologi

    DEFF Research Database (Denmark)

    Wejse, Christian

    2012-01-01

    % 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...

  16. Intellectual property rights and challenges for development of affordable human papillomavirus, rotavirus and pneumococcal vaccines: Patent landscaping and perspectives of developing country vaccine manufacturers.

    Science.gov (United States)

    Chandrasekharan, Subhashini; Amin, Tahir; Kim, Joyce; Furrer, Eliane; Matterson, Anna-Carin; Schwalbe, Nina; Nguyen, Aurélia

    2015-11-17

    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.

  17. A Randomized, Controlled Trial of the Impact of Alternative Dosing Schedules on the Immune Response to Human Rotavirus Vaccine in Rural Ghanaian Infants.

    Science.gov (United States)

    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

    2016-06-01

    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.

  18. Comparative analysis of pentavalent rotavirus vaccine strains and G8 rotaviruses identified during vaccine trial in Africa.

    Science.gov (United States)

    Heylen, Elisabeth; Zeller, Mark; Ciarlet, Max; Lawrence, Jody; Steele, Duncan; Van Ranst, Marc; Matthijnssens, Jelle

    2015-10-06

    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[6] and G8P[1] 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.

  19. Hyperbaric oxygen therapy attenuates central sensitization induced by a thermal injury in humans

    DEFF Research Database (Denmark)

    Rasmussen, V M; Borgen, A E; Jansen, E C

    2015-01-01

    BACKGROUND: Hyperbaric oxygen (HBO2 ) treatment has in animal experiments demonstrated antinociceptive effects. It was hypothesized that these effects would attenuate secondary hyperalgesia areas (SHAs), an expression of central sensitization, after a first-degree thermal injury in humans. METHODS...... was demonstrated. However, in the nine volunteers starting with the control session, a statistical significant attenuation of SHAs was demonstrated in the HBO2 session (P = 0.004). CONCLUSIONS: The results indicate that HBO2 therapy in humans attenuates central sensitization induced by a thermal skin injury......, compared with control. These new and original findings in humans corroborate animal experimental data. The thermal injury model may give impetus to future human neurophysiological studies exploring the central effects of hyperbaric oxygen treatment....

  20. Rotavirus vaccine: a cost effective control measure for India.

    Science.gov (United States)

    Kumar, Arun; Goel, Manish K; Jain, Ram Bilas; Khanna, Pardeep; Vibha, Vibha

    2012-04-01

    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[8] 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.

  1. Human G3P[9] rotavirus strains possessing an identical genotype constellation to AU-1 isolated at high prevalence in Brazil, 1997–1999

    Science.gov (United States)

    Rainwater-Lovett, Kaitlin; Tsutsumi, Hiroyuki

    2015-01-01

    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[9] 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[9] 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

  2. Genetic instability of live, attenuated human immunodeficiency virus type 1 vaccine strains

    NARCIS (Netherlands)

    Berkhout, B.; Verhoef, K.; van Wamel, J. L.; Back, N. K.

    1999-01-01

    Live, attenuated viruses have been the most successful vaccines in monkey models of human immunodeficiency virus type 1 (HIV-1) infection. However, there are several safety concerns about using such an anti-HIV vaccine in humans, including reversion of the vaccine strain to virulence and

  3. The rotavirus vaccine development pipeline.

    Science.gov (United States)

    Kirkwood, Carl D; Ma, Lyou-Fu; Carey, Megan E; Steele, A Duncan

    2017-04-07

    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.

  4. Attenuation correction for the large non-human primate brain imaging using microPET

    Science.gov (United States)

    Naidoo-Variawa, S.; Lehnert, W.; Kassiou, M.; Banati, R.; Meikle, S. R.

    2010-04-01

    Assessment of the biodistribution and pharmacokinetics of radiopharmaceuticals in vivo is often performed on animal models of human disease prior to their use in humans. The baboon brain is physiologically and neuro-anatomically similar to the human brain and is therefore a suitable model for evaluating novel CNS radioligands. We previously demonstrated the feasibility of performing baboon brain imaging on a dedicated small animal PET scanner provided that the data are accurately corrected for degrading physical effects such as photon attenuation in the body. In this study, we investigated factors affecting the accuracy and reliability of alternative attenuation correction strategies when imaging the brain of a large non-human primate (papio hamadryas) using the microPET Focus 220 animal scanner. For measured attenuation correction, the best bias versus noise performance was achieved using a 57Co transmission point source with a 4% energy window. The optimal energy window for a 68Ge transmission source operating in singles acquisition mode was 20%, independent of the source strength, providing bias-noise performance almost as good as for 57Co. For both transmission sources, doubling the acquisition time had minimal impact on the bias-noise trade-off for corrected emission images, despite observable improvements in reconstructed attenuation values. In a [18F]FDG brain scan of a female baboon, both measured attenuation correction strategies achieved good results and similar SNR, while segmented attenuation correction (based on uncorrected emission images) resulted in appreciable regional bias in deep grey matter structures and the skull. We conclude that measured attenuation correction using a single pass 57Co (4% energy window) or 68Ge (20% window) transmission scan achieves an excellent trade-off between bias and propagation of noise when imaging the large non-human primate brain with a microPET scanner.

  5. Attenuation correction for the large non-human primate brain imaging using microPET

    Energy Technology Data Exchange (ETDEWEB)

    Naidoo-Variawa, S; Lehnert, W; Kassiou, M; Banati, R; Meikle, S R [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia)], E-mail: snai3212@uni.sydney.edu.au

    2010-04-21

    Assessment of the biodistribution and pharmacokinetics of radiopharmaceuticals in vivo is often performed on animal models of human disease prior to their use in humans. The baboon brain is physiologically and neuro-anatomically similar to the human brain and is therefore a suitable model for evaluating novel CNS radioligands. We previously demonstrated the feasibility of performing baboon brain imaging on a dedicated small animal PET scanner provided that the data are accurately corrected for degrading physical effects such as photon attenuation in the body. In this study, we investigated factors affecting the accuracy and reliability of alternative attenuation correction strategies when imaging the brain of a large non-human primate (papio hamadryas) using the microPET Focus 220 animal scanner. For measured attenuation correction, the best bias versus noise performance was achieved using a {sup 57}Co transmission point source with a 4% energy window. The optimal energy window for a {sup 68}Ge transmission source operating in singles acquisition mode was 20%, independent of the source strength, providing bias-noise performance almost as good as for {sup 57}Co. For both transmission sources, doubling the acquisition time had minimal impact on the bias-noise trade-off for corrected emission images, despite observable improvements in reconstructed attenuation values. In a [{sup 18}F]FDG brain scan of a female baboon, both measured attenuation correction strategies achieved good results and similar SNR, while segmented attenuation correction (based on uncorrected emission images) resulted in appreciable regional bias in deep grey matter structures and the skull. We conclude that measured attenuation correction using a single pass {sup 57}Co (4% energy window) or {sup 68}Ge (20% window) transmission scan achieves an excellent trade-off between bias and propagation of noise when imaging the large non-human primate brain with a microPET scanner.

  6. Ultrasonic attenuation in human calcaneus from 0.2 to 1.7 MHz.

    Science.gov (United States)

    Wear, K A

    2001-03-01

    Ultrasonic attenuation has been demonstrated to be a useful measurement in the diagnosis of osteoporosis. Most studies have employed ultrasound in a range of frequencies from about 200 kHz-300 kHz to 600 kHz-1 MHz, and many have assumed a linear dependence of attenuation on frequency. In order to investigate the attenuation properties of human calcaneus at higher frequencies, 16 defatted human calcanea were interrogated in vitro using two matched pairs of transducers with center frequencies of 500 kHz and 2.25 MHz. The linear dependence of attenuation on frequency seems to extend up to at least 1.7 MHz. The correlation between attenuation coefficient and frequency from 400 kHz to 1.7 MHz was r = 0.999 (95% confidence interval, CI, = 0.998-1.00). The measurements suggest that some deviations from linear frequency dependence of attenuation may occur at lower frequencies (below 400 kHz), however.

  7. Quantitative PCR Detection and Characterisation of Human Adenovirus, Rotavirus and Hepatitis A Virus in Discharged Effluents of Two Wastewater Treatment Facilities in the Eastern Cape, South Africa.

    Science.gov (United States)

    Adefisoye, Martins Ajibade; Nwodo, Uchechukwu U; Green, Ezekiel; Okoh, Anthony Ifeanyin

    2016-12-01

    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.

  8. Rotavirus in India: Forty Years of Research.

    Science.gov (United States)

    Kang, Gagandeep

    2016-07-08

    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.

  9. Angiotensin II attenuates the natriuresis of water immersion in humans

    DEFF Research Database (Denmark)

    Schou, Morten; Gabrielsen, Anders; Bruun, Niels Eske

    2002-01-01

    The hypothesis was tested that suppression of generation of ANG II is one of the mechanisms of the water immersion (WI)-induced natriuresis in humans. In one protocol, eight healthy young males were subjected to 3 h of 1) WI (WI + placebo), 2) WI combined with ANG II infusion of 0.5 ng. kg(-1). m...

  10. Global Seasonality of Rotavirus Disease

    Science.gov (United States)

    Patel, Manish M.; Pitzer, Virginia; Alonso, Wladimir J.; Vera, David; Lopman, Ben; Tate, Jacqueline; Viboud, Cecile; Parashar, Umesh D.

    2012-01-01

    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

  11. Conditional virus replication as an approach to a safe live attenuated human immunodeficiency virus vaccine

    NARCIS (Netherlands)

    Berkhout, Ben; Verhoef, Koen; Marzio, Giuseppe; Klaver, Bep; Vink, Monique; Zhou, Xue; Das, Atze T.

    2002-01-01

    Despite intensive efforts, no safe and effective vaccine has been developed for the prophylaxis of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Studies with the simian immunodeficiency virus (SIV)/macaque model demonstrated that live attenuated viruses are the most

  12. Possible mechanisms of protection elicited by candidate rotavirus vaccines as determined with the adult mouse model.

    Science.gov (United States)

    Ward, Richard L

    2003-01-01

    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

  13. Rotavirus Type A in Danish Cattle and Swine Herds

    DEFF Research Database (Denmark)

    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...

  14. Rotavirus Group A in Danish Cattle and Swine Herds 2006

    DEFF Research Database (Denmark)

    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...

  15. 75 FR 48706 - Proposed Vaccine Information Materials for Rotavirus Vaccine

    Science.gov (United States)

    2010-08-11

    ... 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...

  16. Defining T-cell-mediated immune responses in rotavirus-infected juvenile rhesus macaques.

    Science.gov (United States)

    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

    2004-10-01

    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.

  17. Genetic Diversity of Rotavirus Strains Circulating in Environmental Water and Bivalve Shellfish in Thailand

    Science.gov (United States)

    Kittigul, Leera; Panjangampatthana, Apinya; Rupprom, Kitwadee; Pombubpa, Kannika

    2014-01-01

    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

  18. Immunological aspects of interaction between rotavirus and the intestine in infancy.

    Science.gov (United States)

    Uhnoo, I; Dharakul, T; Riepenhoff-Talty, M; Ogra, P L

    1988-04-01

    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.

  19. Rotavirus vaccines in routine use.

    Science.gov (United States)

    Tate, Jacqueline E; Parashar, Umesh D

    2014-11-01

    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.

  20. Assessment of the risks for human health of adenoviruses, hepatitis A virus, rotaviruses and enteroviruses in the Buffalo River and three source water dams in the Eastern Cape.

    Science.gov (United States)

    Chigor, Vincent N; Sibanda, Timothy; Okoh, Anthony I

    2014-06-01

    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.

  1. One Family's Struggles with Rotavirus

    Medline Plus

    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 ...

  2. One Family's Struggles with Rotavirus

    Medline Plus

    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 ...

  3. One Family's Struggles with Rotavirus

    Medline Plus

    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. ...

  4. One Family's Struggles with Rotavirus

    Medline Plus

    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 ...

  5. One Family's Struggles with Rotavirus

    Medline Plus

    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. ...

  6. Porcine small intestinal epithelial cell line (IPEC-J2) of rotavirus infection as a new model for the study of innate immune responses to rotaviruses and probiotics.

    Science.gov (United States)

    Liu, Fangning; Li, Guohua; Wen, Ke; Bui, Tammy; Cao, Dianjun; Zhang, Yanming; Yuan, Lijuan

    2010-04-01

    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.

  7. Measurement and analysis of channel attenuation characteristics for an implantable galvanic coupling human-body communication.

    Science.gov (United States)

    Zhang, Shuang; Pun, Sio Hang; Mak, Peng Un; Qin, Yu-Ping; Liu, Yi-He; Vai, Mang I

    2016-11-14

    In this study, an experiment was designed to verify the low power consumption of galvanic coupling human-body communication. A silver electrode (silver content: 99%) is placed in a pig leg and a sine wave signal with the power of 0 dBm is input. Compared with radio frequency communication and antenna transmission communication, attenuation is reduced by approximately 10 to 15 dB, so channel characteristics are highly improved.

  8. Human ?-defensin-2 production upon viral and bacterial co-infection is attenuated in COPD

    OpenAIRE

    Arnason, Jason W.; Murphy, James C.; Kooi, Cora; Wiehler, Shahina; Traves, Suzanne L.; Shelfoon, Christopher; Maciejewski, Barbara; Dumonceaux, Curtis J.; Lewenza, W. Shawn; Proud, David; Leigh, Richard

    2017-01-01

    Viral-bacterial co-infections are associated with severe exacerbations of COPD. Epithelial antimicrobial peptides, including human ?-defensin-2 (HBD-2), are integral to innate host defenses. In this study, we examined how co-infection of airway epithelial cells with rhinovirus and Pseudomonas aeruginosa modulates HBD-2 expression, and whether these responses are attenuated by cigarette smoke and in epithelial cells obtained by bronchial brushings from smokers with normal lung function or from...

  9. molecular identification of rotavirus strains associated with diarrhea

    African Journals Online (AJOL)

    DR. AMINU

    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, ...

  10. Rotavirus Vaccine Cut Kids' Hospitalization, Medical Costs

    Science.gov (United States)

    ... 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 ...

  11. Total mass attenuation coefficient evaluation of ten materials commonly used to simulate human tissue

    Science.gov (United States)

    Ferreira, C. C.; Ximenes, R. E.; Garcia, C. A. B.; Vieira, J. W.; Maia, A. F.

    2010-11-01

    To study the doses received by patient submitted to ionizing radiation, several materials are used to simulate the human tissue and organs. The total mass attenuation coefficient is a reasonable way for evaluating the usage in dosimetry of these materials. The total mass attenuation coefficient is determined by photon energy and constituent elements of the material. Currently, the human phantoms are composed by a unique material that presents characteristics similar to the mean proprieties of the different tissues within the region. Therefore, the phantoms are usually homogeneous and filled with a material similar to soft tissue. We studied ten materials used as soft tissue-simulating. These materials were named: bolus, nylon®, orange articulation wax, red articulation wax, PMMA, modelling clay, bee wax, paraffin 1, paraffin 2 and pitch. The objective of this study was to verify the best material to simulate the human cerebral tissue. We determined the elementary composition, mass density and, therefore, calculated the total mass attenuation coefficient of each material. The results were compared to the values established by the International Commission on Radiation Units and Measurements - ICRU, report n° 44, and by the International Commission on Radiation Protection - ICRP, report n° 89, to determine the best material for this energy interval. These results indicate that new head phantoms can be constructed with nylon®.

  12. Rotaviruses: immunological determinants of protection against infection and disease.

    Science.gov (United States)

    Offit, P A

    1994-01-01

    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

  13. Epidemiologic Association Between FUT2 Secretor Status and Severe Rotavirus Gastroenteritis in Children in the United States

    Science.gov (United States)

    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.

    2016-01-01

    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

  14. Prevalence of rotavirus genotypes in South Korea in 1989–2009: implications for a nationwide rotavirus vaccine program

    Directory of Open Access Journals (Sweden)

    Van Thai Than

    2013-11-01

    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[8], P[4], and P[6] 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&#8211;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[9] virus genotype was observed in the study and has been discussed in many other studies; however, the P[3], P[10] and P[25] 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.

  15. Viraemia is a common finding in immunocompetent children with rotavirus infection.

    Science.gov (United States)

    Chiappini, Elena; Azzari, Chiara; Moriondo, Maria; Galli, Luisa; de Martino, Maurizio

    2005-06-01

    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.

  16. Safety and immunogenicity of RV3-BB human neonatal rotavirus vaccine administered at birth or in infancy: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    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

    2015-12-01

    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

  17. Candidate New Rotavirus Species in Sheltered Dogs, Hungary

    Science.gov (United States)

    Mihalov-Kovács, Eszter; Gellért, Ákos; Marton, Szilvia; Farkas, Szilvia L.; Fehér, Enikő; Oldal, Miklós; Jakab, Ferenc; Martella, Vito

    2015-01-01

    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

  18. The role of serum antibodies in the protection against rotavirus disease: an overview.

    Science.gov (United States)

    Jiang, Baoming; Gentsch, Jon R; Glass, Roger I

    2002-05-15

    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.

  19. Epidemiology of rotavirus diarrhoea in Albania.

    Science.gov (United States)

    Kota, M; Bino, S; Delogu, R; Simaku, A; Neza, B; Ruggeri, F M; Fiore, L

    2014-09-01

    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[8] was the most prevalent genotype (38%), followed by G1P[8] (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.

  20. An atypical rotavirus detected in a child with gastroenteritis in Rio de Janeiro, Brazil

    Directory of Open Access Journals (Sweden)

    H. G. Pereira

    1983-09-01

    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.

  1. LED light attenuation through human dentin: a first step toward pulp photobiomodulation after cavity preparation.

    Science.gov (United States)

    Turrioni, Ana Paula S; Alonso, Juliana R L; Basso, Fernanda G; Moriyama, Lilian T; Hebling, Josimeri; Bagnato, Vanderlei S; De Souza, Costa Carlos A

    2013-12-01

    To evaluate the transdentinal light attenuation of LED at three wavelengths through different dentin thicknesses, simulating cavity preparations of different depths. Forty-two dentin discs of three thicknesses (0.2, 0.5 and 1 mm; n = 14) were prepared from the coronal dentin of extracted sound human molars. The discs were illuminated with a LED light at three wavelengths (450+/-10 nm, 630 +/-10 nm and 850 +/-10 nm) to determine light attenuation. Light transmittance was also measured by spectrophotometry. In terms of minimum (0.2 mm) and maximum (1.0 mm) dentin thicknesses, the percentage of light attenuation varied from 49.3% to 69.9% for blue light, 42.9% to 58.5% for red light and 39.3% to 46.8% for infrared. For transmittance values, an increase was observed for all thicknesses according to greater wavelengths, and the largest variation occurred for the 0.2 mm thickness. All three wavelengths were able to pass through the dentin barrier at different thicknesses. Furthermore, the LED power loss and transmittance showed wide variations, depending on dentin thickness and wavelength.

  2. Mass Attenuation Coefficients of Human Body Organs using MCNPX Monte Carlo Code

    Directory of Open Access Journals (Sweden)

    Huseyin Tekin

    2017-12-01

    Full Text Available Introduction: Investigation of radiation interaction with living organs has always been a thrust area in medical and radiation physics. The investigated results are being used in medical physics for developing improved and sensitive techniques and minimizing radiation exposure. In this study, mass attenuation coefficients of different human organs and biological materials such as adipose, blood, bone, brain, eye lens, lung, muscle, skin, and tissue have been calculated. Materials and Methods: In the present study, Monte Carlo N-Particle eXtended (MCNP-X version 2.4.0 was used for determining mass attenuation coefficients, and the obtained results were compared with earlier investigations (using GEometry ANd Tracking [GEANT4] and FLUKA computer simulation packages for blood, bone, lung, eye lens, adipose, tissue, muscle, brain, and skin materials at different energies. Results: The results of this study showed that the obtained results from MCNP-X were in high accordance with the National Institute of Standards and Technology data. Conclusion: Our findings would be beneficial for use of present simulation technique and mass attenuation coefficients for medical and radiation physics applications.

  3. Detection and Characterization of Rotavirus G and P Types from Children Participating in a Rotavirus Vaccine Trial in Belém, Brazil

    Directory of Open Access Journals (Sweden)

    Mascarenhas JDP

    2002-01-01

    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[8], P[4], P[6] 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[8],G1 and P[4],G2 with 53% and 26.6% of the infections, respectively. Unusual strains accounted for 20.5% including P[4],G1, P[6],G1, P[6],G4, P[6],G5, P[8],G2, P[8],G5. Mixed infections involving P[8+6],G2 and P[8+6],G1 were also noted. The neonatal P[6] 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.

  4. Rotavirus antigen, cytokine, and neutralising antibody profiles in sera of children with and without HIV infection in Blantyre, Malawi.

    Science.gov (United States)

    Hull, Jennifer J; Cunliffe, Nigel; Jere, Khuzwayo C; Moon, Sung-Sil; Wang, Yuhuan; Parashar, Umesh; Jiang, Baoming

    2017-03-01

    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.

  5. Parametric imaging of the local attenuation coefficient in human axillary lymph nodes assessed using optical coherence tomography

    Science.gov (United States)

    Scolaro, Loretta; McLaughlin, Robert A.; Klyen, Blake R.; Wood, Benjamin A.; Robbins, Peter D.; Saunders, Christobel M.; Jacques, Steven L.; Sampson, David D.

    2012-01-01

    We report the use of optical coherence tomography (OCT) to determine spatially localized optical attenuation coefficients of human axillary lymph nodes and their use to generate parametric images of lymphoid tissue. 3D-OCT images were obtained from excised lymph nodes and optical attenuation coefficients were extracted assuming a single scattering model of OCT. We present the measured attenuation coefficients for several tissue regions in benign and reactive lymph nodes, as identified by histopathology. We show parametric images of the measured attenuation coefficients as well as segmented images of tissue type based on thresholding of the attenuation coefficient values. Comparison to histology demonstrates the enhancement of contrast in parametric images relative to OCT images. This enhancement is a step towards the use of OCT for in situ assessment of lymph nodes. PMID:22312589

  6. Molecular characterisation of the rotavirus strains prevalent in Maua, Meru North, Kenya.

    Science.gov (United States)

    Kiulia, N M; Peenze, I; Dewar, J; Nyachieo, A; Galo, M; Omolo, E; Steele, A D; Mwenda, J M

    2006-07-01

    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

  7. Association between mixed rotavirus vaccination types of infants and rotavirus acute gastroenteritis

    Science.gov (United States)

    Mohammed, Anaam; Immergluck, Lilly; Parker, Trisha Chan; Jain, Shabnam; Leong, Traci; Anderson, Evan J.; Jerris, Robert C.

    2017-01-01

    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

  8. Serial observations of chronic rotavirus infection in an immunodeficient child.

    Science.gov (United States)

    Oishi, I; Kimura, T; Murakami, T; Haruki, K; Yamazaki, K; Seto, Y; Minekawa, Y; Funamoto, H

    1991-01-01

    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.

  9. Molecular characterization of group A rotaviruses detected in children with gastroenteritis in Ireland in 2006-2009.

    LENUS (Irish Health Repository)

    Cashman, O

    2012-02-01

    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[4], P[6], P[8] and P[9]) genotypes were detected. Strains G1P[8] 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[8], at least two distinct lineages were identified, both unrelated to P[8] 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.

  10. Human rotavirus strains circulating in Venezuela after vaccine introduction: predominance of G2P[4] and reemergence of G1P[8].

    Science.gov (United States)

    Vizzi, Esmeralda; Piñeros, Oscar A; Oropeza, M Daniela; Naranjo, Laura; Suárez, José A; Fernández, Rixio; Zambrano, José L; Celis, Argelia; Liprandi, Ferdinando

    2017-03-21

    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[4] and 63 (38.2%) G1P[8]. G9P[8], G3P[8] and G2P[6] were found in a lower proportion (7.3%). Remarkable was also the detection of <5% of uncommon combinations (G8P[14], G8P[4], G1P[4] and G4P[4]) 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[4] from February to June 2007 followed by its gradual decline and the reemergence of G1P[8], predominant since January 2008. Phylogenetic analysis of VP7 and VP4 genes revealed a high similarity among G2P[4] and global strains belonging to G2-II and P[4]-V lineages. The amino acid substitution 96D → N, related with reemergence of the G2 genotype elsewhere, was observed. The G1P[8] strains from Caracas were grouped into the lineages G1-I and P[8]-III, along with geographically remote G1P[8] 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

  11. Reduction of Oxidative Stress Attenuates Lipoapoptosis Exacerbated by Hypoxia in Human Hepatocytes

    Directory of Open Access Journals (Sweden)

    Sang Youn Hwang

    2015-02-01

    Full Text Available Chronic intermittent hypoxia, a characteristic of obstructive sleep apnea (OSA, is associated with the progression of simple hepatic steatosis to necroinflammatory hepatitis. We determined whether inhibition of a hypoxia-induced signaling pathway could attenuate hypoxia-exacerbated lipoapoptosis in human hepatocytes. The human hepatocellular carcinoma cell line (HepG2 was used in this study. Palmitic acid (PA-treated groups were used for two environmental conditions: Hypoxia (1% O2 and normoxia (20% O2. Following the treatment, the cell viability was determined by the 3,4-(5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium salt (MTS assay, and the mechanism of lipoapoptosis was evaluated by Western blotting. Hypoxia exacerbated the suppression of hepatocyte growth induced by palmitic acid via activation of mitochondrial apoptotic pathways as a result of endoplasmic reticulum (ER and oxidative stresses. Ammonium pyrrolidine dithiocarbamate, a scavenger of reactive oxygen species, attenuated the hypoxia-exacerbated lipoapoptosis in hepatocytes, whereas glycerol, which reduces ER stress, did not. This may have been because inhibition of oxidative stress decreases the expression of pro-apoptotic proteins, such as caspase 9 and cytochrome c. These results suggested that modulation of apoptotic signaling pathways activated by oxidative stress can aid in identifying novel therapeutic strategies for the treatment of nonalcoholic steatohepatitis (NASH with OSA. Further in vivo studies are necessary to understand the pathophysiologic mechanism of NASH with OSA and to prove the therapeutic effect of the modulation of the signaling pathways.

  12. Dexamethasone and N-acetyl-cysteine attenuate Pseudomonas aeruginosa-induced mucus expression in human airways.

    Science.gov (United States)

    Sprenger, Lisa; Goldmann, Torsten; Vollmer, Ekkehard; Steffen, Armin; Wollenberg, Barbara; Zabel, Peter; Hauber, Hans-Peter

    2011-04-01

    Infection with Pseudomonas aeruginosa (PA) induces mucus hypersecretion in airways. Therapeutic options to attenuate excessive mucus expression are sparse. To investigate the effect of steroids and N-acetyl-cysteine (NAC) on PA-induced mucus expression. Calu-3 cells and explanted human mucosa from the upper airways were stimulated with either PA, lipopolysaccharide from alginate producing PA (smooth, sPA-LPS) or non-alginate producing PA (rough, rPA-LPS). Dexamethasone (DEX) and NAC were added in different concentrations. Expression of mucin (MUC5AC) gene and mucin protein expression was quantified using PAS (periodic acids Schiff) staining and real time PCR. PA, sPA-LPS or rPA-LPS significantly induced mucin protein and MUC5AC gene expression in Calu-3 cells and explanted mucosal tissue (P NAC significantly decreased PA-, sPA-LPS- and rPA-LPS-induced mucin protein expression both in vitro and ex vivo (P 0.05). Our data show that both an anti-inflammatory drug (DEX) and an anti-oxidative agent (NAC) can attenuate PA-induced mucus expression in human airways. These results support the use of steroids and NAC in clinical practice to treat PA-induced mucus hypersecretion. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Vitamin E prevents neutrophil accumulation and attenuates tissue damage in ischemic-reperfused human skeletal muscle.

    Science.gov (United States)

    Formigli, L; Ibba Manneschi, L; Tani, A; Gandini, E; Adembri, C; Pratesi, C; Novelli, G P; Zecchi Orlandini, S

    1997-07-01

    Neutrophil accumulation and the consequent production of oxygen-derived free radicals are involved in the pathogenesis of Ischemia-Reperfusion syndrome. In this study we investigated whether a treatment with Vitamin E, which has antioxidant properties, could attenuate the tissue damage by interfering with the influx of neutrophils within the ischemic and reperfused human skeletal muscle. To this purpose, patients undergoing aortic cross-clamping during the surgical repair of aortic abdominal aneurysm were studied as a model of ischemia-reperfusion of the lower limb muscles. Muscle biopsies from the right femoral quadriceps of patients not receiving and receiving Vitamin E pretreatment before surgery were taken: a) after the induction of anaesthesia, as control samples, and b) after a period of ischemia followed by 30 min of reperfusion. The tissue samples were either routinely processed for morphological study and immunohistochemical analysis to detect an altered expression of specific endothelial adhesion proteins, such as E-selectin and ICAM-1. The results obtained showed that Vitamin E administration was able to prevent the accumulation of neutrophils within the ischemic and reperfused muscle. This beneficial effect of Vitamin E was due to its ability to hinder the expression of E-selectin and ICAM-1, molecules known to increase the adhesiveness of endothelium to circulating neutrophils. After treatment with Vitamin E a marked attenuation of the reperfusion injury was also evident. In conclusion, Vitamin E treatment may be considered a valuable tool for protection against the ischemia-reperfusion damage of human skeletal muscle.

  14. Rotavirus vaccine effectiveness in Hong Kong children.

    Science.gov (United States)

    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

    2016-09-22

    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

  15. Diversity in Rotavirus–Host Glycan Interactions: A “Sweet” SpectrumSummary

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    Sasirekha Ramani

    2016-05-01

    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 glycan–pathogen 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 rotavirus–host 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

  16. Human mesenchymal stem cells attenuate pulmonary hypertension induced by prenatal lipopolysaccharide treatment in rats.

    Science.gov (United States)

    Chou, Hsiu-Chu; Lin, Willie; Chen, Chung-Ming

    2016-10-01

    Intra-amniotic injection of lipopolysaccharide (LPS) induces pulmonary hypertension in newborn rats. This study was designed to test whether human mesenchymal stem cells (MSCs) reduce pulmonary hypertension and alleviate cardiac hypertrophy in prenatal LPS-treated rats. Pregnant Sprague-Dawley rats were injected intraperitoneally with LPS (0.5 mg/kg per day) or untreated on gestational days 20 and 21. Human MSCs (3×10(5) cells and 1×10(6) cells) in 0.03 mL of normal saline (NS) were transplanted intratracheally on postnatal day 5. Four study groups were considered: normal, LPS+NS, LPS+MSCs (3×10(5) cells), and LPS+MSCs (1×10(6) cells). On postnatal day 14, lung and heart tissues were collected for measuring the arterial medial wall thickness (MWT) and β-myosin heavy chain (β-MHC) level as markers of pulmonary hypertension and cardiac hypertrophy, respectively. The LPS+NS group exhibited a significantly higher right ventricle (RV)/[left ventricle (LV)+ interventricular septum (IVS)] thickness ratio and MWT, a greater cardiomyocyte width, a greater number of cardiomyocyte nuclei per squared millimeter, and higher β-MHC expression than those observed in the normal group. Human MSC transplantation (3×10(5) cells and 1×10(6) cells) in LPS-treated rats reduced MWT and the RV/(LV+IVS) thickness ratio to normal levels. This improvement in right ventricular hypertrophy was accompanied by a decrease in toll-like receptor 4 (TLR4), nuclear factor-κB, and tumor necrosis factor-α expression in the heart. Intratracheal human MSCs transplantation can attenuate pulmonary hypertension and right ventricular hypertrophy in prenatal LPS-treated rats; this attenuation may be associated with suppression of TLR4 expression via paracrine pathways. © 2016 John Wiley & Sons Australia, Ltd.

  17. Biochemical characterization of rotavirus receptors in MA104 cells.

    Science.gov (United States)

    Guerrero, C A; Zárate, S; Corkidi, G; López, S; Arias, C F

    2000-10-01

    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

  18. One Family's Struggles with Rotavirus

    Medline Plus

    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 ...

  19. One Family's Struggles with Rotavirus

    Medline Plus

    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 ...

  20. Differences of Rotavirus Vaccine Effectiveness by Country: Likely Causes and Contributing Factors

    Directory of Open Access Journals (Sweden)

    Ulrich Desselberger

    2017-12-01

    Full Text Available Rotaviruses are a major cause of acute gastroenteritis in infants and young children worldwide and in many other mammalian and avian host species. Since 2006, two live-attenuated rotavirus vaccines, Rotarix® and RotaTeq®, have been licensed in >100 countries and are applied as part of extended program of vaccination (EPI schemes of childhood vaccinations. Whereas the vaccines have been highly effective in high-income countries, they were shown to be considerably less potent in low- and middle-income countries. Rotavirus-associated disease was still the cause of death in >200,000 children of <5 years of age worldwide in 2013, and the mortality is concentrated in countries of sub-Saharan Africa and S.E. Asia. Various factors that have been identified or suggested as being involved in the differences of rotavirus vaccine effectiveness are reviewed here. Recognition of these factors will help to achieve gradual worldwide improvement of rotavirus vaccine effectiveness.

  1. Chronic hypoxia attenuates VEGF signaling and angiogenic responses by downregulation of KDR in human endothelial cells.

    Science.gov (United States)

    Olszewska-Pazdrak, Barbara; Hein, Travis W; Olszewska, Paulina; Carney, Darrell H

    2009-05-01

    Coronary artery disease results in progressive vascular stenosis associated with chronic myocardial ischemia. Vascular endothelial growth factor (VEGF) stimulates endothelial cell angiogenic responses to revascularize ischemic tissues; however, the effect of chronic hypoxia on the responsiveness of endothelial cells to VEGF remains unclear. We, therefore, investigated whether hypoxia alters VEGF-stimulated signaling and angiogenic responses in primary human coronary artery endothelial (HCAE) cells. Exposure of HCAE cells to hypoxia (1% O(2)) for 24 h decreased VEGF-stimulated endothelial cell migration ( approximately 82%), proliferation ( approximately 30%), and tube formation. Hypoxia attenuated VEGF-stimulated activation of endothelial nitric oxide (NO) synthase (eNOS) ( approximately 72%) and reduced NO production in VEGF-stimulated cells from 237 +/- 38.8 to 61.3 +/- 28.4 nmol/l. Moreover, hypoxia also decreased the ratio of phosphorylated eNOS to total eNOS in VEGF-stimulated cells by approximately 50%. This effect was not observed in thrombin-stimulated cells, suggesting that hypoxia specifically inhibited VEGF signaling upstream of eNOS phosphorylation. VEGF-induced activation of Akt, ERK1/2, p38, p70S6 kinases, and S6 ribosomal protein was also attenuated in hypoxic cells. Moreover, VEGF-stimulated phosphorylation of VEGF receptor-2 (KDR) at Y996 and Y1175 was decreased by hypoxia. This decrease correlated with a 70 +/- 12% decrease in KDR protein expression. Analysis of mRNA from these cells showed that hypoxia reduced steady-state levels of KDR mRNA by 52 +/- 16% and decreased mRNA stability relative to normoxic cells. Our findings demonstrate that chronic hypoxia attenuates VEGF-stimulated signaling in HCAE cells by specific downregulation of KDR expression. These data provide a novel explanation for the impaired angiogenic responses to VEGF in endothelial cells exposed to chronic hypoxia.

  2. A reverse evidence of rotavirus vaccines impact

    OpenAIRE

    Martinón-Torres, Federico; Aramburo, Angela; Martinón-Torres, Nazareth; Cebey, Miriam; Seoane-Pillado, María Teresa; Redondo-Collazo, Lorenzo; Martinón-Sánchez, Jose Maria

    2013-01-01

    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.

  3. Human neutrophil elastase-mediated goblet cell metaplasia is attenuated in TACE-deficient mice.

    Science.gov (United States)

    Park, Jin-Ah; Sharif, Asma S; Shiomi, Tetsuya; Kobzik, Lester; Kasahara, David I; Tschumperlin, Daniel J; Voynow, Judith; Drazen, Jeffrey M

    2013-05-15

    Neutrophilic inflammation is associated with chronic airway diseases. It has been observed that human neutrophil elastase (HNE), which is secreted by active neutrophils during inflammation, induces both mucin overproduction and goblet cell metaplasia. Several in vitro studies suggest that tumor necrosis factor-α converting enzyme (TACE) regulates the signaling axis that mediates HNE-induced mucin overproduction; however, it is unknown whether TACE performs a similar function in HNE-induced goblet cell metaplasia in vivo. We conducted this study to determine whether the inactivation of Tace gene expression attenuates HNE-induced goblet cell metaplasia in mice. Deletion of Tace is lethal shortly after birth in mice; therefore, we utilized Tace(flox/flox)R26CreER(+/-) mice and induced conditional deletion of Tace using a tamoxifen injection. Wild-type mice were given tamoxifen to control for its effect. Tace conditional deletion mice and wild-type mice were exposed to HNE via nasal instillation three times at 3-day intervals, and the lungs were harvested on day 11 after initial HNE exposure. Using periodic acid-Schiff staining and MUC5AC immunohistochemical staining to visualize goblet cells in the lungs, we found that HNE induced goblet cell metaplasia in the wild-type mice and that HNE-induced goblet cell metaplasia was significantly attenuated in the Tace conditional deletion mice. These findings suggest that TACE could be a potential target in the treatment of goblet cell metaplasia in patients with chronic airway diseases.

  4. Transmission, attenuation and reflection of shear waves in the human brain.

    Science.gov (United States)

    Clayton, Erik H; Genin, Guy M; Bayly, Philip V

    2012-11-07

    Traumatic brain injuries (TBIs) are caused by acceleration of the skull or exposure to explosive blast, but the processes by which mechanical loads lead to neurological injury remain poorly understood. We adapted motion-sensitive magnetic resonance imaging methods to measure the motion of the human brain in vivo as the skull was exposed to harmonic pressure excitation (45, 60 and 80 Hz). We analysed displacement fields to quantify the transmission, attenuation and reflection of distortional (shear) waves as well as viscoelastic material properties. Results suggest that internal membranes, such as the falx cerebri and the tentorium cerebelli, play a key role in reflecting and focusing shear waves within the brain. The skull acts as a low-pass filter over the range of frequencies studied. Transmissibility of pressure waves through the skull decreases and shear wave attenuation increases with increasing frequency. The skull and brain function mechanically as an integral structure that insulates internal anatomic features; these results are valuable for building and validating mathematical models of this complex and important structural system.

  5. The histone deacetylase inhibitor suberoylanilide hydroxamic acid attenuates human astrocyte neurotoxicity induced by interferon-γ

    Directory of Open Access Journals (Sweden)

    Hashioka Sadayuki

    2012-05-01

    Full Text Available Abstract Backgrounds Increasing evidence shows that the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA possesses potent anti-inflammatory and immunomodulatory properties. It is tempting to evaluate the potential of SAHA as a therapeutic agent in various neuroinflammatory and neurodegenerative disorders. Methods We examined the effects of SAHA on interferon (IFN-γ-induced neurotoxicity of human astrocytes and on IFN-γ-induced phosphorylation of signal transducer and activator of transcription (STAT 3 in human astrocytes. We also studied the effects of SAHA on the astrocytic production of two representative IFN-γ-inducible inflammatory molecules, namely IFN-γ-inducible T cell α chemoattractant (I-TAC and intercellular adhesion molecule-1 (ICAM-1. Results SAHA significantly attenuated the toxicity of astrocytes activated by IFN-γ towards SH-SY5Y human neuronal cells. In the IFN-γ-activated astrocytes, SAHA reduced the STAT3 phosphorylation. SAHA also inhibited the IFN-γ-induced astrocytic production of I-TAC, but not ICAM-1. These results indicate that SAHA suppresses IFN-γ-induced neurotoxicity of human astrocytes through inhibition of the STAT3 signaling pathway. Conclusion Due to its anti-neurotoxic and anti-inflammatory properties, SAHA appears to have the therapeutic or preventive potential for a wide range of neuroinflammatory disorders associated with activated astrocytes.

  6. [Prognosis of rotavirus infection in children].

    Science.gov (United States)

    Kharchenko, Y; Lavrukova, S; Yurchenko, I; Movlyanova, N; Eremenko, S

    2014-03-01

    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.

  7. Respuesta inmune adaptativa al rotavirus

    Directory of Open Access Journals (Sweden)

    Manuel A. Franco

    2004-03-01

    . 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.

  8. Triple layered rotavirus VLP production: kinetics of vector replication, mRNA stability and recombinant protein production.

    Science.gov (United States)

    Vieira, Helena L A; Estêvão, Catarina; Roldão, António; Peixoto, Cristina C; Sousa, Marcos F Q; Cruz, Pedro E; Carrondo, Manuel J T; Alves, Paula M

    2005-10-17

    Rotavirus infection causes diarrhoeal disease in infants, killing more than half million children each year. Virus-like particles (VLP) seem to be excellent vaccine candidates, since they are cheaper to produce than attenuated viral vaccines and safer, as they do not contain genetic material. The present work focus on a triple layered particle composed by three rotavirus structural proteins: VP2, VP6 and VP7, produced in an insect cell/baculovirus expressing system. Two strategies were evaluated for 2/6/7 VLP production: co-infection with three monocistronic baculovirus vectors or single-infection with a tricistronic multi-gene baculovirus vector; these strategies were followed at different levels: baculovirus DNA replication kinetics, mRNA stability, protein production and VLP formation. This study highlights some of the reasons why the tricistronic baculovirus strategy is more efficient for production of triple layered rotavirus 2/6/7 VLP than monocistronic co-infection, in particular: (i) the tricistronic vector presents higher DNA replication rates than the monocistronic vectors, (ii) the mRNA stability is invariant for all mRNAs corresponding to VP2, VP6 and VP7 and (iii) the tricistronic baculovirus strategy produces an excess of VP7 over VP6 when compared to the VP7/VP6 stoichiometric ratio in the native rotavirus. Although the co-infection strategy leads to protein production akin to the rotavirus VP7/VP6 stoichiometric ratio, the tricistronic vector strategy yields higher amounts of rotavirus-like particles.

  9. [Pathogenesis of human metapneumovirus infection and research on attenuated live vaccine].

    Science.gov (United States)

    Tang, Mao-Zhi; Dou, Ying; Zhao, Xiao-Dong

    2014-05-01

    Numerous studies have indicated that human metapneumovirus (hMPV) is an important viral pathogen in acute respiratory infections in children, presenting similar manifestations with respiratory syncytial virus (RSV). HMPV infection peaks in the winter-spring season and is more prevalent in younger ages, especially in children less than 1 year old. Host innate immune response has been implicated in recognition of pathogen-associated molecular patterns (PAMPs) of the virus. This recognition occurs through host pattern recognition receptors (PRRs). Toll like receptors (TLRs) are one of the largest class of PRRs which initiate and regulate adaptive immune responses. Some studies have indicated that TLR 3 and TLR 4 may play critical roles in hMPV infection. Construction of recombinant mutant viruses lacking one or two N-linked glycosylation sites in the F protein by using site-directed mutagenesis and reverse genetics may be helpful for developing attenuated live vaccines.

  10. Ultrasound velocity and broadband attenuation as predictors of load-bearing capacities of human calcanei.

    Science.gov (United States)

    Han, S; Medige, J; Davis, J; Fishkin, Z; Mihalko, W; Ziv, I

    1997-01-01

    The main purpose of this study was to determine whether calcaneal ultrasound parameters, measured in the mediolateral direction, reflect load-bearing capacities of human calcanei. Broadband ultrasound attenuation (BUA) and ultrasound velocity (UV) were measured in 20 cadaveric calcanei with a mean age of 74.1 (SD 8.8). Normalized BUA (nBUA) was determined by dividing BUA by the calcaneal thickness obtained using a pulse-echo technique. The bone mineral density (BMD) of each calcaneus was measured by quantitative computed tomography. The calcanei were embedded in PMMA to simulate the midstance physiologic orientation during compressive testing in the load-bearing direction. The failure load, stiffness, and energy absorption were determined for each calcaneus. It was shown that BMD was well correlated with all ultrasound parameters (P 0.5).

  11. Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation

    Science.gov (United States)

    Wang, Jing; Luo, Cheng; Shan, Changliang; You, Qiancheng; Lu, Junyan; Elf, Shannon; Zhou, Yu; Wen, Yi; Vinkenborg, Jan L.; Fan, Jun; Kang, Heebum; Lin, Ruiting; Han, Dali; Xie, Yuxin; Karpus, Jason; Chen, Shijie; Ouyang, Shisheng; Luan, Chihao; Zhang, Naixia; Ding, Hong; Merkx, Maarten; Liu, Hong; Chen, Jing; Jiang, Hualiang; He, Chuan

    2015-12-01

    Copper is a transition metal that plays critical roles in many life processes. Controlling the cellular concentration and trafficking of copper offers a route to disrupt these processes. Here we report small molecules that inhibit the human copper-trafficking proteins Atox1 and CCS, and so provide a selective approach to disrupt cellular copper transport. The knockdown of Atox1 and CCS or their inhibition leads to a significantly reduced proliferation of cancer cells, but not of normal cells, as well as to attenuated tumour growth in mouse models. We show that blocking copper trafficking induces cellular oxidative stress and reduces levels of cellular ATP. The reduced level of ATP results in activation of the AMP-activated protein kinase that leads to reduced lipogenesis. Both effects contribute to the inhibition of cancer cell proliferation. Our results establish copper chaperones as new targets for future developments in anticancer therapies.

  12. Clarithromycin attenuates IL-13–induced periostin production in human lung fibroblasts

    Directory of Open Access Journals (Sweden)

    Kosaku Komiya

    2017-02-01

    Full Text Available Abstract Background Periostin is a biomarker indicating the presence of type 2 inflammation and submucosal fibrosis; serum periostin levels have been associated with asthma severity. Macrolides have immunomodulatory effects and are considered a potential therapy for patients with severe asthma. Therefore, we investigated whether macrolides can also modulate pulmonary periostin production. Methods Using quantitative PCR and ELISA, we measured periostin production in human lung fibroblasts stimulated by interleukin-13 (IL-13 in the presence of two 14-member–ring macrolides—clarithromycin or erythromycin—or a 16-member–ring macrolide, josamycin. Phosphorylation of signal transducers and activators of transcription 6 (STAT6, downstream of IL-13 signaling, was evaluated by Western blotting. Changes in global gene expression profile induced by IL-13 and/or clarithromycin were assessed by DNA microarray analysis. Results Clarithromycin and erythromycin, but not josamycin, inhibited IL-13–stimulated periostin production. The inhibitory effects of clarithromycin were stronger than those of erythromycin. Clarithromycin significantly attenuated STAT6 phosphorylation induced by IL-13. Global gene expression analyses demonstrated that IL-13 increased mRNA expression of 454 genes more than 4-fold, while decreasing its expression in 390 of these genes (85.9%, mainly “extracellular,” “plasma membrane,” or “defense response” genes. On the other hand, clarithromycin suppressed 9.8% of the genes in the absence of IL-13. Clarithromycin primarily attenuated the gene expression of extracellular matrix protein, including periostin, especially after IL-13. Conclusions Clarithromycin suppressed IL-13–induced periostin production in human lung fibroblasts, in part by inhibiting STAT6 phosphorylation. This suggests a novel mechanism of the immunomodulatory effect of clarithromycin in asthmatic airway inflammation and fibrosis.

  13. Efficacy of rhesus rotavirus vaccine MMU-18006 against gastroenteritis due to serotype 1 rotavirus.

    Science.gov (United States)

    Ukae, S; Nakata, S; Adachi, N; Kogawa, K; Chiba, S

    1994-08-01

    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.

  14. Development of primers for sequencing the NSP1, NSP3, and VP6 genes of the group A porcine rotavirus

    Directory of Open Access Journals (Sweden)

    Fernanda Dornelas Florentino Silva

    2014-02-01

    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.

  15. Mitochondrial fragmentation in human macrophages attenuates palmitate-induced inflammatory responses.

    Science.gov (United States)

    Zezina, Ekaterina; Snodgrass, Ryan G; Schreiber, Yannick; Zukunft, Sven; Schürmann, Christoph; Heringdorf, Dagmar Meyer Zu; Geisslinger, Gerd; Fleming, Ingrid; Brandes, Ralf P; Brüne, Bernhard; Namgaladze, Dmitry

    2018-02-02

    Macrophages in adipose tissue contribute to inflammation and the development of insulin resistance in obesity. Exposure of macrophages to saturated fatty acids alters cell metabolism and activates pro-inflammatory signaling. How fatty acids influence macrophage mitochondrial dynamics is unclear. We investigated the mechanism of palmitate-induced mitochondrial fragmentation and its impact on inflammatory responses in primary human macrophages. Fatty acids, such as palmitate, caused mitochondrial fragmentation in human macrophages. Increased mitochondrial fragmentation was also observed in peritoneal macrophages from hyperlipidemic apolipoprotein E knockout mice. Fatty acid-induced mitochondrial fragmentation was independent of the fatty acid chain saturation and required dynamin-related protein 1 (DRP1). Mechanistically, mitochondrial fragmentation was regulated by incorporation of palmitate into mitochondrial phospholipids and their precursors. Palmitate-induced endoplasmic reticulum stress and loss of mitochondrial membrane potential did not contribute to mitochondrial fragmentation. Macrophages treated with palmitate maintained intact mitochondrial respiration and ATP levels. Pharmacological or genetic inhibition of DRP1 enhanced palmitate-induced mitochondrial ROS production, c-Jun phosphorylation, and inflammatory cytokine expression. Our results indicate that mitochondrial fragmentation is a protective mechanism attenuating inflammatory responses induced by palmitate in human macrophages. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Detection of Novel Rotavirus Strain by Vaccine Postlicensure Surveillance

    OpenAIRE

    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.

    2013-01-01

    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[24], in a stool sample from a child who had diarrhea. Unusual rotavirus strains may become more prevalent after vaccine implementation.

  17. Dependence of optical attenuation coefficient and mechanical tension of irradiated human cartilage measured by optical coherence tomography.

    Science.gov (United States)

    Martinho Junior, A C; Freitas, A Z; Raele, M P; Santin, S P; Soares, F A N; Herson, M R; Mathor, M B

    2015-03-01

    As banked human tissues are not widely available, the development of new non-destructive and contactless techniques to evaluate the quality of allografts before distribution for transplantation is very important. Also, tissues will be processed accordingly to standard procedures and to minimize disease transmission most tissue banks will include a decontamination or sterilization step such as ionizing radiation. In this work, we present a new method to evaluate the internal structure of frozen or glycerol-processed human cartilages, submitted to various dosis of irradiation, using the total optical attenuation coefficient retrieved from optical coherence tomography (OCT) images. Our results show a close relationship between tensile properties and the total optical attenuation coefficient of cartilages. Therefore, OCT associated with the total optical attenuation coefficient open a new window to evaluate quantitatively biological changes in processed tissues.

  18. Molecular characterization of human G8P[4] rotavirus strains in Italy: proposal of a more complete subclassification of the G8 genotype in three major lineages.

    Science.gov (United States)

    Ianiro, G; Delogu, R; Bonomo, P; Castiglia, P; Ruggeri, F M; Fiore, L

    2014-01-01

    In 2011, two children with acute rotavirus gastroenteritis were hospitalized in Sardinia, Italy. Two RVA strains with G8P[4] 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[4]-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[4] 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[4] 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.

  19. [Research progress in rotavirus VP4 subunit vaccine].

    Science.gov (United States)

    Jia, Lianzhi; Li, Tingdong; Ge, Shengxiang

    2017-07-25

    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.

  20. Rotavirus vaccine stability in the aquatic environment.

    Science.gov (United States)

    Moresco, V; Damazo, N A; Barardi, C R M

    2016-02-01

    To evaluate the thermal and length of stability of the Rotaviruses (RV) vaccine (RotaTeq) in the aquatic environment. Surface freshwater, brackish and drinking water were spiked with RV vaccine strain and stored at 22 and 4°C. The virus infectivity and genome persistence were evaluated by plaque assay and RT-qPCR, respectively, up to 180 days. Infectious RV vaccine particles showed to be less stable in the brackish water matrix than in surface and drinking water either at 22 or 4°C. The estimated T90 values obtained by the linear regression model were 18, 55 and 59 days, respectively for brackish, surface and drinking water stored at 22°C and 68, 154 and 240 days at 4°C. As expected, the genome persistence showed to be less affected by length and temperature of storage in all the matrices evaluated. The evidence of high stability of the RV vaccine in water matrices reinforces the importance for surveillance of RV vaccines strains in the environment regarding the potential occurrence of unexpected infections and virus genomic reassortments. The presence of reassortants and the shedding of the live attenuated vaccine strains after vaccination can compromise the vaccine safety by introducing new viral variants in the environment. © 2015 The Society for Applied Microbiology.

  1. Original Research Rotavirus antigen, cytokine, and neutralising ...

    African Journals Online (AJOL)

    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, ...

  2. Experimental reproduction of rotavirus and Salmonella pullorum ...

    African Journals Online (AJOL)

    ADEYEYE

    2017-07-10

    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.

  3. EPIDEMIOLOGY OF ROTAVIRUS AND ASTROVIRUS INFECTIONS ...

    African Journals Online (AJOL)

    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 ...

  4. Gene disruption of Plasmodium falciparum p52 results in attenuation of malaria liver stage development in cultured primary human hepatocytes.

    Directory of Open Access Journals (Sweden)

    Ben C L van Schaijk

    Full Text Available Difficulties with inducing sterile and long lasting protective immunity against malaria with subunit vaccines has renewed interest in vaccinations with attenuated Plasmodium parasites. Immunizations with sporozoites that are attenuated by radiation (RAS can induce strong protective immunity both in humans and rodent models of malaria. Recently, in rodent parasites it has been shown that through the deletion of a single gene, sporozoites can also become attenuated in liver stage development and, importantly, immunization with these sporozoites results in immune responses identical to RAS. The promise of vaccination using these genetically attenuated sporozoites (GAS depends on translating the results in rodent malaria models to human malaria. In this study, we perform the first essential step in this transition by disrupting, p52, in P. falciparum an ortholog of the rodent parasite gene, p36p, which we had previously shown can confer long lasting protective immunity in mice. These P. falciparum P52 deficient sporozoites demonstrate gliding motility, cell traversal and an invasion rate into primary human hepatocytes in vitro that is comparable to wild type sporozoites. However, inside the host hepatocyte development is arrested very soon after invasion. This study reveals, for the first time, that disrupting the equivalent gene in both P. falciparum and rodent malaria Plasmodium species generates parasites that become similarly arrested during liver stage development and these results pave the way for further development of GAS for human use.

  5. Rapid and sensitive detection of rotavirus molecular signatures using surface enhanced Raman spectroscopy.

    Directory of Open Access Journals (Sweden)

    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.

  6. Histo-blood group antigens as receptors for rotavirus, new understanding on rotavirus epidemiology and vaccine strategy.

    Science.gov (United States)

    Jiang, Xi; Liu, Yang; Tan, Ming

    2017-04-12

    The success of the two rotavirus (RV) vaccines (Rotarix and RotaTeq) in many countries endorses a live attenuated vaccine approach against RVs. However, the lower efficacies of both vaccines in many low- and middle-income countries indicate a need to improve the current RV vaccines. The recent discovery that RVs recognize histo-blood group antigens (HBGAs) as potential receptors has significantly advanced our understanding of RV diversity, evolution and epidemiology, providing important new insights into the performances of current RV vaccines in different populations and emphasizing a P-type-based vaccine approach. New understanding of RV diversity and evolution also raises a fundamental question about the 'Jennerian' approach, which needs to be addressed for future development of live attenuated RV vaccines. Alternative approaches to develop safer and more cost-effective subunit vaccines against RVs are also discussed.

  7. Increasing cognitive load attenuates right arm swing in healthy human walking

    Science.gov (United States)

    Killeen, Tim; Easthope, Christopher S.; Filli, Linard; Lőrincz, Lilla; Schrafl-Altermatt, Miriam; Brugger, Peter; Linnebank, Michael; Curt, Armin; Zörner, Björn; Bolliger, Marc

    2017-01-01

    Human arm swing looks and feels highly automated, yet it is increasingly apparent that higher centres, including the cortex, are involved in many aspects of locomotor control. The addition of a cognitive task increases arm swing asymmetry during walking, but the characteristics and mechanism of this asymmetry are unclear. We hypothesized that this effect is lateralized and a Stroop word-colour naming task-primarily involving left hemisphere structures-would reduce right arm swing only. We recorded gait in 83 healthy subjects aged 18-80 walking normally on a treadmill and while performing a congruent and incongruent Stroop task. The primary measure of arm swing asymmetry-an index based on both three-dimensional wrist trajectories in which positive values indicate proportionally smaller movements on the right-increased significantly under dual-task conditions in those aged 40-59 and further still in the over-60s, driven by reduced right arm flexion. Right arm swing attenuation appears to be the norm in humans performing a locomotor-cognitive dual-task, confirming a prominent role of the brain in locomotor behaviour. Women under 60 are surprisingly resistant to this effect, revealing unexpected gender differences atop the hierarchical chain of locomotor control.

  8. Rotavirus infection in hospitalized children and estimates of disease burden in Kyrgyzstan, 2005-2007.

    Science.gov (United States)

    Flem, Elmira T; Kasymbekova, Kaliya T; Vainio, Kirsti; Gentsch, Jon; Abdikarimov, Sabirjan T; Glass, Roger I; Bresee, Joseph S

    2009-11-20

    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.

  9. Burden of Norovirus and Rotavirus in Children after Rotavirus Vaccine Introduction, Cochabamba, Bolivia

    Science.gov (United States)

    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

    2016-01-01

    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[8] was the most prevalent rotavirus genotype (44.0% of typed specimens) and G2P[4] 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

  10. Burden of Norovirus and Rotavirus in Children After Rotavirus Vaccine Introduction, Cochabamba, Bolivia.

    Science.gov (United States)

    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

    2016-01-01

    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[8] was the most prevalent rotavirus genotype (44.0% of typed specimens) and G2P[4] 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.

  11. First Molecular Detection of Group A Rotavirus in Urban and Hospital Sewage systems by Nested-RT PCR in Shiraz, Iran

    Directory of Open Access Journals (Sweden)

    Yahya Tahamtan

    2013-05-01

    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.

  12. Genome-Wide Evolutionary Analyses of G1P[8] Strains Isolated Before and After Rotavirus Vaccine Introduction.

    Science.gov (United States)

    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

    2015-08-08

    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[8] rotaviruses are the most prominent genotype in humans, and a total of 157 G1P[8] 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[8] 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[8] 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[8] 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.

  13. Genome-Wide Evolutionary Analyses of G1P[8] Strains Isolated Before and After Rotavirus Vaccine Introduction

    Science.gov (United States)

    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.

    2015-01-01

    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[8] rotaviruses are the most prominent genotype in humans, and a total of 157 G1P[8] 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[8] 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[8] 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[8] 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

  14. Memory T-cell response to rotavirus detected with a gamma interferon enzyme-linked immunospot assay.

    Science.gov (United States)

    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

    2005-05-01

    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.

  15. Longitudinal studies of neutralizing antibody responses to rotavirus in stools and sera of children following severe rotavirus gastroenteritis.

    Science.gov (United States)

    Coulson, B S

    1998-11-01

    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.

  16. HPW-RX40 prevents human platelet activation by attenuating cell surface protein disulfide isomerases

    Directory of Open Access Journals (Sweden)

    Po-Hsiung Kung

    2017-10-01

    Full Text Available Protein disulfide isomerase (PDI present at platelet surfaces has been considered to play an important role in the conformational change and activation of the integrin glycoprotein IIb/IIIa (GPIIb/IIIa and thus enhances platelet aggregation. Growing evidences indicated that platelet surface PDI may serve as a potential target for developing of a new class of antithrombotic agents. In the present study, we investigated the effects of HPW-RX40, a chemical derivative of β-nitrostyrene, on platelet activation and PDI activity. HPW-RX40 inhibited platelet aggregation, GPIIb/IIIa activation, and P-selectin expression in human platelets. Moreover, HPW-RX40 reduced thrombus formation in human whole blood under flow conditions, and protects mice from FeCl3-induced carotid artery occlusion. HPW-RX40 inhibited the activity of recombinant PDI family proteins (PDI, ERp57, and ERp5 as well as suppressed cell surface PDI activity of platelets in a reversible manner. Exogenous addition of PDI attenuated the inhibitory effect of HPW-RX40 on GPIIb/IIIa activation. Structure-based molecular docking simulations indicated that HPW-RX40 binds to the active site of PDI by forming hydrogen bonds. In addition, HPW-RX40 neither affected the cell viability nor induced endoplasmic reticulum stress in human cancer A549 and MDA-MB-231 cells. Taken together, our results suggest that HPW-RX40 is a reversible and non-cytotoxic PDI inhibitor with antiplatelet effects, and it may have a potential for development of novel antithrombotic agents.

  17. Rotavirus genotypes in children in the Basque Country (North of Spain): rapid and intense emergence of the G12[P8] genotype.

    Science.gov (United States)

    Cilla, G; Montes, M; Gomariz, M; Alkorta, M; Iturzaeta, A; Perez-Yarza, E G; Perez-Trallero, E

    2013-04-01

    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.

  18. Impact of rotavirus vaccine introduction on rotavirus-associated seizures and a related possible mechanism.

    Science.gov (United States)

    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

    2015-05-01

    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.

  19. Hyperoxia attenuates muscle sympathetic nerve activity following isocapnic hypoxia in humans.

    Science.gov (United States)

    Querido, Jordan S; Kennedy, Paul M; Sheel, A William

    2010-04-01

    Hypoxia may sensitize the carotid chemoreceptors, resulting in a sustained elevation of muscle sympathetic nerve activity (MSNA) that outlasts the hypoxic stimulus. To test this hypothesis, we determined the effect of carotid body inhibition on the sustained elevation of MSNA following isocapnic hypoxia in humans. Seven healthy subjects (5 male, 2 female) breathed 100% O(2) (hyperoxia) for 1 min before (2 interventions) and after (2-3 interventions) 20 min of isocapnic hypoxia (80% arterial oxyhemoglobin saturation). MSNA was continuously recorded from the common peroneal nerve with microneurography. There was no effect of hyperoxia on MSNA before exposure to isocapnic hypoxia. During the isocapnic hypoxia exposure, there was an increase in minute ventilation and heart rate that subsided once hypoxia was terminated. In contrast, there was an increase in MSNA burst frequency that persisted for approximately 25 min after cessation of the stimulus. Hyperoxia resulted in a transient reduction in MSNA burst frequency of 28% (P 0.05) in the three posthypoxia interventions, respectively. Our results suggest that input from the carotid chemoreceptors is obligatory for the sustained elevation of MSNA initiated by chemoreflex stimulation. We attribute the decrease in MSNA to a transient hyperoxia-induced attenuation of carotid chemoreceptor sensitivity.

  20. Recombinant human leptin attenuates stress axis activity in common carp (Cyprinus carpio L.).

    Science.gov (United States)

    Gorissen, Marnix; Bernier, Nicholas J; Manuel, Remy; de Gelder, Stefan; Metz, Juriaan R; Huising, Mark O; Flik, Gert

    2012-08-01

    Proper functioning of the endocrine stress axis requires communication between the stress axis and other regulatory mechanisms. We here describe an intimate interplay between the stress axis and recombinant human leptin (rhLeptin) in a teleostean fish, the common carp Cyprinus carpio. Restraint stress (by netting up to 96h) increased plasma cortisol but did not affect hepatic leptin expression. Perifusion of pituitary glands or head kidneys with rhLeptin revealed direct effects of rhLeptin on both tissues. RhLeptin suppresses basal and CRF-induced ACTH-secretion in a rapid and concentration-dependent manner. The rhLeptin effect persisted for over an hour after administration had been terminated. RhLeptin decreases basal interrenal cortisol secretion in vitro, and by doing so attenuates ACTH-stimulated cortisol production; rhLeptin does not affect interrenal ACTH-sensitivity. Our findings show that the endocrine stress axis activity and leptin are inseparably linked in a teleostean fish, a notion relevant to further our insights in the evolution of leptin physiology in vertebrates. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Verifying the attenuation of earplugs in situ: method validation on human subjects including individualized numerical simulations.

    Science.gov (United States)

    Bockstael, Annelies; Van Renterghem, Timothy; Botteldooren, Dick; D'Haenens, Wendy; Keppler, Hannah; Maes, Leen; Philips, Birgit; Swinnen, Freya; Vinck, Bart

    2009-03-01

    The microphone in real ear (MIRE) protocol allows the assessment of hearing protector's (HPD) attenuation in situ by measuring the difference between the sound pressure outside and inside the ear canal behind the HPD. Custom-made earplugs have been designed with an inner bore to insert the MIRE probe containing two microphones, the reference microphone measuring the sound pressure outside and the measurement microphone registering the sound pressure behind the HPD. Previous research on a head and torso simulator reveals a distinct difference, henceforth called transfer function, between the sound pressure at the MIRE measurement microphone and the sound pressure of interest at the eardrum. In the current study, similar measurements are carried out on humans with an extra microphone to measure the sound pressure at the eardrum. The resulting transfer functions confirm the global frequency dependency found earlier, but also show substantial variability between the ears with respect to the exact frequency and amplitude of the transfer functions' extrema. In addition, finite-difference time-domain numerical models of an ear canal with earplug are developed for each individual ear by including its specific geometrical parameters. This approach leads to a good resemblance between the simulations and their corresponding measurements.

  2. Bed rest attenuates sympathetic and pressor responses to isometric exercise in antigravity leg muscles in humans.

    Science.gov (United States)

    Kamiya, Atsunori; Michikami, Daisaku; Shiozawa, Tomoki; Iwase, Satoshi; Hayano, Junichiro; Kawada, Toru; Sunagawa, Kenji; Mano, Tadaaki

    2004-05-01

    Although spaceflight and bed rest are known to cause muscular atrophy in the antigravity muscles of the legs, the changes in sympathetic and cardiovascular responses to exercises using the atrophied muscles remain unknown. We hypothesized that bed rest would augment sympathetic responses to isometric exercise using antigravity leg muscles in humans. Ten healthy male volunteers were subjected to 14-day 6 degrees head-down bed rest. Before and after bed rest, they performed isometric exercises using leg (plantar flexion) and forearm (handgrip) muscles, followed by 2-min postexercise muscle ischemia (PEMI) that continues to stimulate the muscle metaboreflex. These exercises were sustained to fatigue. We measured muscle sympathetic nerve activity (MSNA) in the contralateral resting leg by microneurography. In both pre- and post-bed-rest exercise tests, exercise intensities were set at 30 and 70% of the maximum voluntary force measured before bed rest. Bed rest attenuated the increase in MSNA in response to fatiguing plantar flexion by approximately 70% at both exercise intensities (both P antigravity leg muscles.

  3. Recombinant human soluble thrombomodulin attenuates FK506-induced endothelial dysfunction through prevention of Akt inactivation.

    Science.gov (United States)

    Eguchi, Ryoji; Fujimori, Yoshihiro; Okada, Masaya; Tamaki, Hiroya; Wakabayashi, Ichiro; Ogawa, Hiroyasu

    2014-04-15

    Thrombomodulin (TM), a transmembrane glycoprotein on vascular endothelial cells, is a naturally occurring anticoagulant. Recombinant human soluble TM (rTM), composed of the extracellular domain of TM, also shows anti-coagulant and anti-inflammatory activity, but the effects of rTM on microangiopathy remain unclear. We reported that FK506 induced endothelial dysfunction through inactivation of Akt and extracellular-regulated kinase 1/2 using a three-dimensional culture blood vessel model. In the present study, we examined the effects of rTM on FK506-induced endothelial dysfunction. We found that rTM suppressed FK506-induced endothelial cell death, but not the breakdown of capillary-like tube structures. rTM prevented FK506-induced inactivation of Akt, but not of extracellular-regulated kinase 1/2. Akt inhibition by LY294002 abrogated the preventive effect of rTM on FK506-induced Akt inactivation and the suppressive effect of rTM on FK506-induced cell death. These results suggest that rTM attenuates FK506-induced endothelial dysfunction through prevention of Akt inactivation. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. DAPK2 Downregulation Associates With Attenuated Adipocyte Autophagic Clearance in Human Obesity.

    Science.gov (United States)

    Soussi, Hedi; Reggio, Sophie; Alili, Rohia; Prado, Cecilia; Mutel, Sonia; Pini, Maria; Rouault, Christine; Clément, Karine; Dugail, Isabelle

    2015-10-01

    Adipose tissue dysfunction in obesity has been linked to low-grade inflammation causing insulin resistance. Transcriptomic studies have identified death-associated protein kinase 2 (DAPK2) among the most strongly downregulated adipose tissue genes in human obesity, but the role of this kinase is unknown. We show that mature adipocytes rather than the stromal vascular cells in adipose tissue mainly expressed DAPK2 and that DAPK2 mRNA in obese patients gradually recovered after bariatric surgery-induced weight loss. DAPK2 mRNA is also downregulated in high-fat diet-induced obese mice. Adenoviral-mediated DAPK2 overexpression in 3T3-L1 adipocytes did not affect lipid droplet size or cell viability but did increase autophagic clearance in nutrient-rich conditions, dependent on protein kinase activity. Conversely, DAPK2 inhibition in human preadipocytes by small interfering RNA decreased LC3-II accumulation rates with lysosome inhibitors. This led us to assess autophagic clearance in adipocytes freshly isolated from subcutaneous adipose tissue of obese patients. Severe reduction in autophagic flux was observed in obese adipocytes compared with control adipocytes, inversely correlated to fat cell lipids. After bariatric surgery, adipocyte autophagic clearance partially recovered proportional to the extent of fat cell size reduction. This study links adipocyte expression of an autophagy-regulating kinase, lysosome-mediated clearance and fat cell lipid accumulation; it demonstrates obesity-related attenuated autophagy in adipocytes, and identifies DAPK2 dependence in this regulation. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  5. Attenuation of food allergy symptoms following treatment with human milk oligosaccharides in a mouse model.

    Science.gov (United States)

    Castillo-Courtade, L; Han, S; Lee, S; Mian, F M; Buck, R; Forsythe, P

    2015-09-01

    The prebiotic nature of human milk oligosaccharides (HMOs) and increasing evidence of direct immunomodulatory effects of these sugars suggest that they may have some therapeutic potential in allergy. Here, we assess the effect of two HMOs, 2'-fucosyllactose and 6'-sialyllactose, on symptomatology and immune responses in an ovalbumin-sensitized mouse model of food allergy. The effects of oral treatment with 2'-fucosyllactose and 6'-sialyllactose on anaphylactic symptoms induced by oral ovalbumin (OVA) challenge in sensitized mice were investigated. Mast cell functions in response to oral HMO treatment were also measured in the passive cutaneous anaphylaxis model, and direct effects on IgE-mediated degranulation of mast cells were assessed. Daily oral treatment with 2'-fucosyllactose or 6'-sialyllactose attenuated food allergy symptoms including diarrhea and hypothermia. Treatment with HMOs also suppressed antigen-induced increases in mouse mast cell protease-1 in serum and mast cell numbers in the intestine. These effects were associated with increases in the CD4(+) CD25(+) IL-10(+) cell populations in the Peyer's patches and mesenteric lymph nodes, while 6'-sialyllactose also induced increased IL-10 and decreased TNF production in antigen-stimulated splenocytes. Both 2'-fucosyllactose and 6'-sialyllactose reduced the passive cutaneous anaphylaxis response, but only 6'-sialyllactose directly inhibited mast cell degranulation in vitro, at high concentrations. Our results suggest that 2'-fucosyllactose and 6'-sialyllactose reduce the symptoms of food allergy through induction of IL-10(+) T regulatory cells and indirect stabilization of mast cells. Thus, human milk oligosaccharides may have therapeutic potential in allergic disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Impact of rotavirus vaccination on child mortality, morbidity, and rotavirus-related hospitalizations in Bolivia.

    Science.gov (United States)

    Inchauste, Lucia; Patzi, Maritza; Halvorsen, Kjetil; Solano, Susana; Montesano, Raul; Iñiguez, Volga

    2017-08-01

    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.

  7. Progesterone receptor membrane component 1 deficiency attenuates growth while promoting chemosensitivity of human endometrial xenograft tumors.

    Science.gov (United States)

    Friel, Anne M; Zhang, Ling; Pru, Cindy A; Clark, Nicole C; McCallum, Melissa L; Blok, Leen J; Shioda, Toshi; Peluso, John J; Rueda, Bo R; Pru, James K

    2015-01-28

    Endometrial cancer is the leading gynecologic cancer in women in the United States with 52,630 women predicted to be diagnosed with the disease in 2014. The objective of this study was to determine if progesterone (P4) receptor membrane component 1 (PGRMC1) influenced endometrial cancer cell viability in response to chemotherapy in vitro and in vivo. A lentiviral-based shRNA knockdown approach was used to generate stable PGRMC1-intact and PGRMC1-deplete Ishikawa endometrial cancer cell lines that also lacked expression of the classical progesterone receptor (PGR). Progesterone treatment inhibited mitosis of PGRMC1-intact, but not PGRMC1-deplete cells, suggesting that PGRMC1 mediates the anti-mitotic actions of P4. To test the hypothesis that PGRMC1 attenuates chemotherapy-induced apoptosis, PGRMC1-intact and PGRMC1-deplete cells were treated in vitro with vehicle, P4 (1 µM), doxorubicin (Dox, 2 µg/ml), or P4 + Dox for 48 h. Doxorubicin treatment of PGRMC1-intact cells resulted in a significant increase in cell death; however, co-treatment with P4 significantly attenuated Dox-induced cell death. This response to P4 was lost in PGRMC1-deplete cells. To extend these observations in vivo, a xenograft model was employed where PGRMC1-intact and PGRMC1-deplete endometrial tumors were generated following subcutaneous and intraperitoneal inoculation of immunocompromised NOD/SCID and nude mice, respectively. Tumors derived from PGRMC1-deplete cells grew slower than tumors from PGRMC1-intact cells. Mice harboring endometrial tumors were then given three treatments of vehicle (1:1 cremophor EL: ethanol + 0.9% saline) or chemotherapy [Paclitaxel (15 mg/kg, i.p.) followed after an interval of 30 minutes by CARBOplatin (50 mg/kg)] at five day intervals. In response to chemotherapy, tumor volume decreased approximately four-fold more in PGRMC1-deplete tumors when compared with PGRMC1-intact control tumors, suggesting that PGRMC1 promotes tumor cell viability

  8. Natural immunity to rotavirus infection in children.

    Science.gov (United States)

    Malik, Jyoti; Bhan, Maharaj K; Ray, Pratima

    2008-08-01

    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.

  9. Complex evolutionary patterns of two rare human G3P[9] rotavirus strains possessing a feline/canine-like H6 genotype on an AU-1-like genotype constellation.

    Science.gov (United States)

    Wang, Yuan-Hong; Pang, Bei-Bei; Zhou, Xuan; Ghosh, Souvik; Tang, Wei-Feng; Peng, Jin-Song; Hu, Quan; Zhou, Dun-Jin; Kobayashi, Nobumichi

    2013-06-01

    The group A rotavirus (RVA) G3P[9] is a rare VP7-VP4 genotype combination, detected occasionally in humans and cats. Other than the prototype G3P[9] strain, RVA/Human- tc/JPN/AU-l/1982/G3P3[9], the whole genomes of only two human G3P[9] RVA strains and two feline G3P[9] 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[9] RVA strains, RVA/Human-tc/CHN/L621/2006/G3P[9] and RVA/Human-wt/CHN/E2451/2011/G3P[9], 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[9] 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[9] 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

  10. Presencia de rotavirus durante un proceso de compostaje. Abonos como vectores de contaminación viral

    Directory of Open Access Journals (Sweden)

    María Mercedes Martínez

    2009-12-01

    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.

  11. Rotavirus infections in Galapagos sea lions.

    Science.gov (United States)

    Coria-Galindo, Elsa; Rangel-Huerta, Emma; Verdugo-Rodríguez, Antonio; Brousset, Dulce; Salazar, Sandie; Padilla-Noriega, Luis

    2009-07-01

    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.

  12. Molecular epideMiology of rotaviruses during rotavirus vaccine introduction in slovenia

    Directory of Open Access Journals (Sweden)

    Andrej Steyer

    2009-08-01

    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[8] 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.

  13. Murine model of rotavirus infection.

    Science.gov (United States)

    Feng, N; Franco, M A; Greenberg, H B

    1997-01-01

    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.

  14. [Universal vaccination for Rotavirus infection control].

    Science.gov (United States)

    Mita, Valentin; Capanna, Alessandra; Gervasi, Giuseppe; Zaratti, Laura; Franco, Elisabetta

    2015-01-01

    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.

  15. [Comparative analysis on clinical manifestations for gastroenteritis caused by norovirus and rotavirus].

    Science.gov (United States)

    Deng, Li; Jia, Li-ying; Qian, Yuan; Chen, Dong-mei; Zhang, You; Zhang, Yan-ling

    2009-04-01

    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.

  16. Evaluating Rotavirus and Norovirus transport processes in standardised and natural soil-water columns experiments

    Science.gov (United States)

    Gamazo, Pablo; Schijven, Jack; Victoria, Matias; Alvareda, Elena; López Tort, Fernando; Ramos, Julián; Lizasoain, Andrés; Sapriza, Gonzalo; Castells, Matias; Colina, Rodney

    2017-04-01

    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.

  17. Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans.

    Science.gov (United States)

    Kox, Matthijs; van Eijk, Lucas T; Zwaag, Jelle; van den Wildenberg, Joanne; Sweep, Fred C G J; van der Hoeven, Johannes G; Pickkers, Peter

    2014-05-20

    Excessive or persistent proinflammatory cytokine production plays a central role in autoimmune diseases. Acute activation of the sympathetic nervous system attenuates the innate immune response. However, both the autonomic nervous system and innate immune system are regarded as systems that cannot be voluntarily influenced. Herein, we evaluated the effects of a training program on the autonomic nervous system and innate immune response. Healthy volunteers were randomized to either the intervention (n = 12) or control group (n = 12). Subjects in the intervention group were trained for 10 d in meditation (third eye meditation), breathing techniques (i.a., cyclic hyperventilation followed by breath retention), and exposure to cold (i.a., immersions in ice cold water). The control group was not trained. Subsequently, all subjects underwent experimental endotoxemia (i.v. administration of 2 ng/kg Escherichia coli endotoxin). In the intervention group, practicing the learned techniques resulted in intermittent respiratory alkalosis and hypoxia resulting in profoundly increased plasma epinephrine levels. In the intervention group, plasma levels of the anti-inflammatory cytokine IL-10 increased more rapidly after endotoxin administration, correlated strongly with preceding epinephrine levels, and were higher. Levels of proinflammatory mediators TNF-α, IL-6, and IL-8 were lower in the intervention group and correlated negatively with IL-10 levels. Finally, flu-like symptoms were lower in the intervention group. In conclusion, we demonstrate that voluntary activation of the sympathetic nervous system results in epinephrine release and subsequent suppression of the innate immune response in humans in vivo. These results could have important implications for the treatment of conditions associated with excessive or persistent inflammation, such as autoimmune diseases.

  18. The Dynamic cerebral autoregulatory adaptive response to noradrenaline is attenuated during systemic inflammation in humans.

    Science.gov (United States)

    Berg, Ronan M G; Plovsing, Ronni R; Bailey, Damian M; Holstein-Rathlou, Niels-Henrik; Møller, Kirsten

    2015-07-01

    Vasopressor support is used widely for maintaining vital organ perfusion pressure in septic shock, with implications for dynamic cerebral autoregulation (dCA). This study investigated whether a noradrenaline-induced steady state increase in mean arterial blood pressure (MAP) would enhance dCA following lipopolysaccharide (LPS) infusion, a human-experimental model of the systemic inflammatory response during early sepsis. The dCA in eight healthy males was examined prior to and during an intended noradrenaline-induced MAP increase of approximately 30 mmHg. This was performed at baseline and repeated after a 4-h intravenous LPS infusion. The assessments of dCA were based on transfer function analysis of spontaneous oscillations between MAP and middle cerebral artery blood flow velocity measured by transcranial Doppler ultrasound in the low frequency range (0.07-0.20 Hz). Prior to LPS, noradrenaline administration was associated with a decrease in gain (1.18 (1.12-1.35) vs 0.93 (0.87-0.97) cm/mmHg per s; P noradrenaline administration changed neither gain (0.91 (0.85-1.01) vs 0.87 (0.81-0.97) cm/mmHg per s; P = 0.46) nor phase (1.10 (1.04-1.30) vs 1.37 (1.23-1.51) radians; P = 0.64). The improvement of dCA to a steady state increase in MAP is attenuated during an LPS-induced systemic inflammatory response. This may suggest that vasopressor treatment with noradrenaline offers no additional neuroprotective effect by enhancing dCA in patients with early sepsis. © 2015 Wiley Publishing Asia Pty Ltd.

  19. Anti-apoptotic activity of human matrix Metalloproteinase-2 attenuates diabetes mellitus.

    Science.gov (United States)

    Nishihama, Kota; Yasuma, Taro; Yano, Yutaka; D' Alessandro-Gabazza, Corina N; Toda, Masaaki; Hinneh, Josephine A; Tonto, Prince Baffour; Takeshita, Atsuro; Totoki, Toshiaki; Mifuji-Moroka, Rumi; Kobayashi, Tetsu; Iwasa, Motoh; Takei, Yoshiyuki; Morser, John; Cann, Isaac; Gabazza, Esteban C

    2018-01-20

    Chronic progression of diabetes is associated with decreased pancreatic islet mass due to apoptosis of β-cells. Patients with diabetes have increased circulating matrix metalloproteinase-2 (MMP2); however, the physiological significance has remained elusive. This study tested the hypothesis that MMP2 inhibits cell apoptosis, including islet β-cells. Samples from diabetic patients and newly developed transgenic mice overexpressing human MMP2 (hMMP2) were harnessed, and diabetes was induced with streptozotocin. Circulating hMMP2 was significantly increased in diabetic patients compared to controls and significantly correlated with the serum C-peptide levels. The diabetic hMMP2 transgenic mice showed significant improvements in glycemia, glucose tolerance and insulin secretion compared to diabetic wild type mice. Importantly, the increased hMMP2 levels in mice correlated with significant reduction in islet β-cell apoptosis compared to wild-type counterparts, and an inhibitor of hMMP2 reversed this mitigating activity against diabetes. The increased activation of Akt and BAD induced by hMMP2 in β-cells compared to controls, links this signaling pathway to the anti-apoptotic activity of hMMP2, a property that was reversible by both an hMMP2 inhibitor and antibody against integrin-β3. Overall, this study demonstrates that increased expression of hMMP2 may attenuate the severity of diabetes by protecting islet β-cells from apoptosis through an integrin-mediated activation of the Akt/BAD pathway. Copyright © 2018. Published by Elsevier Inc.

  20. Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes.

    Science.gov (United States)

    Chien, Shao-Ju; Chen, Te-Chuan; Kuo, Hsing-Chun; Chen, Cheng-Nan; Chang, Shun-Fu

    2015-03-13

    Homocysteine and pro-inflammatory mediators such as cyclooxygenase-2 (COX-2) have been linked to vascular dysfunction and risks of cardiovascular diseases. Fulvic acid (FA), a class of compounds of humic substances, possesses various pharmacological properties. However, the effect of FA on inflammatory responses of the monocytes remains unclear. We investigated the regulatory effect of FA on homocysteine-induced COX-2 expression in human monocytes. Peripheral blood monocytes and U937 cells were used for all experiments. Real-time PCR and ELISA assay were used to analyze the COX-2 mRNA expression and PGE2 secretion, respectively. Specific inhibitors were used to investigate the mechanism of homocysteine-mediating COX-2 mRNA expression and PGE2 secretion. Luciferase assay, transcription factor ELISA, and chromatin immunoprecipitation were used to determine the role of nuclear factor-κB in FA-mediated inhibition of homocysteine effect on monocytes. The results show that pretreating monocytes with FA inhibited the homocysteine-induced COX-2 expression in a dose-dependent manner. Stimulation of U937 monocytes with homocysteine induced rapid increases in the phosphorylation of ERK and JNK; the inhibitor for ERK and JNK attenuated the homocysteine-induced nuclear factor-κB activation and COX-2 expression. Transcription factor ELISA and chromatin immunoprecipitation assays showed that FA blocked the homocysteine-induced increases in the binding activity and in vivo promoter binding of nuclear factor-κB in monocytes. Our findings provide a molecular mechanism by which FA inhibits homocysteine-induced COX-2 expression in monocytes, and a basis for using FA in pharmaceutical therapy against inflammation.

  1. Probiotics and colostrum/milk differentially affect neonatal humoral immune responses to oral rotavirus vaccine.

    Science.gov (United States)

    Chattha, Kuldeep S; Vlasova, Anastasia N; Kandasamy, Sukumar; Esseili, Malak A; Siegismund, Christine; Rajashekara, Gireesh; Saif, Linda J

    2013-04-08

    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.

  2. Rotavirus vaccine and health-care utilization for rotavirus gastroenteritis in Tsu City, Japan.

    Science.gov (United States)

    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

    2016-01-01

    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[8] to G1P[8] and to G2P[4]. 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.

  3. Rotavirus vaccine and health-care utilization for rotavirus gastroenteritis in Tsu City, Japan

    Science.gov (United States)

    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

    2016-01-01

    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[8] to G1P[8] and to G2P[4]. 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

  4. Rotavirus strains in neglected animal species including lambs, goats and camelids.

    Science.gov (United States)

    Papp, Hajnalka; Malik, Yashpal S; Farkas, Szilvia L; Jakab, Ferenc; Martella, Vito; Bányai, Krisztián

    2014-01-01

    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.

  5. ~hift in genomic RNA patterns of human jotaviruses isolated from ...

    African Journals Online (AJOL)

    1991-02-02

    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.

  6. Effect of monovalent rotavirus vaccine on rotavirus disease burden and circulating rotavirus strains among children in Morocco.

    Science.gov (United States)

    Benhafid, Mohammed; Elomari, Nezha; Azzouzi Idrissi, Meryem; Rguig, Ahmed; Gentsch, Jon R; Parashar, Umesh; Elaouad, Rajae

    2015-06-01

    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[4] and G9P[8] 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[4] and G9P[8] 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.

  7. A highly attenuated recombinant human respiratory syncytial virus lacking the G protein induces long-lasting protection in cotton rats.

    Science.gov (United States)

    Widjojoatmodjo, Myra N; Boes, Jolande; van Bers, Marleen; van Remmerden, Yvonne; Roholl, Paul J M; Luytjes, Willem

    2010-06-02

    Respiratory syncytial virus (RSV) is a primary cause of serious lower respiratory tract illness for which there is still no safe and effective vaccine available. Using reverse genetics, recombinant (r)RSV and an rRSV lacking the G gene (DeltaG) were constructed based on a clinical RSV isolate (strain 98-25147-X). Growth of both recombinant viruses was equivalent to that of wild type virus in Vero cells, but was reduced in human epithelial cells like Hep-2. Replication in cotton rat lungs could not be detected for DeltaG, while rRSV was 100-fold attenuated compared to wild type virus. Upon single dose intranasal administration in cotton rats, both recombinant viruses developed high levels of neutralizing antibodies and conferred comparable long-lasting protection against RSV challenge; protection against replication in the lungs lasted at least 147 days and protection against pulmonary inflammation lasted at least 75 days. Collectively, the data indicate that a single dose immunization with the highly attenuated DeltaG as well as the attenuated rRSV conferred long term protection in the cotton rat against subsequent RSV challenge, without inducing vaccine enhanced pathology. Since DeltaG is not likely to revert to a less attenuated phenotype, we plan to evaluate this deletion mutant further and to investigate its potential as a vaccine candidate against RSV infection.

  8. Rotavirus epidemiology before and after vaccine introduction

    Directory of Open Access Journals (Sweden)

    Andrêssa S.F. Assis

    2013-09-01

    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.

  9. Protect Your Child from Rotavirus Disease

    Science.gov (United States)

    ... 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 ...

  10. Rotavirus immune responses and correlates of protection.

    Science.gov (United States)

    Angel, Juana; Franco, Manuel A; Greenberg, Harry B

    2012-08-01

    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.

  11. 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▿

    Science.gov (United States)

    Lou, Fangfei; Neetoo, Hudaa; Li, Junan; Chen, Haiqiang; Li, Jianrong

    2011-01-01

    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

  12. Molecular characterisation of the NSP4 gene of group A human rotavirus G2P[4] strains circulating in São Paulo, Brazil, from 1994 and 2006 to 2010

    Directory of Open Access Journals (Sweden)

    Jéssica Wildgrube Bertol

    2015-09-01

    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[4] 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[4] strains displayed genotype E2; one strain (2.4% displayed genotype E1. These results are consistent with the proposed linkage between VP4/VP7 (G2P[4] 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 G2P[4]E1 strain reinforces the idea that new genotype combinations emerge through reassortment and independent segregation.

  13. Molecular characterisation of the NSP4 gene of group A human rotavirus G2P[4] strains circulating in São Paulo, Brazil, from 1994 and 2006 to 2010.

    Science.gov (United States)

    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

    2015-09-01

    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[4] 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[4] strains displayed genotype E2; one strain (2.4%) displayed genotype E1. These results are consistent with the proposed linkage between VP4/VP7 (G2P[4]) 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 G2P[4]E1 strain reinforces the idea that new genotype combinations emerge through reassortment and independent segregation.

  14. Attenuation of VEGFR-2 expression by sFlt-1 and low oxygen in human placenta.

    Science.gov (United States)

    Nevo, Ori; Lee, Dennis K; Caniggia, Isabella

    2013-01-01

    Vascular endothelial growth factor receptor 2 (VEGFR-2), the primary receptor for VEGF, is crucial for normal endothelial function. sFlt-1, a truncated and soluble form of VEGFR-1 which binds and inhibits VEGF, is increased in preeclampsia and is positively regulated by low oxygen. Here, we investigated the effects of sFlt-1 and hypoxia on VEGFR-2 expression and signaling in the human placenta. VEGFR-2 transcript and protein levels were significantly decreased in preeclamptic placentae compared to controls (1.82 and 1.85 fold, respectively). An inverse correlation was observed for VEGFR-2 and sFlt-1 levels in both singleton and twin placentae from patients with preeclampsia. Immunofluorescence analyses revealed co-localization of VEGFR-2 and sFlt-1 in placental vasculature and co-immunoprecipitation analyses confirmed VEGFR-2 and sFlt-1 interaction only in preeclamptic placentae compared to age-matched controls. VEGFR-2 transcript and protein levels from explants cultured in 3% O2 were significantly decreased compared to those incubated at 20% O2 (5.9 and 12.47 fold, respectively). Also, VEGFR-2 transcript levels were significantly decreased in early first trimester placentae (low oxygen environment) compared to late first trimester placentae (2.05 fold). We next explored whether sFlt-1 directly affects VEGFR-2 expression. Treatment of first trimester placental explants with sFlt-1 resulted in significantly decreased levels of VEGFR-2 (2.03 fold) and downstream signaling proteins phospho-ERK (1.60 fold) and phospho-Akt (1.64 fold). Our findings show a novel hypoxia-induced and PE-related down-regulation of VEGFR-2 in the human placenta. sFlt-1, which is known to be increased in hypoxic conditions and PE, directly attenuates VEGFR-2 expression and signaling. A direct interaction between sFlt-1 and VEGFR-2 may represent an important mechanism in VEGFR-2 regulation, inhibition of VEGFR-2-mediated processes in placentation and a novel platform to examine the onset of

  15. Experimental reproduction of rotavirus and Salmonella pullorum ...

    African Journals Online (AJOL)

    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 ...

  16. Rotavirus immune responses and correlates of protection

    OpenAIRE

    Angel, Juana; Franco, Manuel A.; Greenberg, Harry B.

    2012-01-01

    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...

  17. Attenuated Human Parainfluenza Virus Type 1 Expressing Ebola Virus Glycoprotein GP Administered Intranasally Is Immunogenic in African Green Monkeys.

    Science.gov (United States)

    Lingemann, Matthias; Liu, Xueqiao; Surman, Sonja; Liang, Bo; Herbert, Richard; Hackenberg, Ashley D; Buchholz, Ursula J; Collins, Peter L; Munir, Shirin

    2017-05-15

    The recent 2014-2016 Ebola virus (EBOV) outbreak prompted increased efforts to develop vaccines against EBOV disease. We describe the development and preclinical evaluation of an attenuated recombinant human parainfluenza virus type 1 (rHPIV1) expressing the membrane-anchored form of EBOV glycoprotein GP, as an intranasal (i.n.) EBOV vaccine. GP was codon optimized and expressed either as a full-length protein or as an engineered chimeric form in which its transmembrane and cytoplasmic tail (TMCT) domains were replaced with those of the HPIV1 F protein in an effort to enhance packaging into the vector particle and immunogenicity. GP was inserted either preceding the N gene (pre-N) or between the N and P genes (N-P) of rHPIV1 bearing a stabilized attenuating mutation in the P/C gene (CΔ170). The constructs grew to high titers and efficiently and stably expressed GP. Viruses were attenuated, replicating at low titers over several days, in the respiratory tract of African green monkeys (AGMs). Two doses of candidates expressing GP from the pre-N position elicited higher GP neutralizing serum antibody titers than the N-P viruses, and unmodified GP induced higher levels than its TMCT counterpart. Unmodified EBOV GP was packaged into the HPIV1 particle, and the TMCT modification did not increase packaging or immunogenicity but rather reduced the stability of GP expression during in vivo replication. In conclusion, we identified an attenuated and immunogenic i.n. vaccine candidate expressing GP from the pre-N position. It is expected to be well tolerated in humans and is available for clinical evaluation.IMPORTANCE EBOV hemorrhagic fever is one of the most lethal viral infections and lacks a licensed vaccine. Contact of fluids from infected individuals, including droplets or aerosols, with mucosal surfaces is an important route of EBOV spread during a natural outbreak, and aerosols also might be exploited for intentional virus spread. Therefore, vaccines that protect

  18. Dynamic model of rotavirus transmission and the impact of rotavirus vaccination in Kyrgyzstan.

    Science.gov (United States)

    de Blasio, Birgitte Freiesleben; Kasymbekova, Kaliya; Flem, Elmira

    2010-11-23

    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.

  19. Impact of rotavirus vaccination on child mortality, morbidity, and rotavirus-related hospitalizations in Bolivia

    Directory of Open Access Journals (Sweden)

    Lucia Inchauste

    2017-08-01

    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.

  20. Australian Rotavirus Surveillance Program annual report, 2012.

    Science.gov (United States)

    Kirkwood, Carl D; Roczo-Farkas, Susie; Bishop, Ruth F; Barnes, Graeme L

    2014-03-31

    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[8] was the dominant type in this reporting period, identified in 35% of strains nationally. Genotype G2P[4] was the second most common strain nationally, representing 28% of samples, followed by genotype G12P[8] (23%). This represents the first report where G12P[8] 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[4] was more common in states and territories using Rotarix while G1P[8] 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. copyright@health.gov.au

  1. Epigallocatechin-3-gallate attenuates the AIM2-induced secretion of IL-1β in human epidermal keratinocytes.

    Science.gov (United States)

    Yun, Mihee; Seo, Gimoon; Lee, Ji-Young; Chae, Gue Tae; Lee, Seong-Beom

    2015-11-27

    The pro-inflammatory cytokine interleukin-1β (IL-1β) plays a central role in the pathogenesis of psoriasis. Keratinocytes are a major source of IL-1β and express absent in melanoma 2 (AIM2). AIM2 recognizes a double-stranded DNA and initiates the IL-1β-processing of inflammasome. The AIM2 inflammasome is a cytosolic multiprotein complex composed of AIM2, an apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1. Epigallocatechin-3-Gallate (EGCG), a major polyphenolic component of green tea, has anti-inflammatory properties. In the current study, we investigated the issue of whether or how EGCG suppresses AIM2 inflammasome in human epidermal keratinocytes, neonatal (HEKn). Treatment with EGCG, before or after IFN-γ priming, attenuated poly(dA:dT)-induced IL-1β secretion in HEKn cells. Pre-treatment with EGCG reduced the level of IFN-γ-induced priming signal via the down-regulation of pro-IL-1β and pro-capspase-1 in HEKn cells. Furthermore, treatment with EGCG attenuated poly(dA:dT)-induced ASC oligomerization and caspase-1 activation in IFN-γ-primed HEKn cells. These results suggest that EGCG attenuates AIM2-induced IL-1β secretion by suppressing both IFN-γ-mediated priming and poly(dA:dT)-induced ASC oligomerization of inflammasomes in human epidermal keratinocytes. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. NF-kB signalling is attenuated by the E7 protein from cutaneous human papillomaviruses

    DEFF Research Database (Denmark)

    Byg, Luise M; Stensson, Jessica; Vasiljevic, Natasa

    2012-01-01

    -¿B pathway leading to an attenuation of the activity. There is a possible link between development of non melanoma skin cancer and cutaneous Beta-papillomavirus but if these HPV types attenuate the NF-¿B pathway is unclear. Seven different E7 proteins, representing four out of the five different species....... In addition, E7 proteins from the cutaneous HPV types demonstrated interaction with IKKa but not with IKKß. The deregulation of the NF-¿B pathway by cutaneous HPVs might contribute to the pathogenesis of non-melanoma skin cancers and its precursors....

  3. Rotavirus Disease Mechanisms Diarrhea, Vomiting and Inflammation : How and Why

    OpenAIRE

    Hagbom, Marie

    2015-01-01

    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...

  4. Group A Rotavirus Associated with Encephalitis in Red Fox.

    Science.gov (United States)

    Busi, Chiara; Martella, Vito; Papetti, Alice; Sabelli, Cristiano; Lelli, Davide; Alborali, G Loris; Gibelli, Lucia; Gelmetti, Daniela; Lavazza, Antonio; Cordioli, Paolo; Boniotti, M Beatrice

    2017-09-01

    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.

  5. Molecular characterisation of the rotavirus strains prevalent in Maua ...

    African Journals Online (AJOL)

    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 ...

  6. Frequency of Rotavirus Infection among Children with Diarrhea in ...

    African Journals Online (AJOL)

    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 ...

  7. Prevalence of rotavirus infections and strain types detected among ...

    African Journals Online (AJOL)

    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.

  8. Epidemiology of rotavirus diarrhea in children under 5 years in ...

    African Journals Online (AJOL)

    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 ...

  9. Longitudinal Studies of Neutralizing Antibody Responses to Rotavirus in Stools and Sera of Children following Severe Rotavirus Gastroenteritis

    OpenAIRE

    Coulson, Barbara S.

    1998-01-01

    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...

  10. Australian Rotavirus Surveillance Program annual report, 2014.

    Science.gov (United States)

    Kirkwood, Carl D; Roczo-Farkas, Suzie

    2015-09-30

    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[8] was the dominant genotype in this reporting period, identified in 29.6% of strains nationally. Genotype G1P[8] was the 2nd most common strain nationally, representing 22.9% of samples, followed by genotype G3P[8] (14.9%). This report highlights the continued significance of G12P[8] 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[8] being the dominant genotype (29%) followed by G12P[8] as the 2nd most common genotype (26%). Fluctuations in genotype distribution were also observed based on the vaccine type in use. Genotype G12P[8] was more common in states and territories using RotaTeq, while G1P[8] 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[8] 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.

  11. Antiviral effects of Lactobacillus ruminis SPM0211 and Bifidobacterium longum SPM1205 and SPM1206 on rotavirus-infected Caco-2 cells and a neonatal mouse model.

    Science.gov (United States)

    Kang, Joo Yeon; Lee, Do Kyung; Ha, Nam Joo; Shin, Hea Soon

    2015-11-01

    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.

  12. Molecular characterization of rotavirus isolated from alpaca (Vicugna pacos) crias with diarrhea in the Andean Region of Cusco, Peru.

    Science.gov (United States)

    Garmendia, Antonio E; Lopez, Wellington; Ortega, Nastassja; Chamorro, Marycris J

    2015-10-22

    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.

  13. Hospital-based surveillance and analysis of genotype variation in Nicaragua after the introduction of the pentavalent rotavirus vaccine.

    Science.gov (United States)

    Khawaja, Shazia; Cardellino, Anna; Mast, T Christopher

    2014-01-01

    A live, attenuated, pentavalent rotavirus vaccine (RV5) was introduced in Nicaragua in 2006 through a 3-year partnership between Merck & Co, Inc., and the Nicaraguan Ministry of Health. Nicaragua was the first developing nation to include rotavirus vaccine in its national childhood vaccine program. To monitor the possibility of changing circulating rotavirus strains after the introduction of RV5, we determined the genotypes responsible for rotavirus gastroenteritis-related hospitalization during the first 3 postvaccine years. Stool samples were collected from children with acute gastroenteritis who presented to any of 6 participating hospitals within 7-14 days of symptom onset. Samples positive for rotavirus antigen were analyzed for P and G genotypes using a reverse transcription polymerase chain reaction method. Overall, the predominant strains were G2P[4] (41.5%), G1P[8] (40.6%), G4P[8] (5.1%) and G3P[8] (4.7%). Strain predominance varied by season. During the 2007 season, G4P[8] (53.2%) and G2P[4] (40.5%) predominated. In the 2008 season, G2P[4] (77.9%) and G1P[8] (12.6%) were predominant, while in the 2009 season, G1P[8] (79.3%) and G3P[8] (7.8%) were predominant. No new or unexpected strains were predominant in the years immediately following the introduction of RV5 into Nicaragua. RV5 does not appear to have substantially altered the historical pattern of seasonal fluctuation in rotavirus genotypes.

  14. B vitamins attenuate the epigenetic effects of ambient fine particles in a pilot human intervention trial

    OpenAIRE

    Zhong, Jia; Karlsson, Oskar; Wang, Guan; Li, Jun; Guo, Yichen; Lin, Xinyi; Zemplenyi, Michele; Sanchez-Guerra, Marco; Trevisi, Letizia; Urch, Bruce; Speck, Mary; Liang, Liming; Coull, Brent A; Koutrakis, Petros; Silverman, Frances

    2017-01-01

    Air pollution is a major public health concern worldwide. The molecular mechanistic underpinnings of the health effects of air pollution are not fully understood, and the lack of individual-level preventative options represent a critical knowledge gap. Our study demonstrated the epigenetic effects of air pollution and suggested that B vitamins might be used as prevention to complement regulations to attenuate the impact of air pollution on the epigenome. Our study inaugurated a line of resear...

  15. Effect of rotavirus vaccine on diarrhea mortality in different socioeconomic regions of Mexico.

    Science.gov (United States)

    Gastañaduy, Paul A; Sánchez-Uribe, Edgar; Esparza-Aguilar, Marcelino; Desai, Rishi; Parashar, Umesh D; Patel, Manish; Richardson, Vesta

    2013-04-01

    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.

  16. Prolyl Oligopeptidase Inhibition Attenuates Steatosis in the L02 Human Liver Cell Line.

    Directory of Open Access Journals (Sweden)

    Da Zhou

    Full Text Available Prolyl oligopeptidase (POP is a serine endopeptidase that is widely distributed in vivo, particularly in the liver. Significant changes in functional mitochondrial proteins involved with mitochondrial oxidoreductases/transporters and nucleic acid binding proteins were observed after POP inhibition in the liver, which suggested a role of POP in regulating liver energy metabolism. Steatosis in nonalcoholic fatty liver disease (NAFLD is associated with disturbances in lipid and energy metabolism in hepatocytes. Here, we aimed to study the effect of POP on hepatocyte steatosis.The human liver cell line L02 was used to investigate the biological effects of POP. An in vitro cell model of steatosis was successfully induced with oleic acid and palmitic acid. L02 cells were also subjected to S17092 (a POP inhibitor at different concentrations for 24 or 48 h. Ac-SDKP levels and POP activity were measured to assess the rate of inhibition of POP by S17092. The POP gene and protein expression levels were detected using real-time PCR and Western blots, respectively. Oil red O staining was performed and the triglyceride levels in the L02 cells were also measured. Cell proliferation and apoptosis were detected using CCK-8 and flow cytometry, respectively. The expression of genes involved in lipid metabolism was detected using real-time PCR. The effects of POP inhibition on LC3B II were detected by Western blot.Compared with the control, the POP mRNA levels increased by approximately 30%, and the POP protein levels increased by almost 60% in the steatotic L02 cells. After S17092 (0.026~130 μM incubation for 24 or 48 h, cell proliferation was significantly decreased in the free fatty acid (FFA-treated cells at 26-130 μM; however, S17092 did not affect the proliferation of L02 cells after 24 h of incubation with S17092 at 0.026-65 μM without FFA treatment. S17092 treatment (13 and 26 μM also elicited no significant effect on apoptosis in normal L02 cells, but

  17. Analysis of rotavirus antigenemia and extraintestinal manifestations in children with rotavirus gastroenteritis.

    Science.gov (United States)

    Sugata, Ken; Taniguchi, Koki; Yui, Akiko; Miyake, Fumi; Suga, Sadao; Asano, Yoshizo; Ohashi, Masahiro; Suzuki, Kyoko; Nishimura, Naoko; Ozaki, Takao; Yoshikawa, Tetsushi

    2008-08-01

    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.

  18. Scoring system to distinguish between rotavirus and non-rotavirus diarrhea in children

    Directory of Open Access Journals (Sweden)

    Atika Akbari

    2017-01-01

    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.

  19. Rotavirus vaccination within the South African Expanded Programme on Immunisation.

    Science.gov (United States)

    Seheri, L Mapaseka; Page, Nicola A; Mawela, Mothahadini P B; Mphahlele, M Jeffrey; Steele, A Duncan

    2012-09-07

    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.

  20. Rotavirus genotypes in Malaysia and Universal rotavirus vaccination

    Science.gov (United States)

    Lee, Way Seah; Lim, Benjamin Tze Ying; Chai, Pei Fan; Kirkwood, Carl D.; Lee, Jimmy Kok Foo

    2012-01-01

    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

  1. Full-length genome analysis of G2, G9 and G11 porcine group A rotaviruses.

    Science.gov (United States)

    Martel-Paradis, Olivier; Laurin, Marc-André; Martella, Vito; Sohal, Jagdip Singh; L'Homme, Yvan

    2013-02-22

    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[34] 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[5]. 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.

  2. Incidence of rotavirus gastroenteritis by age in African, Asian and European children: Relevance for timing of rotavirus vaccination

    Science.gov (United States)

    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

    2016-01-01

    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

  3. Identification of G8 rotavirus strains determined as G12 by rotavirus genotyping PCR: updating the current genotyping methods.

    Science.gov (United States)

    Aladin, Farah; Nawaz, Sameena; Iturriza-Gómara, Miren; Gray, Jim

    2010-04-01

    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[8], G2P[4] and G9P[8] 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.

  4. Molecular analysis of group A rotaviruses detected in adults and adolescents with severe acute gastroenteritis in Italy in 2012.

    Science.gov (United States)

    Ianiro, Giovanni; Delogu, Roberto; Bonomo, Paolo; Fiore, Lucia; Ruggeri, Franco M

    2014-06-01

    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[8], G2P[4], G4P[8], and G9P[8], except an uncommon G3P[19] 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.

  5. Healthy aging attenuates task-related specialization in the human medial temporal lobe

    DEFF Research Database (Denmark)

    Ramsøy, Thomas Z.; Liptrot, Matthew George; Skimminge, Arnold Jesper Møller

    2012-01-01

    of task related changes in the blood oxygen level-dependent (BOLD) signal was performed in native space after correction for gender effects and individual differences in cerebral blood flow. The hippocampus, amygdala, and parahippocampal, perirhinal, entorhinal, and temporopolar cortices of right and left...... prominent in the recognition stage. During recognition, the larger response to objects gradually decreased with age in all ROIs apart from left temporopolar and entorhinal cortex. An age-related attenuation was also present during encoding, but only in right parahippocampus and amygdala. Our results suggest...

  6. Human β-defensin-2 production upon viral and bacterial co-infection is attenuated in COPD.

    Science.gov (United States)

    Arnason, Jason W; Murphy, James C; Kooi, Cora; Wiehler, Shahina; Traves, Suzanne L; Shelfoon, Christopher; Maciejewski, Barbara; Dumonceaux, Curtis J; Lewenza, W Shawn; Proud, David; Leigh, Richard

    2017-01-01

    Viral-bacterial co-infections are associated with severe exacerbations of COPD. Epithelial antimicrobial peptides, including human β-defensin-2 (HBD-2), are integral to innate host defenses. In this study, we examined how co-infection of airway epithelial cells with rhinovirus and Pseudomonas aeruginosa modulates HBD-2 expression, and whether these responses are attenuated by cigarette smoke and in epithelial cells obtained by bronchial brushings from smokers with normal lung function or from COPD patients. When human airway epithelial cells from normal lungs were infected with rhinovirus, Pseudomonas aeruginosa, or the combination, co-infection with rhinovirus and bacteria resulted in synergistic induction of HBD-2 (peffects of Pseudomonas aeruginosa were mediated via interactions of flagellin with TLR5. The effects of HRV-16 depended upon viral replication but did not appear to be mediated via the intracellular RNA helicases, retinoic acid-inducible gene-I or melanoma differentiation-associated gene-5. Cigarette smoke extract significantly decreased HBD-2 production in response to co-infection. Attenuated production was also observed following co-infection of cells obtained from healthy smokers or COPD patients compared to healthy controls (pexposure to HRV-16 and Pseudomonas aeruginosa induces synergistic production of HBD-2 from epithelial cells and that this synergistic induction of HBD-2 is reduced in COPD patients. This may contribute to the more severe exacerbations these patients experience in response to viral-bacterial co-infections.

  7. Attenuated Human Parainfluenza Virus Type 1 (HPIV1) Expressing the Fusion Glycoprotein of Human Respiratory Syncytial Virus (RSV) as a Bivalent HPIV1/RSV Vaccine

    Science.gov (United States)

    Mackow, Natalie; Amaro-Carambot, Emérito; Liang, Bo; Surman, Sonja; Lingemann, Matthias; Yang, Lijuan; Collins, Peter L.

    2015-01-01

    ABSTRACT Live attenuated recombinant human parainfluenza virus type 1 (rHPIV1) was investigated as a vector to express the respiratory syncytial virus (RSV) fusion (F) glycoprotein, to provide a bivalent vaccine against RSV and HPIV1. The RSV F gene was engineered to include HPIV1 transcription signals and inserted individually into three gene locations in each of the two attenuated rHPIV1 backbones. Each backbone contained a single previously described attenuating mutation that was stabilized against deattenuation, specifically, a non-temperature-sensitive deletion mutation involving 6 nucleotides in the overlapping P/C open reading frames (ORFs) (CΔ170) or a temperature-sensitive missense mutation in the L ORF (LY942A). The insertion sites in the genome were pre-N (F1), N-P (F2), or P-M (F3) and were identical for both backbones. In vitro, the presence of the F insert reduced the rate of virus replication, but the final titers were the same as the final titer of wild-type (wt) HPIV1. High levels of RSV F expression in cultured cells were observed with rHPIV1-CΔ170-F1, -F2, and -F3 and rHPIV1-LY942A-F1. In hamsters, the rHPIV1-CΔ170-F1, -F2, and -F3 vectors were moderately restricted in the nasal turbinates, highly restricted in lungs, and genetically stable in vivo. Among the CΔ170 vectors, the F1 virus was the most immunogenic and protective against wt RSV challenge. The rHPIV1-LY942A vectors were highly restricted in vivo and were not detectably immunogenic or protective, indicative of overattenuation. The CΔ170-F1 construct appears to be suitably attenuated and immunogenic for further development as a bivalent intranasal pediatric vaccine. IMPORTANCE There are no vaccines for the pediatric respiratory pathogens RSV and HPIV. We are developing live attenuated RSV and HPIV vaccines for use in virus-naive infants. Live attenuated RSV strains in particular are difficult to develop due to their poor growth and physical instability, but these obstacles could be

  8. Prevalence of rotavirus, norovirus and enterovirus in diarrheal diseases in Himachal Pradesh, India.

    Science.gov (United States)

    Jain, Swapnil; Thakur, Nutan; Grover, Neelam; Vashistt, Jitendraa; Changotra, Harish

    2016-03-01

    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.

  9. A waterborne outbreak of epidemic diarrhea due to group A rotavirus in Malatya, Turkey.

    Science.gov (United States)

    Koroglu, Mehmet; Yakupogullari, Yusuf; Otlu, Baris; Ozturk, Serhat; Ozden, Mehmet; Ozer, Ali; Sener, Kemal; Durmaz, Riza

    2011-01-01

    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.

  10. Molecular characterization of group A rotavirus isolates obtained from hospitalized children in Salvador, Bahia, Brazil

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    Karina Serravalle

    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[8] 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.

  11. Nicotinamide attenuates aquaporin 3 overexpression induced by retinoic acid through inhibition of EGFR/ERK in cultured human skin keratinocytes.

    Science.gov (United States)

    Song, Xiuzu; Xu, Aie; Pan, Wei; Wallin, Brittany; Kivlin, Rebecca; Lu, Shan; Cao, Cong; Bi, Zhigang; Wan, Yinsheng

    2008-08-01

    The most common adverse effects that are related to all-trans retinoic acid (atRA) treatment are irritation and dryness of the skin. atRA therapy is reported to impair barrier function as achieved by trans-epidermal water loss (TEWL). Treatment with nicotinamide prior to initiation of atRA therapy provides additional barrier protection and thus reduces susceptibility of retinoic acid. Our previous studies showed that atRA upregulates aquaporin 3 (AQP3) in cultured human skin keratinocytes and fibroblasts. Others have demonstrated that in atopic dermatitis, overexpression of AQP3 is linked to elevated TEWL and that nicotinamide treatment reduces skin TEWL. In this study, we observed that while atRA upregulates AQP3 expression in cultured human skin keratinocytes (HaCaT cells), nicotinamide attenuates the effect of atRA in a concentration-dependent manner. atRA treatment induces EGFR and ERK activation. PD153035, an EGFR inhibitor, and U0126, an ERK inhibitor, inhibit atRA-induced upregulation of AQP3. Nicotinamide also inhibits atRA-induced activation of EGFR/ERK signal transduction and decreases water permeability by downregulating AQP3 expression. Collectively, our results indicate that the effect of atRA on AQP3 expression is at least partly mediated by EGFR/ERK signaling in cultured human skin keratinocytes. Nicotinamide attenuates atRA-induced AQP3 expression through inhibition of EGFR/ERK signal transduction and eventually decreases water permeability and water loss. Our study provides insights into the molecular mechanism through which nicotinamide reverses the side effects of dryness in human skin after treatment with atRA.

  12. Attenuation by a Human Body and Trees as well as Material Penetration Loss in 26 and 39 GHz Millimeter Wave Bands

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    Qi Wang

    2017-01-01

    Full Text Available This paper investigates the attenuation by a human body and trees as well as material penetration loss at 26 and 39 GHz by measurements and theoretical modeling work. The measurements were carried out at a large restaurant and a university campus by using a time domain channel sounder. Meanwhile, the knife-edge (KE model and one-cylinder and two-cylinder models based on uniform theory of diffraction (UTD are applied to model the shape of a human body and predict its attenuation in theory. The ITU (International Telecommunication Union and its modified models are used to predict the attenuation by trees. The results show that the upper bound of the KE model is better to predict the attenuation by a human body compared with UTD one-cylinder and two-cylinder models at both 26 and 39 GHz. ITU model overestimates the attenuation by willow trees, and a modified attenuation model by trees is proposed based on our measurements at 26 GHz. Penetration loss for materials such as wood and glass with different types and thicknesses is measured as well. The measurement and modeling results in this paper are significant and necessary for simulation and planning of fifth-generation (5G mm-wave radio systems in ITU recommended frequency bands at 26 and 39 GHz.

  13. Incidence of rotavirus and circulating genotypes in Northeast Brazil during 7 years of national rotavirus vaccination.

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    Ricardo Q Gurgel

    Full Text Available BACKGROUND AND AIMS: Rotavirus causes severe diarrhoea and Brazil introduced the Rotarix G1P[8] 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[4]; except in 2009, when most cases were G1P[8]. Very few G2P[4] were detected from 2011 and 50% cases in 2012 were G8P[4]. 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[4] genotype predominance disappeared over time and may be replaced by other heterotypic genotypes.

  14. Molecular characterization of rotavirus isolates from select Canadian pediatric hospitals

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    McDermid Andrew

    2012-11-01

    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[8], 45 were G3P[8], 22 were G2P[4], 13 were G9P[8], 3 were G4P[8] and 2 were G9P[4]. 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.

  15. Molecular characterization of rotavirus isolates from select Canadian pediatric hospitals

    Science.gov (United States)

    2012-01-01

    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[8], 45 were G3P[8], 22 were G2P[4], 13 were G9P[8], 3 were G4P[8] and 2 were G9P[4]. 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

  16. The Dynamic cerebral autoregulatory adaptive response to noradrenaline is attenuated during systemic inflammation in humans

    DEFF Research Database (Denmark)

    Berg, Ronan M. G.; Plovsing, Ronni R.; Bailey, Damian M.

    2015-01-01

    , noradrenaline administration was associated with a decrease in gain (1.18 (1.12-1.35) vs 0.93 (0.87-0.97) cm/mmHg per s; P radians; P = 0.58). After LPS, noradrenaline administration changed neither gain (0.91 (0.85-1.01) vs 0.87 (0.......81-0.97) cm/mmHg per s; P = 0.46) nor phase (1.10 (1.04-1.30) vs 1.37 (1.23-1.51) radians; P = 0.64). The improvement of dCA to a steady state increase in MAP is attenuated during an LPS-induced systemic inflammatory response. This may suggest that vasopressor treatment with noradrenaline offers no additional...

  17. Propofol attenuates high glucose-induced superoxide anion accumulation in human umbilical vein endothelial cells.

    Science.gov (United States)

    Wang, Jiaqiang; Jiang, Hui; Wang, Jing; Zhao, Yanjun; Zhu, Yun; Zhu, Minmin

    2016-12-01

    Perioperative hyperglycemia is a common clinical metabolic disorder. Hyperglycemia could induce endothelial apoptosis, dysfunction, and inflammation, resulting in endothelial injury. Propofol is a widely used anesthetic drug in clinical settings. Our previous studies indicated that propofol attenuated high glucose-induced endothelial apoptosis, dysfunction, and inflammation via inhibiting reactive oxygen species (ROS) accumulation. However, the mechanisms by which propofol reduces high glucose-induced endothelial ROS accumulation are still obscure. In this study, we examined how propofol attenuates high glucose-induced endothelial ROS accumulation. Compared with 5 mm glucose treatment, 15 mm glucose upregulated the expression of pin-1, phosphatase A2 (PP2A), p66shc and mitochondrial p66shc expression, increased p66shc -Ser36 phosphorylation, and O2·- accumulation. More importantly, although propofol had no effect on 15 mm glucose-induced p66shc -Ser36 phosphorylation and pin-1 expression, propofol could downregulated PP2A expression and p66shc expression in whole-cell and mitochondrion, resulting in the reduction of O2·- accumulation. Moreover, we demonstrated that the antioxidative effect of propofol was similar to that of calyculin A, an inhibitor of PP2A. In contrast, FTY720, an activator of PP2A, antagonized the effect of propofol. Our data indicated that the antioxidative effect of propofol was achieved by downregulating PP2A expression, resulting in the inhibition of p66shc -Ser36 dephosphorylation and mitochondrial p66shc expression. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  18. Lycopene attenuates Aβ1-42 secretion and its toxicity in human cell and Caenorhabditis elegans models of Alzheimer disease.

    Science.gov (United States)

    Chen, Wei; Mao, Liuqun; Xing, Huanhuan; Xu, Lei; Fu, Xiang; Huang, Liyingzi; Huang, Dongling; Pu, Zhijun; Li, Qinghua

    2015-11-03

    Growing evidence suggests concentration of lycopene was reduced in plasma of patients with Alzheimer disease (AD). Lycopene, a member of the carotenoid family, has been identified as an antioxidant to attenuate oxidative damage and has neuroprotective role in several AD models. However, whether lycopene is involved in the pathogenesis of AD and molecular underpinnings are elusive. In this study, we found that lycopene can significantly delay paralysis in the Aβ1-42-transgenic Caenorhabditis elegans strain GMC101. Lycopene treatment reduced Aβ1-42 secretion in SH-SY5Y cells overexpressing the Swedish mutant form of human β-amyloid precursor protein (APPsw). Next, we found lycopene can down-regulate expression level of β-amyloid precursor protein(APP) in APPsw cells. Moreover, lycopene treatment can not change endogenous reactive oxygen species level and apoptosis in APPsw cells. However, lycopene treatment protected against H2O2-induced oxidative stress and copper-induced damage in APPsw cells. Collectively, our data support that elevated lycopene contributes to the lower pathogenesis of AD. Our findings suggest that increasing lycopene in neurons may be a novel approach to attenuate onset and development of AD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. The presence of a dog attenuates cortisol and heart rate in the Trier Social Stress Test compared to human friends.

    Science.gov (United States)

    Polheber, John P; Matchock, Robert L

    2014-10-01

    Limited research has addressed how social support in the form of a pet can affect both sympathetic and hypothalamic-pituitary-adrenal reactivity in response to a psychological challenge. The present study examined the effects of social support on salivary cortisol and heart rate (HR). Forty-eight participants were randomly assigned to three different conditions (human friend, novel dog, or control). All participants completed the Trier Social Stress Test and provided cortisol, HR, and State-Trait Anxiety Inventory measures. For participants paired with a dog, overall cortisol levels were attenuated throughout the experimental procedure, and HR was attenuated during the Trier Social Stress Test. For all groups, state anxiety increased after the Trier Social Stress Test, and HR during the Trier Social Stress Test was a predictor of cortisol. These results suggest that short-term exposure to a novel dog in an unfamiliar setting can be beneficial. They also suggest a possible mechanism for the beneficial effect associated with affiliation with pets.

  20. Rotavirus vaccine AVANT/GlaxoSmithKline.

    Science.gov (United States)

    Jones, T

    2001-07-01

    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 [328635], [333677]. Following a licensing agreement, the vaccine was refined and renamed RIX-4414 [371713]. 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 [365202]. 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 [358963]. 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 [411122].

  1. WHO working group on the quality, safety and efficacy of japanese encephalitis vaccines (live attenuated) for human use, Bangkok, Thailand, 21-23 February 2012.

    Science.gov (United States)

    Trent, Dennis W; Minor, Philip; Jivapaisarnpong, Teeranart; Shin, Jinho

    2013-11-01

    Japanese encephalitis (JE) is one of the most important viral encephalitides in Asia. Two live-attenuated vaccines have been developed and licensed for use in countries in the region. Given the advancement of immunization of humans with increasing use of live-attenuated vaccines to prevent JE, there is increased interest to define quality standards for their manufacture, testing, nonclinical studies, and clinical studies to assess their efficacy and safety in humans. To this end, WHO convened a meeting with a group of international experts in February 2012 to develop guidelines for evaluating the quality, safety and efficacy of live-attenuated JE virus vaccines for prevention of human disease. This report summarizes collective views of the participants on scientific and technical issues that need to be considered in the guidelines. Copyright © 2013. Published by Elsevier Ltd.. All rights reserved.

  2. Distribution of rotavirus G and P genotypes approximately two years following the introduction of rotavirus vaccines in South Korea.

    Science.gov (United States)

    Shim, Jung Ok; Thai Than, Van; Ryoo, Eell; Lim, Inseok; Yoon, Yoosik; Kim, Kijeong; Chung, Sang-In; Kim, Wonyong

    2013-07-01

    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[8] (72.6%), followed by P[6] (19.1%) and P[4] (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.

  3. Effectiveness of rotavirus vaccine against hospitalized rotavirus diarrhea: A case-control study.

    Science.gov (United States)

    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

    2014-05-13

    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[8] 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[4] and in 15% G1P[8]. Genotype-specific VE (two doses) was 89% (95%CI: 78-95), for G1P[8] and 76% (95%CI: 64-84) for G2P[4]. 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[8] and G2P[4]. 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.

  4. Pronóstico de la diarrea por rotavirus Prognosis of rotavirus diarrhea

    Directory of Open Access Journals (Sweden)

    Felipe Mota-Hernández

    2001-12-01

    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

  5. Gene deleted live attenuated Leishmania vaccine candidates against visceral leishmaniasis elicit pro-inflammatory cytokines response in human PBMCs.

    Science.gov (United States)

    Avishek, Kumar; Kaushal, Himanshu; Gannavaram, Sreenivas; Dey, Ranadhir; Selvapandiyan, Angamuthu; Ramesh, V; Negi, Narender Singh; Dubey, Uma S; Nakhasi, Hira L; Salotra, Poonam

    2016-09-14

    Currently no effective vaccine is available for human visceral leishmaniasis(VL) caused by Leishmania donovani. Previously, we showed that centrin1 and p27gene deleted live attenuated Leishmania parasites (LdCen1(-/-) and Ldp27(-/-)) are safe, immunogenic and protective in animal models. Here, to assess the correlates of protection, we evaluated immune responses induced by LdCen1(-/-) and Ldp27(-/-) in human blood samples obtained from healthy, healed VL (HVL), post kala-azar dermal leishmaniasis(PKDL) and VL subjects. Both parasites infected human macrophages, as effectively as the wild type parasites. Further, LdCen1(-/-) and Ldp27(-/-) strongly stimulated production of pro-inflammatory cytokines including, IL-12, IFN-γ, TNF-α, IL-2, IL-6 and IL-17 in the PBMCs obtained from individuals with a prior exposure to Leishmania (HVL and PKDL). There was no significant stimulation of anti-inflammatory cytokines (IL-4 and IL-10). Induction of Th1 biased immune responses was supported by a remarkable increase in IFN-γ secreting CD4(+) and CD8(+) T cells and IL-17 secreting CD4(+) cells in PBMCs from HVL cases with no increase in IL-10 secreting T cells. Hence, LdCen1(-/-) and Ldp27(-/-) are promising as live vaccine candidates against VL since they elicit strong protective immune response in human PBMCs from HVL, similar to the wild type parasite infection, mimicking a naturally acquired protection following cure.

  6. Multi-frequency characterization of the speed of sound and attenuation coefficient for longitudinal transmission of freshly excised human skulls

    Energy Technology Data Exchange (ETDEWEB)

    Pichardo, Samuel [Department of Electrical Engineering, Lakehead University and Image-guided Interventions, Thunder Bay Regional Research Institute, 980 Oliver Road, Thunder Bay, ON, P7B 6V4 (Canada); Sin, Vivian W; Hynynen, Kullervo, E-mail: pichards@tbh.net [Department of Medical Biophysics, University of Toronto, and Research Imaging and Centre for Research in Image-Guided Therapeutics Sunnybrook Health Sciences Centre, Rm S6-65b, 2075 Bayview Ave., Toronto, ON, M4N 3M5 (Canada)

    2011-01-07

    For medical applications of ultrasound inside the brain, it is necessary to understand the relationship between the apparent density of skull bone and its corresponding speed of sound and attenuation coefficient. Although there have been previous studies exploring this phenomenon, there is still a need to extend the measurements to cover more of the clinically relevant frequency range. The results of measurements of the longitudinal speed of sound and attenuation coefficient are presented for specimens of human calvaria. The study was performed for the frequencies of 0.27, 0.836, 1.402, 1.965 and 2.525 MHz. Specimens were obtained from fresh cadavers through a protocol with the Division of Anatomy of the University of Toronto. The protocol was approved by the Research Ethics Board of Sunnybrook Health Sciences Centre. The specimens were mounted in polycarbonate supports that were marked for stereoscopic positioning. Computer tomography (CT) scans of the skulls mounted on their supports were performed, and a three-dimensional skull surface was reconstructed. This surface was used to guide a positioning system to ensure the normal sound incidence of an acoustic signal. This signal was produced by a focused device with a diameter of 5 cm and a focal length of 10 cm. Measurements of delay in time of flight were carried out using a needle hydrophone. Measurements of effective transmitted energy were carried out using a radiation force method with a 10 {mu}g resolution scale. Preliminary functions of speed of sound and attenuation coefficient, both of which are related to apparent density, were established using a multi-layer propagation model that takes into account speed of sound, density and thickness of the layer. An optimization process was executed from a large set of random functions and the best functions were chosen for those ones that closest reproduced the experimental observations. The final functions were obtained after a second pass of the optimization

  7. Incidence and cost of rotavirus hospitalizations in Denmark

    DEFF Research Database (Denmark)

    Fischer, Thea Kølsen; Nielsen, Nete Munk; Wohlfahrt, Jan

    2007-01-01

    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....

  8. Options for improving effectiveness of rotavirus vaccines in developing countries

    Science.gov (United States)

    Cowley, Daniel; Bogdanovic-Sakran, Nada; Hutton, Melanie L.; Lyras, Dena; Kirkwood, Carl D.; Buttery, Jim P.

    2017-01-01

    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

  9. Isovolemic hemodilution with glutaraldehyde-polymerized human placenta hemoglobin (PolyPHb) attenuated rat liver ischemia/reperfusion injury.

    Science.gov (United States)

    You, Zhen; Li, Qian; Li, Bei; Yang, Chengmin; Liu, Jin; Li, Tao

    2014-04-01

    This study was to investigate whether glutaraldehyde-polymerized human placenta hemoglobin (PolyPHb) could attenuate ischemia/reperfusion (I/R)-induced liver injury. Isovolemic hemodilution of SD rats was performed by exchanging 15% total blood volume with PolyPHb. I/R was induced by left liver lobes pedicle cross-clamping for 60 min and reperfusion for 2 h. Blood pressure moderately elevated after PolyPHb infusion and returned to basal level within 10 min. The hepatic histopathological damage and the activities of liver injury markers were reduced by PolyPHb. The TUNEL staining and caspase assay indicated hepatic apoptosis was also inhibited. Therefore, our findings suggest PolyPHb can reduce liver I/R injury.

  10. Psilocybin-induced deficits in automatic and controlled inhibition are attenuated by ketanserin in healthy human volunteers.

    Science.gov (United States)

    Quednow, Boris B; Kometer, Michael; Geyer, Mark A; Vollenweider, Franz X

    2012-02-01

    The serotonin-2A receptor (5-HT(2A)R) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioral inhibition deficits of schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of sensorimotor gating and response inhibition in humans, but it is unclear so far whether the 5-HT(2A)R or 5-HT(1A)R agonist properties of its bioactive metabolite psilocin account for these effects. Thus, we investigated whether psilocybin-induced deficits in automatic and controlled inhibition in healthy humans could be attenuated by the 5-HT(2A/2C)R antagonist ketanserin. A total of 16 healthy participants received placebo, ketanserin (40 mg p.o.), psilocybin (260 μg/kg p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and counterbalanced order. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response. The effects on psychopathological core dimensions and behavioral inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and selectively increased errors in the interference condition of the Stroop Test. Stroop interference and Stroop effect of the response latencies were increased under psilocybin as well. Psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects. These findings suggest that the disrupting effects of psilocybin on automatic and controlled inhibition processes are attributable to 5-HT(2A)R stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT(2A)R system.

  11. Rotavirus-specific subclass antibody and cytokine responses in Bangladeshi children with rotavirus diarrhoea.

    Science.gov (United States)

    Azim, Tasnim; Zaki, M Hasan; Podder, Goutam; Sultana, Novera; Salam, M Abdus; Rahman, S Moshfiqur; Sefat-e-Khuda; Sack, David A

    2003-02-01

    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.

  12. Antibiotic Treatment Suppresses Rotavirus Infection and Enhances Specific Humoral Immunity

    Science.gov (United States)

    Uchiyama, Robin; Chassaing, Benoit; Zhang, Benyue; Gewirtz, Andrew T.

    2014-01-01

    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

  13. Rotavirus in the Netherlands : Background information for the Health Council

    OpenAIRE

    Verberk, J.D.M.; Bruijning, P.C.; de Melker, Hester

    2017-01-01

    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...

  14. Rotavirus in the Netherlands : Background information for the Health Council

    OpenAIRE

    Verkerk JDM; Bruijning-Verhagen P; Melker H de; RVP; I. V.,

    2017-01-01

    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 ...

  15. Cost-effectiveness of Rotavirus vaccination in Vietnam

    OpenAIRE

    Kim, Sun-Young; Goldie, Sue J; Salomon, Joshua A

    2009-01-01

    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, ...

  16. Evaluation of rotavirus dsRNA load in specimens and body fluids from experimentally infected juvenile macaques by real-time PCR.

    Science.gov (United States)

    Zhao, Wei; Xia, Mingjing; Bridges-Malveo, Tamika; Cantú, Mayra; McNeal, Monica M; Choi, Anthony H; Ward, Richard L; Sestak, Karol

    2005-10-25

    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.

  17. Euphorbia kansui Attenuates Insulin Resistance in Obese Human Subjects and High-Fat Diet-Induced Obese Mice

    Directory of Open Access Journals (Sweden)

    Seung-Wook Lee

    2017-01-01

    Full Text Available Background. Obesity is a main cause of insulin resistance (IR, metabolic syndrome, and fatty liver diseases. This study evaluated Euphorbia kansui radix (Euphorbia as a potential treatment option for obesity and obesity-induced IR in obese human and high-fat diet- (HFD- induced obese mice. Methods. In the human study, we analyzed the body weight change of 14 patients who took a single dose of 6 g of Euphorbia powder. In the animal study, male mice were divided into three groups: normal chow, HFD, and Euphorbia (high-fat diet and 100 mg/Kg Euphorbia once per week. Body weight, epididymal fat pad weight, fasting blood glucose, fasting insulin, HOMA-IR, and oral glucose tolerance test were measured. Also, macrophage infiltration and expression of CD68, tumor necrosis factor- (TNF- α, interferon- (IFN- γ, and interleukin- (IL- 6 genes in the liver and adipose tissue were analyzed. Results. The human study showed that Euphorbia has a potential effect on body weight loss. In the in vivo study, body weight, epididymal fat weight, glucose level, IR, expression of CD68, TNF-α, IFN-r, and IL-6 genes, and macrophages in liver and adipose tissue were significantly reduced by Euphorbia. Conclusions. These results suggest that Euphorbia attenuates obesity and insulin resistance via anti-inflammatory effects.

  18. Follow-Up Study of Children with Mixed Rotavirus Infection

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    Yu.B. Belan

    2016-02-01

    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.

  19. Surveillance of Rotavirus Diarrhea in Hasan Sadikin Hospital Bandung

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    Dwi Prasetyo

    2010-12-01

    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[1] (37.5% and P[6] (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.

  20. Respuesta inmune innata humana al rotavirus

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    Juanita Angel

    2004-03-01

    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.

  1. Attenuation of vaccinia virus by the expression of human Flt3 ligand

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    Sanda Miloslav

    2010-05-01

    Full Text Available Abstract Background Vaccinia virus, one of the best known members of poxvirus family, has a wide host range both in vivo and in vitro. The expression of Flt3 ligand (FL by recombinant vaccinia virus (rVACV highly influenced properties of the virus in dependence on the level of expression. Results High production of FL driven by the strong synthetic promoter decreased the growth of rVACV in macrophage cell line J774.G8 in vitro as well as its multiplication in vivo when inoculated in mice. The inhibition of replication in vivo was mirrored in low levels of antibodies against vaccinia virus (anti-VACV which nearly approached to the negative serum level in non-infected mice. Strong FL expression changed not only the host range of the recombinant but also the basic protein contents of virions. The major proteins - H3L and D8L - which are responsible for the virus binding to the cells, and 28 K protein that serves as a virulence factor, were changed in the membrane portion of P13-E/L-FL viral particles. The core virion fraction contained multiple larger, uncleaved proteins and a higher amount of cellular proteins compared to the control virus. The overexpression of FL also resulted in its incorporation into the viral core of P13-E/L-FL IMV particles. In contrary to the equimolar ratio of glycosylated and nonglycosylated FL forms found in cells transfected with the expression plasmid, the recombinant virus incorporated mainly the smaller, nonglycosylated FL. Conclusions It has been shown that the overexpression of the Flt3L gene in VACV results in the attenuation of the virus in vivo.

  2. High dose compressive loads attenuate bone mineral loss in humans with spinal cord injury

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    Dudley-Javoroski, S.; Saha, P. K.; Liang, G.; Li, C.; Gao, Z.

    2012-01-01

    Summary People with spinal cord injury (SCI) lose bone and muscle integrity after their injury. Early doses of stress, applied through electrically induced muscle contractions, preserved bone density at high-risk sites. Appropriately prescribed stress early after the injury may be an important consideration to prevent bone loss after SCI. Introduction Skeletal muscle force can deliver high compressive loads to bones of people with spinal cord injury (SCI). The effective osteogenic dose of load for the distal femur, a chief site of fracture, is unknown. The purpose of this study is to compare three doses of bone compressive loads at the distal femur in individuals with complete SCI who receive a novel stand training intervention. Methods Seven participants performed unilateral quadriceps stimulation in supported stance [150% body weight (BW) compressive load—“High Dose” while opposite leg received 40% BW—“Low Dose”]. Five participants stood passively without applying quadriceps electrical stimulation to either leg (40% BW load—“Low Dose”). Fifteen participants performed no standing (0% BW load—“Untrained”) and 14 individuals without SCI provided normative data. Participants underwent bone mineral density (BMD) assessment between one and six times over a 3-year training protocol. Results BMD for the High Dose group significantly exceeded BMD for both the Low Dose and the Untrained groups (p0.05), indicating that BMD for participants performing passive stance did not differ from individuals who performed no standing. High-resolution CT imaging of one High Dose participant revealed 86% higher BMD and 67% higher trabecular width in the High Dose limb. Conclusion Over 3 years of training, 150% BW compressive load in upright stance significantly attenuated BMD decline when compared to passive standing or to no standing. High-resolution CT indicated that trabecular architecture was preserved by the 150% BW dose of load. PMID:22187008

  3. Allogeneic pASC transplantation in humanized pigs attenuates cardiac remodeling post-myocardial infarction.

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    Rafael Dariolli

    Full Text Available Cell therapy repair strategies using adult mesenchymal stromal cells have shown promising evidence to prevent cardiac deterioration in rodents even in the absence of robust differentiation of the cells into cardiomyocytes. We tested whether increasing doses of porcine adipose-tissue derived mesenchymal stem cells (pASCs increase cardiac tissue perfusion in pigs post-myocardial infarction (MI receiving angiotensin-converting-enzyme inhibitor (ACE inhibitors and Beta-blockers similarly to patients. Female pigs were subjected to MI induction by sponge permanent occlusion of left circumflex coronary artery (LCx generating approximately 10% of injured LV area with minimum hemodynamic impact. We assessed tissue perfusion by real time myocardial perfusion echocardiography (RTMPE using commercial microbubbles before and following pASCs treatment. Four weeks after the occlusion of the left circumflex artery, we transplanted placebo or pASCs (1, 2 and 4x106 cells/Kg BW into the myocardium. The highest dose of pASCs increased myocardial vessel number and blood flow in the border (56% and 3.7-fold, respectively and in the remote area (54% and 3.9-fold, respectively while the non-perfused scar area decreased (up to 38%. We also found an increase of immature collagen fibers, although the increase in total tissue collagen and types I and III was similar in all groups. Our results provide evidence that pASCs-induced stimulation of tissue perfusion and accumulation of immature collagen fibers attenuates adverse remodeling post-MI beyond the normal beneficial effects associated with ACE inhibition and beta-blockade.

  4. Comparison of Rotavirus and Norovirus transport in standardised and natural soil-water systems

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    Gamazo, P. A.; Schijven, J. F.; Victoria, M.; Alvareda, E.; Lopez, F.; Ramos, J.; Lizasoain, A.; Sapriza-Azuri, G.; Castells, M.; Colina, R.

    2016-12-01

    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

  5. Short nights attenuate light-induced circadian phase advances in humans.

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    Burgess, Helen J; Eastman, Charmane I

    2005-08-01

    In humans, sleep duration often determines the night (dark) length experienced, because we close our eyes when we sleep and are exposed to artificial or natural light when we are awake. Although it is recognized that there is an increasing trend in modern society toward shorter sleep time, it is not known how short nights (long photoperiods) affect the human circadian system. In this study we investigated for the first time the effects of night length on circadian phase shifts to light in humans. Eight young healthy subjects experienced 2 wk of 6-h sleep episodes in the dark (short nights) and 2 wk of long 9-h sleep episodes (long nights) in counterbalanced order. After each series of nights, they were exposed to four 30-min pulses of morning bright light (approximately 5000 lux) that advanced by 1 h/d for 3 consecutive days while night (dark) length was maintained at 6 or 9 h. Circadian phase was determined from the circadian rhythm of melatonin in dim light before and after the 3-d bright light treatments. The phase advance in the melatonin rhythm during the short nights was less than half of that observed during the long nights (P < 0.05). This result shows for the first time that people who curtail their sleep may unwittingly reduce their circadian responsiveness to morning light. This finding also demonstrates that sleep length can alter human circadian function and has important implications for enhancing the treatment of circadian rhythm sleep disorders.

  6. Terbutaline-induced desensitization of beta 2-adrenoceptor in vivo function in humans: attenuation by ketotifen

    NARCIS (Netherlands)

    Brodde, O. E.; Petrasch, S.; Bauch, H. J.; Daul, A.; Gnadt, M.; Oefler, D.; Michel, M. C.

    1992-01-01

    Use of beta-adrenoceptor agonists in long-term treatment of patients with chronic asthma bronchiale or heart failure is of limited value because beta-adrenoceptor desensitization develops. The antiallergic drug ketotifen prevents beta-adrenoceptor agonist-induced desensitization of rat and human

  7. Evaluation of the antigenicity and reactogenicity of varying formulations of the rhesus rotavirus-based quadrivalent and the M37 rotavirus vaccine candidates.

    Science.gov (United States)

    Perez-Schael, I; Blanco, M; Garcia, D; White, L; Alfonzo, E; Crespo, I; Cunto, W; Pittman, A L; Kapikian, A Z; Flores, J

    1994-04-01

    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)

  8. CP-25 Attenuates the Activation of CD4+ T Cells Stimulated with Immunoglobulin D in Human.

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    Wu, Yu-Jing; Chen, Heng-Shi; Chen, Wen-Sheng; Dong, Jin; Dong, Xiao-Jie; Dai, Xing; Huang, Qiong; Wei, Wei

    2018-01-01

    Researchers have shown that the level of immunoglobulin D (IgD) is often elevated in patients with autoimmune diseases. The possible roles of IgD on the function of human T cell activation are still unclear. Paeoniflorin-6'-O-benzene sulfonate (code: CP-25), the chemistry structural modifications of paeoniflorin, was a novel drug of anti-inflammation and immunomodulation. The aims of this study were to determine if human CD4+ T cells could be activated by IgD via the IgD receptor (IgDR)-Lck pathway and whether the novel compound CP-25 could affect the activation of T cells by regulating Lck. Human CD4+ T cells were purified from peripheral blood mononuclear cells using microbeads. T cell viability and proliferation were detected by Cell Counting Kit-8 and CFSE Cell Proliferation Kit. Cytokines secreted by T cells were assessed with the Quantibody Human Inflammation Array. The binding affinity and expression of IgDR on T cells were detected by flow cytometry, and protein expression of IgDR, Lck, and P-Lck were analyzed by western blot. IgD was shown to bind to IgDR on CD4+ T cells in a concentration-dependent manner and stimulate the activation and proliferation of these cells by enhancing phosphorylation of the activating tyrosine residue of Lck (Tyr394). CP-25 inhibited the IgD-stimulated activation and proliferation of CD4+ T cells, as well as the production of inflammatory cytokines; it was thus suggested that this process might be related to the downregulation of Lck (Tyr394) phosphorylation. These results demonstrate that IgD amplifies the activation of CD4+ T cells, which could be mediated by Lck phosphorylation. Further, CP-25, via its ability to modulate Lck, is a novel potential therapeutic agent for the treatment of human autoimmune diseases.

  9. Hypoxia attenuates inflammatory mediators production induced by Acanthamoeba via Toll-like receptor 4 signaling in human corneal epithelial cells

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    Pan, Hong [Department of Ophthalmology, Qilu Hospital, Shandong University, 107, Wenhua Xi Road, Jinan 250012 (China); The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, 107, Wenhua Xi Road, Jinan 250012 (China); Wu, Xinyi, E-mail: xywu8868@163.com [Department of Ophthalmology, Qilu Hospital, Shandong University, 107, Wenhua Xi Road, Jinan 250012 (China)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer Hypoxia attenuates Acanthamoeba-induced the production of IL-8 and IFN-{beta}. Black-Right-Pointing-Pointer Hypoxia inhibits TLR4 expression in a time-dependent manner in HCECs. Black-Right-Pointing-Pointer Hypoxia inhibits Acanthamoeba-induced the activation of NF-{kappa}B and ERK1/2 in HCECs. Black-Right-Pointing-Pointer Hypoxia decreases Acanthamoeba-induced inflammatory response via TLR4 signaling. Black-Right-Pointing-Pointer LPS-induced the secretion of IL-6 and IL-8 is abated by hypoxia via TLR4 signaling. -- Abstract: Acanthamoeba keratitis (AK) is a vision-threatening corneal infection that is intimately associated with contact lens use which leads to hypoxic conditions on the corneal surface. However, the effect of hypoxia on the Acanthamoeba-induced host inflammatory response of corneal epithelial cells has not been studied. In the present study, we investigated the effect of hypoxia on the Acanthamoeba-induced production of inflammatory mediators interleukin-8 (IL-8) and interferon-{beta} (IFN-{beta}) in human corneal epithelial cells and then evaluated its effects on the Toll-like receptor 4 (TLR4) signaling, including TLR4 and myeloid differentiation primary response gene (88) (MyD88) expression as well as the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-{kappa}B) and extracellular signal-regulated kinases 1/2 (ERK1/2). We then studied the effect of hypoxia on a TLR4-specific inflammatory response triggered by the TLR4 ligand lipopolysaccharide (LPS). Our data showed that hypoxia significantly decreased the production of IL-8 and IFN-{beta}. Furthermore, hypoxia attenuated Acanthamoeba-triggered TLR4 expression as well as the activation of NF-{kappa}B and ERK1/2, indicating that hypoxia abated Acanthamoeba-induced inflammatory responses by affecting TLR4 signaling. Hypoxia also inhibited LPS-induced IL-6 and IL-8 secretion, myeloid differentiation primary response gene (88

  10. Physical Exercise Enhanced Heat Shock Protein 60 Expression and Attenuated Inflammation in the Adipose Tissue of Human Diabetic Obese

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    Abdelkrim Khadir

    2018-02-01

    Full Text Available Heat shock protein 60 (HSP60 is a key protein in the crosstalk between cellular stress and inflammation. However, the status of HSP60 in diabetes and obesity is unclear. In the present study, we investigated the hypothesis that HSP60 expression levels in the adipose tissue of human obese adults with and without diabetes are different and physical exercise might affect these levels. Subcutaneous adipose tissue (SAT and blood samples were collected from obese adults with and without diabetes (n = 138 and n = 92, respectively, at baseline; n = 43 for both groups after 3 months of physical exercise. Conventional RT-PCR, immunohistochemistry, immunofluorescence, and ELISA were used to assess the expression and secretion of HSP60. Compared with obese adults without diabetes, HSP60 mRNA and protein levels were decreased in SAT in diabetic obese together with increased inflammatory marker expression and glycemic levels but lower VO2 Max. More interestingly, a 3-month physical exercise differentially affected HSP60 expression and the heat shock response but attenuated inflammation in both groups, as reflected by decreased endogenous levels of IL-6 and TNF-α. Indeed, HSP60 expression levels in SAT were significantly increased by exercise in the diabetes group, whereas they were decreased in the non-diabetes group. These results were further confirmed using immunofluorescence microscopy and anti-HSP60 antibody in SAT. Exercise had only marginal effects on HSP60 secretion and HSP60 autoantibody levels in plasma in both obese with and without diabetes. Physical exercise differentially alleviates cellular stress in obese adults with and without diabetes despite concomitant attenuation of the inflammatory response.

  11. Pro-Leu-glycinamide and its peptidomimetic, PAOPA, attenuate haloperidol induced vacuous chewing movements in rat: A model of human tardive dyskinesia.

    Science.gov (United States)

    Sharma, S; Paladino, P; Gabriele, J; Saeedi, H; Henry, P; Chang, M; Mishra, R K; Johnson, R L

    2003-02-01

    In the present experimental paradigm, we examine the effect of L-prolyl-L-leucyl-glycinamide (PLG) co-administration with haloperidol on vacuous chewing mov