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Sample records for human rotavirus vaccine

  1. Rotavirus vaccines

    Directory of Open Access Journals (Sweden)

    Kang G

    2006-01-01

    Full Text Available Rotavirus, the most common cause of severe diarrhea and a leading cause of mortality in children, has been a priority target for vaccine development for the past several years. The first rotavirus vaccine licensed in the United States was withdrawn because of an association of the vaccine with intussusception. However, the need for a vaccine is greatest in the developing world, because the benefits of preventing deaths due to rotavirus disease are substantially greater than the risk of intussusception. Early vaccines were based on animal strains. More recently developed and licenced vaccines are either animal-human reassortants or are based on human strains. In India, two candidate vaccines are in the development process, but have not yet reached efficacy trials. Many challenges regarding vaccine efficacy and safety remain. In addition to completing clinical evaluations of vaccines in development in settings with the highest disease burden and virus diversity, there is also a need to consider alternative vaccine development strategies.

  2. Rotavirus Vaccine

    Science.gov (United States)

    Why get vaccinated?Rotavirus is a virus that causes diarrhea, mostly in babies and young children. The diarrhea can be severe, and lead ... and fever are also common in babies with rotavirus.Before rotavirus vaccine, rotavirus disease was a common ...

  3. Rotavirus vaccines

    Science.gov (United States)

    Yen, Catherine; Tate, Jacqueline E; Hyde, Terri B; Cortese, Margaret M; Lopman, Benjamin A; Jiang, Baoming; Glass, Roger I; Parashar, Umesh D

    2014-01-01

    Rotavirus is the leading cause of severe diarrhea among children rotavirus vaccines have been efficacious and effective, with many countries reporting substantial declines in diarrheal and rotavirus-specific morbidity and mortality. However, the full public health impact of these vaccines has not been realized. Most countries, including those with the highest disease burden, have not yet introduced rotavirus vaccines into their national immunization programs. Research activities that may help inform vaccine introduction decisions include (1) establishing effectiveness, impact, and safety for rotavirus vaccines in low-income settings; (2) identifying potential strategies to improve performance of oral rotavirus vaccines in developing countries, such as zinc supplementation; and (3) pursuing alternate approaches to oral vaccines, such as parenteral immunization. Policy- and program-level barriers, such as financial implications of new vaccine introductions, should be addressed to ensure that countries are able to make informed decisions regarding rotavirus vaccine introduction. PMID:24755452

  4. 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.

  5. Human neonatal rotavirus vaccine (RV3-BB) targets rotavirus from birth

    Science.gov (United States)

    Thobari, Jarir At; Satria, Cahya Dewi; Handley, Amanda; Watts, Emma; Cowley, Daniel; Nirwati, Hera; Ackland, James; Standish, Jane; Justice, Frances; Byars, Gabrielle; Lee, Katherine J.; Barnes, Graeme L.; Bachtiar, Novilia S.; Icanervilia, Ajeng Viska; Boniface, Karen; Bogdanovic-Sakran, Nada; Pavlic, Daniel; Bishop, Ruth F.; Kirkwood, Carl D.; Buttery, Jim P.; Soenarto, Yati

    2018-01-01

    Background A birth dose strategy using a neonatal rotavirus vaccine to target early prevention of rotavirus disease may address remaining barriers to global vaccine implementation. Methods We conducted a randomized, placebo-controlled trial in Indonesia to evaluate the efficacy of an oral human neonatal rotavirus vaccine (RV3-BB) to prevent rotavirus gastroenteritis. Healthy newborns received three doses of RV3-BB administered in a neonatal schedule at 0-5 days, 8 and 14 weeks or infant schedule at 8, 14 and 18 weeks, or placebo. Laboratory-confirmed rotavirus gastroenteritis was graded using a modified Vesikari score. The primary analysis was efficacy against severe rotavirus gastroenteritis from two weeks after all doses to 18 months in the combined vaccine group (neonatal and infant schedule) compared with placebo. Results Vaccine efficacy against severe rotavirus gastroenteritis to 18 months was 63% in the combined vaccine group (95% CI 34, 80; p<0.001), 75% in the neonatal vaccine group (95% confidence interval [CI] 44, 91; p<0.001) and 51% in the infant vaccine group (95% CI 7, 76; p=0.03) in the per protocol analysis, with similar results in the intention-to-treat analysis. Vaccine efficacy to 12 months was 94% in the neonatal vaccine group (95%CI 56, 99; p=0.006). Vaccine take occurred in 78/83 (94%) in the neonatal vaccine group and 83/84 (99%) in the infant vaccine group. The vaccine was well tolerated, with similar incidence of adverse events in vaccine and placebo recipients. Conclusion RV3-BB was efficacious, immunogenic and well-tolerated when administered in a neonatal or infant schedule in Indonesia. PMID:29466164

  6. Human Neonatal Rotavirus Vaccine (RV3-BB) to Target Rotavirus from Birth.

    Science.gov (United States)

    Bines, Julie E; At Thobari, Jarir; Satria, Cahya Dewi; Handley, Amanda; Watts, Emma; Cowley, Daniel; Nirwati, Hera; Ackland, James; Standish, Jane; Justice, Frances; Byars, Gabrielle; Lee, Katherine J; Barnes, Graeme L; Bachtiar, Novilia S; Viska Icanervilia, Ajeng; Boniface, Karen; Bogdanovic-Sakran, Nada; Pavlic, Daniel; Bishop, Ruth F; Kirkwood, Carl D; Buttery, Jim P; Soenarto, Yati

    2018-02-22

    A strategy of administering a neonatal rotavirus vaccine at birth to target early prevention of rotavirus gastroenteritis may address some of the barriers to global implementation of a rotavirus vaccine. We conducted a randomized, double-blind, placebo-controlled trial in Indonesia to evaluate the efficacy of an oral human neonatal rotavirus vaccine (RV3-BB) in preventing rotavirus gastroenteritis. Healthy newborns received three doses of RV3-BB, administered according to a neonatal schedule (0 to 5 days, 8 weeks, and 14 weeks of age) or an infant schedule (8 weeks, 14 weeks, and 18 weeks of age), or placebo. The primary analysis was conducted in the per-protocol population, which included only participants who received all four doses of vaccine or placebo within the visit windows, with secondary analyses performed in the intention-to-treat population, which included all participants who underwent randomization. Among the 1513 participants in the per-protocol population, severe rotavirus gastroenteritis occurred up to the age of 18 months in 5.6% of the participants in the placebo group (28 of 504 babies), in 1.4% in the neonatal-schedule vaccine group (7 of 498), and in 2.7% in the infant-schedule vaccine group (14 of 511). This resulted in a vaccine efficacy of 75% (95% confidence interval [CI], 44 to 91) in the neonatal-schedule group (PBill and Melinda Gates Foundation and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612001282875 .).

  7. 75 FR 48706 - Proposed Vaccine Information Materials for Rotavirus Vaccine

    Science.gov (United States)

    2010-08-11

    ... Vaccine Information Materials for Rotavirus Vaccine AGENCY: Centers for Disease Control and Prevention... information materials for rotavirus vaccine. DATES: Written comments are invited and must be received on or... (chickenpox), pneumococcal conjugate, rotavirus, hepatitis A, meningococcal, human papillomavirus (HPV), and...

  8. 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

  9. Efficacy of a pentavalent human-bovine reassortant rotavirus vaccine against rotavirus gastroenteritis among American Indian children.

    Science.gov (United States)

    Grant, Lindsay R; Watt, James P; Weatherholtz, Robert C; Moulton, Lawrence H; Reid, Raymond; Santosham, Mathuram; O'Brien, Katherine L

    2012-02-01

    Before the widespread use of rotavirus vaccines, rotavirus was a leading cause of gastroenteritis among children. Navajo and White Mountain Apache children suffer a disproportionate burden of severe rotavirus disease compared with the general U.S. population. We enrolled Navajo and White Mountain Apache infants in a multicenter, double-blind, placebo-controlled trial of pentavalent human-bovine reassortant rotavirus vaccine (PRV). Subjects received 3 doses of vaccine or placebo at 4 to 10 week intervals, with the first dose given between 6 and 12 weeks of age. Gastroenteritis episodes were identified by active surveillance. Disease severity was determined by a standardized scoring system. There were 509 and 494 randomized children who received vaccine and placebo, respectively. Among placebo recipients, the incidence of rotavirus gastroenteritis was 34.2 episodes/100 child-years (95% confidence interval [95% CI]: 25.8-38.9) versus 8.1 episodes/100 child-years (95% CI: 5.4-12.5) in the vaccine group. The percentage of rotavirus episodes caused by serotypes G1, G2, and G3 was 72.3%, 23.4%, and 2.1%, respectively. There were no severe rotavirus episodes among vaccinees and 4 among placebo recipients. PRV was 77.1% (95% CI: 59.7-87.6), 89.5% (95% CI: 65.9-97.9), and 82.9% (95% CI: 61.1-93.6) effective against G1-G4 rotavirus disease, severe and moderate rotavirus disease combined, and outpatient visits for rotavirus disease, respectively. The risk of adverse events was similar for the vaccine and placebo groups. PRV was highly effective in preventing rotavirus disease and related health care utilization in these American Indian infants. Vaccine efficacy and immunogenicity were similar to the overall study population enrolled in the multicenter trial.

  10. 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.

  11. 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...

  12. 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; Duncan Steele, A; Neuzil, Kathleen M; Cunliffe, Nigel A

    2012-04-27

    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 the 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. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Dose response and efficacy of a live, attenuated human rotavirus vaccine in Mexican infants.

    Science.gov (United States)

    Ruiz-Palacios, Guillermo M; Guerrero, M Lourdes; Bautista-Márquez, Aurora; Ortega-Gallegos, Hilda; Tuz-Dzib, Fernando; Reyes-González, Leticia; Rosales-Pedraza, Gustavo; Martínez-López, Julia; Castañón-Acosta, Erika; Cervantes, Yolanda; Costa-Clemens, SueAnn; DeVos, Beatrice

    2007-08-01

    Immunization against rotavirus has been proposed as the most cost-effective intervention to reduce the disease burden associated with this infection worldwide. The objective of this study was to determine the dose response, immunogenicity, and efficacy of 2 doses of an oral, attenuated monovalent G1[P8] human rotavirus vaccine in children from the same setting in Mexico, where the natural protection against rotavirus infection was studied. From June 2001 through May 2003, 405 healthy infants were randomly assigned to 1 of 3 vaccine groups (virus concentrations 10(4.7), 10(5.2), and 10(5.8) infectious units) and to a placebo group and were monitored to the age of 2 years. The vaccine/placebo was administered concurrently with diphtheria-tetanus toxoid-pertussis/hepatitis B/Haemophilus influenzae type b vaccine at 2 and 4 months of age. After the administration of the first vaccine/placebo dose, weekly home visits to collect information regarding infant health were conducted. Stool samples were collected during each gastroenteritis episode and tested for rotavirus antigen and serotype. The vaccine was well tolerated and induced a greater rate of seroconversion than observed in infants who received placebo. For the pooled vaccine groups, efficacy after 2 oral doses was 80% and 95% against any and severe rotavirus gastroenteritis, respectively. Efficacy was 100% against severe rotavirus gastroenteritis and 70% against severe gastroenteritis of any cause with the vaccine at the highest virus concentration (10(5.8) infectious units). The predominant infecting rotavirus serotype in this cohort was wild-type G1 (85%). Adverse events, including fever, irritability, loss of appetite, cough, diarrhea, and vomiting, were similar among vaccinees and placebo recipients. This new oral, live, attenuated human rotavirus vaccine was safe, immunogenic, and highly efficacious in preventing any and, more importantly, severe rotavirus gastroenteritis in healthy infants. This vaccine

  14. Human rotavirus genotypes circulating in Brazil before and after a nationwide rotavirus vaccination program established in 2006

    Directory of Open Access Journals (Sweden)

    Caruzo TAR

    2011-04-01

    Full Text Available Thabata AR CaruzoGenetics, Evolution and Bioagents Department, Institute of Biology, State University of Campinas, Campinas, São Paulo, BrazilAbstract: Accounting for an estimated 600,000 deaths worldwide each year, rotaviruses are recognized as the most important etiologic agents causing severe acute gastroenteritis among children under the age of five years. In Brazil, until rotavirus vaccination was established in the public health system in 2006, acute gastroenteritis striking children under five years and caused by these viruses was clearly associated with 3.5 million episodes of diarrhea, 650,000 visits to outpatient health care facilities, 92,000 hospitalizations, and 850 deaths each year. After the introduction of the rotavirus vaccine in Brazil in March 2006, studies all over the country have been comparing rotavirus genotypes circulating in the recent pre- and postvaccination era. Most of these studies have reported a high prevalence of the G2P[4] genotype and also a decrease in rotavirus detection all over Brazil after the introduction of the vaccine. So far, these are preliminary studies, as a longer period of time is necessary to establish if this high prevalence of G2P[4] is due to selective pressure by the vaccine on the circulating viruses or to a normal genotype fluctuation, and if it will have any impact on vaccine efficacy in the future. This review describes results from the most recent studies addressing this issue and on rotavirus genotypic variability in Brazil.Keywords: human rotavirus, vaccine, genotypes, prevalence, Brazil

  15. 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

    2013-01-01

    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 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. PMID:23839157

  16. 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

  17. 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

    2010-01-28

    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. (Clinical

  18. 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.

  19. 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.

  20. Rotavirus vaccines and vaccination in Latin America

    Directory of Open Access Journals (Sweden)

    Linhares Alexandre C.

    2000-01-01

    Full Text Available Worldwide, rotaviruses account for more than 125 million cases of infantile gastroenteritis and nearly 1 million deaths per year, mainly in developing countries. Rather than other control measures, vaccination is most likely to have a major impact on rotavirus disease incidence. The peak incidence of rotavirus diarrhea occurs between 6 and 24 months of age. In developing countries, however, cases are not uncommon among children younger than 6 months. G serotypes 1 to 4 are responsible for most disease, but there are indications that in Brazil that G type 5 is of emerging epidemiological importance. Both homotypic and heterotypic responses are elicited during natural rotavirus infection, and the immunological response at the intestinal mucosal surface is probably the more consistent predictor of clinical immunity. With the primary objective of protecting children against life-threatening dehydrating diarrhea, many approaches to rotavirus vaccine development have been attempted. One vaccine, the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV, was given licensing approval in the United States of America, introduced to the market, and later withdrawn. A number of studies have found better efficacy of RRV-TV in developed countries than in developing ones. Field trials with a 4 X 10(4 plaque-forming units (PFU preparation of RRV-TV have been carried out in two countries in Latin America, Brazil and Peru. Those trials yielded protective efficacy rates against all rotavirus diarrhea ranging from 18% to 35%. Data from a large catchment trial in Venezuela with a higher RRV-TV dose, of 4 X 10(5 PFU/dose, indicated an efficacy rate of 48% against all rotavirus diarrhea and 88% against severe rotavirus diarrhea. It appears that breast-feeding does not compromise the efficacy of RRV-TV if three doses of the vaccine are administered. Similarly, possible interference of oral poliovirus vaccine with the "take" of the rotavirus vaccine can be

  1. Rotavirus vaccines and vaccination in Latin America

    Directory of Open Access Journals (Sweden)

    Alexandre C. Linhares

    2000-11-01

    Full Text Available Worldwide, rotaviruses account for more than 125 million cases of infantile gastroenteritis and nearly 1 million deaths per year, mainly in developing countries. Rather than other control measures, vaccination is most likely to have a major impact on rotavirus disease incidence. The peak incidence of rotavirus diarrhea occurs between 6 and 24 months of age. In developing countries, however, cases are not uncommon among children younger than 6 months. G serotypes 1 to 4 are responsible for most disease, but there are indications that in Brazil that G type 5 is of emerging epidemiological importance. Both homotypic and heterotypic responses are elicited during natural rotavirus infection, and the immunological response at the intestinal mucosal surface is probably the more consistent predictor of clinical immunity. With the primary objective of protecting children against life-threatening dehydrating diarrhea, many approaches to rotavirus vaccine development have been attempted. One vaccine, the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV, was given licensing approval in the United States of America, introduced to the market, and later withdrawn. A number of studies have found better efficacy of RRV-TV in developed countries than in developing ones. Field trials with a 4 X 10(4 plaque-forming units (PFU preparation of RRV-TV have been carried out in two countries in Latin America, Brazil and Peru. Those trials yielded protective efficacy rates against all rotavirus diarrhea ranging from 18% to 35%. Data from a large catchment trial in Venezuela with a higher RRV-TV dose, of 4 X 10(5 PFU/dose, indicated an efficacy rate of 48% against all rotavirus diarrhea and 88% against severe rotavirus diarrhea. It appears that breast-feeding does not compromise the efficacy of RRV-TV if three doses of the vaccine are administered. Similarly, possible interference of oral poliovirus vaccine with the "take" of the rotavirus vaccine can be

  2. 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.

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

    OpenAIRE

    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

    2016-01-01

    : 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:...

  4. 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

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

    Science.gov (United States)

    Steele, Andrew Duncan; Neuzil, Kathleen M; Cunliffe, Nigel A; Madhi, Shabir A; Bos, Pieter; Ngwira, Bagrey; Witte, Desiree; Todd, Stacy; Louw, Cheryl; Kirsten, Mari; Aspinall, Sanet; Van Doorn, Leen Jan; Bouckenooghe, Alain; Suryakiran, Pemmaraju V; Han, Htay Htay

    2012-09-13

    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. 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. 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%; 87.0%) and P[6] was 55.2% (95% CI: -6

  6. 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

  7. 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.

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    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

  8. 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.

  9. Efficacy and immunogenicity of live-attenuated human rotavirus vaccine in breast-fed and formula-fed European infants.

    Science.gov (United States)

    Vesikari, Timo; Prymula, Roman; Schuster, Volker; Tejedor, Juan-C; Cohen, Robert; Bouckenooghe, Alain; Damaso, Silvia; Han, Htay Htay

    2012-05-01

    Rotavirus is the main cause of severe gastroenteritis and diarrhea in infants and young children less than 5 years of age. Potential impact of breast-feeding on the efficacy and immunogenicity of human rotavirus G1P[8] vaccine was examined in this exploratory analysis. Healthy infants (N = 3994) aged 6-14 weeks who received 2 doses of human rotavirus vaccine/placebo according to a 0-1 or 0-2 month schedule were followed for rotavirus gastroenteritis during 2 epidemic seasons. Rotavirus IgA seroconversion rate (anti-IgA antibody concentration ≥ 20 mIU/mL) and geometric mean concentrations were measured prevaccination and 1-2 months post-dose 2. Vaccine efficacy against any and severe rotavirus gastroenteritis was analyzed according to the infants being breast-fed or exclusively formula-fed at the time of vaccination. Antirotavirus IgA seroconversion rate was 85.5% (95% confidence interval [CI]: 82.4-88.3) in breast-fed and 89.2% (95% CI: 84.2-93) in exclusively formula-fed infants; geometric mean concentrations in the respective groups were 185.8 U/mL (95% CI: 161.4-213.9) and 231.5 U/mL (95% CI: 185.9-288.2). Vaccine efficacy was equally high in breast-fed and exclusively formula-fed children in the first season but fell in breast-fed infants in the second rotavirus season. During the combined 2-year efficacy follow-up period, vaccine efficacy against any rotavirus gastroenteritis was 76.2% (95% CI: 68.7-82.1) and 89.8% (95% CI: 77.6-95.9) and against severe rotavirus gastroenteritis 88.4% (95% CI: 81.6-93) and 98.1% (95% CI: 88.2-100) in the breast-fed and exclusively formula-fed infants, respectively. The difference in immunogenicity of human rotavirus vaccine in breast-fed and exclusively formula-fed infants was small. Vaccine efficacy was equally high in breast-fed and exclusively formula-fed children in the first season. Breast-feeding seemed to reduce slightly the efficacy in the second season.

  10. 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.

  11. Concomitant use of an oral live pentavalent human-bovine reassortant rotavirus vaccine with licensed parenteral pediatric vaccines in the United States.

    Science.gov (United States)

    Rodriguez, Zoe M; Goveia, Michelle G; Stek, Jon E; Dallas, Michael J; Boslego, John W; DiNubile, Mark J; Heaton, Penny M

    2007-03-01

    A live pentavalent rotavirus vaccine (PRV) containing 5 human-bovine (WC3) reassortants expressing human serotypes G1, G2, G3, G4 and P1A[8] was evaluated in a blinded, placebo-controlled study. Possible interactions between PRV and concomitantly administered licensed pediatric vaccines were investigated in a United States-based nested substudy (Concomitant Use Study) of the Rotavirus Efficacy and Safety Trial. From 2002 to 2003, healthy infants approximately 6 to 12 weeks of age at entry were randomized to receive either 3 oral doses of PRV or placebo at 4- to 10-week intervals. Subjects were also to receive combined Haemophilus influenzae type b and hepatitis B vaccine (2 doses), diphtheria and tetanus toxoids and acellular pertussis vaccine (3 doses), inactivated poliovirus vaccine (2 doses) and pneumococcal conjugate vaccine (3 doses) on the same day; oral poliovirus vaccine was not administered. Immunogenicity was assessed by measuring antibody responses to PRV and antigens contained in the licensed vaccines. Cases of rotavirus gastroenteritis were defined by forceful vomiting and/or -3 watery or looser-than-normal stools within a 24-hour period, and detection of rotavirus antigen in the stool. Safety was assessed by reporting of adverse events using diary cards. The Concomitant Use Study enrolled 662 subjects in the PRV group and 696 subjects in the placebo group. For the 17 antigens in the concomitantly administered vaccines, antibody responses were similar in PRV and placebo recipients, except for moderately diminished antibody responses to the pertactin component of pertussis vaccine. Efficacy of PRV against rotavirus gastroenteritis of any severity was 89.5% (95% CI = 26.5-99.8%). PRV was generally well tolerated when given concomitantly with the prespecified vaccines. In this study, antibody responses to the concomitantly administered vaccines were generally similar in PRV and placebo recipients. PRV was efficacious and well tolerated when given

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

    Science.gov (United States)

    ... Resources Maternal Immunization Resources Related Links Vaccines & Immunizations Rotavirus and the Vaccine (Drops) to Prevent It Language: ... the vaccine. Why should my child get the rotavirus vaccine? The rotavirus vaccine: Protects your child from ...

  13. Rotavirus infection and the current status of rotavirus vaccines

    Directory of Open Access Journals (Sweden)

    Shou-Chien Chen

    2012-04-01

    Full Text Available Among children, rotaviruses are the most common cause of severe gastroenteritis worldwide and of diarrheal deaths in developing countries. Current vaccines (e.g., Rotarix, GlaxoSmithKline Biologicals; RotaTeq, Merck and Company effectively reduce rotaviral gastroenteritis, emergency department visits, and hospitalizations. The tremendous burden of rotavirus-related diarrhea in children across the world continues to drive the remarkable pace of vaccine development. This review assesses the global epidemiological and economic burden of rotavirus diseases, summarizes the relevant principles of the development of rotavirus vaccines, and presents data on the efficacy and effectiveness of currently licensed vaccines in both developed and developing countries.

  14. Prevention of rotavirus gastroenteritis in infants and children: rotavirus vaccine safety, efficacy, and potential impact of vaccines

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    Aruna Chandran

    2010-07-01

    Full Text Available Aruna Chandran1, Sean Fitzwater1, Anjie Zhen2, Mathuram Santosham11Department of International Health, Division of Health Systems, 2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USAAbstract: Rotavirus infection is the most common cause of severe gastroenteritis globally, with greater than 86% of deaths occurring in low-income and middle-income countries. There are two rotavirus vaccines currently licensed in the United States and prequalified by the World Health Organization. RV1 is a monovalent attenuated human rotavirus strain, given orally in two doses. RV5 is a pentavalent human-bovine reassortant rotavirus vaccine, given orally in three doses. A third rotavirus vaccine, LLV, is a lamb rotavirus strain given orally as a single dose, which is currently available only in China. RV1 and RV5 have been shown to be highly efficacious in developed countries, and initial results from trials in Africa and Asia are promising as well. At least three other vaccines are in development, which are being developed by manufacturers of developing countries. Further studies are needed to clarify issues including administration of oral rotavirus vaccines with breastfeeding and other oral vaccines, and alterations in dosing schedule. Using new data on global diarrheal burden, rotavirus is estimated to cause 390,000 deaths in children younger than 5 years. Should rotavirus vaccines be introduced in the routine immunization programs of all countries, a potential of 170,000 deaths could be prevented annually. The largest impact on mortality would be seen in low-income and middle-income countries, despite poor immunization coverage and lower efficacy. Therefore, international efforts are needed to ensure that rotavirus vaccines reach the populations with highest burden of rotavirus disease.Keywords: vaccination, mortality, rotavirus, gastroenteritis

  15. Development of a rotavirus vaccine: clinical safety, immunogenicity, and efficacy of the pentavalent rotavirus vaccine, RotaTeq.

    Science.gov (United States)

    Ciarlet, Max; Schödel, Florian

    2009-12-30

    Initial approaches for rotavirus vaccines were based on the classical "Jennerian" approach and utilized simian and bovine rotavirus strains, which provided cross-protection against human rotavirus strains but did not cause illness in infants and young children because of their species-specific tropism. The demonstrated efficacy of these vaccines was not consistent across studies. Thus, human-animal reassortants containing an animal rotavirus backbone with human rotavirus surface G and/or P proteins were developed, which demonstrated more consistent efficacy than that observed with the non-reassortant rotavirus strains. The pentavalent rotavirus vaccine, RotaTeq, contains 5 human-bovine reassortant rotaviruses consisting of a bovine (WC3) backbone with human rotavirus surface proteins representative of the most common G (G1, G2, G3, G4) or P (P1A[8]) types worldwide. The present review focuses on the development of the pentavalent rotavirus vaccine RotaTeq. Results of a large-scale Phase III clinical study showed that three doses of RotaTeq were immunogenic, efficacious, and well tolerated with no increased clinical risk of intussusception. RotaTeq was efficacious against rotavirus gastroenteritis of any severity (74%) and severe disease (98-100%), using a validated clinical scoring system. Reductions in rotavirus-associated hospitalizations and emergency department (ED) visits, for up to 2 years post-vaccination, were 95% in Europe, 97% in the United States, and 90% in the Latin American/Caribbean regions. RotaTeq was recently shown to be up to 100% effective in routine use in the US in reducing hospitalizations and ED visits and 96% effective in reducing physician visits. Additional studies in 8 different locations in the US have shown 85-95% reduction in rotavirus-associated hospitalizations and/or ED visits in the first 2-2.5 years of routine use.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

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

    Science.gov (United States)

    Zaman, K; Sack, David A; Neuzil, Kathleen M; Yunus, Mohammad; Moulton, Lawrence H; Sugimoto, Jonathan D; Fleming, Jessica A; Hossain, Ilias; Arifeen, Shams El; Azim, Tasnim; Rahman, Mustafizur; Lewis, Kristen D C; Feller, Andrea J; Qadri, Firdausi; Halloran, M Elizabeth; Cravioto, Alejandro; Victor, John C

    2017-04-01

    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, 23.2% to 55

  19. Rotavirus vaccination in Europe: drivers and barriers.

    Science.gov (United States)

    Parez, N; Giaquinto, C; Du Roure, C; Martinon-Torres, F; Spoulou, V; Van Damme, P; Vesikari, T

    2014-05-01

    Rotavirus gastroenteritis is a vaccine-preventable disease that confers a high medical and economic burden in more developed countries and can be fatal in less developed countries. Two vaccines with high efficacy and good safety profiles were approved and made available in Europe in 2006. We present an overview of the status of rotavirus vaccination in Europe. We discuss the drivers (including high effectiveness and effect of universal rotavirus vaccination) and barriers (including low awareness of disease burden, perception of unfavourable cost-effectiveness, and potential safety concerns) to the implementation of universal rotavirus vaccination in Europe. By February, 2014, national universal rotavirus vaccination had been implemented in Belgium, Luxembourg, Austria, Finland, Greece, Luxembourg, Norway, and the UK. Four other German states have issued recommendations and reimbursement is provided by sickness funds. Other countries were at various stages of recommending or implementing universal rotavirus vaccination. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Human rotavirus vaccine is highly efficacious when coadministered with routine expanded program of immunization vaccines including oral poliovirus vaccine in Latin America.

    Science.gov (United States)

    Tregnaghi, Miguel W; Abate, Héctor J; Valencia, Alejandra; Lopez, Pio; Da Silveira, Themis Reverbel; Rivera, Luis; Rivera Medina, Doris Maribel; Saez-Llorens, Xavier; Gonzalez Ayala, Silvia Elena; De León, Tirza; Van Doorn, Leen-Jan; Pilar Rubio, Maria Del; Suryakiran, Pemmaraju Venkata; Casellas, Javier M; Ortega-Barria, Eduardo; Smolenov, Igor V; Han, Htay-Htay

    2011-06-01

    The efficacy of a rotavirus vaccine against severe rotavirus gastroenteritis when coadministered with routine Expanded Program on Immunization (EPI) vaccines including oral polio vaccine (OPV) was evaluated in this study. Double-blind, randomized (2:1), placebo-controlled study conducted across 6 Latin American countries. Healthy infants (N = 6568) 6 to 12 weeks of age received 2 doses of RIX4414 vaccine or placebo following a 0, 1- to 2-month schedule. Routine vaccines including OPV were coadministered according to local EPI schedule. Vaccine efficacy (VE) against severe rotavirus gastroenteritis caused by circulating wild-type rotavirus from 2 weeks post-Dose 2 until 1 year of age was calculated with 95% confidence interval [CI]. Safety was assessed during the entire study period. Immunogenicity of RIX4414 and OPV was also assessed. During the efficacy follow-up period (mean duration = 7.4 months), 7 and 19 cases of severe rotavirus gastroenteritis were reported in the vaccine and placebo groups, respectively, with a VE of 81.6% (95% CI: 54.4-93.5). VE against severe rotavirus gastroenteritis caused by G1 type was 100% (95% CI: rotavirus types, respectively. There was no difference (P = 0.514) in the incidence of serious adverse events reported in the 2 groups. Antirotavirus IgA seropositivity rate at 1 to 2 months post-Dose 2 was 61.4% (95% CI: 53.7-68.6) in the RIX4414 group; similar seroprotection rates (≥96.0%) against the 3 antipoliovirus types was observed 1 month post-Dose 3 of OPV in both groups. RIX4414 was highly efficacious against severe rotavirus gastroenteritis caused by the circulating wild-type rotavirus (G1 and non-G1) when coadministered with routine EPI vaccines including OPV.

  1. Molecular and biological characterization of the 5 human-bovine rotavirus (WC3)-based reassortant strains of the pentavalent rotavirus vaccine, RotaTeq (registered)

    International Nuclear Information System (INIS)

    Matthijnssens, Jelle; Joelsson, Daniel B.; Warakomski, Donald J.; Zhou, Tingyi; Mathis, Pamela K.; Maanen, Marc-Henri van; Ranheim, Todd S.; Ciarlet, Max

    2010-01-01

    RotaTeq (registered) is a pentavalent rotavirus vaccine that contains five human-bovine reassortant strains (designated G1, G2, G3, G4, and P1) on the backbone of the naturally attenuated tissue culture-adapted parental bovine rotavirus (BRV) strain WC3. The viral genomes of each of the reassortant strains were completely sequenced and compared pairwise and phylogenetically among each other and to human rotavirus (HRV) and BRV reference strains. Reassortants G1, G2, G3, and G4 contained the VP7 gene from their corresponding HRV parent strains, while reassortants G1 and G2 also contained the VP3 gene (genotype M1) from the HRV parent strain. The P1 reassortant contained the VP4 gene from the HRV parent strain and all the other gene segments from the BRV WC3 strain. The human VP7s had a high level of overall amino acid identity (G1: 95-99%, G2: 94-99% G3: 96-100%, G4: 93-99%) when compared to those of representative rotavirus strains of their corresponding G serotypes. The VP4 of the P1 reassortant had a high identity (92-97%) with those of serotype P1A[8] HRV reference strains, while the BRV VP7 showed identities ranging from 91% to 94% to those of serotype G6 HRV strains. Sequence analyses of the BRV or HRV genes confirmed that the fundamental structure of the proteins in the vaccine was similar to those of the HRV and BRV references strains. Sequences analyses showed that RotaTeq (registered) exhibited a high degree of genetic stability as no mutations were identified in the material of each reassortant, which undergoes two rounds of replication cycles in cell culture during the manufacturing process, when compared to the final material used to fill the dosing tubes. The infectivity of each of the reassortant strains of RotaTeq (registered) , like HRV strains, did not require the presence of sialic acid residues on the cell surface. The molecular and biologic characterization of RotaTeq (registered) adds to the significant body of clinical data supporting the

  2. 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.

  3. 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.

  4. Inactivated rotavirus vaccine induces protective immunity in gnotobiotic piglets.

    Science.gov (United States)

    Wang, Yuhuan; Azevedo, Marli; Saif, Linda J; Gentsch, Jon R; Glass, Roger I; Jiang, Baoming

    2010-07-26

    Live oral rotavirus vaccines that are effective in middle and high income countries have been much less immunogenic and effective among infants in resource-limited settings. Several hypotheses might explain this difference, including neutralization of the vaccine by high levels of maternal antibody in serum and breast milk, severe malnutrition, and interference by other flora and viruses in the gut. We have pursued development of an alternative parenteral rotavirus vaccine with the goal of inducing comparable levels of immunogenicity and efficacy in populations throughout the world regardless of their income levels. In the present study, we assessed the immunogenicity and protection of a candidate inactivated rotavirus vaccine (IRV), the human strain CDC-9 (G1P[8]) formulated with aluminum phosphate, against rotavirus infection in gnotobiotic piglets. Three doses of IRV induced high titers of rotavirus-specific IgG and neutralizing activity in the sera of gnotobiotic piglets and protection against shedding of rotavirus antigen following oral challenge with a homologous virulent human strain Wa (G1P[8]). Our findings demonstrate the proof of concept for an IRV in a large animal model and provide evidence and justification for further clinical development as an alternative candidate vaccine. Published by Elsevier Ltd.

  5. 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

  6. 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.

  7. Efficacy of human rotavirus vaccine against severe gastroenteritis in Malawian children in the first two years of life: a randomized, 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

    2012-04-27

    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 1773 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 to 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 to the G1P[8

  8. Rotavirus vaccine effectiveness in preventing hospitalizations due to gastroenteritis: a descriptive epidemiological study from Germany.

    Science.gov (United States)

    Pietsch, C; Liebert, U G

    2018-04-10

    Rotavirus infections are common causes of infant hospitalization. The present study examined the effectiveness of anti-rotavirus vaccination in preventing rotavirus-related hospitalizations in Germany, following its state and nationwide introductions in 2008 and 2013, respectively. During 15 consecutive seasons 9557 stool samples of hospitalized children of 5 years and younger with acute gastroenteritis were screened for rotavirus A. Rotavirus G and P genotypes were assessed after vaccine introduction. Vaccine effectiveness was determined by comparison of rotavirus incidence in pre-vaccine and post-vaccine cohorts. The herd effect was calculated as the difference between the observed reduction of rotavirus-related hospitalizations and the expected direct vaccine effect. The number of rotavirus-related hospitalizations declined after vaccine introduction. Approximately 26% (503/1955) of prevented cases could be attributed to the herd effect. Human rotaviruses of genotypes G3P[8], G1P[8], G9P[8], G4P[8], G2P[4] and G12P[8] were most frequent. Uncommon genotypes remained rare. The direct, indirect, total and overall vaccine effectiveness was 86% (95% confidence interval (CI) 83.2-89.1%), 48% (95% CI 42.8-52.6%), 93% (95% CI 91.3-94.3%) and 69% (95% CI 66.5-72.0%), respectively. There was no significant difference in vaccine-type or in genotype-specific vaccine effectiveness. Anti-rotavirus vaccination efficiently reduced rotavirus-related hospitalizations in Germany in the past decade. The vaccines analysed in this article provide a broadly heterologous and long-lasting protection. The herd effect substantially contributed to the observed drop in the number of incidences of severe rotavirus infections. Presumably, constant high vaccine coverage will lead to a continued upward trend in the overall vaccine efficiency. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  9. Efficacy, safety and immunogenicity of a human rotavirus vaccine (RIX4414) in Hong Kong children up to three years of age: a randomized, controlled trial.

    Science.gov (United States)

    Lau, Yu-Lung; Nelson, E Anthony S; Poon, Kin-Hung; Chan, Paul K S; Chiu, Susan; Sung, Rita; Leung, Chi Wai; Ng, Daniel; Ma, Yee Man; Chan, Desmond; Lee, Tsz Leung; Tang, Joyce; Kwan, Yat Wah; Ip, Patricia; Ho, Marco; Fung, Lai-Wah Eva; Tang, Haiwen; Suryakiran, P V; Han, Htay Htay; Bock, Hans

    2013-04-26

    A phase III, double-blind, randomized, controlled trial was conducted in Hong Kong to evaluate the efficacy, safety and immunogenicity of a human rotavirus vaccine, RIX4414 (Rotarix) against severe rotavirus gastroenteritis in children up to three years of age. Healthy infants aged 6-12 weeks were enrolled between 08-December-2003 and 31-August-2005 and received two oral doses of either RIX4414 vaccine (N=1513) or placebo (N=1512) given 2 months apart. Vaccine efficacy was assessed from two weeks post-Dose 2 until the children were two and three years of age. Anti-rotavirus IgA seroconversion rate was calculated pre-vaccination and 1-2 months post-Dose 2 using ELISA (cut-off=20 U/mL) for 100 infants. Safety was assessed until the children were two years of age; serious adverse events (SAEs) were recorded throughout the study period. In children aged two and three years of life, vaccine efficacy against severe rotavirus gastroenteritis was 95.6% (95% CI: 73.1%-99.9%) and 96.1% (95% CI: 76.5%-99.9%), respectively. The seroconversion rate 1-2 months after the second dose of RIX4414 was 97.5% (95% CI: 86.8%-99.9%). At least one SAE was recorded in 439 and 477 infants who were administered RIX4414 and placebo, respectively (p-value=0.130). Six intussusception cases were reported (RIX4414=4; placebo=2) and none was assessed to be vaccine-related. RIX4414 was efficacious, immunogenic and safe in the prevention of rotavirus gastroenteritis for at least two years post-vaccination in Hong Kong children. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. 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.

  11. 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, G V J A; Prasad, Sai; Rao, T S; Boslego, John; Bhan, Maharaj Kishan

    2014-06-21

    Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed in these countries. We aimed to assess the efficacy and tolerability of a monovalent human-bovine rotavirus vaccine for severe rotavirus gastroenteritis in low-resource urban and rural settings in India. We did a randomised double-blind, placebo-controlled, multicentre trial at three sites in Delhi (urban), Pune (rural), and Vellore (urban and rural) between March 11, 2011, and Nov 5, 2012. Infants aged 6-7 weeks were randomly assigned (2:1), via a central interactive voice or web response system with a block size of 12, to receive either three doses of oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6-7 weeks, 10 weeks, and 14 weeks. Infants' families, study investigators, paediatricians in referral hospitals, laboratory staff, and committee members were all masked to treatment allocation. The primary outcome was incidence of severe rotavirus gastroenteritis (≥11 on the Vesikari scale). Efficacy outcomes and adverse events were ascertained through active surveillance. Analysis was by intention to treat and per protocol. The trial is registered with Clinical Trial Registry-India (CTRI/2010/091/000102) and ClinicalTrials.gov (NCT01305109). 4532 infants were assigned to receive the 116E vaccine and 2267 to receive placebo, of whom 4354 (96%) and 2187 (96%) infants, respectively, were included in the primary per-protocol efficacy analysis. 71 events of severe rotavirus gastroenteritis were reported in 4752 person-years in infants in the vaccine group compared with 76 events in 2360 person-years in those in the placebo group; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0-66·9; p=0·0013) and 56·4% (36·6-70·1; protavirus gastroenteritis episode was 55 (95% CI 37-97). The incidence of severe rotavirus gastroenteritis per 100 person-years was 1·5

  12. Public health impact and cost effectiveness of mass vaccination with live attenuated human rotavirus vaccine (RIX4414) in India: model based analysis.

    Science.gov (United States)

    Rose, Johnie; Hawthorn, Rachael L; Watts, Brook; Singer, Mendel E

    2009-09-25

    To examine the public health impact of mass vaccination with live attenuated human rotavirus vaccine (RIX4414) in a birth cohort in India, and to estimate the cost effectiveness and affordability of such a programme. Decision analytical Markov model encompassing all direct medical costs. Infection risk and severity depended on age, number of previous infections, and vaccination history; probabilities of use of inpatient and outpatient health services depended on symptom severity. Published clinical, epidemiological, and economic data. When possible, parameter estimates were based on data specific for India. Population Simulated Indian birth cohort followed for five years. Decrease in rotavirus gastroenteritis episodes (non-severe and severe), deaths, outpatient visits, and admission to hospital; incremental cost effectiveness ratio of vaccination expressed as net cost in 2007 rupees per life year saved. In the base case, vaccination prevented 28,943 (29.7%) symptomatic episodes, 6981 (38.2%) severe episodes, 164 deaths (41.0%), 7178 (33.3%) outpatient visits, and 812 (34.3%) admissions to hospital per 100,000 children. Vaccination cost 8023 rupees (about pound100, euro113, $165) per life year saved, less than India's per capita gross domestic product, a common criterion for cost effectiveness. The net programme cost would be equivalent to 11.6% of the 2006-7 budget of the Indian Department of Health and Family Welfare. Model results were most sensitive to variations in access to outpatient care for those with severe symptoms. If this parameter was increased to its upper limit, the incremental cost effectiveness ratio for vaccination still fell between one and three times the per capita gross domestic product, meeting the World Health Organization's criterion for "cost effective" interventions. Uncertainty analysis indicated a 94.7% probability that vaccination would be cost effective according to a criterion of one times per capita gross domestic product per life

  13. Rotavirus vaccines in Israel: Uptake and impact.

    Science.gov (United States)

    Muhsen, Khitam; Cohen, Daniel

    2017-07-03

    We present an overview of the impact of universal rotavirus immunization with the pentavalent vaccine, RotaTeq, which was introduced in Israel in 2010. The vaccine is given free of charge at age 2, 4 and 6 months, with an 80% coverage that was shortly achieved during the universal immunization period. Compared to pre-universal immunization years (2008-2010), a reduction of 66-68% in the incidence of rotavirus gastroenteritis (RVGE) hospitalizations was observed in 2011-2015 among children aged 0-23 months in central and northern Israel. In southern Israel a reduction of 80-88% in RVGE hospital visit rate was found among Jewish children aged 0-23 months in 2011-2013. Among Bedouins, the respective decline was 62-75%. A significant reduction of 59% was also observed in RVGE clinic visits, presumably representing less severe illness. Indirect benefit was evident in children aged 24-59 months who were ineligible for universal immunization. Vaccine effectiveness against RVGE hospitalization was estimated at 86% in children aged 6-23 months. Changes in the circulating rotavirus genotypes occurred but the contribution of vaccine induced immune pressure is unclear. Universal rotavirus immunization was followed by an impressive decrease in the burden of RVGE in young children in Israel, likely attributed to good vaccine coverage and effectiveness.

  14. 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 rotavirus vaccine (BRV-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

  15. 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

  16. Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy infants.

    Science.gov (United States)

    Araujo, Eliete C; Clemens, Sue Ann C; Oliveira, Consuelo S; Justino, Maria Cleonice A; Rubio, Pilar; Gabbay, Yvone B; da Silva, Veronilce B; Mascarenhas, Joana D P; Noronha, Vânia L; Clemens, Ralf; Gusmão, Rosa Helena P; Sanchez, Nervo; Monteiro, Talita Antônia F; Linhares, Alexandre C

    2007-01-01

    To determine the safety, immunogenicity and efficacy of two doses of rotavirus vaccine in healthy Brazilian infants. 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 >or= 11 defined as severe GE. 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. RIX4414 was highly immunogenic with a low reactogenicity profile and did not interfere with seroresponse to diphtheria, tetanus, pertussis, hepatitis B and Hib antigens. Two doses of RIX4414 provided significant protection against severe GE caused by RV.

  17. Annual changes in rotavirus hospitalization rates before and after rotavirus vaccine implementation in the United States.

    Science.gov (United States)

    Shah, Minesh P; Dahl, Rebecca M; Parashar, Umesh D; Lopman, Benjamin A

    2018-01-01

    Hospitalizations for rotavirus and acute gastroenteritis (AGE) have declined in the US with rotavirus vaccination, though biennial peaks in incidence in children aged less than 5 years occur. This pattern may be explained by lower rotavirus vaccination coverage in US children (59% to 73% from 2010-2015), resulting in accumulation of susceptible children over two successive birth cohorts. Retrospective cohort analysis of claims data of commercially insured US children aged rotavirus and for AGE from the 2002-2015 rotavirus seasons were examined. Median age and rotavirus vaccination coverage for biennial rotavirus seasons during pre-vaccine (2002-2005), early post-vaccine (2008-2011) and late post-vaccine (2012-2015) years. Age-stratified hospitalization rates decreased from pre-vaccine to early post-vaccine and then to late post-vaccine years. The clearest biennial pattern in hospitalization rates is the early post-vaccine period, with higher rates in 2009 and 2011 than in 2008 and 2010. The pattern diminishes in the late post-vaccine period. For rotavirus hospitalizations, the median age and the difference in age between biennial seasons was highest during the early post-vaccine period; these differences were not observed for AGE hospitalizations. There was no significant difference in vaccination coverage between biennial seasons. These observations provide conflicting evidence that incomplete vaccine coverage drove the biennial pattern in rotavirus hospitalizations that has emerged with rotavirus vaccination in the US. As this pattern is diminishing with higher vaccine coverage in recent years, further increases in vaccine coverage may reach a threshold that eliminates peak seasons in hospitalizations.

  18. 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

  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. Efficacy and safety of an oral live attenuated human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in Latin American infants: a randomised, double-blind, placebo-controlled phase III study.

    Science.gov (United States)

    Linhares, Alexandre C; Velázquez, F Raúl; Pérez-Schael, Irene; Sáez-Llorens, Xavier; Abate, Hector; Espinoza, Felix; López, Pío; Macías-Parra, Mercedes; Ortega-Barría, Eduardo; Rivera-Medina, Doris Maribel; Rivera, Luis; Pavía-Ruz, Noris; Nuñez, Ernesto; Damaso, Silvia; Ruiz-Palacios, Guillermo M; De Vos, Béatrice; O'Ryan, Miguel; Gillard, Paul; Bouckenooghe, Alain

    2008-04-05

    Peak incidence of rotavirus gastroenteritis is seen in infants between 6 and 24 months of age. We therefore aimed to assess the 2-year efficacy and safety of an oral live attenuated human rotavirus vaccine for prevention of severe gastroenteritis in infants. 15 183 healthy infants aged 6-13 weeks from ten Latin American countries randomly assigned in a 1 to 1 ratio to receive two oral doses of RIX4414 or placebo at about 2 and 4 months of age in a double-blind, placebo-controlled phase III study were followed up until about 2 years of age. Primary endpoint was vaccine efficacy from 2 weeks after dose two until 1 year of age. Treatment allocation was concealed from investigators and parents of participating infants. Efficacy follow-up for gastroenteritis episodes was undertaken from 2 weeks after dose two until about 2 years of age. Analysis was according to protocol. This study is registered with ClinicalTrials.gov, number NCT00140673 (eTrack444563-023). 897 infants were excluded from the according-to-protocol analysis. Fewer cases (protavirus gastroenteritis were recorded for the combined 2-year period in the RIX4414 group (32 [0.4%] of 7205; 95% CI 0.3-0.6) than in the placebo group (161 [2.3%] of 7081; 1.9-2.6), resulting in a vaccine efficacy of 80.5% (71.3-87.1) to 82.1% (64.6-91.9) against wild-type G1, 77.5% (64.7-86.2) against pooled non-G1 strains, and 80.5% (67.9-88.8) against pooled non-G1 P[8] strains. Vaccine efficacy for hospital admission for rotavirus gastroenteritis was 83.0% (73.1-89.7) and for admission for diarrhoea of any cause was 39.3% (29.1-48.1). No cases of intussusception were reported during the second year of follow-up. Two doses of RIX4414 were effective against severe rotavirus gastroenteritis during the first 2 years of life in a Latin American setting. Inclusion of RIX4414 in routine paediatric immunisations should reduce the burden of rotavirus gastroenteritis worldwide.

  1. Group A rotavirus gastroenteritis: post-vaccine era, genotypes and zoonotic transmission

    Science.gov (United States)

    Luchs, Adriana; Timenetsky, Maria do Carmo Sampaio Tavares

    2016-01-01

    ABSTRACT This article provides a review of immunity, diagnosis, and clinical aspects of rotavirus disease. It also informs about the changes in epidemiology of diarrheal disease and genetic diversity of circulating group A rotavirus strains following the introduction of vaccines. Group A rotavirus is the major pathogen causing gastroenteritis in animals. Its segmented RNA genome can lead to the emergence of new or unusual strains in human populations via interspecies transmission and/or reassortment events. PMID:27462899

  2. 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 rotavirus-related AGE was assessed using data from the active surveillance hospitals. Compared with the 2001-2008 pre-vaccine baseline, the mean number of rotavirus-related hospitalizations was reduced by 40.8% (95% confidence interval (CI) 21.7-66.4%) among children rotavirus disease. Over the post-vaccine period, changes in rotavirus epidemiology were observed, manifested by variations in seasonality and by a shift in the mean age of those with rotavirus infection. The significant decrease in main AGE-related health indicators in children rotavirus vaccine provides evidence of a substantial public health impact of rotavirus vaccination in Bolivia, as a measure for protecting children against AGE. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Lack of nonspecific protection against all-cause nonrotavirus gastroenteritis by vaccination with orally administered rotavirus vaccine.

    Science.gov (United States)

    Grant, Lindsay; Watt, James; Moulton, Lawrence; Weatherholtz, Robert; Reid, Raymond; Santosham, Mathuram; O'Brien, Katherine

    2013-06-01

    Acute gastroenteritis (AGE) is recognized as a global, common threat to child survival, especially in developing countries. Rotavirus, in particular, has been implicated as a leading cause of severe AGE; however, there are numerous other pathogens that also cause AGE. Several studies have demonstrated that oral vaccination against rotavirus has generated the unanticipated benefit of protecting against AGE caused by nonrotavirus pathogens. Safety and efficacy of the pentavalent bovine-human reassortant rotavirus vaccine were studied in multiple populations, including children of the Navajo and White Mountain Apache tribes in the southwestern United States. Stool specimens were collected from children with AGE and tested for rotavirus using an enzyme immunoassay. Analyses were conducted to detect the presence or absence of a vaccine effect on incidence, severity, and duration of AGE in which rotavirus was not detected. The majority of AGE (N = 558: 472 nonrotavirus vs 86 rotavirus) occurred between August 2002 and March 2004 among children ranging from ages 4 to 23 months. The incidence of nonrotavirus AGE was similar by vaccine groups with an incidence rate ratio of 1.07 (incidence rate ratio = vaccinated/unvaccinated, 95% confidence interval 0.89-1.29). The hazards of first, second, third, or any AGE in which rotavirus was not detected differed little by vaccination status (P > 0.05). Duration of symptoms and severity of nonrotavirus AGE were similar by vaccine group. There was no vaccine effect on frequency or severity of nonrotavirus AGE.

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

    Directory of Open Access Journals (Sweden)

    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

  5. Dynamic modeling of cost-effectiveness of rotavirus vaccination, Kazakhstan.

    Science.gov (United States)

    Freiesleben de Blasio, Birgitte; Flem, Elmira; Latipov, Renat; Kuatbaeva, Ajnagul; Kristiansen, Ivar Sønbø

    2014-01-01

    The government of Kazakhstan, a middle-income country in Central Asia, is considering the introduction of rotavirus vaccination into its national immunization program. We performed a cost-effectiveness analysis of rotavirus vaccination spanning 20 years by using a synthesis of dynamic transmission models accounting for herd protection. We found that a vaccination program with 90% coverage would prevent ≈880 rotavirus deaths and save an average of 54,784 life-years for children vaccine cost at vaccination program costs would be entirely offset. To further evaluate efficacy of a vaccine program, benefits of indirect protection conferred by vaccination warrant further study.

  6. Performance of rotavirus vaccines in developed and developing countries

    OpenAIRE

    Jiang, Victoria; Jiang, Baoming; Tate, Jacqueline; Parashar, Umesh D; Patel, Manish M

    2010-01-01

    The World Health Organization estimates that rotavirus diarrhea results in approximately half a million deaths and approximately 2.4 million hospitalizations in developing countries each year. Two live oral rotavirus vaccines, RotaTeq® (RV 5; Merck) and Rotarix® (RV 1; GlaxoSmithKline) with good efficacy against severe rotavirus disease and a reassuring safety profile could substantially impact the burden of rotavirus disease. In April 2009, WHO provided a recommendation for global introducti...

  7. Rotavirus Vaccines: a story of success with challenges ahead

    Science.gov (United States)

    O’Ryan, Miguel

    2017-01-01

    Approximately 40 years have passed since the discovery of the rotavirus and 10 years since the introduction and progressive dissemination of rotavirus vaccines worldwide. Currently, 92 countries have introduced rotavirus vaccines into national or subnational programs with evident impact in disease reduction. Two vaccines have been widely used, and four additional vaccines have been licensed and are being used in defined regions. In this context, one main issue that remains unsolved is the lower vaccine efficacy/effectiveness in low-income countries. An additional partially answered issue relates to rotavirus strain circulation in vaccinated populations. These issues are discussed in this review. The most imperative challenge ahead is to fulfill the WHO’s recommendation to introduce rotavirus vaccines in all countries. PMID:28928954

  8. 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

  9. 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

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

    Science.gov (United States)

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

    2017-04-03

    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.

  11. 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.

  12. 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

  13. 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.

  14. Efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RV5) in healthy Chinese infants: A randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Mo, Zhaojun; Mo, Yi; Li, Mingqiang; Tao, Junhui; Yang, Xu; Kong, Jilian; Wei, Dingkai; Fu, Botao; Liao, Xueyan; Chu, Jianli; Qiu, Yuanzheng; Hille, Darcy A; Nelson, Micki; Kaplan, Susan S

    2017-10-13

    A randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RotaTeq™, RV5) against rotavirus gastroenteritis (RVGE). 4040 participants aged 6-12weeks were enrolled and randomly assigned to either 3 oral doses of RV5 (n=2020) or placebo (n=2020), administered ∼4weeks apart. The participants also received OPV and DTaP in a concomitant or staggered fashion. The primary objective was to evaluate vaccine efficacy (VE) against naturally-occurring RVGE at least 14days following the third dose. Key secondary objectives included: VE against naturally-occurring severe RVGE and VE against severe and any-severity RVGE caused by rotavirus serotypes contained in the vaccine, occurring at least 14days after the third dose. All adverse events (AEs) were collected for 30days following each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. (ClinicalTrials.gov registry: NCT02062385). VE against RVGE of any-severity caused by any serotype was 69.3% (95% CI: 54.5, 79.7). The secondary efficacy analysis showed an efficacy of: 78.9% (95% CI: 59.1, 90.1) against severe RVGE caused by any serotype; 69.9% (95% CI: 55.2, 80.3) and 78.9% (95% CI: 59.1, 90.1) against any-severity and severe RVGE caused by serotypes contained in the vaccine, respectively. Within 30days following any vaccination, 53.5% (1079/2015) and 53.3% (1077/2019) of participants reported at least one AE, and 5.8% (116/2015) and 5.7% (116/2019) reported SAEs in the vaccine and placebo groups, respectively. No SAEs were considered vaccine-related in recipients of RV5. Two intussusception cases were reported in recipients of RV5 who recovered after receiving treatment. Neither was considered vaccine-related. In Chinese infants, RV5 was efficacious against any-severity and severe RVGE caused by any serotype and generally well

  15. Impact and Effectiveness of Monovalent Rotavirus Vaccine Against Severe Rotavirus Diarrhea in Ghana.

    Science.gov (United States)

    Armah, George; Pringle, Kimberly; Enweronu-Laryea, Christabel C; Ansong, Daniel; Mwenda, Jason M; Diamenu, Stanley K; Narh, Clement; Lartey, Belinda; Binka, Fred; Grytdal, Scott; Patel, Manish; Parashar, Umesh; Lopman, Ben

    2016-05-01

    Ghana was among the first African nations to introduce monovalent rotavirus vaccine (RV1) into its childhood immunization schedule in April 2012. We aimed to assess the impact of vaccine introduction on rotavirus and acute gastroenteritis (AGE) hospitalizations and to estimate vaccine effectiveness (VE). Using data from 2 teaching hospitals, monthly AGE and rotavirus admissions by age were examined 40 months before and 31 months after RV1 introduction using interrupted time-series analyses. From January 2013, we enrolled children vaccination by rotavirus case-patient status, controlling for potential confounders. Vaccine coverage ranged from 95% to 100% for dose 1 and 93% to 100% for dose 2. In the first 3 years after vaccine introduction, the percentage of hospital admissions positive for rotavirus fell from 48% in the prevaccine period to 28% (49% adjusted rate reduction; 95% confidence interval [CI], 32%-63%) postvaccination among vaccine coverage, it was not possible to arrive at robust VE estimates; any-dose VE against rotavirus hospitalization was estimated at 60% (95% CI, -2% to 84%;P= .056). Results from the first 3 years following RV1 introduction suggest substantial reductions of pediatric diarrheal disease as a result of vaccination. Our VE estimate is consistent with the observed rotavirus decrease and with efficacy estimates from elsewhere in sub-Saharan Africa. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  16. Diarrheal Diseases Hospitalization in Yemen before and after Rotavirus Vaccination

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    Mohammed Amood AL-Kamarany

    2016-01-01

    Full Text Available The study aims to assess the impact of rotavirus vaccine introduction on diarrheal diseases hospitalization and to identify the rotavirus genotypes most prevalent before and after vaccine introduction among children ≤ 5 years of age. Rotarix™ ® rotavirus vaccine is currently licensed for infants in Yemen and was introduced in 2012. The vaccination course consists of two doses. The first dose is administrated at 6 weeks of age and the second dose is completed by 10 weeks. Based on a longitudinal observational study, we assessed the impact of vaccination on rotavirus hospitalization before and after vaccination among children ≤ 5 years of age at the Yemeni-Swedish Hospital (YSH in Taiz, Yemen. Prevaccination covered January 2009–July 2012 during which 2335 fecal samples were collected from children ≤ 5 years old. Postvaccination covered January 2013–December 2014 during which 1114 fecal samples were collected. Rotavirus was detected by Enzyme Linkage Immunosorbent Assay (ELISA. The incidence of rotavirus hospitalization decreased from 43.79% in 2009 to 10.54% in 2014. Hospitalization due to rotavirus diarrhea was reduced by 75.93%. Vaccine coverage increased from 23% in 2012 to 72% in 2014. Also, the results showed that the most predominant genotypes in prevaccination period were G2P[4] (55.0%, followed by G1P[8] (15.0%, while in postvaccination period G1P[8] (31% was the predominant genotype, followed by G9P[8] (27.5%. In conclusion, rotavirus vaccination in Yemen resulted in sharp reduction in diarrheal hospitalization. A successful rotavirus vaccination program in Yemen will rely upon efficient vaccine delivery systems and sustained vaccine efficacy against diverse and evolving rotavirus strains.

  17. Human rotavirus vaccine (RIX4414) efficacy in the first two years of life: a randomized, placebo-controlled trial in China.

    Science.gov (United States)

    Li, Rong-cheng; Huang, Teng; Li, Yanping; Luo, Dong; Tao, Junhui; Fu, Botao; Si, Guoai; Nong, Yi; Mo, Zhaojun; Liao, XueYan; Luan, Ivy; Tang, Haiwen; Rathi, Niraj; Karkada, Naveen; Han, Htay Htay

    2014-01-01

    Rotaviruses (RV) are a major cause of severe gastroenteritis (GE) in children agedefficacy of two oral doses of the human rotavirus vaccine (RIX4414) in infants during the first two years of life (113808/NCT01171963). Healthy infants aged 6-16 weeks were randomized (1:1) to receive two oral doses of either the RIX4414 vaccine/placebo according to a 0, 1 month schedule. Vaccine efficacy (VE) against severe RVGE was assessed from two weeks post-Dose 2 up until the end of the second RV season and calculated with its 95% confidence intervals (CI). The primary efficacy objective was met if the lower limit of the 95% CI on VE was ≥10%. Unsolicited symptoms reported during the 31-d post-vaccination follow-up period and serious adverse events (SAEs) reported throughout the study were assessed. Of 3333 enrolled infants, 3148 were included in the according-to-protocol efficacy cohort. Over two consecutive RV seasons, fewer severe RVGE episodes were reported in the RIX4414 group (n=21) vs. the placebo group (n=75). VE against severe RVGE was 72% (95% CI: 54.1-83.6); the lower limit of the 95% CI on VE was >10%. The number of unsolicited symptoms and SAEs reported was similar between both groups. Thirteen deaths (RIX4414=6; placebo=7) occurred during the study. All SAEs and deaths in the RIX4414 group were considered unrelated to vaccination. Two oral doses of RIX4414 vaccine provided a substantial level of protection against severe RVGE in Chinese children during the first two years of life.

  18. Influence of oral polio vaccines on performance of the monovalent and pentavalent rotavirus vaccines.

    Science.gov (United States)

    Patel, Manish; Steele, A Duncan; Parashar, Umesh D

    2012-04-27

    In recent years, two live, oral rotavirus vaccines have been successfully tested in developing and industrialized countries, and both vaccines are now recommended by the World Health Organization for all children worldwide. Both immunogenicity and efficacy of these rotavirus vaccines has been lower in developing compared to industrialized settings. We reviewed the data on the effect of trivalent OPV on the immunogenicity and efficacy of two rotavirus vaccines currently recommended by the WHO. While rotavirus vaccines have not affected immune responses to OPV, in general, the immune responses (i.e., antibody levels) to rotavirus vaccination were lower when rotavirus vaccines were co-administered with OPV. Limited data suggests that the interference is greater after the first dose of OPV, presumably because the first dose is associated with greatest intestinal replication of vaccine polio virus strains, and this interference is largely overcome with subsequent rotavirus vaccine doses. Despite the lower immunogenicity, one large efficacy study in middle income Latin American countries showed no decrease in protective efficacy of rotavirus vaccine in infants receiving concurrent OPV. While these data are encouraging and support simultaneous administration of rotavirus vaccines and OPV, additional evidence should be gathered as rotavirus vaccines are used more widely in developing country settings, where OPV is routinely used, rather than inactivated polio vaccine. Published by Elsevier Ltd.

  19. Impact and cost-effectiveness of rotavirus vaccination in Bangladesh.

    Science.gov (United States)

    Pecenka, Clint; Parashar, Umesh; Tate, Jacqueline E; Khan, Jahangir A M; Groman, Devin; Chacko, Stephen; Shamsuzzaman, Md; Clark, Andrew; Atherly, Deborah

    2017-07-13

    Diarrheal disease is a leading cause of child mortality globally, and rotavirus is responsible for more than a third of those deaths. Despite substantial decreases, the number of rotavirus deaths in children under five was 215,000 per year in 2013. Of these deaths, approximately 41% occurred in Asia and 3% of those in Bangladesh. While Bangladesh has yet to introduce rotavirus vaccination, the country applied for Gavi support and plans to introduce it in 2018. This analysis evaluates the impact and cost-effectiveness of rotavirus vaccination in Bangladesh and provides estimates of the costs of the vaccination program to help inform decision-makers and international partners. This analysis used Pan American Health Organization's TRIVAC model (version 2.0) to examine nationwide introduction of two-dose rotavirus vaccination in 2017, compared to no vaccination. Three mortality scenarios (low, high, and midpoint) were assessed. Benefits and costs were examined from the societal perspective over ten successive birth cohorts with a 3% discount rate. Model inputs were locally acquired and complemented by internationally validated estimates. Over ten years, rotavirus vaccination would prevent 4000 deaths, nearly 500,000 hospitalizations and 3 million outpatient visits in the base scenario. With a Gavi subsidy, cost/disability adjusted life year (DALY) ratios ranged from $58/DALY to $142/DALY averted. Without a Gavi subsidy and a vaccine price of $2.19 per dose, cost/DALY ratios ranged from $615/DALY to $1514/DALY averted. The discounted cost per DALY averted was less than the GDP per capita for nearly all scenarios considered, indicating that a routine rotavirus vaccination program is highly likely to be cost-effective. Even in a low mortality setting with no Gavi subsidy, rotavirus vaccination would be cost-effective. These estimates exclude the herd immunity benefits of vaccination, so represent a conservative estimate of the cost-effectiveness of rotavirus vaccination

  20. A randomized Phase III clinical trial to assess the efficacy of a bovine-human reassortant pentavalent rotavirus vaccine in Indian infants.

    Science.gov (United States)

    Kulkarni, Prasad S; Desai, Sajjad; Tewari, Tushar; Kawade, Anand; Goyal, Nidhi; Garg, Bishan Swarup; Kumar, Dinesh; Kanungo, Suman; Kamat, Veena; Kang, Gagandeep; Bavdekar, Ashish; Babji, Sudhir; Juvekar, Sanjay; Manna, Byomkesh; Dutta, Shanta; Angurana, Rama; Dewan, Deepika; Dharmadhikari, Abhijeet; Zade, Jagdish K; Dhere, Rajeev M; Fix, Alan; Power, Maureen; Uprety, Vidyasagar; Parulekar, Varsha; Cho, Iksung; Chandola, Temsunaro R; Kedia, Vikash K; Raut, Abhishek; Flores, Jorge

    2017-10-27

    Rotavirus is the most common cause of moderate-to-severe infant diarrhoea in developing countries, resulting in enormous morbidity, mortality, and economic burden. A bovine-human reassortant pentavalent rotavirus vaccine (BRV-PV) targeting the globally most common strains was developed in India and tested in a randomized, double-blind, placebo-controlled end-point driven Phase III efficacy clinical trial implemented at six sites across India. Infants 6 to 8weeks of age were randomized (1:1) to receive three oral doses of BRV-PV or placebo at 6, 10, and 14weeks of age along with routine vaccines. Home visit surveillance was conducted to detect severe rotavirus gastroenteritis (SRVGE) and safety outcomes until the children reached two years of age. A total of 3749 infants received BRV-PV while 3751 received placebo. At the time of the primary end-point (when the minimum number of cases needed for analysis were accrued) the vaccine efficacy against SRVGE was 36% (95% CI 11.7, 53.6, p=0.0067) in the per protocol (PP) analysis, and 41.9% (95% CI 21.1, 57.3, p=0.0005) in the intent to treat (ITT) analysis. Vaccine efficacy over the entire follow-up period (until children reached two years of age) was 39.5% (95% CI 26.7, 50, protavirus cases (VSRVGE, Vesikari score≥16) was 60.5% (95% CI 17.7, 81, p=0.0131) at the time of the primary analysis and 54.7% (95% CI 29.7, 70.8, p=0.0004) for the complete follow-period in the PP population. The incidence of solicited, unsolicited, and serious adverse events were similar in both the vaccine and placebo groups. Likewise, the number of intussusceptions and deaths were similar between both groups. Thus, BRV-PV is an effective, well tolerated and safe vaccine in Indian infants. (Trial registration: Clinical Trials.Gov [NCT 02133690] and Clinical Trial Registry of India [CTRI/2013/05/003667]). Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Cost-effectiveness of Rotavirus vaccination in Vietnam

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    Goldie Sue J

    2009-01-01

    Full Text Available Abstract Background Rotavirus is the most common cause of severe diarrhea leading to hospitalization or disease-specific death among young children. New rotavirus vaccines have recently been approved. Some previous studies have provided broad qualitative insights into the health and economic consequences of introducing the vaccines into low-income countries, representing several features of rotavirus infection, such as varying degrees of severity and age-dependency of clinical manifestation, in their model-based analyses. We extend this work to reflect additional features of rotavirus (e.g., the possibility of reinfection and varying degrees of partial immunity conferred by natural infection, and assess the influence of the features on the cost-effectiveness of rotavirus vaccination. Methods We developed a Markov model that reflects key features of rotavirus infection, using the most recent data available. We applied the model to the 2004 Vietnamese birth cohort and re-evaluated the cost-effectiveness (2004 US dollars per disability-adjusted life year [DALY] of rotavirus vaccination (Rotarix® compared to no vaccination, from both societal and health care system perspectives. We conducted univariate sensitivity analyses and also performed a probabilistic sensitivity analysis, based on Monte Carlo simulations drawing parameter values from the distributions assigned to key uncertain parameters. Results Rotavirus vaccination would not completely protect young children against rotavirus infection due to the partial nature of vaccine immunity, but would effectively reduce severe cases of rotavirus gastroenteritis (outpatient visits, hospitalizations, or deaths by about 67% over the first 5 years of life. Under base-case assumptions (94% coverage and $5 per dose, the incremental cost per DALY averted from vaccination compared to no vaccination would be $540 from the societal perspective and $550 from the health care system perspective. Conclusion

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

    African Journals Online (AJOL)

    2014-06-17

    Jun 17, 2014 ... vaccine with strains peculiar to this environment should be introduced. ..... Safety and efficacy of an attenuated vaccine against severe rotavirus ... prevalence of adenovirus serotypes 40 and 41, astrovirus, and rotavirus.

  3. NEW PREVENTION OPPORTUNITIES OF INFECTIOUS DISEASES. VACCINATION AGAINST ROTAVIRUS

    Directory of Open Access Journals (Sweden)

    T. A. Grechukha

    2013-01-01

    Full Text Available The article covers the problem of the burden of rotavirus disease. Rotavirus infection is the leading cause of mortality among children under 5 years of age and is a major problem for a public healthcare. The world is actively engaged in the prevention of rotavirus infection since 2005. There is a lot of data on the efficacy and safety of this vaccine. Different foreign investigations have shown the herd immunity of the vaccine. The authors present data about the effectiveness and safety of vaccines, established during clinical studies of the foreign scientists.

  4. Incorporation of a rotavirus vaccine into the national immunisation schedule in the United Kingdom: a review.

    Science.gov (United States)

    Nakagomi, Osamu; Iturriza-Gomara, Miren; Nakagomi, Toyoko; Cunliffe, Nigel A

    2013-11-01

    Rotavirus, the commonest cause of severe acute gastroenteritis in infants and young children worldwide, imposes a large health and economic burden on the British society, accounting for an estimated 14,300 hospitalisations and 133,000 general practitioner consultations each year among children aged rotavirus vaccine, Rotarix (GlaxoSmithKline Biologicals, Belgium), was introduced into the UK childhood immunisation programme in 2013. This article provides a review of the product profile of the Rotarix vaccine for use in the national immunisation programme in the UK from an expert perspective. This single G1P[8] strain-based human rotavirus vaccine has demonstrated high efficacy in preventing severe rotavirus gastroenteritis in the first 3 years of life in middle- and high-income countries. In countries that have adopted rotavirus vaccine in childhood immunisation programmes, indirect benefits (herd protection) have been observed among older, unvaccinated children and adults. When the first dose is administered between 6 and 14 weeks of age and the last dose by 24 weeks of age, Rotarix carries a small risk of intussusception within the week of vaccination. However, this small risk may at most result in a negligible population attributable risk at the end of the first year of life. Overall, the rotavirus immunisation programme is expected to provide substantial health benefits to the UK population.

  5. Rotavirus epidemiology and vaccine demand: considering Bangladesh chapter through the book of global disease burden.

    Science.gov (United States)

    Mahmud-Al-Rafat, Abdullah; Muktadir, Abdul; Muktadir, Hasneen; Karim, Mahbubul; Maheshwari, Arpan; Ahasan, Mohammad Mainul

    2018-02-01

    Rotavirus is the major cause of gastroenteritis in children throughout the world. Every year, a large number of children aged rotavirus-related diarrhoeal diseases. Though these infections are vaccine-preventable, the vast majority of children in low-income countries suffer from the infection. The situation leads to severe economic loss and constitutes a major public health problem. We searched electronic databases including PubMed and Google scholar using the following words: "features of rotavirus," "epidemiology of rotavirus," "rotavirus serotypes," "rotavirus in Bangladesh," "disease burden of rotavirus," "rotavirus vaccine," "low efficacy of rotavirus vaccine," "inactivated rotavirus vaccine". Publications until July 2017 have been considered for this work. Currently, two live attenuated vaccines are available throughout the world. Many countries have included rotavirus vaccines in national immunization program to reduce the disease burden. However, due to low efficacy of the available vaccines, satisfactory outcome has not yet been achieved in developing countries such as Bangladesh. Poor economic, public health, treatment, and sanitation status of the low-income countries necessitate the need for the most effective rotavirus vaccines. Therefore, the present scenario demands the development of a highly effective rotavirus vaccine. In this regard, inactivated rotavirus vaccine concept holds much promise for reducing the current disease burden. Recent advancements in developing an inactivated rotavirus vaccine indicate a significant progress towards disease prophylaxis and control.

  6. Oral live attenuated human rotavirus vaccine (RotarixTM offers sustained high protection against severe G9P[8] rotavirus gastroenteritis during the first two years of life in Brazilian children

    Directory of Open Access Journals (Sweden)

    Maria Cleonice A Justino

    2012-11-01

    Full Text Available In a large Phase III trial conducted in 10 Latin American countries, the safety and efficacy of the live attenuated monovalent rotavirus vaccine RIX4414 was evaluated in 15,183 healthy infants followed up during the first two years of life. Belém was the only site in Brazil included in this multicentre trial. The study in Belém included a subset of 653 infants who were followed up until 24 months of age for protection against severe rotavirus gastroenteritis. These subjects were randomly assigned in a 1:1 ratio to receive two doses of vaccine (n = 328 or two doses of placebo (n = 325 at approximately two and four months of age. Of the 653 enrolled infants, 23 dropped out during the study period. For the combined two-year period, the efficacy of RIX4414 was 72.3% [95% confidence interval (CI 37.5-89.1%] against severe rotavirus-related gastroenteritis, reaching a protection rate of 81.8% (95% CI 36.4-96.6% against circulating wild-type G9 rotavirus strains. It is concluded that two doses of RIX4414 are highly efficacious against severe rotavirus gastroenteritis in Belém during the first two years of life and provide high protection against the worldwide emergence and spread of G9P[8] strains.

  7. Effectiveness of Monovalent and Pentavalent Rotavirus Vaccines in Guatemala.

    Science.gov (United States)

    Gastañaduy, Paul A; Contreras-Roldán, Ingrid; Bernart, Chris; López, Beatriz; Benoit, Stephen R; Xuya, Marvin; Muñoz, Fredy; Desai, Rishi; Quaye, Osbourne; Tam, Ka Ian; Evans-Bowen, Diana K; Parashar, Umesh D; Patel, Manish; McCracken, John P

    2016-05-01

    Concerns remain about lower effectiveness and waning immunity of rotavirus vaccines in resource-poor populations. We assessed vaccine effectiveness against rotavirus in Guatemala, where both the monovalent (RV1; 2-dose series) and pentavalent (RV5; 3-dose series) vaccines were introduced in 2010. A case-control evaluation was conducted in 4 hospitals from January 2012 to August 2013. Vaccine status was compared between case patients (children with laboratory-confirmed rotavirus diarrhea) and 2 sets of controls: nondiarrhea "hospital" controls (matched by birth date and site) and nonrotavirus "test-negative" diarrhea controls (adjusted for age, birth month/year, and site). Vaccine effectiveness ([1 - odds ratio of vaccination] × 100%) was computed using logistic regression models. We evaluated 213 case patients, 657 hospital controls, and 334 test-negative controls. Effectiveness of 2-3 doses of a rotavirus vaccine against rotavirus requiring emergency department visit or hospitalization was 74% (95% confidence interval [CI], 58%-84%) with hospital controls, and 52% (95% CI, 26%-69%) with test-negative controls. Using hospital controls, no significant difference in effectiveness was observed between infants 6-11 months (74% [95% CI, 18%-92%]) and children ≥12 months of age (71% [95% CI, 44%-85%]) (P= .85), nor between complete courses of RV1 (63% [95% CI, 23%-82%]) and RV5 (69% [95% CI, 29%-87%]) (P= .96). An uncommon G12P[8] strain, partially heterotypic to strains in both vaccines, was identified in 89% of cases. RV1 and RV5 were similarly effective against severe rotavirus diarrhea caused by a heterotypic strain in Guatemala. This supports broader implementation of rotavirus vaccination in low-income countries where >90% global deaths from rotavirus occur. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  8. Effectiveness of rotavirus vaccines against hospitalisations in Japan.

    Science.gov (United States)

    Fujii, Yoshiyuki; Noguchi, Atsuko; Miura, Shinobu; Ishii, Haruka; Nakagomi, Toyoko; Nakagomi, Osamu; Takahashi, Tsutomu

    2017-07-11

    In Japan, rotavirus hospitalisation occurs at a rate from 2.8 to 13.7 per 1000 child-years among children age less than 5 years, and it imposes a substantial burden to the healthcare system in the country. While both monovalent (RV1) and pentavalent (RV5) rotavirus vaccines are licensed in Japan, neither has been incorporated in the national infant immunization programme. In this study, we estimated vaccine effectiveness (VE) in Japan. This study was conducted in Yuri-Kumiai General Hospital located in a city in the north-western part of Japan. Age-eligible children for rotavirus vaccination were enrolled if they were hospitalized for rotavirus gastroenteritis between September 2013 and August 2016. Rotavirus gastroenteritis was defined by the detection of rotavirus antigen by immunochromatography. "Vaccinated" was defined as infant inoculated with at least one dose of either RV1 or RV5. A conditional logistic regression analysis was performed by modelling the year of birth, year of admission, residence of the children and vaccination status, and by matching the age of cases with that of test-negative controls. The adjusted odds ratio of the vaccinated over unvaccinated was then used to calculate VE in the formula of (1 - adjusted odds ratio) × 100. Out of the 244 patients enrolled, rotavirus antigen was detected in 55 (22.5%) of whom 10 (18.2%) were vaccinated, whereas 94 (49.7%) of 189 test-negative controls were vaccinated. During the study period, the vaccine uptake rate in the controls increased from 36.2% to 61.8%. On the other hand, the vaccination coverage over the three years was 64.2% in Yuri-Honjo city (three quarters of the catchment), and 91.4% in Nikaho city (one quarter of the catchment). The VE was calculated to be 70.4% (95% confidence interval: 36.0-86.4%, P = 0.002). The point estimate of the VE was lower but its 95% confidence interval overlaps those of the efficacies obtained from clinical trials in Japan. The rotavirus vaccine was

  9. Impact of routine rotavirus vaccination on all-cause and rotavirus hospitalizations during the first four years following vaccine introduction in Rwanda.

    Science.gov (United States)

    Sibomana, Hassan; Rugambwa, Celse; Mwenda, Jason M; Sayinzoga, Felix; Iraguha, Gisele; Uwimana, Jeanine; Parashar, Umesh D; Tate, Jacqueline E

    2018-05-10

    Rwanda introduced pentavalent rotavirus vaccine into its national immunization program in 2012. To determine the long-term impact of rotavirus vaccine on disease burden in a high burden setting, we examined trends in rotavirus and all-cause diarrhea hospitalizations in the first four years following rotavirus vaccine introduction. We used data from an active surveillance system, from a review of pediatric ward registries, and from the Health Management Information System to describe trends in rotavirus and all-cause diarrhea hospitalizations from January 2009 through December 2016. Percent reductions were calculated to compare the number of all-cause and rotavirus diarrhea hospitalizations pre- and post-rotavirus vaccine introduction. The proportion of diarrhea hospitalizations due to rotavirus declined by 25-44% among all children introduction to 12-13% post-vaccine introduction. In the national hospital discharge data, substantial decreases were observed in all-cause diarrhea hospitalizations among children introduction era. Published by Elsevier Ltd.

  10. Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand

    OpenAIRE

    Chen, Mee-Yew; Kirkwood, Carl D.; Bines, Julie; Cowley, Daniel; Pavlic, Daniel; Lee, Katherine J.; Orsini, Francesca; Watts, Emma; Barnes, Graeme; Danchin, Margaret

    2017-01-01

    Background: Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time o...

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

    Directory of Open Access Journals (Sweden)

    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

  12. Estimating the herd immunity effect of rotavirus vaccine.

    Science.gov (United States)

    Pollard, Suzanne L; Malpica-Llanos, Tanya; Friberg, Ingrid K; Fischer-Walker, Christa; Ashraf, Sania; Walker, Neff

    2015-07-31

    Diarrhea is one of the leading causes of death in children under 5, and an estimated 39% of these deaths are attributable to rotavirus. Currently two live, oral rotavirus vaccines have been introduced on the market; however, the herd immunity effect associated with rotavirus vaccine has not yet been quantified. The purpose of this meta-analysis was to estimate the herd immunity effects associated with rotavirus vaccines. We performed a systematic literature review of articles published between 2008 and 2014 that measured the impact of rotavirus vaccine on severe gastroenteritis (GE) morbidity or mortality. We assessed the quality of published studies using a standard protocol and conducted meta-analyses to estimate the herd immunity effect in children less than one year of age across all years presented in the studies. We conducted these analyses separately for studies reporting a rotavirus-specific GE outcome and those reporting an all-cause GE outcome. In studies reporting a rotavirus-specific GE outcome, four of five of which were conducted in the United States, the median herd effect across all study years was 22% [19-25%]. In studies reporting an all-cause GE outcome, all of which were conducted in Latin America, the median herd effect was 24.9% [11-30%]. There is evidence that rotavirus vaccination confers a herd immunity effect in children under one year of age in the United States and Latin American countries. Given the high variability in vaccine efficacy across regions, more studies are needed to better examine herd immunity effects in high mortality regions. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Rotavirus vaccines: safety, efficacy and public health impact.

    Science.gov (United States)

    Gray, J

    2011-09-01

    Rotaviruses are the cause of acute gastroenteritis, and disease is widespread amongst infants and young children throughout the world. Also, rotavirus is associated with significant mortality in developing countries with more than 500 000 children dying each year as a result of the severe dehydration associated with rotavirus disease. Efforts have been ongoing for more than 30 years to develop a safe and effective rotavirus vaccine. Currently, two vaccines, RotaRix and RotaTeq, have been licensed for use in many countries throughout the world following comprehensive safety and efficiency trials. Monitoring their effectiveness after licensure has confirmed that their incorporation into early childhood vaccination schedules can significantly prevent severe rotavirus diarrhoea, which would have resulted in hospitalizations, emergency room visits or increased diarrhoea-related mortality. Although the efficacy of both vaccines is lower at approximately 40-59% in developing countries, their use could significantly reduce the mortality associated with rotavirus disease that is concentrated in these countries. © 2011 The Association for the Publication of the Journal of Internal Medicine.

  14. Heterogeneity of Rotavirus Vaccine Efficacy Among Infants in Developing Countries.

    Science.gov (United States)

    Gruber, Joann F; Hille, Darcy A; Liu, G Frank; Kaplan, Susan S; Nelson, Micki; Goveia, Michelle G; Mast, T Christopher

    2017-01-01

    Rotavirus is the leading cause of severe diarrhea worldwide in young children. Although rotavirus vaccine efficacy is high in developed countries, efficacy is lower in developing countries. Here, we investigated heterogeneity of rotavirus vaccine efficacy by infant characteristics in developing countries. An exploratory, post hoc analysis was conducted using randomized controlled trial data of the pentavalent rotavirus vaccine (RV5) conducted in Africa and Asia (NCT00362648). Infants received either 3 doses of vaccine/placebo and were followed for up to 2 years. Within subgroups, vaccine efficacies and 95% confidence intervals (CIs) against rotavirus gastroenteritis (RVGE) were estimated using Poisson regression. We assessed heterogeneity of efficacy by age at first dose, gender, breastfeeding status and nutrition status. African children receiving the first dose at efficacy (23.7%; 95% CI: -8.2%-46.3%) than those vaccinated at ≥8 weeks (59.1%; 95% CI: 34.0%-74.6%). Marginally statistically significant differences were observed by age at first dose, gender and underweight status in Ghana and gender in Asian countries. Heterogeneity of efficacy was observed for age at first dose in African countries. This was an exploratory analysis; additional studies are needed to validate these results.

  15. Cost effectiveness of a pentavalent rotavirus vaccine in Oman.

    Science.gov (United States)

    Al Awaidy, Salah Thabit; Gebremeskel, Berhanu G; Al Obeidani, Idris; Al Baqlani, Said; Haddadin, Wisam; O'Brien, Megan A

    2014-06-17

    Rotavirus gastroenteritis (RGE) is the leading cause of diarrhea in young children in Oman, incurring substantial healthcare and economic burden. We propose to formally assess the potential cost effectiveness of implementing universal vaccination with a pentavalent rotavirus vaccine (RV5) on reducing the health care burden and costs associated with rotavirus gastroenteritis (RGE) in Oman A Markov model was used to compare two birth cohorts, including children who were administered the RV5 vaccination versus those who were not, in a hypothetical group of 65,500 children followed for their first 5 years of life in Oman. The efficacy of the vaccine in reducing RGE-related hospitalizations, emergency department (ED) and office visits, and days of parental work loss for children receiving the vaccine was based on the results of the Rotavirus Efficacy and Safety Trial (REST). The outcome of interest was cost per quality-adjusted life year (QALY) gained from health care system and societal perspectives. A universal RV5 vaccination program is projected to reduce, hospitalizations, ED visits, outpatient visits and parental work days lost due to rotavirus infections by 89%, 80%, 67% and 74%, respectively. In the absence of RV5 vaccination, RGE-related societal costs are projected to be 2,023,038 Omani Rial (OMR) (5,259,899 United States dollars [USD]), including 1,338,977 OMR (3,481,340 USD) in direct medical costs. However, with the introduction of RV5, direct medical costs are projected to be 216,646 OMR (563,280 USD). Costs per QALY saved would be 1,140 OMR (2,964 USD) from the health care payer perspective. An RV5 vaccination program would be considered cost saving, from the societal perspective. Universal RV5 vaccination in Oman is likely to significantly reduce the health care burden and costs associated with rotavirus gastroenteritis and may be cost-effective from the payer perspective and cost saving from the societal perspective.

  16. Rotavirus vaccination and herd immunity: an evidence-based review

    Directory of Open Access Journals (Sweden)

    Seybolt LM

    2012-06-01

    Full Text Available Lorna M Seybolt, Rodolfo E BéguéDepartment of Pediatrics, Division of Infectious Diseases, Louisiana State University Health Sciences Center, New Orleans, LA, USAAbstract: Until recently, rotavirus was the most common cause of diarrhea in infants and young children with over 100 million cases and 400,000 deaths every year worldwide. Yet, its epidemiology is changing rapidly with the introduction of two rotavirus vaccines in the mid 2000s. Both vaccines were shown to be highly efficacious in prelicensure studies to reduce severe rotavirus disease; the efficacy being more pronounced in high- and middle-income countries than in low-income countries. Herd immunity – the indirect protection of unimmunized individuals as a result of others being immunized – was not expected to be a benefit of rotavirus vaccination programs since the vaccines were thought to reduce severe disease but not to decrease virus transmission significantly. Postlicensure studies, however, have suggested that this assumption may need reassessment. Studies in a variety of settings have shown evidence of greater than expected declines in rotavirus disease. While these studies were not designed specifically to detect herd immunity – and few failed to detect this phenomenon – the consistency of the evidence is compelling. These studies are reviewed and described here. While further work is needed, clarifying the presence of herd immunity is not just an academic exercise but an important issue for rotavirus control, especially in lower income countries where the incidence of the disease is highest and the direct protection of the vaccines is lower.Keywords: rotavirus, vaccine, herd immunity, efficacy

  17. Cost-effectiveness analysis of rotavirus vaccination in Argentina.

    Science.gov (United States)

    Urueña, Analía; Pippo, Tomás; Betelu, María Sol; Virgilio, Federico; Hernández, Laura; Giglio, Norberto; Gentile, Ángela; Diosque, Máximo; Vizzotti, Carla

    2015-05-07

    Rotavirus is a leading cause of severe diarrhea in children under 5. In Argentina, the most affected regions are the Northeast and Northwest, where hospitalizations and deaths are more frequent. This study estimated the cost-effectiveness of adding either of the two licensed rotavirus vaccines to the routine immunization schedule. The integrated TRIVAC vaccine cost-effectiveness model from the Pan American Health Organization's ProVac Initiative (Version 2.0) was used to assess health benefits, costs savings, life-years gained (LYGs), DALYs averted, and cost/DALY averted of vaccinating 10 successive cohorts, from the health care system and societal perspectives. Two doses of monovalent (RV1) rotavirus vaccine and three doses of pentavalent (RV5) rotavirus vaccine were each compared to a scenario assuming no vaccination. The price/dose was US$ 7.50 and US$ 5.15 for RV1 and RV5, respectively. We ran both a national and sub-national analysis, discounting all costs and benefits 3% annually. Our base case results were compared to a range of alternative univariate and multivariate scenarios. The number of LYGs was 5962 and 6440 for RV1 and RV5, respectively. The cost/DALY averted when compared to no vaccination from the health care system and societal perspective was: US$ 3870 and US$ 1802 for RV1, and US$ 2414 and US$ 358 for RV5, respectively. Equivalent figures for the Northeast were US$ 1470 and US$ 636 for RV1, and US$ 913 and US$ 80 for RV5. Therefore, rotavirus vaccination was more cost-effective in the Northeast compared to the whole country; and, in the Northwest, health service's costs saved outweighed the cost of introducing the vaccine. Vaccination with either vaccine compared to no vaccination was highly cost-effective based on WHO guidelines and Argentina's 2011 per capita GDP of US$ 9090. Key variables influencing results were vaccine efficacy, annual loss of efficacy, relative coverage of deaths, vaccine price, and discount rate. Compared to no

  18. 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

  19. Potential safety issues and other factors that may affect the introduction and uptake of rotavirus vaccines

    Science.gov (United States)

    Aliabadi, N.; Tate, J.E.; Parashar, U.D.

    2018-01-01

    Rotavirus vaccines have demonstrated significant impact in reducing the burden of morbidity and mortality from childhood diarrhoea in countries that have implemented routine vaccination to date. Despite this success, in many countries, rotavirus vaccine coverage remains lower than that of other routine childhood vaccines. Several issues may potentially affect vaccine uptake, namely safety concerns related to intussusception with consequent age restrictions on rotavirus vaccination, contamination with porcine circovirus, vaccine-derived reassortant strains and hospitalization in newborn nurseries at time of administration of live oral rotavirus vaccine. In addition to these safety concerns, other factors may also affect uptake, including lower vaccine efficacy in the developing world, potential emergence of strains escaping from vaccine protection resulting in lower overall impact of a vaccination programme and sustainable vaccine financing. Although further work is needed to address some of these concerns, global policy bodies have reaffirmed that the benefits of rotavirus vaccination outweigh the risks, and vaccine use is recommended globally. PMID:27129416

  20. Potential safety issues and other factors that may affect the introduction and uptake of rotavirus vaccines.

    Science.gov (United States)

    Aliabadi, N; Tate, J E; Parashar, U D

    2016-12-01

    Rotavirus vaccines have demonstrated significant impact in reducing the burden of morbidity and mortality from childhood diarrhoea in countries that have implemented routine vaccination to date. Despite this success, in many countries, rotavirus vaccine coverage remains lower than that of other routine childhood vaccines. Several issues may potentially affect vaccine uptake, namely safety concerns related to intussusception with consequent age restrictions on rotavirus vaccination, contamination with porcine circovirus, vaccine-derived reassortant strains and hospitalization in newborn nurseries at time of administration of live oral rotavirus vaccine. In addition to these safety concerns, other factors may also affect uptake, including lower vaccine efficacy in the developing world, potential emergence of strains escaping from vaccine protection resulting in lower overall impact of a vaccination programme and sustainable vaccine financing. Although further work is needed to address some of these concerns, global policy bodies have reaffirmed that the benefits of rotavirus vaccination outweigh the risks, and vaccine use is recommended globally. Published by Elsevier Ltd.

  1. Dynamic Modeling of Cost-effectiveness of Rotavirus Vaccination, Kazakhstan

    Science.gov (United States)

    Flem, Elmira; Latipov, Renat; Kuatbaeva, Ajnagul; Kristiansen, Ivar Sønbø

    2014-01-01

    The government of Kazakhstan, a middle-income country in Central Asia, is considering the introduction of rotavirus vaccination into its national immunization program. We performed a cost-effectiveness analysis of rotavirus vaccination spanning 20 years by using a synthesis of dynamic transmission models accounting for herd protection. We found that a vaccination program with 90% coverage would prevent ≈880 rotavirus deaths and save an average of 54,784 life-years for children <5 years of age. Indirect protection accounted for 40% and 60% reduction in severe and mild rotavirus gastroenteritis, respectively. Cost per life year gained was US $18,044 from a societal perspective and US $23,892 from a health care perspective. Comparing the 2 key parameters of cost-effectiveness, mortality rates and vaccine cost at vaccination program costs would be entirely offset. To further evaluate efficacy of a vaccine program, benefits of indirect protection conferred by vaccination warrant further study. PMID:24378188

  2. Rotavirus vaccine effectiveness in low-income settings: An evaluation of the test-negative design

    OpenAIRE

    Schwartz, Lauren M.; Halloran, M. Elizabeth; Rowhani-Rahbar, Ali; Neuzil, Kathleen M.; Victor, John C.

    2017-01-01

    Background The test-negative design (TND), an epidemiologic method currently used to measure rotavirus vaccine (RV) effectiveness, compares the vaccination status of rotavirus-positive cases and rotavirus-negative controls meeting a pre-defined case definition for acute gastroenteritis. Despite the use of this study design in low-income settings, the TND has not been evaluated to measure rotavirus vaccine effectiveness. Methods This study builds upon prior methods to evaluate the use of the T...

  3. Rotavirus Infection in the Auckland Region After the Implementation of Universal Infant Rotavirus Vaccination: Impact on Hospitalizations and Laboratory Implications.

    Science.gov (United States)

    McAuliffe, Gary N; Taylor, Susan L; Drinković, Dragana; Roberts, Sally A; Wilson, Elizabeth M; Best, Emma J

    2018-01-01

    In July 2014, New Zealand introduced universal infant vaccination with RotaTeq (Merk & Co.) administered as 3 doses at 6 weeks, 3 and 5 months of age. We sought to assess the impact of rotavirus vaccination on gastroenteritis (GE) hospitalizations in the greater Auckland region and analyze changes in rotavirus testing in the period around vaccine introduction. Hospitalizations, laboratory testing rates and methods were compared between the pre-vaccine period (2009-2013), post-vaccine period (January 2015 to December 2015) and year of vaccine introduction (2014). There was a 68% decline in rotavirus hospitalizations of children Auckland region. However, continued rotavirus testing at pre-vaccine rates risks generating false positive results. Laboratories and clinicians should consider reviewing their testing algorithms before vaccine introduction.

  4. 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 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 Venezuelan post-vaccine G1P[8] could have conditioned their re-emergence and a more efficient dissemination into susceptible population. The results suggest that natural fluctuations of genotypes in combination with forces driving the genetic evolution could determine the spread of novel strains, whose long-term effect on the efficacy of available vaccines should be determined.

  5. Cost-effectiveness of rotavirus vaccination in Kenya and Uganda.

    Science.gov (United States)

    Sigei, Charles; Odaga, John; Mvundura, Mercy; Madrid, Yvette; Clark, Andrew David

    2015-05-07

    Rotavirus vaccines have the potential to prevent a substantial amount of life-threatening gastroenteritis in young African children. This paper presents the results of prospective cost-effectiveness analyses for rotavirus vaccine introduction for Kenya and Uganda. In each country, a national consultant worked with a national technical working group to identify appropriate data and validate study results. Secondary data on demographics, disease burden, health utilization, and costs were used to populate the TRIVAC cost-effectiveness model. The baseline analysis assumed an initial vaccine price of $0.20 per dose, corresponding to Gavi, the Vaccine Alliance stipulated copay for low-income countries. The incremental cost-effectiveness of a 2-dose rotavirus vaccination schedule was evaluated for 20 successive birth cohorts from the government perspective in both countries, and from the societal perspective in Uganda. Between 2014 and 2033, rotavirus vaccination can avert approximately 60,935 and 216,454 undiscounted deaths and hospital admissions respectively in children under 5 years in Kenya. In Uganda, the respective number of undiscounted deaths and hospital admission averted is 70,236 and 329,779 between 2016 and 2035. Over the 20-year period, the discounted vaccine program costs are around US$ 80 million in Kenya and US$ 60 million in Uganda. Discounted government health service costs avoided are US$ 30 million in Kenya and US$ 10 million in Uganda (or US$ 18 million including household costs). The cost per disability-adjusted life-year (DALY) averted from a government perspective is US$ 38 in Kenya and US$ 34 in Uganda (US$ 29 from a societal perspective). Rotavirus vaccine introduction is highly cost-effective in both countries in a range of plausible 'what-if' scenarios. The involvement of national experts improves the quality of data used, is likely to increase acceptability of the results in decision-making, and can contribute to strengthened national

  6. Impact of rotavirus vaccination on rotavirus and all-cause gastroenteritis in peri-urban Kenyan children.

    Science.gov (United States)

    Wandera, Ernest Apondi; Mohammad, Shah; Bundi, Martin; Komoto, Satoshi; Nyangao, James; Kathiiko, Cyrus; Odoyo, Erick; Miring'u, Gabriel; Taniguchi, Koki; Ichinose, Yoshio

    2017-09-12

    A monovalent rotavirus vaccine (RV1) was introduced into the National Immunization Program in Kenya in July 2014. We examined the impact of the vaccine on hospitalization for all-cause acute gastroenteritis (AGE) and rotavirus-specific AGE and strain distribution at a large referral hospital which serves a predominantly peri-urban population in Central Kenya. Data on rotavirus AGE and strain distribution were derived from ongoing hospital-based AGE surveillance. Hospital administrative data were used to compare trends in all-cause AGE. Pre-vaccine (July 2009-June 2014) and post-vaccine (July 2014-June 2016) periods were compared for changes in hospitalization for all-cause AGE and rotavirus AGE and strain distribution. Following the vaccine introduction, the proportion of children aged rotavirus declined by 30% (95% CI: 19-45%) in the first year and 64% (95% CI: 49-77%) in the second year. Reductions in rotavirus positivity were most pronounced among the vaccine-eligible group (rotavirus and all-cause AGE were reduced substantially. There was an increased detection of G2P[4], G3P[6] and G3P[8], which coincided temporally with the timing of the vaccine introduction. Thus, introducing the rotavirus vaccine into the routine immunization program in Kenya has resulted in a notable decline in rotavirus and all-cause AGE hospitalizations in Central Kenya. This provides early evidence for public health policy makers in Kenya to support the sustained use of the rotavirus vaccine in routine immunizations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Effectiveness of Pentavalent Rotavirus Vaccine Under Conditions of Routine Use in Rwanda.

    Science.gov (United States)

    Tate, Jacqueline E; Ngabo, Fidele; Donnen, Philippe; Gatera, Maurice; Uwimana, Jeannine; Rugambwa, Celse; Mwenda, Jason M; Parashar, Umesh D

    2016-05-01

    Rotavirus vaccine efficacy is lower in low-income countries than in high-income countries. Rwanda was one of the first low-income countries in sub-Saharan Africa to introduce rotavirus vaccine into its national immunization program. We sought to evaluate rotavirus vaccine effectiveness (VE) in this setting. VE was assessed using a case-control design. Cases and test-negative controls were children who presented with a diarrheal illness to 1 of 8 sentinel district hospitals and 10 associated health centers and had a stool specimen that tested positive (cases) or negative (controls) for rotavirus by enzyme immunoassay. Due to high vaccine coverage almost immediately after vaccine introduction, the analysis was restricted to children 7-18 weeks of age at time of rotavirus vaccine introduction. VE was calculated as (1 - odds ratio) × 100, where the odds ratio was the adjusted odds ratio for the rotavirus vaccination rate among case-patients compared with controls. Forty-eight rotavirus-positive and 152 rotavirus-negative children were enrolled. Rotavirus-positive children were significantly less likely to have received rotavirus vaccine (33/44 [73%] unvaccinated) compared with rotavirus-negative children (81/136 [59%] unvaccinated) (P= .002). A full 3-dose series was 75% (95% confidence interval [CI], 31%-91%) effective against rotavirus gastroenteritis requiring hospitalization or a health center visit and was 65% (95% CI, -80% to 93%) in children 6-11 months of age and 81% (95% CI, 25%-95%) in children ≥12 months of age. Rotavirus vaccine is effective in preventing rotavirus disease in Rwandan children who began their rotavirus vaccine series from 7 to 18 weeks of age. Protection from vaccination was sustained after the first year of life. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  8. Cost-effectiveness of rotavirus vaccination in the Netherlands; the results of a consensus model

    NARCIS (Netherlands)

    Rozenbaum, M.H.; Mangen, M.J.J.; Giaquinto, C.; Wilschut, J.C.; Hak, E.; Postma, M.J.

    2011-01-01

    Background: Each year rotavirus gastroenteritis results in thousands of paediatric hospitalisations and primary care visits in the Netherlands. While two vaccines against rotavirus are registered, routine immunisation of infants has not yet been implemented. Existing cost-effectiveness studies

  9. Estimated reductions in hospitalizations and deaths from childhood diarrhea following implementation of rotavirus vaccination in Africa.

    Science.gov (United States)

    Shah, Minesh P; Tate, Jacqueline E; Mwenda, Jason M; Steele, A Duncan; Parashar, Umesh D

    2017-10-01

    Rotavirus is the leading cause of hospitalizations and deaths from diarrhea. 33 African countries had introduced rotavirus vaccines by 2016. We estimate reductions in rotavirus hospitalizations and deaths for countries using rotavirus vaccination in national immunization programs and the potential of vaccine introduction across the continent. Areas covered: Regional rotavirus burden data were reviewed to calculate hospitalization rates, and applied to under-5 population to estimate baseline hospitalizations. Rotavirus mortality was based on 2013 WHO estimates. Regional pre-licensure vaccine efficacy and post-introduction vaccine effectiveness studies were used to estimate summary effectiveness, and vaccine coverage was applied to calculate prevented hospitalizations and deaths. Uncertainties around input parameters were propagated using boot-strapping simulations. In 29 African countries that introduced rotavirus vaccination prior to end 2014, 134,714 (IQR 112,321-154,654) hospitalizations and 20,986 (IQR 18,924-22,822) deaths were prevented in 2016. If all African countries had introduced rotavirus vaccines at benchmark immunization coverage, 273,619 (47%) (IQR 227,260-318,102) hospitalizations and 47,741 (39%) (IQR 42,822-52,462) deaths would have been prevented. Expert commentary: Rotavirus vaccination has substantially reduced hospitalizations and deaths in Africa; further reductions are anticipated as additional countries implement vaccination. These estimates bolster wider introduction and continued support of rotavirus vaccination programs.

  10. Outstanding challenges for rotavirus vaccine introduction in low-income countries

    DEFF Research Database (Denmark)

    Ustrup, Marte; Madsen, Lizell B; Bygbjerg, Ib C

    2011-01-01

    Rotavirus infections are the most common cause of severe diarrhoea in children worldwide. Two internationally licensed rotavirus vaccines have proven to be efficacious in middle and high-income countries and they could potentially be valuable tools for the prevention of rotavirus....... There is also a need for political commitment to prevent rotavirus infections as well as a need for an overall strengthening of the health systems in low-income countries. If these challenges were met, rotavirus vaccination could substantially improve child health and survival from rotavirus...

  11. Cost-effectiveness of rotavirus vaccination in Albania.

    Science.gov (United States)

    Ahmeti, Albana; Preza, Iria; Simaku, Artan; Nelaj, Erida; Clark, Andrew David; Felix Garcia, Ana Gabriela; Lara, Carlos; Hoestlandt, Céline; Blau, Julia; Bino, Silvia

    2015-05-07

    Rotavirus vaccines have been introduced in several European countries but can represent a considerable cost, particularly for countries that do not qualify for any external financial support. This study aimed to evaluate the cost-effectiveness of introducing rotavirus vaccination into Albania's national immunization program and to inform national decision-making by improving national capacity to conduct economic evaluations of new vaccines. The TRIVAC model was used to assess vaccine impact and cost-effectiveness. The model estimated health and economic outcomes attributed to 10 successive vaccinated birth cohorts (2013-2022) from a government and societal perspective. Epidemiological and economic data used in the model were based on national cost studies, and surveillance data, as well as estimates from the scientific literature. Cost-effectiveness was estimated for both the monovalent (RV1) and pentavalent vaccines (RV5). A multivariate scenario analysis (SA) was performed to evaluate the uncertainty around the incremental cost-effectiveness ratios (ICERs). With 3% discounting of costs and health benefits over the period 2013-2022, rotavirus vaccination in Albania could avert 51,172 outpatient visits, 14,200 hospitalizations, 27 deaths, 950 disability-adjusted life-years (DALYs), and gain 801 life-years. When both vaccines were compared to no vaccination, the discounted cost per DALY averted was US$ 2008 for RV1 and US$ 5047 for RV5 from a government perspective. From the societal perspective the values were US$ 517 and US$ 3556, respectively. From both the perspectives, the introduction of rotavirus vaccine to the Albanian immunization schedule is either cost-effective or highly cost-effective for a range of plausible scenarios. In most scenarios, including the base-case scenario, the discounted cost per DALY averted was less than three times the gross domestic product (GDP) per capita. However, rotavirus vaccination was not cost-effective when rotavirus cases

  12. Reaching every child with rotavirus vaccine: Report from the 10th African rotavirus symposium held in Bamako, Mali.

    Science.gov (United States)

    Sow, Samba O; Steele, A Duncan; Mwenda, Jason M; Armah, George E; Neuzil, Kathleen M

    2017-10-09

    The Center for Vaccine Development - Mali (CVD - Mali), the World Health Organization's regional office in Africa (WHO/AFRO), and the CVD at the University of Maryland School of Medicine hosted the 10th African Rotavirus Symposium in Bamako, Mali on 1-2 June 2016. The symposium is coordinated by WHO/AFRO, the Regional Rotavirus Reference Laboratories, and the African Rotavirus Network (ARN), with support from the Bill & Melinda Gates Foundation. The event brings together leading rotavirus researchers, scientists, and policy-makers from across Africa and the world. Over 150 participants, from 31 countries, including 27 in Africa, joined forces to address the theme "Reaching Every Child in Africa with Rotavirus Vaccines." This symposium, the first in francophone Africa, occurred at an unprecedented time when 33 African countries had introduced rotavirus vaccines into their national immunization programs. The symposium concluded with a Call to Action to introduce rotavirus vaccines in the 21 remaining African countries, to increase access in countries with existing vaccination programs, and to continue surveillance and research on rotavirus and other diarrheal diseases. Copyright © 2017.

  13. Rotavirus vaccine and diarrhea mortality: quantifying regional variation in effect size

    OpenAIRE

    Fischer Walker, Christa L; Black, Robert E

    2011-01-01

    Abstract Background Diarrhea mortality remains a leading cause of child death and rotavirus vaccine an effective tool for preventing severe rotavirus diarrhea. New data suggest vaccine efficacy may vary by region. Methods We reviewed published vaccine efficacy trials to estimate a regional-specific effect of vaccine efficacy on severe rotavirus diarrhea and hospitalizations. We assessed the quality of evidence using a standard protocol and conducted meta-analyses where more than 1 data point ...

  14. Implementation of Rotavirus Surveillance and Vaccine Introduction - World Health Organization African Region, 2007-2016.

    Science.gov (United States)

    Mwenda, Jason M; Burke, Rachel M; Shaba, Keith; Mihigo, Richard; Tevi-Benissan, Mable Carole; Mumba, Mutale; Biey, Joseph Nsiari-Muzeyi; Cheikh, Dah; Poy MSc, Alain; Zawaira, Felicitas R; Aliabadi, Negar; Tate, Jacqueline E; Hyde, Terri; Cohen, Adam L; Parashar, Umesh D

    2017-11-03

    Rotavirus is a leading cause of severe pediatric diarrhea globally, estimated to have caused 120,000 deaths among children aged rotavirus vaccination for all infants worldwide (2). Two rotavirus vaccines are currently licensed globally: the monovalent Rotarix vaccine (RV1, GlaxoSmithKline; 2-dose series) and the pentavalent RotaTeq vaccine (RV5, Merck; 3-dose series). This report describes progress of rotavirus vaccine introduction (3), coverage (using estimates from WHO and the United Nations Children's Fund [UNICEF]) (4), and impact on pediatric diarrhea hospitalizations in the WHO African Region. By December 2016, 31 (66%) of 47 countries in the WHO African Region had introduced rotavirus vaccine, including 26 that introduced RV1 and five that introduced RV5. Among these countries, rotavirus vaccination coverage (completed series) was 77%, according to WHO/UNICEF population-weighted estimates. In 12 countries with surveillance data available before and after vaccine introduction, the proportion of pediatric diarrhea hospitalizations that were rotavirus-positive declined 33%, from 39% preintroduction to 26% following rotavirus vaccine introduction. These results support introduction of rotavirus vaccine in the remaining countries in the region and continuation of rotavirus surveillance to monitor impact.

  15. Impact of rotavirus vaccines in low and middle-income countries.

    Science.gov (United States)

    Sindhu, Kulandaipalayam Natarajan Chella; Babji, Sudhir; Ganesan, Santhosh Kumar

    2017-10-01

    Rotavirus vaccines are playing a pivotal role in improving lives of infants and young children in low and middle-income countries (LMICs). Many of these countries have adopted the vaccine into their routine immunization, whereas others are considering introduction. This article provides an update on the impact of rotavirus vaccines in LMICs on morbidity and mortality in children aged less than 5 years, and their cost-effectiveness. The WHO, in 2013, updated its recommendation to prioritize introduction of rotavirus vaccines in the routine immunization schedule, without age restrictions. Despite the decreased efficacy of the vaccines in LMICs, data from Sub-Saharan Africa have demonstrated a decrease in rotavirus-related morbidity, with some sites reporting an indirect protective effect on children age ineligible to receive the vaccine. Even with improvements in sanitation, nutritional status in children, and other health-related indices in LMICs, the use of rotavirus vaccines will play an important role in preventing rotavirus-related gastroenteritis. Economic models predict a reduction in economic burden because of rotavirus-related health costs, making vaccine introduction cost-effective in resource-constrained settings. Increasing evidence from impact studies shows the significant impact of rotavirus vaccination on hospitalizations and economic burden because of rotavirus gastroenteritis in LMICs. Universal rotavirus vaccination is recommended, and introductions should be monitored by robust surveillance systems to measure effectiveness and impact.

  16. Global Impact of Rotavirus Vaccination on Childhood Hospitalizations and Mortality From Diarrhea.

    Science.gov (United States)

    Burnett, Eleanor; Jonesteller, Christine L; Tate, Jacqueline E; Yen, Catherine; Parashar, Umesh D

    2017-06-01

    In 2006, 2 rotavirus vaccines were licensed. We summarize the impact of rotavirus vaccination on hospitalizations and deaths from rotavirus and all-cause acute gastroenteritis (AGE) during the first 10 years since vaccine licensure, including recent evidence from countries with high child mortality. We used standardized guidelines (PRISMA) to identify observational evaluations of rotavirus vaccine impact among children rotavirus AGE were reduced by a median of 67% overall and 71%, 59%, and 60% in countries with low, medium, and high child mortality, respectively. Implementation of rotavirus vaccines has substantially decreased hospitalizations from rotavirus and all-cause AGE. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  17. Effectiveness and impact of rotavirus vaccines in Europe, 2006-2014.

    Science.gov (United States)

    Karafillakis, Emilie; Hassounah, Sondus; Atchison, Christina

    2015-04-27

    Prior to the introduction of rotavirus vaccines in 2006, rotavirus was the leading cause of severe gastroenteritis among European children rotavirus vaccines in Europe following the first eight years of routine use. Four publication databases were searched, yielding 276 unique citations from February 1st, 2006 to July 31st, 2014. Twenty four studies on effectiveness (n=9) and impact (n=15) met the inclusion criteria. Across Europe, vaccine effectiveness against rotavirus-related healthcare utilisation ranged from 68% to 98%, consistent with efficacy data from clinical trials. Reductions in rotavirus hospitalisations ranged from 65% to 84%, consistent with findings from post-marketing studies from the US and Latin America. We confirm the significant public health benefit of rotavirus vaccination in Europe and provide further evidence to support implementation of universal rotavirus vaccination in all European countries. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    Science.gov (United States)

    Wang, Yuhuan; Vlasova, Anastasia; Velasquez, Daniel E; Saif, Linda J; Kandasamy, Sukumar; Kochba, Efrat; Levin, Yotam; Jiang, Baoming

    2016-01-01

    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(OH)3] 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Estimating rotavirus gastroenteritis hospitalisations by using hospital episode statistics before and after the introduction of rotavirus vaccine in Australia.

    Science.gov (United States)

    Jayasinghe, Sanjay; Macartney, Kristine

    2013-01-30

    Hospital discharge records and laboratory data have shown a substantial early impact from the rotavirus vaccination program that commenced in 2007 in Australia. However, these assessments are affected by the validity and reliability of hospital discharge coding and stool testing to measure the true incidence of hospitalised disease. The aim of this study was to assess the validity of these data sources for disease estimation, both before and after, vaccine introduction. All hospitalisations at a major paediatric centre in children aged <5 years from 2000 to 2009 containing acute gastroenteritis (AGE) ICD 10 AM diagnosis codes were linked to hospital laboratory stool testing data. The validity of the rotavirus-specific diagnosis code (A08.0) and the incidence of hospitalisations attributable to rotavirus by both direct estimation and with adjustments for non-testing and miscoding were calculated for pre- and post-vaccination periods. A laboratory record of stool testing was available for 36% of all AGE hospitalisations (n=4948) the rotavirus code had high specificity (98.4%; 95% CI, 97.5-99.1%) and positive predictive value (96.8%; 94.8-98.3%), and modest sensitivity (61.6%; 58-65.1%). Of all rotavirus test positive hospitalisations only a third had a rotavirus code. The estimated annual average number of rotavirus hospitalisations, following adjustment for non-testing and miscoding was 5- and 6-fold higher than identified, respectively, from testing and coding alone. Direct and adjusted estimates yielded similar percentage reductions in annual average rotavirus hospitalisations of over 65%. Due to the limited use of stool testing and poor sensitivity of the rotavirus-specific diagnosis code routine hospital discharge and laboratory data substantially underestimate the true incidence of rotavirus hospitalisations and absolute vaccine impact. However, this data can still be used to monitor vaccine impact as the effects of miscoding and under-testing appear to be

  1. Reduction in Rotavirus-associated Acute Gastroenteritis Following Introduction of Rotavirus Vaccine Into Australia's National Childhood Vaccine Schedule

    NARCIS (Netherlands)

    Buttery, Jim P.; Lambert, Stephen B.; Grimwood, Keith; Nissen, Michael D.; Field, Emma J.; Macartney, Kristine K.; Akikusa, Jonathan D.; Kelly, Julian J.; Kirkwood, Carl D.

    Introduction: Rotavirus vaccines were introduced into the funded Australian National Immunization Program (NIP) in July 2007. Due to purchasing arrangements, individual states and territories chose either a 2-dose RV1 (Rotarix, GSK) regimen or 3-dose RV5 (Rotateq, Merck/CSL) regimen. This allowed

  2. Rotavirus vaccine effectiveness in low-income settings: An evaluation of the test-negative design.

    Science.gov (United States)

    Schwartz, Lauren M; Halloran, M Elizabeth; Rowhani-Rahbar, Ali; Neuzil, Kathleen M; Victor, John C

    2017-01-03

    The test-negative design (TND), an epidemiologic method currently used to measure rotavirus vaccine (RV) effectiveness, compares the vaccination status of rotavirus-positive cases and rotavirus-negative controls meeting a pre-defined case definition for acute gastroenteritis. Despite the use of this study design in low-income settings, the TND has not been evaluated to measure rotavirus vaccine effectiveness. This study builds upon prior methods to evaluate the use of the TND for influenza vaccine using a randomized controlled clinical trial database. Test-negative vaccine effectiveness (VE-TND) estimates were derived from three large randomized placebo-controlled trials (RCTs) of monovalent (RV1) and pentavalent (RV5) rotavirus vaccines in sub-Saharan Africa and Asia. Derived VE-TND estimates were compared to the original RCT vaccine efficacy estimates (VE-RCTs). The core assumption of the TND (i.e., rotavirus vaccine has no effect on rotavirus-negative diarrhea) was also assessed. TND vaccine effectiveness estimates were nearly equivalent to original RCT vaccine efficacy estimates. Neither RV had a substantial effect on rotavirus-negative diarrhea. This study supports the TND as an appropriate epidemiologic study design to measure rotavirus vaccine effectiveness in low-income settings. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  3. Household transmission of rotavirus in a community with rotavirus vaccination in Quininde, Ecuador.

    Directory of Open Access Journals (Sweden)

    Ben Lopman

    Full Text Available We studied the transmission of rotavirus infection in households in peri-urban Ecuador in the vaccination era.Stool samples were collected from household contacts of child rotavirus cases, diarrhea controls and healthy controls following presentation of the index child to health facilities. Rotavirus infection status of contacts was determined by RT-qPCR. We examined factors associated with transmissibility (index-case characteristics and susceptibility (household-contact characteristics.Amongst cases, diarrhea controls and healthy control household contacts, infection attack rates (iAR were 55%, 8% and 2%, (n = 137, 130, 137 respectively. iARs were higher from index cases with vomiting, and amongst siblings. Disease ARs were higher when the index child was <18 months and had vomiting, with household contact <10 years and those sharing a room with the index case being more susceptible. We found no evidence of asymptomatic infections leading to disease transmission.Transmission rates of rotavirus are high in households with an infected child, while background infections are rare. We have identified factors associated with transmission (vomiting/young age of index case and susceptibility (young age/sharing a room/being a sibling of the index case. Vaccination may lead to indirect benefits by averting episodes or reducing symptoms in vaccinees.

  4. Rotavirus diarrhea disease burden in Peru: the need for a rotavirus vaccine and its potential cost savings.

    Science.gov (United States)

    Ehrenkranz, P; Lanata, C F; Penny, M E; Salazar-Lindo, E; Glass, R I

    2001-10-01

    To assess the disease burden of rotavirus diarrhea in Peru as well the need for and the potential cost savings with a rotavirus vaccine in that country. To assess the burden of rotavirus diarrhea in Peru, we reviewed published and unpublished reports where rotavirus was sought as the etiologic agent of diarrhea in children. Rotavirus detection rates obtained from these studies were combined with diarrhea incidence rates from a number of national surveys in order to estimate both the burden of rotavirus diarrhea in the country and its associated medical costs. Rotavirus is a significant cause of morbidity and mortality in Peruvian children. In their first 5 years of life, an estimated 1 in 1.6 children will experience an episode of rotavirus diarrhea, 1 in 9.4 will seek medical care, 1 in 19.7 will require hospitalization, and 1 in 375 will die of the disease. Per year, this represents approximately 384,000 cases, 64,000 clinic visits, 30,000 hospitalizations, and 1,600 deaths. The annual cost of medical care alone for these children is approximately US$ 2.6 million--and that does not take into account the indirect or societal costs of the illness and the deaths. Rotavirus immunization provides the prospect of decreasing the morbidity and mortality from diarrhea in Peru, but a vaccine regimen would have to be relatively inexpensive, a few dollars or less per child. Future cost-effectiveness analyses should explore the total costs (medical as well as indirect or societal) associated with rotavirus diarrhea. Newly licensed vaccines should be tested according to both their ability to avert deaths and their efficacy with fewer than three doses. All three of these factors could increase the cost savings associated with a rotavirus vaccine.

  5. Rotavirus diarrhea disease burden in Peru: the need for a rotavirus vaccine and its potential cost savings

    Directory of Open Access Journals (Sweden)

    Peter Ehrenkranz

    2001-10-01

    Full Text Available Objective. To assess the disease burden of rotavirus diarrhea in Peru as well the need for and the potential cost savings with a rotavirus vaccine in that country. Methods. To assess the burden of rotavirus diarrhea in Peru, we reviewed published and unpublished reports where rotavirus was sought as the etiologic agent of diarrhea in children. Rotavirus detection rates obtained from these studies were combined with diarrhea incidence rates from a number of national surveys in order to estimate both the burden of rotavirus diarrhea in the country and its associated medical costs. Results. Rotavirus is a significant cause of morbidity and mortality in Peruvian children. In their first 5 years of life, an estimated 1 in 1.6 children will experience an episode of rotavirus diarrhea, 1 in 9.4 will seek medical care, 1 in 19.7 will require hospitalization, and 1 in 375 will die of the disease. Per year, this represents approximately 384 000 cases, 64 000 clinic visits, 30 000 hospitalizations, and 1 600 deaths. The annual cost of medical care alone for these children is approximately US$ 2.6 million--and that does not take into account the indirect or societal costs of the illness and the deaths. Conclusions. Rotavirus immunization provides the prospect of decreasing the morbidity and mortality from diarrhea in Peru, but a vaccine regimen would have to be relatively inexpensive, a few dollars or less per child. Future cost-effectiveness analyses should explore the total costs (medical as well as indirect or societal associated with rotavirus diarrhea. Newly licensed vaccines should be tested according to both their ability to avert deaths and their efficacy with fewer than three doses. All three of these factors could increase the cost savings associated with a rotavirus vaccine.

  6. 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

  7. The cost-effectiveness of rotavirus vaccination in Armenia.

    Science.gov (United States)

    Jit, Mark; Yuzbashyan, Ruzanna; Sahakyan, Gayane; Avagyan, Tigran; Mosina, Liudmila

    2011-11-08

    The cost-effectiveness of introducing infant rotavirus vaccination in Armenia in 2012 using Rotarix(R) was evaluated using a multiple birth cohort model. The model considered the cost and health implications of hospitalisations, primary health care consultations and episodes not leading to medical care in children under five years old. Rotavirus vaccination is expected to cost the Ministry of Health $220,000 in 2012, rising to $830,000 in 2016 following termination of GAVI co-financing, then declining to $260,000 in 2025 due to vaccine price maturity. It may reduce health care costs by $34,000 in the first year, rising to $180,000 by 2019. By 2025, vaccination may be close to cost saving to the Ministry of Health if the vaccine purchase price declines as expected. Once coverage has reached high levels, vaccination may prevent 25,000 cases, 3000 primary care consultations, 1000 hospitalisations and 8 deaths per birth cohort vaccinated. The cost per disability-adjusted life year (DALY) saved is estimated to be about $650 from the perspective of the Ministry of Health, $850 including costs accrued to both the Ministry and to GAVI, $820 from a societal perspective excluding indirect costs and $44 from a societal perspective including indirect costs. Since the gross domestic product per capita of Armenia in 2008 was $3800, rotavirus vaccination is likely to be regarded as "very cost-effective" from a WHO standpoint. Vaccination may still be "very cost-effective" if less favourable assumptions are used regarding vaccine price and disease incidence, as long as DALYs are not age-weighted. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. A proposed framework for evaluating and comparing efficacy estimates in clinical trials of new rotavirus vaccines.

    Science.gov (United States)

    Neuzil, Kathleen M; Zaman, K; Victor, John C

    2014-08-11

    Oral rotavirus vaccines have yielded different point estimates of efficacy when tested in different populations. While population and environmental factors may account for these differences, study design characteristics should also be considered. We review the study design elements of rotavirus vaccine trials that may affect point estimates of efficacy, and propose a framework for evaluating new rotavirus vaccines. Copyright © 2014. Published by Elsevier Ltd.

  9. The role of the intestinal microbiome in rotavirus vaccine immunogenicity : An exploration from correlation to causation

    NARCIS (Netherlands)

    Harris, V.C.

    2018-01-01

    Rotavirus (RV) is one of the leading causes of serious gastroenteritis and diarrheal deaths in children under the age of five across the globe. Rotavirus vaccines (RVV) protect infants, reducing rotavirus disease, diarrheal outpatient visits, hospitalizations, and deaths following introduction into

  10. Rotavirus Vaccine Response Correlates with the Infant Gut Microbiota Composition in Pakistan

    NARCIS (Netherlands)

    Harris, Vanessa; Ali, Asad; Fuentes, Susana; Korpela, Katri; Kazi, Momin; Tate, Jacqueline; Parashar, Umesh; Wiersinga, W. Joost; Giaquinto, Carlo; de Weerth, Carolina; de Vos, Willem M.

    2017-01-01

    Background Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide, and ninety-five percent of rotavirus deaths occur in Africa and Asia. Rotavirus vaccines (RVV) can dramatically reduce RV deaths, but have low efficacy in low-income settings where they are most needed.

  11. Rotavirus vaccine response correlates with the infant gut microbiota composition in Pakistan

    NARCIS (Netherlands)

    Harris, Vanessa C.; Ali, Asad; Fuentes, Susana; Korpela, Katri; Kazi, Momin; Tate, Jacqueline; Parashar, Umesh; Wiersinga, W.J.; Giaquinto, Carlo; Weerth, de Carolina; Vos, de Willem M.

    2017-01-01

    Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and ninety-five percent of rotavirus deaths occur in Africa and Asia. Rotavirus vaccines (RVV) can dramatically reduce RV deaths, but have low efficacy in low-income settings where they are most needed. The

  12. 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.

  13. Rotavirus Symptoms

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    ... Search Form Controls Cancel Submit Search The CDC Rotavirus Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Rotavirus Home About Rotavirus Symptoms Transmission Treatment Photos Vaccination ...

  14. Rotavirus Treatment

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    ... Search Form Controls Cancel Submit Search The CDC Rotavirus Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Rotavirus Home About Rotavirus Symptoms Transmission Treatment Photos Vaccination ...

  15. Value of post-licensure data on benefits and risks of vaccination to inform vaccine policy: The example of rotavirus vaccines.

    Science.gov (United States)

    Parashar, Umesh D; Cortese, Margaret M; Payne, Daniel C; Lopman, Benjamin; Yen, Catherine; Tate, Jacqueline E

    2015-11-27

    In 1999, the first rhesus-human reassortant rotavirus vaccine licensed in the United States was withdrawn within a year of its introduction after it was linked with intussusception at a rate of ∼1 excess case per 10,000 vaccinated infants. While clinical trials of 60,000-70,000 infants of each of the two current live oral rotavirus vaccines, RotaTeq (RV5) and Rotarix (RV1), did not find an association with intussusception, post-licensure studies have documented a risk in several high and middle income countries, at a rate of ∼1-6 excess cases per 100,000 vaccinated infants. However, considering this low risk against the large health benefits of vaccination that have been observed in many countries, including in countries with a documented vaccine-associated intussusception risk, policy makers and health organizations around the world continue to support the routine use of RV1 and RV5 in national infant immunization programs. Because the risk and benefit data from affluent settings may not be directly applicable to developing countries, further characterization of any associated intussusception risk following rotavirus vaccination as well as the health benefits of vaccination is desirable for low income settings. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Ltd.. All rights reserved.

  16. Cost-Effectiveness of Rotavirus Vaccination in France-Accounting for Indirect Protection.

    Science.gov (United States)

    Yamin, Dan; Atkins, Katherine E; Remy, Vanessa; Galvani, Alison P

    Vaccination against rotavirus has shown great potential for reducing the primary cause of severe childhood gastroenteritis. Previous economic evaluations of rotavirus vaccination in France have not modeled the potential impact of vaccines on disease burden via reduced transmission. To determine the cost-effectiveness of the introduction of pentavalent rotavirus vaccination into the French infant vaccination schedule. We developed an age-structured model of rotavirus transmission calibrated to 6 years of French gastroenteritis incidence and vaccine clinical trial data. We evaluated the cost-effectiveness of pentavalent rotavirus vaccination considering that 75% of infants would receive the three-dose vaccine course. Our model predicts that rotavirus vaccination will decrease rotavirus gastroenteritis incidence and associated clinical outcomes in vaccinated and unvaccinated individuals, delay the seasonal peak of infection, and increase the age of infection. From the societal perspective, our base-case scenario predicts that vaccination coverage would be cost-effective at €115 or €135 per vaccine course at €28,500 and €39,500/quality-adjusted life-year (QALY) gained, respectively, and suggests that almost 95% of the financial benefits will be recouped within the first 5 years following vaccination implementation. From the third-party payer perspective, incremental cost-effectiveness ratios ranged from €12,500 to €20,000/QALY, respectively. Our uncertainty analysis suggests that findings were sensitive to various assumptions including the number of hospitalizations, outpatient visits, and the extent of QALY losses per rotavirus episode. Introducing pentavalent rotavirus vaccination into the French infant vaccination schedule would significantly reduce the burden of rotavirus disease in children, and could be cost-effective under plausible conditions. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by

  17. Rotavirus Vaccines: a story of success with challenges ahead [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Miguel O’Ryan

    2017-08-01

    Full Text Available Approximately 40 years have passed since the discovery of the rotavirus and 10 years since the introduction and progressive dissemination of rotavirus vaccines worldwide. Currently, 92 countries have introduced rotavirus vaccines into national or subnational programs with evident impact in disease reduction. Two vaccines have been widely used, and four additional vaccines have been licensed and are being used in defined regions. In this context, one main issue that remains unsolved is the lower vaccine efficacy/effectiveness in low-income countries. An additional partially answered issue relates to rotavirus strain circulation in vaccinated populations. These issues are discussed in this review. The most imperative challenge ahead is to fulfill the WHO’s recommendation to introduce rotavirus vaccines in all countries.

  18. Potential Impact of Accelerating the Primary Dose of Rotavirus Vaccine in Infants

    OpenAIRE

    Halvorson, Elizabeth E.; Peters, Timothy R.; Snively, Beverly M.; Poehling, Katherine A.

    2012-01-01

    We estimated the potential impact of administering the first dose of rotavirus vaccine at 6 weeks (42 days of life) instead of 2 months of age, which is permissible for all U.S. vaccines recommended at 2 months of age, on rotavirus hospitalization rates. We used published data for hospitalization rates, vaccine coverage, and vaccine efficacy after one dose and assumed a two-week delay in seroconversion after vaccine administration in the United States. Administering the first dose of rotaviru...

  19. Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand

    Science.gov (United States)

    Chen, Mee-Yew; Kirkwood, Carl D.; Bines, Julie; Cowley, Daniel; Pavlic, Daniel; Lee, Katherine J.; Orsini, Francesca; Watts, Emma; Barnes, Graeme; Danchin, Margaret

    2017-01-01

    ABSTRACT Background: Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident. Methods: Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0–5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression. Results: Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05). Conclusions: The level of IgA in colostrum or breast milk and level of placental Ig

  20. Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand.

    Science.gov (United States)

    Chen, Mee-Yew; Kirkwood, Carl D; Bines, Julie; Cowley, Daniel; Pavlic, Daniel; Lee, Katherine J; Orsini, Francesca; Watts, Emma; Barnes, Graeme; Danchin, Margaret

    2017-05-04

    Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident. Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0-5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression. Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05). The level of IgA in colostrum or breast milk and level of placental IgG and SNA did not impact on the serum IgA response or

  1. Pharmacoeconomic spotlight on rotavirus vaccine RIX4414 (Rotarix™) in developed countries.

    Science.gov (United States)

    Plosker, Greg L

    2012-12-01

    The most common cause of severe diarrhea in infants and young children is rotavirus gastroenteritis (RVGE), which is associated with significant morbidity, healthcare resource use, and direct and indirect costs in industrialized nations. The monovalent rotavirus vaccine RIX4414 (Rotarix™) is administered as a two-dose oral series in infants and has demonstrated protective efficacy against RVGE in clinical trials conducted in developed countries. In addition, various naturalistic studies have demonstrated 'real-world' effectiveness after the introduction of widespread rotavirus vaccination programs in the community setting. Numerous cost-effectiveness analyses have been conducted in developed countries in which a universal rotavirus vaccination program using RIX4414 was compared with no universal rotavirus vaccination program. There was a high degree of variability in base-case results across studies even when the studies were conducted in the same country, often reflecting differences in the selection of data sources or assumptions used to populate the models. In addition, results were sensitive to plausible changes in a number of key input parameters. As such, it is not possible to definitively state whether a universal rotavirus vaccination program with RIX4414 is cost effective in developed countries, although results of some analyses in some countries suggest this is the case. In addition, international guidelines advocate universal vaccination of infants and children against rotavirus. It is also difficult to draw conclusions regarding the cost effectiveness of rotavirus vaccine RIX4414 relative to that of the pentavalent rotavirus vaccine, which is administered as a three-dose oral series. Although indirect comparisons in cost-effectiveness analyses indicate that RIX4414 provided more favorable incremental cost-effectiveness ratios when each vaccine was compared with no universal rotavirus vaccination program, results were generally sensitive to vaccine

  2. Trends in diarrhea hospitalizations among infants at three hospitals in Tanzania before and after rotavirus vaccine introduction.

    Science.gov (United States)

    Lyamuya, Faraja; Michael, Fausta; Jani, Bhavin; Fungo, Yohana; Chambo, Alfred; Chami, Inviolatha; Bulali, Regina; Mpamba, Amina; Cholobi, Happy; Kallovya, Dotto; Kamugisha, Christopher; Mwenda, Jason M; Cortese, Margaret M

    2018-04-11

    The Tanzania Ministry of Health introduced monovalent human rotavirus vaccine in January 2013, to be administered at ages 6 and 10 weeks. Data suggest there was high vaccine uptake. We used hospital ward registers from 3 hospitals to examine trends in diarrhea hospitalizations among infants before and after vaccine introduction. Ward registers from Dodoma Regional Referral Hospital (Central Tanzania), and two hospitals in Mbeya (Southwest area), Mbeya Zonal Referral Hospital and Mbalizi Hospital, were used to tally admissions for diarrhea among children by age group, month and year. Rotavirus surveillance had started at these hospitals in early 2013; the proportion of infants enrolled and rotavirus-EIA positive were examined by month to determine peak periods of rotavirus disease post-vaccine introduction. Registers were available for 2-4 prevaccine years and 2-3 post introduction years. At Dodoma Regional Referral Hospital, compared with the mean of 2011 and 2012, diarrhea hospitalizations among infants were 26% lower in 2015 and 58% lower in 2016. The diarrhea peak shifted later in the year first by 1 and then by 2-3 months from prevaccine. At the Mbeya hospitals, the number of diarrhea admissions in prevaccine period varied substantially by year. At Mbeya Referral Hospital, diarrhea hospitalizations among infants were lower by 25-37% in 2014 and 11-26% in 2015, while at Mbalizi Hospital, these hospitalizations were 4% lower in 2014 and 14% higher in 2015. Rotavirus testing data demonstrated a lowering of the prevaccine peak, a shift in timing of the peak months and indicated that other diarrheal peaks in post-introduction years were not due to rotavirus. In this ecological evaluation, total diarrhea hospitalizations among infants were lower (≥25% lower in ≥1 year) following introduction in 2 of 3 hospitals. There are challenges in using ward registers to ascertain possible impact of rotavirus vaccine introduction on trends in hospitalizations for

  3. Emergence of Double- and Triple-Gene Reassortant G1P[8] Rotaviruses Possessing a DS-1-Like Backbone after Rotavirus Vaccine Introduction in Malawi.

    Science.gov (United States)

    Jere, Khuzwayo C; Chaguza, Chrispin; Bar-Zeev, Naor; Lowe, Jenna; Peno, Chikondi; Kumwenda, Benjamin; Nakagomi, Osamu; Tate, Jacqueline E; Parashar, Umesh D; Heyderman, Robert S; French, Neil; Cunliffe, Nigel A; Iturriza-Gomara, Miren

    2018-02-01

    To combat the high burden of rotavirus gastroenteritis, multiple African countries have introduced rotavirus vaccines into their childhood immunization programs. Malawi incorporated a G1P[8] rotavirus vaccine (Rotarix) into its immunization schedule in 2012. Utilizing a surveillance platform of hospitalized rotavirus gastroenteritis cases, we examined the phylodynamics of G1P[8] rotavirus strains that circulated in Malawi before (1998 to 2012) and after (2013 to 2014) vaccine introduction. Analysis of whole genomes obtained through next-generation sequencing revealed that all randomly selected prevaccine G1P[8] strains sequenced ( n = 32) possessed a Wa-like genetic constellation, whereas postvaccine G1P[8] strains ( n = 18) had a DS-1-like constellation. Phylodynamic analyses indicated that postvaccine G1P[8] strains emerged through reassortment events between human Wa- and DS-1-like rotaviruses that circulated in Malawi from the 1990s and hence were classified as atypical DS-1-like reassortants. The time to the most recent common ancestor for G1P[8] strains was from 1981 to 1994; their evolutionary rates ranged from 9.7 × 10 -4 to 4.1 × 10 -3 nucleotide substitutions/site/year. Three distinct G1P[8] lineages chronologically replaced each other between 1998 and 2014. Genetic drift was the likely driver for lineage turnover in 2005, whereas replacement in 2013 was due to reassortment. Amino acid substitution within the outer glycoprotein VP7 of G1P[8] strains had no impact on the structural conformation of the antigenic regions, suggesting that it is unlikely that they would affect recognition by vaccine-induced neutralizing antibodies. While the emergence of DS-1-like G1P[8] rotavirus reassortants in Malawi was therefore likely due to natural genotype variation, vaccine effectiveness against such strains needs careful evaluation. IMPORTANCE The error-prone RNA-dependent RNA polymerase and the segmented RNA genome predispose rotaviruses to genetic mutation and

  4. Differential profiles and inhibitory effect on rotavirus vaccines of nonantibody components in breast milk from mothers in developing and developed countries.

    Science.gov (United States)

    Moon, Sung-Sil; Tate, Jacqueline E; Ray, Pratima; Dennehy, Penelope H; Archary, Derseree; Coutsoudis, Anna; Bland, Ruth; Newell, Marie-Louise; Glass, Roger I; Parashar, Umesh; Jiang, Baoming

    2013-08-01

    Live oral rotavirus vaccines have been less immunogenic and efficacious for children of developing countries than for those in middle income and industrialized countries, and the basis for these differences is not fully understood. Recently, we demonstrated that breastmilk from mothers in India had significantly higher IgA and neutralizing activity against rotavirus that could reduce the effective titer of rotavirus vaccines reaching the gut when compared with that from mothers in the United States. We extended our study to understand the specific contribution of those nonantibody components in breastmilk to the neutralizing activity against rotavirus vaccine we observed. Breastmilk samples were collected from mothers of breast-feeding infants aged between 4 and 29 weeks (ie, vaccine eligible age) in India (N = 40), South Africa (N = 50) and the United States (N = 51). We examined breastmilk for lactoferrin, lactadherin, rotavirus-specific IgA and neutralizing activity against 3 rotavirus vaccine strains (Rotarix, RotaTeq G1 and 116E) using enzyme immunoassays, a plaque reduction assay or a microneutralization assay. We observed higher levels of lactoferrin, lactadherin, IgA and neutralizing activity in breastmilk specimens from Indian and South African women than those from American women. We demonstrated positive associations between levels of lactoferrin or IgA and neutralizing activity in Indian and South African specimens, but not in American specimens. We demonstrated that the inhibitory effect of lactoferrin was dose- or species-dependent, as evidenced by greater reduction in titer of Rotarix and 116E by human lactoferrin. Lactadherin also exhibited inhibitory activity to rotavirus vaccines but appeared to be less effective. The lower immunogenicity and efficacy of rotavirus vaccines in developing countries could be explained, in part, by synergistic inhibitory effect of high levels of antibody and nonantibody components in breastmilk consumed by infants at

  5. Tandem truncated rotavirus VP8* subunit protein with T cell epitope as non-replicating parenteral vaccine is highly immunogenic.

    Science.gov (United States)

    Wen, Xiaobo; Cao, Dianjun; Jones, Ronald W; Hoshino, Yasutaka; Yuan, Lijuan

    2015-01-01

    The two currently available live oral rotavirus vaccines, Rotarix(®) and RotaTeq(®), are highly efficacious in the developed countries. However, the efficacy of such vaccines in resource deprived countries in Africa and Southeast Asia is low. We reported previously that a bacterially-expressed rotavirus P2-P[8] ΔVP8* subunit vaccine candidate administered intramuscularly elicited high-titers of neutralizing antibodies in guinea pigs and mice and significantly shortened the duration of diarrhea in neonatal gnotobiotic pigs upon oral challenge with virulent human rotavirus Wa strain. To further improve its vaccine potential and provide wider coverage against rotavirus strains of global and regional epidemiologic importance, we constructed 2 tandem recombinant VP8* proteins, P2-P[8] ΔVP8*-P[8] ΔVP8* and P2-P[8] ΔVP8*-P[6] ΔVP8* based on Escherichia coli expression system. The two resulting recombinant tandem proteins were highly soluble and P2-P[8] ΔVP8*-P[8] ΔVP8* was generated with high yield. Moreover, guinea pigs immunized intramuscularly by 3 doses of the P2-P[8] ΔVP8*-P[8] ΔVP8* or P2-P[8] ΔVP8*-P[6] ΔVP8* vaccine with aluminum phosphate adjuvant developed high titers of homotypic and heterotypic neutralizing antibodies against human rotaviruses bearing G1-G4, G8, G9 and G12 with P[8], P[4] or P[6] combination. The results suggest that these 2 subunit vaccines in monovalent or bivalent formulation can provide antigenic coverage to almost all the rotavirus G (VP7) types and major P (VP4) types of global as well as regional epidemiologic importance.

  6. Report of the 5th European expert meeting on rotavirus vaccination (EEROVAC).

    Science.gov (United States)

    de Hoog, Marieke L A; Vesikari, Timo; Giaquinto, Carlo; Huppertz, Hans-Iko; Martinon-Torres, Federico; Bruijning-Verhagen, Patricia

    2018-04-03

    The Fifth European Expert Meeting on Rotavirus Vaccination was convened in Utrecht, The Netherlands, in March 2017. The 2-day meeting included invited lectures as well as original oral and poster presentations and brought together experts from 21 countries. Summary findings of the meeting include: Rotavirus vaccination programmes in Europe have resulted in reductions of 60-90% in rotavirus outpatient visits and hospitalizations. Long term trends indicate this impact is sustained over the years. Herd effects, protecting unvaccinated children and neonates too young to be vaccinated have been observed in many European countries. Early evidence now also suggests that rotavirus vaccination may be instrumental in the prevention of celiac disease. Special attention should be given to preterm infants, who may age out of the vaccination window before hospital discharge and to HIV infected children who are at increased risk of severe rotavirus AGE. There is a small but increased risk of IS following rotavirus vaccination and parents should therefore be informed about possible signs and symptoms of IS. New insights in rotavirus genetic susceptibility and interactions with microbiome may open opportunities for interventions to improve protection by vaccination, in particular in LMIC. The development of several novel rotavirus vaccines discussed at the meeting is also promising in this respect.

  7. Balancing safety, efficacy and cost: Improving rotavirus vaccine adoption in low- and middle-income countries

    Directory of Open Access Journals (Sweden)

    Anant Bhan

    2011-12-01

    Full Text Available Diarrheal disease caused by rotavirus claims approximately 500 000 lives each year, mostly in low-income countries. Many of these deaths are preventable through the use of available rotavirus vaccines. Yet, in spite of a WHO recommendation that these vaccines be adopted into all national immunization programs, only a few countries have done so.

  8. Impact of Rotavirus Vaccination on Hospitalisations in Belgium : Comparing Model Predictions with Observed Data

    NARCIS (Netherlands)

    Standaert, Baudouin; Gomez, Jorge A.; Raes, Marc; Debrus, Serge; Raul Velazquez, F.; Postma, Maarten J.

    2013-01-01

    Background: Published economic assessments of rotavirus vaccination typically use modelling, mainly static Markov cohort models with birth cohorts followed up to the age of 5 years. Rotavirus vaccination has now been available for several years in some countries, and data have been collected to

  9. Rotavirus vaccine and diarrhea mortality: quantifying regional variation in effect size

    Directory of Open Access Journals (Sweden)

    Black Robert E

    2011-04-01

    Full Text Available Abstract Background Diarrhea mortality remains a leading cause of child death and rotavirus vaccine an effective tool for preventing severe rotavirus diarrhea. New data suggest vaccine efficacy may vary by region. Methods We reviewed published vaccine efficacy trials to estimate a regional-specific effect of vaccine efficacy on severe rotavirus diarrhea and hospitalizations. We assessed the quality of evidence using a standard protocol and conducted meta-analyses where more than 1 data point was available. Results Rotavirus vaccine prevented severe rotavirus episodes in all regions; 81% of episodes in Latin America, 42.7% of episodes in high-mortality Asia, 50% of episodes in sub-Saharan Africa, 88% of episodes low-mortality Asia and North Africa, and 91% of episodes in developed countries. The effect sizes observed for preventing severe rotavirus diarrhea will be used in LiST as the effect size for rotavirus vaccine on rotavirus-specific diarrhea mortality. Conclusions Vaccine trials have not measured the effect of vaccine on diarrhea mortality. The overall quality of the evidence and consistency observed across studies suggests that estimating mortality based on a severe morbidity reduction is highly plausible.

  10. An update of “Cost-effectiveness of rotavirus vaccination in the Netherlands: the results of a Consensus Rotavirus Vaccine model”

    Directory of Open Access Journals (Sweden)

    Tu Hong Anh T

    2013-01-01

    Full Text Available Abstract Background To update a cost-effectiveness analysis of rotavirus vaccination in the Netherlands previously published in 2011. Methods The rotavirus burden of disease and the indirect protection of older children and young adults (herd protection were updated. Results When updated data was used, routine infant rotavirus vaccination in the Netherlands would potentially become an even more cost-effective strategy than previously estimated with the incremental cost per QALY at only €3,000-4,000. Break-even total vaccination costs were indicated at €92–122, depending on the applied threshold. Conclusions We concluded that the results on potentially favourable cost-effectiveness in the previous study remained valid, however, the new data suggested that previous results might represent an underestimation of the economic attractiveness of rotavirus vaccination.

  11. Cost-effectiveness of universal rotavirus vaccination in reducing rotavirus gastroenteritis in Ireland.

    LENUS (Irish Health Repository)

    Tilson, L

    2011-10-06

    We evaluated the cost-effectiveness of universal infant rotavirus (RV) vaccination compared to current standard of care of "no vaccination". Two RV vaccines are currently licensed in Ireland: Rotarix and RotaTeq. A cohort model used in several European countries was adapted using Irish epidemiological, resource utilisation and cost data. The base case model considers the impact of Rotarix vaccination on health-related quality of life of children under five years old from a healthcare payer perspective. Other scenarios explored the use of RotaTeq, impact on one caregiver, on societal costs and on cases that do not seek medical attention. Cost was varied between the vaccine list price (€100\\/course) in the base case and an assumed tender price (€70\\/course). One-way and probabilistic sensitivity analyses were conducted. Implementing universal RV vaccination may prevent around 1970 GP visits, 3280 A&E attendances and 2490 hospitalisations. A vaccination programme was estimated to cost approximately €6.54 million per year but €4.65 million of this would be offset by reducing healthcare resource use. The baseline ICER was €112,048\\/QALY and €72,736\\/QALY from the healthcare payer and societal perspective, respectively, falling to €68,896 and €43,916\\/QALY, respectively, if the impact on one caregiver was considered. If the price fell to €70 per course, universal RV vaccination would be cost saving under all scenarios. Results were sensitive to vaccination costs, incidence of RV infection and direct medical costs. Universal RV vaccination would not be cost-effective under base case assumptions. However, it could be cost-effective at a lower vaccine price or from a wider societal perspective.

  12. Progress in the introduction of the rotavirus vaccine in Latin America and the Caribbean: four years of accumulated experience.

    Science.gov (United States)

    de Oliveira, Lucia Helena; Danovaro-Holliday, M Carolina; Sanwogou, N Jennifer; Ruiz-Matus, Cuauhtemoc; Tambini, Gina; Andrus, Jon Kim

    2011-01-01

    Two effective and safe rotavirus vaccines became available in 2006 and have been recommended for use in all countries by the World Health Organization. This article provides an update on the use of rotavirus vaccine in Latin American and Caribbean (LAC) countries. Data reported by LAC countries to the Pan American Health Organization (PAHO) were reviewed. As of May 2010, 14 LAC countries and 1 territory have introduced the rotavirus vaccine into their national expanded program on immunization (EPI). Reported coverage levels for rotavirus vaccine are lower than those for other EPI vaccines recommended at the same age. A total of 15 LAC countries are part of the PAHO's LAC rotavirus surveillance network; 12 of them are using the vaccine. LAC countries are conducting several studies on rotavirus vaccine effectiveness, cost-effectiveness, and monitoring safety. Also, LAC countries are generating lessons learned on the public health implications of introducing a new vaccine into the EPI. Nine countries and the Cayman Islands pay for the entire cost of the vaccine using government funds. All but 2 countries purchase their rotavirus vaccine through PAHO's Revolving Fund. Rotavirus vaccine introduction in LAC has been faster than for other new vaccines, but coverage levels need to increase to maximize the effect of the intervention. Rotavirus surveillance needs to expand and be strengthened to better assess the effect of vaccine use. LAC countries will continue to provide useful data to monitor rotavirus trends and vaccine effect.

  13. Immunogenicity and protective efficacy of yeast extracts containing rotavirus-like particles: a potential veterinary vaccine.

    Science.gov (United States)

    Rodríguez-Limas, William A; Pastor, Ana Ruth; Esquivel-Soto, Ernesto; Esquivel-Guadarrama, Fernando; Ramírez, Octavio T; Palomares, Laura A

    2014-05-19

    Rotavirus is the most common cause of severe diarrhea in many animal species of economic interest. A simple, safe and cost-effective vaccine is required for the control and prevention of rotavirus in animals. In this study, we evaluated the use of Saccharomyces cerevisiae extracts containing rotavirus-like particles (RLP) as a vaccine candidate in an adult mice model. Two doses of 1mg of yeast extract containing rotavirus proteins (between 0.3 and 3 μg) resulted in an immunological response capable of reducing the replication of rotavirus after infection. Viral shedding in all mice groups diminished in comparison with the control group when challenged with 100 50% diarrhea doses (DD50) of murine rotavirus strain EDIM. Interestingly, when immunizing intranasally protection against rotavirus infection was observed even when no increase in rotavirus-specific antibody titers was evident, suggesting that cellular responses were responsible of protection. Our results indicate that raw yeast extracts containing rotavirus proteins and RLP are a simple, cost-effective alternative for veterinary vaccines against rotavirus. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Rotavirus vaccine strain transmission by vaccinated infants in the foster home.

    Science.gov (United States)

    Miura, Hiroki; Kawamura, Yoshiki; Sugata, Ken; Koshiyama, Nozomi; Yoshikawa, Akiko; Komoto, Satoshi; Taniguchi, Koki; Ihira, Masaru; Yoshikawa, Tetsushi

    2017-01-01

    Previous studies have demonstrated the transmission of rotavirus vaccine strains from vaccinated children to nonvaccinated siblings. We sought to fully elucidate the safety of rotavirus (RV) vaccination in closed contact circumstance, such as the foster home for future assessment of the vaccine safety in an neonatal intensive care unit. Stool samples were collected from 4 RV vaccinated (160 samples) and 23 unvaccinated (766 samples) infants. RV viral RNA loads were measured using real-time reverse transcription polymerase chain reaction (RT-PCR). RV vaccine strain RNA was persistently detected in stool samples collected from the four vaccine recipients and one unvaccinated infant, but not in the stool samples collected from the 22 other unvaccinated infants. The unvaccinated infant who tested positive for the RV vaccine strain was vaccinated prior to enrollment in this study. The quantitative real-time RT-PCR data revealed a peak viral RNA load 1 week after vaccination followed by a gradual decrease. The current study suggests that RV vaccination may be safe in a close contact environment because there was limited transmission from RV vaccinated to unvaccinated infants. J. Med. Virol. 89:79-84, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Delayed Dosing of Oral Rotavirus Vaccine Demonstrates Decreased Risk of Rotavirus Gastroenteritis Associated With Serum Zinc: A Randomized Controlled Trial.

    Science.gov (United States)

    Colgate, E Ross; Haque, Rashidul; Dickson, Dorothy M; Carmolli, Marya P; Mychaleckyj, Josyf C; Nayak, Uma; Qadri, Firdausi; Alam, Masud; Walsh, Mary Claire; Diehl, Sean A; Zaman, K; Petri, William A; Kirkpatrick, Beth D

    2016-09-01

    Rotavirus is the world's leading cause of childhood diarrheal death. Despite successes, oral rotavirus vaccines are less effective in developing countries. In an urban slum of Dhaka, we performed active diarrhea surveillance to evaluate monovalent G1P[8] rotavirus vaccine (RV1) efficacy and understand variables contributing to risk of rotavirus diarrhea (RVD). We performed a randomized controlled trial of monovalent oral rotavirus vaccine (RV1). Seven hundred healthy infants received RV1 or no RV1 (1:1) using delayed dosing (10 and 17 weeks) and were followed for 1 year. Intensive diarrhea surveillance was performed. The primary outcome was ≥1 episode of RVD. Nutritional, socioeconomic, and immunologic factors were assessed by logistic regression best-subsets analysis for association with risk of RVD and interactions with vaccine arm. Incidence of all RVD was 38.3 cases per 100 person-years. Per-protocol RV1 efficacy was 73.5% (95% confidence interval [CI], 45.8%-87.0%) against severe RVD and 51% (95% CI, 33.8%-63.7%) against all RVD. Serum zinc level (odds ratio [OR], 0.77; P = .002) and lack of rotavirus immunoglobulin A (IgA) seroconversion (OR, 1.95; P = .018) were associated with risk of RVD, independent of vaccination status. Water treatment and exclusive breastfeeding were of borderline significance. Factors not associated with RVD included height for age at 10 weeks, vitamin D, retinol binding protein, maternal education, household income, and sex. In an urban slum with high incidence of RVD, the efficacy of RV1 against severe RVD was higher than anticipated in the setting of delayed dosing. Lower serum zinc level and lack of IgA seroconversion were associated with increased risk of RVD independent of vaccination. NCT01375647. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  16. Efficacy of the oral pentavalent rotavirus vaccine in Mali.

    Science.gov (United States)

    Sow, Samba O; Tapia, Milagritos; Haidara, Fadima C; Ciarlet, Max; Diallo, Fatoumata; Kodio, Mamoudou; Doumbia, Moussa; Dembélé, Rokiatou D; Traoré, Oumou; Onwuchekwa, Uma U; Lewis, Kristen D C; Victor, John C; Steele, A Duncan; Neuzil, Kathleen M; Kotloff, Karen L; Levine, Myron M

    2012-04-27

    The oral, pentavalent rotavirus vaccine (PRV), RotaTeq was assessed for prevention of severe rotavirus gastroenteritis (RVGE) in young children in two multi-site, randomized, placebo-controlled field trials; one in Asia (Vietnam and Bangladesh) and the other in sub-Saharan Africa (Ghana, Kenya and Mali). The efficacy results for the Mali site of the multi-country trial are presented here. We randomly assigned infants in a 1:1 ratio to receive 3 doses of PRV/placebo at approximately 6, 10, and 14 weeks of age. Gastroenteritis episodes were captured passively at the local health centers and by home visits. The primary study outcome was severe RVGE, as defined by a score of ≥ 11 using the Vesikari Clinical Scoring System occurring ≥ 14 days after the third dose until the end of the study. Other efficacy analyses included efficacy against severe RVGE through the first year and during the second years of life, as well as efficacy after receiving at least one dose of vaccine. In total, 1960 infants were enrolled in the trial at the Mali site and sera were collected on a subset of infants (approximately 150) for immunogenicity testing. In the first year of follow-up, largely due to cultural practices to visit traditional healers as the first point of care, the point estimate of efficacy was unreliable: the per protocol vaccine efficacy against severe RVGE was 1% (95% confidence interval [CI]: -431.7, 81.6); the intention-to-treat vaccine efficacy was 42.9% (95% CI: -125.7, 87.7). During the second year of follow-up, after the surveillance system was modified to adapt to local customs and health care seeking practices, the point estimate of per-protocol vaccine efficacy was 19.2% (95% CI: -23.1,47.3%). 82.5% of Malian infants (95% CI: 70.1,91.3%) who received PRV mounted a seroresponse (≥ 3-fold rise from baseline (prevaccination) to post-dose 3 vaccination) of anti-rotavirus immunoglobulin A antibody, with a post third-dose geometric mean titer (GMT) of 31.3 units

  17. Costs of diarrheal disease and the cost-effectiveness of a rotavirus vaccination program in kyrgyzstan.

    Science.gov (United States)

    Flem, Elmira T; Latipov, Renat; Nurmatov, Zuridin S; Xue, Yiting; Kasymbekova, Kaliya T; Rheingans, Richard D

    2009-11-01

    We examined the cost-effectiveness of a rotavirus immunization program in Kyrgyzstan, a country eligible for vaccine funding from the GAVI Alliance. We estimated the burden of rotavirus disease and its economic consequences by using national and international data. A cost-effectiveness analysis was conducted from government and societal perspectives, along with a range of 1-way sensitivity analyses. Rotavirus-related hospitalizations and outpatient visits cost US$580,864 annually, of which $421,658 (73%) is direct medical costs and $159,206 (27%) is nonmedical and indirect costs. With 95% coverage, vaccination could prevent 75% of rotavirus-related hospitalizations and deaths and 56% of outpatient visits and could avert $386,193 (66%) in total costs annually. The medical break-even price at which averted direct medical costs equal vaccination costs is $0.65/dose; the societal break-even price is $1.14/dose for a 2-dose regimen. At the current GAVI Alliance-subsidized vaccine price of $0.60/course, rotavirus vaccination is cost-saving for the government. Vaccination is cost-effective at a vaccine price $9.41/dose, according to the cost-effectiveness standard set by the 2002 World Health Report. Addition of rotavirus vaccines to childhood immunization in Kyrgyzstan could substantially reduce disease burden and associated costs. Vaccination would be cost-effective from the national perspective at a vaccine price $9.41 per dose.

  18. Impact of rotavirus vaccination on hospitalisations in Belgium: comparing model predictions with observed data.

    Directory of Open Access Journals (Sweden)

    Baudouin Standaert

    Full Text Available BACKGROUND: Published economic assessments of rotavirus vaccination typically use modelling, mainly static Markov cohort models with birth cohorts followed up to the age of 5 years. Rotavirus vaccination has now been available for several years in some countries, and data have been collected to evaluate the real-world impact of vaccination on rotavirus hospitalisations. This study compared the economic impact of vaccination between model estimates and observed data on disease-specific hospitalisation reductions in a country for which both modelled and observed datasets exist (Belgium. METHODS: A previously published Markov cohort model estimated the impact of rotavirus vaccination on the number of rotavirus hospitalisations in children aged <5 years in Belgium using vaccine efficacy data from clinical development trials. Data on the number of rotavirus-positive gastroenteritis hospitalisations in children aged <5 years between 1 June 2004 and 31 May 2006 (pre-vaccination study period or 1 June 2007 to 31 May 2010 (post-vaccination study period were analysed from nine hospitals in Belgium and compared with the modelled estimates. RESULTS: The model predicted a smaller decrease in hospitalisations over time, mainly explained by two factors. First, the observed data indicated indirect vaccine protection in children too old or too young for vaccination. This herd effect is difficult to capture in static Markov cohort models and therefore was not included in the model. Second, the model included a 'waning' effect, i.e. reduced vaccine effectiveness over time. The observed data suggested this waning effect did not occur during that period, and so the model systematically underestimated vaccine effectiveness during the first 4 years after vaccine implementation. CONCLUSIONS: Model predictions underestimated the direct medical economic value of rotavirus vaccination during the first 4 years of vaccination by approximately 10% when assessing

  19. Rotavirus vaccine a€“ What are the concerns of the developing countries?

    OpenAIRE

    SHAH, Nitin K

    2010-01-01

    It is estimated that 0.6 million children die annually due to rotavirus diarrhea under the age of 5 years world over. 90% of these deaths occur in developing countries. Western data suggests that current rotavirus vaccines have 85-95% efficacy against severe rotavirus gastroenteritis (RVGE). There are concerns while using the same in developing countries. Data from African trial has shown 76% efficacy against severe RVGE. Efficacy in malnourished children has been found to be 73% as against 7...

  20. Effectiveness of pneumococcal conjugate vaccine and rotavirus ...

    African Journals Online (AJOL)

    Immunisation has contributed greatly to the control of vaccine-preventable diseases and therefore to improvements in health and survival, especially among young children, and remains one of the most successful and cost-effective public health interventions. This remains true for many of the newer, more expensive ...

  1. Understanding reduced rotavirus vaccine efficacy in low socio-economic settings.

    Directory of Open Access Journals (Sweden)

    Benjamin A Lopman

    Full Text Available Rotavirus vaccine efficacy ranges from >90% in high socio-economic settings (SES to 50% in low SES. With the imminent introduction of rotavirus vaccine in low SES countries, understanding reasons for reduced efficacy in these settings could identify strategies to improve vaccine performance.We developed a mathematical model to predict rotavirus vaccine efficacy in high, middle and low SES based on data specific for each setting on incidence, protection conferred by natural infection and immune response to vaccination. We then examined factors affecting efficacy.Vaccination was predicted to prevent 93%, 86% and 51% of severe rotavirus gastroenteritis in high, middle and low SES, respectively. Also predicted was that vaccines are most effective against severe disease and efficacy declines with age in low but not high SES. Reduced immunogenicity of vaccination and reduced protection conferred by natural infection are the main factors that compromise efficacy in low SES.The continued risk of severe disease in non-primary natural infections in low SES is a key factor underpinning reduced efficacy of rotavirus vaccines. Predicted efficacy was remarkably consistent with observed clinical trial results from different SES, validating the model. The phenomenon of reduced vaccine efficacy can be predicted by intrinsic immunological and epidemiological factors of low SES populations. Modifying aspects of the vaccine (e.g. improving immunogenicity in low SES and vaccination program (e.g. additional doses may bring improvements.

  2. Understanding reduced rotavirus vaccine efficacy in low socio-economic settings.

    Science.gov (United States)

    Lopman, Benjamin A; Pitzer, Virginia E; Sarkar, Rajiv; Gladstone, Beryl; Patel, Manish; Glasser, John; Gambhir, Manoj; Atchison, Christina; Grenfell, Bryan T; Edmunds, W John; Kang, Gagandeep; Parashar, Umesh D

    2012-01-01

    Rotavirus vaccine efficacy ranges from >90% in high socio-economic settings (SES) to 50% in low SES. With the imminent introduction of rotavirus vaccine in low SES countries, understanding reasons for reduced efficacy in these settings could identify strategies to improve vaccine performance. We developed a mathematical model to predict rotavirus vaccine efficacy in high, middle and low SES based on data specific for each setting on incidence, protection conferred by natural infection and immune response to vaccination. We then examined factors affecting efficacy. Vaccination was predicted to prevent 93%, 86% and 51% of severe rotavirus gastroenteritis in high, middle and low SES, respectively. Also predicted was that vaccines are most effective against severe disease and efficacy declines with age in low but not high SES. Reduced immunogenicity of vaccination and reduced protection conferred by natural infection are the main factors that compromise efficacy in low SES. The continued risk of severe disease in non-primary natural infections in low SES is a key factor underpinning reduced efficacy of rotavirus vaccines. Predicted efficacy was remarkably consistent with observed clinical trial results from different SES, validating the model. The phenomenon of reduced vaccine efficacy can be predicted by intrinsic immunological and epidemiological factors of low SES populations. Modifying aspects of the vaccine (e.g. improving immunogenicity in low SES) and vaccination program (e.g. additional doses) may bring improvements.

  3. Cryptosporidium spp. and rotavirus gastroenteritis and change of incidence after rotavirus vaccination among children in Raparin Pediatrics Hospital, Erbil, Iraq

    Directory of Open Access Journals (Sweden)

    Sally S. Azeez

    2017-11-01

    Full Text Available Background: Watery diarrhea is the most common medical problem among infants and young children, caused by different microbial etiology including Cryptosporidium spp. and rotavirus, which are usually misdiagnosed in conventional stool test. This study aimed to investigate the incidence of Cryptosporidium and rotavirus gastroenteritis among children in Erbil as well as evaluate the efficacy of rotavirus vaccination procedure applied in Erbil.Methods: Fecal specimens were collected from 400 children (boys and girls, aged one month to five years old, who attended Raparin Pediatrics Hospital in Erbil complaining from diarrhea, between January to August 2014. Modified Ziehl Neelsen technique and nested PCR were used for detection of cryptosporidiosis while rotavirus infection was detected by rapid CerTest.Results: Rate of detection of cryptosporidiosis was remarkably higher using PCR than Ziehl-Neelsen stain (0% versus 6%, and the infection was slightly higher among boys (6.25% vs 5.55% and children ≤2 years (11.7%. The peak of infection reached during spring season (March and April (9.5%. The detection rate of rotavirus was 32.0%, which was slightly higher among males (34.4% vs 30.0% and in children between one to three years old (39.3%. The highest detection rate (38.6% was recorded during winter season (January and February. The infection was significantly higher among non-vaccinated children (65.9% vs 14.1%; p<0.05.Conclusion: The incidence of cryptosporidiosis is declining. However, rotavirus gastroenteritis was relatively high among young children in Erbil. Rotateq vaccine significantly reduced the incidence of rotavirus infection.

  4. Significant correlation between the infant gut microbiome and rotavirus vaccine response in rural Ghana

    NARCIS (Netherlands)

    Harris, V.C.; Armah, G.; Fuentes, S.; Korpela, K.E.; Parashar, U.; Victor, J.C.; Tate, J.; Weerth, C. de; Giaquinto, C.; Wiersinga, W.J.; Lewis, K.D.C.; Vos, W.M. de

    2017-01-01

    Background. Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and ninety-five percent of RV deaths occur in Africa and Asia where rotavirus vaccines (RVV) have lower efficacy. We hypothesize that differences in intestinal microbiome composition correlate with the

  5. Analysis by rotavirus gene 6 reverse transcriptase-polymerase chain reaction assay of rotavirus-positive gastroenteritis cases observed during the vaccination phase of the Rotavirus Efficacy and Safety Trial (REST)

    Science.gov (United States)

    Matson, David O; Vesikari, Timo; Dennehy, Penelope; Dallas, Michael D; Goveia, Michelle G; Itzler, Robbin F; Ciarlet, Max

    2014-01-01

    During the vaccination phase of the Rotavirus Efficacy and Safety Trial (REST), the period between the administration of dose 1 through 13 days after the administration of dose 3, there were more wild-type rotavirus gastroenteritis (RVGE) cases among vaccine recipients compared with placebo recipients using the protocol-specified microbiological plaque assay in the clinical-efficacy cohort, a subset of subjects where vaccine efficacy against RVGE of any severity was assessed. In this study, a rotavirus genome segment 6-based reverse transcriptase–polymerase chain reaction assay was applied post hoc to clarify the accuracy of type categorization of all these RVGE cases in vaccine recipients during the vaccination phase of REST. The assay characterized 147 (90%) of 163 re-assayed RVGE cases or rotavirus-associated health care contacts as type-determinable: either wild-type or vaccine-type rotavirus strains. In the clinical-efficacy cohort (N = 5673), 19 (18.8%) of 101 samples from RVGE cases contained wild-type rotavirus, 70 (69.3%) vaccine virus, and 12 (11.9%) were indeterminable. In the large-scale cohort (N = 68,038), 10 (34.5%) of 29 samples from RVGE-related health care contacts contained wild-type rotavirus strains, 15 (51.7%) vaccine-type rotavirus strains, and 4 (13.8%) were indeterminable. Of the 33 samples from RVGE cases in placebo recipients, all were confirmed to contain wild-type rotaviruses. Altogether, this post-hoc re-evaluation showed that the majority (75%) of type-determinable RVGE cases or health care contacts that occurred during the vaccination phase of REST in vaccine recipients were associated with vaccine-type rotavirus strains rather than wild-type rotavirus strains. PMID:25424931

  6. Analysis by rotavirus gene 6 reverse transcriptase-polymerase chain reaction assay of rotavirus-positive gastroenteritis cases observed during the vaccination phase of the Rotavirus Efficacy and Safety Trial (REST).

    Science.gov (United States)

    Matson, David O; Vesikari, Timo; Dennehy, Penelope; Dallas, Michael D; Goveia, Michelle G; Itzler, Robbin F; Ciarlet, Max

    2014-01-01

    During the vaccination phase of the Rotavirus Efficacy and Safety Trial (REST), the period between the administration of dose 1 through 13 days after the administration of dose 3, there were more wild-type rotavirus gastroenteritis (RVGE) cases among vaccine recipients compared with placebo recipients using the protocol-specified microbiological plaque assay in the clinical-efficacy cohort, a subset of subjects where vaccine efficacy against RVGE of any severity was assessed. In this study, a rotavirus genome segment 6-based reverse transcriptase-polymerase chain reaction assay was applied post hoc to clarify the accuracy of type categorization of all these RVGE cases in vaccine recipients during the vaccination phase of REST. The assay characterized 147 (90%) of 163 re-assayed RVGE cases or rotavirus-associated health care contacts as type-determinable: either wild-type or vaccine-type rotavirus strains. In the clinical-efficacy cohort (N = 5673), 19 (18.8%) of 101 samples from RVGE cases contained wild-type rotavirus, 70 (69.3%) vaccine virus, and 12 (11.9%) were indeterminable. In the large-scale cohort (N = 68,038), 10 (34.5%) of 29 samples from RVGE-related health care contacts contained wild-type rotavirus strains, 15 (51.7%) vaccine-type rotavirus strains, and 4 (13.8%) were indeterminable. Of the 33 samples from RVGE cases in placebo recipients, all were confirmed to contain wild-type rotaviruses. Altogether, this post-hoc re-evaluation showed that the majority (75%) of type-determinable RVGE cases or health care contacts that occurred during the vaccination phase of REST in vaccine recipients were associated with vaccine-type rotavirus strains rather than wild-type rotavirus strains.

  7. An update of cost-effectiveness of rotavirus vaccination in indonesia: Takinga birth-dose vaccination strategy into account

    NARCIS (Netherlands)

    Suwantika, A.A.; Setiawan, D.; Atthobari, J.; Postma, M.J.

    2014-01-01

    Objectives: Rotavirus infection was reported as the major cause of severe diarrhea in children under 5-years-old in Indonesia. A low cost rotavirus vaccine to protect infants from birth has been developed for developing countries, such as Indonesia. This study aims to update our initial analysis on

  8. A benefit-risk analysis of rotavirus vaccination, France, 2015.

    Science.gov (United States)

    Lamrani, Adnane; Tubert-Bitter, Pascale; Hill, Catherine; Escolano, Sylvie

    2017-12-01

    IntroductionTwo vaccines available for protection against rotavirus gastroenteritis (RVGE), Rotarix and RotaTeq, have contributed to a large decrease in the incidence of paediatric diarrhoea in countries where they have been used. However, they have also led to a small increase in the risk of intussusception. Methods: We compare the number of prevented hospitalisations for RVGE to the number of vaccine-induced hospitalised intussusceptions in France. Results: With 9.5% coverage (French 2015 estimation), vaccination was estimated to prevent, annually, a median of 1,074 hospitalisations (2.5th and 97.5th percentiles (2.5th-97.5th): 810-1,378) and 1.4 deaths (2.5th-97.5th: 1.2-1.6) from RVGE. It was also estimated to cause, annually, 5.0 hospitalisations (2.5th-97.5th: 3.2-7.7) and 0.005 deaths (2.5th-97.5th: 0.001-0.015) from intussusception. The benefit-risk ratio is therefore 214 (2.5th-97.5th: 128-362) for hospitalisations and 273 (2.5th-97.5th: 89-1,228) for deaths. Under a hypothetical 92% coverage, rotavirus vaccination with Rotarix would avoid 10,459 (2.5th-97.5th: 7,702-13,498) hospitalisations for RVGE and induce 47.0 (2.5th-97.5th: 25.1-81.4) hospitalisations for intussusception annually, thereby preventing 13.7 (2.5th-97.5th: 11.1-15.2) deaths and inducing 0.05 (2.5th-97.5th: 0.01-0.15) deaths. Conclusion: The benefit-risk ratio in France is similar to that of other European countries.

  9. Comparative evaluation of the potential impact of rotavirus versus hpv vaccination in GAVI-eligible countries: A preliminary analysis focused on the relative disease burden

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    Chang Joshua

    2011-06-01

    Full Text Available Abstract Background Immunization policymakers at global and local levels need to establish priorities among new vaccines competing for limited resources. However, comparison of the potential impact of single vaccination programs is challenging, primarily due to the limited number of vaccine analyses as well as their differing analytic approaches and reporting formats. The purpose of this study is to provide early insight into how the comparative impact of different new vaccines could be assessed in resource-poor settings with respect to affordability, cost-effectiveness, and distributional equity. Methods We compared the health, economic, and financial consequences of introducing the two vaccines in 72 GAVI-eligible countries using a number of different outcome measures to evaluate affordability, cost-effectiveness, and distributional equity. We use simple static models to standardize the analytic framework and improve comparability between the two new vaccines. These simple models were validated by leveraging previously developed, more complex models for rotavirus and human papillomavirus (HPV. Results With 70% coverage of a single-age cohort of infants and pre-adolescent girls, the lives saved with rotavirus (~274,000 and HPV vaccines (~286,000 are similar, although the timing of averted mortality differs; rotavirus-attributable deaths occur in close proximity to infection, while HPV-related cancer deaths occur largely after age 30. Deaths averted per 1000 vaccinated are 5.2 (rotavirus and 12.6 (HPV. Disability-adjusted life years (DALYs averted were ~7.15 million (rotavirus and ~1.30 million (HPV, reflecting the greater influence of discounting on the latter, given the lagtime between vaccination and averted cancer. In most countries (68 for rotavirus and 66 for HPV, at the cost of I$25 per vaccinated individual the incremental cost per DALY averted was lower than each country's GDP per capita. Financial resources required for vaccination

  10. Comparative evaluation of the potential impact of rotavirus versus HPV vaccination in GAVI-eligible countries: a preliminary analysis focused on the relative disease burden.

    Science.gov (United States)

    Kim, Sun-Young; Sweet, Steven; Chang, Joshua; Goldie, Sue J

    2011-06-16

    Immunization policymakers at global and local levels need to establish priorities among new vaccines competing for limited resources. However, comparison of the potential impact of single vaccination programs is challenging, primarily due to the limited number of vaccine analyses as well as their differing analytic approaches and reporting formats. The purpose of this study is to provide early insight into how the comparative impact of different new vaccines could be assessed in resource-poor settings with respect to affordability, cost-effectiveness, and distributional equity. We compared the health, economic, and financial consequences of introducing the two vaccines in 72 GAVI-eligible countries using a number of different outcome measures to evaluate affordability, cost-effectiveness, and distributional equity. We use simple static models to standardize the analytic framework and improve comparability between the two new vaccines. These simple models were validated by leveraging previously developed, more complex models for rotavirus and human papillomavirus (HPV). With 70% coverage of a single-age cohort of infants and pre-adolescent girls, the lives saved with rotavirus (~274,000) and HPV vaccines (~286,000) are similar, although the timing of averted mortality differs; rotavirus-attributable deaths occur in close proximity to infection, while HPV-related cancer deaths occur largely after age 30. Deaths averted per 1000 vaccinated are 5.2 (rotavirus) and 12.6 (HPV). Disability-adjusted life years (DALYs) averted were ~7.15 million (rotavirus) and ~1.30 million (HPV), reflecting the greater influence of discounting on the latter, given the lagtime between vaccination and averted cancer. In most countries (68 for rotavirus and 66 for HPV, at the cost of I$25 per vaccinated individual) the incremental cost per DALY averted was lower than each country's GDP per capita. Financial resources required for vaccination with rotavirus are higher than with HPV since both

  11. The Impact of Rotavirus Vaccination on Discounted Net Tax Revenue in Egypt A Government Perspective Analysis

    NARCIS (Netherlands)

    Connolly, Mark P.; Topachevskyi, Oleksandr; Standaert, Baudouin; Ortega, Omayra; Postma, Maarten

    2012-01-01

    Background: We evaluated national rotavirus (RV) immunization programme costs to estimate how resulting changes in morbidity and mortality will influence government fiscal accounts over time. The assumption was that increased childhood survival in vaccinated cohorts leads to increased numbers of

  12. Prevalence of rotavirus genotypes in children younger than 5 years of age before the introduction of a universal rotavirus vaccination program: report of rotavirus surveillance in Turkey.

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    Riza Durmaz

    Full Text Available BACKGROUND: Group A rotaviruses are the most common causative agent of acute gastroenteritis among children less than 5 years of age throughout the world. This sentinel surveillance study was aimed to obtain baseline data on the rotavirus G and P genotypes across Turkey before the introduction of a universal rotavirus vaccination program. METHODS: Rotavirus antigen-positive samples were collected from 2102 children less than 5 years of age who attended hospitals participating in the Turkish Rotavirus Surveillance Network. Rotavirus antigen was detected in the laboratories of participating hospitals by commercial serological tests such as latex agglutination, immunochromatographic test or enzyme immunoassay. Rotavirus G and P genotypes were determined by reverse transcription polymerase chain reaction (RT-PCR using consensus primers detecting the VP7 and VP4 genes, followed by semi-nested type-specific multiplex PCR. RESULTS: RT-PCR found rotavirus RNA in 1644 (78.2% of the samples tested. The highest rate of rotavirus positivity (38.7% was observed among children in the 13 to 24 month age group, followed by children in the age group of 25 to 36 months (28.3%. A total of eight different G types, six different P types, and 42 different G-P combinations were obtained. Four common G types (G1, G2, G3, and G9 and two common P types (P[8] and P[4] accounted for 95.1% and 98.8% of the strains, respectively. G9P[8] was the most common G/P combination found in 40.5% of the strains followed by G1P[8] (21.6%, G2P[8] (9.3%, G2P[4] (6.5%, G3P[8] (3.5%, and finally, G4P[8] (3.4%. These six common genotypes included 83.7% of the strains tested in this study. The rate of uncommon genotypes was 14%. CONCLUSION: The majority of the strains analyzed belonged to the G1-G4 and G9 genotypes, suggesting high coverage of current rotavirus vaccines. This study also demonstrates a dramatic increase in G9 genotype across the country.

  13. Prevalence of Rotavirus Genotypes in Children Younger than 5 Years of Age before the Introduction of a Universal Rotavirus Vaccination Program: Report of Rotavirus Surveillance in Turkey

    Science.gov (United States)

    Durmaz, Riza; Kalaycioglu, Atila Taner; Acar, Sumeyra; Bakkaloglu, Zekiye; Karagoz, Alper; Korukluoglu, Gulay; Ertek, Mustafa; Torunoglu, Mehmet Ali

    2014-01-01

    Background Group A rotaviruses are the most common causative agent of acute gastroenteritis among children less than 5 years of age throughout the world. This sentinel surveillance study was aimed to obtain baseline data on the rotavirus G and P genotypes across Turkey before the introduction of a universal rotavirus vaccination program. Methods Rotavirus antigen-positive samples were collected from 2102 children less than 5 years of age who attended hospitals participating in the Turkish Rotavirus Surveillance Network. Rotavirus antigen was detected in the laboratories of participating hospitals by commercial serological tests such as latex agglutination, immunochromatographic test or enzyme immunoassay. Rotavirus G and P genotypes were determined by reverse transcription polymerase chain reaction (RT-PCR) using consensus primers detecting the VP7 and VP4 genes, followed by semi-nested type-specific multiplex PCR. Results RT-PCR found rotavirus RNA in 1644 (78.2%) of the samples tested. The highest rate of rotavirus positivity (38.7%) was observed among children in the 13 to 24 month age group, followed by children in the age group of 25 to 36 months (28.3%). A total of eight different G types, six different P types, and 42 different G–P combinations were obtained. Four common G types (G1, G2, G3, and G9) and two common P types (P[8] and P[4]) accounted for 95.1% and 98.8% of the strains, respectively. G9P[8] was the most common G/P combination found in 40.5% of the strains followed by G1P[8] (21.6%), G2P[8] (9.3%), G2P[4] (6.5%), G3P[8] (3.5%), and finally, G4P[8] (3.4%). These six common genotypes included 83.7% of the strains tested in this study. The rate of uncommon genotypes was 14%. Conclusion The majority of the strains analyzed belonged to the G1–G4 and G9 genotypes, suggesting high coverage of current rotavirus vaccines. This study also demonstrates a dramatic increase in G9 genotype across the country. PMID:25437502

  14. Prevalence of rotavirus antibodies in breast milk and inhibitory effects to rotavirus vaccines.

    Science.gov (United States)

    Trang, Nguyen V; Braeckman, Tessa; Lernout, Tinne; Hau, Vu T B; Anh, Le T K; Luan, Le T; Van Damme, Pierre; Anh, Dang D

    2014-01-01

    Rotavirus (RV) is the most common cause of childhood diarrhea worldwide, and several vaccines have been successfully developed to reduce the burden of disease. However, lower vaccine immunogenicity and efficacy in developing countries might be related to the virus-neutralizing activity of breast milk. We examined possible differences in breast milk antibody levels (total IgA antibody, RV-specific antibodies, and RV-neutralizing antibodies) between healthy mothers living in a rural area (n=145) and mothers living in an urban area (n=147) of Vietnam. Total IgA concentration was significantly higher in samples from mothers in the rural region than in samples from mothers in the urban region, whereas urban mothers had significantly higher RV-specific IgA antibody titers than did rural mothers. Neutralizing antibodies against RV strain G1P[8] were undetected in nearly one-half of the breast milk samples (45-48%), whereas the majority of the remaining samples had low antibody titers (2-16). Despite these low titers, the breast milk still reduced vaccine strain titers (2×10(6) plaque forming units/mL) up to 80% or more, even at a milk-to-virus ratio of 1:8. An increase in neutralizing anti-G1P[8] antibody titers (Pvaccine efficacy and immunogenicity in Vietnamese infants.

  15. Recombinant monovalent llama-derived antibody fragments (VHH to rotavirus VP6 protect neonatal gnotobiotic piglets against human rotavirus-induced diarrhea.

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    Celina G Vega

    Full Text Available Group A Rotavirus (RVA is the leading cause of severe diarrhea in children. The aims of the present study were to determine the neutralizing activity of VP6-specific llama-derived single domain nanoantibodies (VHH nanoAbs against different RVA strains in vitro and to evaluate the ability of G6P[1] VP6-specific llama-derived single domain nanoantibodies (VHH to protect against human rotavirus in gnotobiotic (Gn piglets experimentally inoculated with virulent Wa G1P[8] rotavirus. Supplementation of the daily milk diet with 3B2 VHH clone produced using a baculovirus vector expression system (final ELISA antibody -Ab- titer of 4096; virus neutralization -VN- titer of 256 for 9 days conferred full protection against rotavirus associated diarrhea and significantly reduced virus shedding. The administration of comparable levels of porcine IgG Abs only protected 4 out of 6 of the animals from human RVA diarrhea but significantly reduced virus shedding. In contrast, G6P[1]-VP6 rotavirus-specific IgY Abs purified from eggs of hyperimmunized hens failed to protect piglets against human RVA-induced diarrhea or virus shedding when administering similar quantities of Abs. The oral administration of VHH nanoAb neither interfered with the host's isotype profiles of the Ab secreting cell responses to rotavirus, nor induced detectable host Ab responses to the treatment in serum or intestinal contents. This study shows that the oral administration of rotavirus VP6-VHH nanoAb is a broadly reactive and effective treatment against rotavirus-induced diarrhea in neonatal pigs. Our findings highlight the potential value of a broad neutralizing VP6-specific VHH nanoAb as a treatment that can complement or be used as an alternative to the current strain-specific RVA vaccines. Nanobodies could also be scaled-up to develop pediatric medication or functional food like infant milk formulas that might help treat RVA diarrhea.

  16. Recombinant monovalent llama-derived antibody fragments (VHH) to rotavirus VP6 protect neonatal gnotobiotic piglets against human rotavirus-induced diarrhea.

    Science.gov (United States)

    Vega, Celina G; Bok, Marina; Vlasova, Anastasia N; Chattha, Kuldeep S; Gómez-Sebastián, Silvia; Nuñez, Carmen; Alvarado, Carmen; Lasa, Rodrigo; Escribano, José M; Garaicoechea, Lorena L; Fernandez, Fernando; Bok, Karin; Wigdorovitz, Andrés; Saif, Linda J; Parreño, Viviana

    2013-01-01

    Group A Rotavirus (RVA) is the leading cause of severe diarrhea in children. The aims of the present study were to determine the neutralizing activity of VP6-specific llama-derived single domain nanoantibodies (VHH nanoAbs) against different RVA strains in vitro and to evaluate the ability of G6P[1] VP6-specific llama-derived single domain nanoantibodies (VHH) to protect against human rotavirus in gnotobiotic (Gn) piglets experimentally inoculated with virulent Wa G1P[8] rotavirus. Supplementation of the daily milk diet with 3B2 VHH clone produced using a baculovirus vector expression system (final ELISA antibody -Ab- titer of 4096; virus neutralization -VN- titer of 256) for 9 days conferred full protection against rotavirus associated diarrhea and significantly reduced virus shedding. The administration of comparable levels of porcine IgG Abs only protected 4 out of 6 of the animals from human RVA diarrhea but significantly reduced virus shedding. In contrast, G6P[1]-VP6 rotavirus-specific IgY Abs purified from eggs of hyperimmunized hens failed to protect piglets against human RVA-induced diarrhea or virus shedding when administering similar quantities of Abs. The oral administration of VHH nanoAb neither interfered with the host's isotype profiles of the Ab secreting cell responses to rotavirus, nor induced detectable host Ab responses to the treatment in serum or intestinal contents. This study shows that the oral administration of rotavirus VP6-VHH nanoAb is a broadly reactive and effective treatment against rotavirus-induced diarrhea in neonatal pigs. Our findings highlight the potential value of a broad neutralizing VP6-specific VHH nanoAb as a treatment that can complement or be used as an alternative to the current strain-specific RVA vaccines. Nanobodies could also be scaled-up to develop pediatric medication or functional food like infant milk formulas that might help treat RVA diarrhea.

  17. Did Large-Scale Vaccination Drive Changes in the Circulating Rotavirus Population in Belgium?

    Science.gov (United States)

    Pitzer, Virginia E.; Bilcke, Joke; Heylen, Elisabeth; Crawford, Forrest W.; Callens, Michael; De Smet, Frank; Van Ranst, Marc; Zeller, Mark; Matthijnssens, Jelle

    2015-01-01

    Vaccination can place selective pressures on viral populations, leading to changes in the distribution of strains as viruses evolve to escape immunity from the vaccine. Vaccine-driven strain replacement is a major concern after nationwide rotavirus vaccine introductions. However, the distribution of the predominant rotavirus genotypes varies from year to year in the absence of vaccination, making it difficult to determine what changes can be attributed to the vaccines. To gain insight in the underlying dynamics driving changes in the rotavirus population, we fitted a hierarchy of mathematical models to national and local genotype-specific hospitalization data from Belgium, where large-scale vaccination was introduced in 2006. We estimated that natural- and vaccine-derived immunity was strongest against completely homotypic strains and weakest against fully heterotypic strains, with an intermediate immunity amongst partially heterotypic strains. The predominance of G2P[4] infections in Belgium after vaccine introduction can be explained by a combination of natural genotype fluctuations and weaker natural and vaccine-induced immunity against infection with strains heterotypic to the vaccine, in the absence of significant variation in strain-specific vaccine effectiveness against disease. However, the incidence of rotavirus gastroenteritis is predicted to remain low despite vaccine-driven changes in the distribution of genotypes. PMID:26687288

  18. Genetic Diversity of Circulating Rotavirus Strains in Tanzania Prior to the Introduction of Vaccination

    Science.gov (United States)

    Moyo, Sabrina J.; Blomberg, Bjørn; Hanevik, Kurt; Kommedal, Oyvind; Vainio, Kirsti; Maselle, Samuel Y.; Langeland, Nina

    2014-01-01

    Background Tanzania currently rolls out vaccination against rotavirus-diarrhea, a major cause of child illness and death. As the vaccine covers a limited number of rotavirus variants, this study describes the molecular epidemiology of rotavirus among children under two years in Dar es Salaam, Tanzania, prior to implementation of vaccination. Methods Stool specimens, demographic and clinical information, were collected from 690 children admitted to hospital due to diarrhea (cases) and 545 children without diarrhea (controls) during one year. Controls were inpatient or children attending child health clinics. Rotavirus antigen was detected using ELISA and positive samples were typed by multiplex semi-nested PCR and sequencing. Results The prevalence of rotavirus was higher in cases (32.5%) than in controls (7.7%, Protavirus prevalence was higher in cool (23.9%) than hot months (17.1%) of the year (P = 0.012). We also observed significant seasonal variation of G genotypes. Rotavirus was most frequently found in the age group of four to six months. The prevalence of rotavirus in cases was lower in stunted children (28.9%) than in non-stunted children (40.1%, P = 0.003) and lower in HIV-infected (15.4%, 4/26) than in HIV-uninfected children (55.3%, 42/76, PRotavirus infection and circulating genotypes showed seasonal variation. This study also suggests that rotavirus may not be an opportunistic pathogen in children infected with HIV. PMID:24844631

  19. Burden of paediatric Rotavirus Gastroenteritis (RVGE and potential benefits of a universal Rotavirus vaccination programme with a pentavalent vaccine in Spain

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    Diez-Domingo Javier

    2010-08-01

    Full Text Available Abstract Background Rotavirus is the most common cause of gastroenteritis in young children worldwide. The aim of the study was to assess the health outcomes and the economic impact of a universal rotavirus vaccination programme with RotaTeq, the pentavalent rotavirus vaccine, versus no vaccination programme in Spain. Methods A birth cohort was followed up to the age of 5 using a cohort model. Epidemiological parameters were taken from the REVEAL study (a prospective epidemiological study conducted in Spain, 2004-2005 and from the literature. Direct and indirect costs were assessed from the national healthcare payer and societal perspectives by combining health care resource utilisation collected in REVEAL study and unit costs from official sources. RotaTeq per protocol efficacy data was taken from a large worldwide rotavirus clinical trial (70,000 children. Health outcomes included home care cases, General Practioner (GP/Paediatrician, emergency department visits, hospitalisations and nosocomial infections. Results The model estimates that the introduction of a universal rotavirus vaccination programme with RotaTeq (90% coverage rate would reduce the rotavirus gastroenteritis (RVGE burden by 75% in Spain; 53,692 home care cases, 35,187 GP/Paediatrician visits, 34,287 emergency department visits, 10,987 hospitalisations and 2,053 nosocomial infections would be avoided. The introduction of RotaTeq would avoid about 76% of RVGE-related costs from both perspectives: €22 million from the national health system perspective and €38 million from the societal perspective. Conclusions A rotavirus vaccination programme with RotaTeq would reduce significantly the important medical and economic burden of RVGE in Spain.

  20. 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

    2017-01-01

    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. PMID:28400594

  1. Effectiveness of pentavalent rotavirus vaccine in a large urban population in the United States.

    Science.gov (United States)

    Boom, Julie A; Tate, Jacqueline E; Sahni, Leila C; Rench, Marcia A; Hull, Jennifer J; Gentsch, Jon R; Patel, Manish M; Baker, Carol J; Parashar, Umesh D

    2010-02-01

    The goal was to assess the effectiveness of complete (3-dose) or partial (1- or 2-dose) immunization with pentavalent rotavirus vaccine (RV5) against rotavirus acute gastroenteritis (AGE) in US clinical practice. A case-control evaluation was conducted in February through June 2008 at an emergency department in Houston, Texas. Case patients with rotavirus AGE (N = 90) were identified through testing for rotavirus in fecal specimens obtained from 205 children 15 days through 23 months of age presenting with AGE. Control groups included rotavirus-negative AGE patients (N = 115), concurrently enrolled patients with acute respiratory infection (ARI) (N = 228), and up to 10 age- and zip code-matched children sampled from the Houston-Harris County Immunization Registry (HHCIR) for each case patient >8 months of age. Immunization data were obtained from parent records, health care providers, and/or the HHCIR. Vaccine effectiveness was calculated as 1 minus odds of RV5 vaccination for case patients versus control patients, after adjustment for age at presentation and birth date. The vaccine effectiveness of a complete RV5 series was 89% (95% confidence interval [CI]: 70%-96%) and 85% (95% CI: 55%-95%) with rotavirus-negative AGE and ARI control patients, respectively. Immunization data were available for 44% of case patients (n = 40) from the HHCIR; the estimated 3-dose vaccine effectiveness with these HHCIR control patients was 82% (95% CI: 19%-96%). A complete RV5 series conferred 100% protection (95% CI: 71%-100%) against severe rotavirus disease requiring hospitalization and 96% protection (95% CI: 72%-99%) against disease requiring intravenous hydration. Vaccine effectiveness of 1 and 2 doses against hospitalization and emergency department visits was 69% (95% CI: 13%-89%) and 81% (95% CI: 13%-96%), respectively, using rotavirus-negative AGE and ARI control groups combined. In this setting, a complete series of RV5 was highly effective against severe rotavirus AGE

  2. Health and economic impact of rotavirus vaccination in GAVI-eligible countries

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    Slichter David

    2010-05-01

    Full Text Available Abstract Background Rotavirus infection is responsible for about 500,000 deaths annually, and the disease burden is disproportionately borne by children in low-income countries. Recently the World Health Organization (WHO has released a global recommendation that all countries include infant rotavirus vaccination in their national immunization programs. Our objective was to provide information on the expected health, economic and financial consequences of rotavirus vaccines in the 72 GAVI support-eligible countries. Methods We synthesized population-level data from various sources (primarily from global-level databases for the 72 countries eligible for the support by the GAVI Alliance (GAVI-eligible countries in order to estimate the health and economic impact associated with rotavirus vaccination programs. The primary outcome measure was incremental cost (in 2005 international dollars [I$] per disability-adjusted life year (DALY averted. We also projected the expected reduction in rotavirus disease burden and financial resources required associated with a variety of scale-up scenarios. Results Under the base-case assumptions (70% coverage, vaccinating one single birth cohort would prevent about 55% of rotavirus associated deaths in the 72 GAVI-eligible countries. Assuming I$25 per vaccinated child (~$5 per dose, the number of countries with the incremental cost per DALY averted less than I$200 was 47. Using the WHO's cost-effectiveness threshold based on per capita GDP, the vaccines were considered cost-effective in 68 of the 72 countries (~94%. A 10-year routine rotavirus vaccination would prevent 0.9-2.8 million rotavirus associated deaths among children under age 5 in the poorest parts of the world, depending on vaccine scale-up scenarios. Over the same intervention period, rotavirus vaccination programs would also prevent 4.5-13.3 million estimated cases of hospitalization and 41-107 million cases of outpatient clinic visits in the same

  3. Transplacental rotavirus IgG interferes with immune response to live oral rotavirus vaccine ORV-116E in Indian infants.

    Science.gov (United States)

    Appaiahgari, Mohan Babu; Glass, Roger; Singh, Shakti; Taneja, Sunita; Rongsen-Chandola, Temsunaro; Bhandari, Nita; Mishra, Sukhdev; Vrati, Sudhanshu

    2014-02-03

    The lower immune response and efficacy of live oral rotavirus (RV) vaccines tested in developing countries may be due in part to high levels of pre-existing RV antibodies transferred to the infant from mother via the placenta. The candidate RV vaccine strain 116E was isolated from a newborn indicating that it might grow well even in the presence of this transplacental rotavirus antibody. Since the immune response to this vaccine among infants in the Indian subcontinent has been greater than that of the commercially licensed vaccines, we questioned whether this might be due to the ability of RV 116E to grow well in infants despite the presence of maternal RV antibody. To this end, we tested pre-immunization sera from Indian infants enrolled in a phase Ia/IIb trial of candidate RV vaccine ORV-116E for transplacental RV IgG to see whether it affected the immune responses and seroconversion to the vaccine. We found that the high titers of transplacental RV IgG diminished the immune responses of infants to ORV-116E vaccine. However, the vaccine was able to overcome the inhibitory effect of this RV IgG in a dose-dependent manner. This report clearly demonstrates the interference of maternal antibody on RV vaccine immunogenicity in infants in a field study as well as the ability of ORV-116E to overcome this interference when used at a higher dose. Copyright © 2013. Published by Elsevier Ltd.

  4. Group A rotavirus gastroenteritis: post-vaccine era, genotypes and zoonotic transmission.

    Science.gov (United States)

    Luchs, Adriana; Timenetsky, Maria do Carmo Sampaio Tavares

    2016-01-01

    ABSTRACTThis article provides a review of immunity, diagnosis, and clinical aspects of rotavirus disease. It also informs about the changes in epidemiology of diarrheal disease and genetic diversity of circulating group A rotavirus strains following the introduction of vaccines. Group A rotavirus is the major pathogen causing gastroenteritis in animals. Its segmented RNA genome can lead to the emergence of new or unusual strains in human populations via interspecies transmission and/or reassortment events.RESUMOEste artigo fornece uma revisão sobre imunidade, diagnóstico e aspectos clínicos da doença causada por rotavírus. Também aponta as principais mudanças no perfil epidemiológico da doença diarreica e na diversidade genética das cepas circulantes de rotavírus do grupo A, após a introdução vacinal. O rotavírus do grupo A é o principal patógeno associado à gastroenterite em animais. Seu genoma RNA segmentado pode levar ao surgimento de cepas novas ou incomuns na população humana, por meio de transmissão entre espécies e eventos de rearranjo.

  5. Decreased performance of live attenuated, oral rotavirus vaccines in low-income settings: causes and contributing factors.

    Science.gov (United States)

    Velasquez, Daniel E; Parashar, Umesh; Jiang, Baoming

    2018-02-01

    Numerous studies have shown that the oral rotavirus vaccines are less effective in infants born in low income countries compared to those born in developed countries. Identifying the specific factors in developing countries that decrease and/or compromise the protection that rotavirus vaccines offer, could lead to a path for designing new strategies for the vaccines' improvement. Areas covered: We accessed PubMed to identify rotavirus vaccine performance studies (i.e., efficacy, effectiveness and immunogenicity) and correlated performance with several risk factors. Here, we review the factors that might contribute to the low vaccine efficacy, including passive transfer of maternal rotavirus antibodies, rotavirus seasonality, oral polio vaccine (OPV) administered concurrently, microbiome composition and concomitant enteric pathogens, malnutrition, environmental enteropathy, HIV, and histo blood group antigens. Expert commentary: We highlight two major factors that compromise rotavirus vaccines' efficacy: the passive transfer of rotavirus IgG antibodies to infants and the  co-administration of rotavirus vaccines with OPV. We also identify other potential risk factors that require further research because the data about their interference with the efficacy of rotavirus vaccines are inconclusive and at times conflicting.

  6. Synthesizing evidences for policy translation: a public health discourse on rotavirus vaccine in India.

    Science.gov (United States)

    Panda, Samiran; Das, Aritra; Samanta, Saheli

    2014-08-11

    The debate on the relevance of rotavirus vaccine to immunization program in India, where 27 million children are born every year, rages on. We synthesized the issues raised during these debates and reviewed the current literature to identify themes that could inform public health policy decision. The paradigm we used integrated disease burden data, host and environmental factors, vaccine efficacy, immunization program issues, and economic considerations. Our synthesis reveals that substantive country specific information on disease burden and economic impact of rotavirus illness in India is constrained by lack of public discussion and qualitative studies on mothers' perceptions of the vaccine in concern. The need to improve the performance of current immunization program against six major vaccine preventable diseases (tuberculosis, diphtheria, tetanus, pertussis, polio, and measles) is often cited as a priority over introduction of rotavirus vaccine. Health in India being a state subject, we emphasize that the states which are in a position to reap the benefit of rotavirus vaccine, due to their good immunization program performance, should not be restrained from doing so. Meanwhile, the poorly performing states should step up their vaccination program and increase immunization coverage. Scientific, ethical and societal concerns captured through multiple sources indicate that the introduction of rotavirus vaccine would be a good investment for India. Copyright © 2014. Published by Elsevier Ltd.

  7. Thresholds for decision-making: informing the cost-effectiveness and affordability of rotavirus vaccines in Malaysia.

    Science.gov (United States)

    Loganathan, Tharani; Ng, Chiu-Wan; Lee, Way-Seah; Hutubessy, Raymond C W; Verguet, Stéphane; Jit, Mark

    2018-03-01

    Cost-effectiveness thresholds (CETs) based on the Commission on Macroeconomics and Health (CMH) are extensively used in low- and middle-income countries (LMICs) lacking locally defined CETs. These thresholds were originally intended for global and regional prioritization, and do not reflect local context or affordability at the national level, so their value for informing resource allocation decisions has been questioned. Using these thresholds, rotavirus vaccines are widely regarded as cost-effective interventions in LMICs. However, high vaccine prices remain a barrier towards vaccine introduction. This study aims to evaluate the cost-effectiveness, affordability and threshold price of universal rotavirus vaccination at various CETs in Malaysia. Cost-effectiveness of Rotarix and RotaTeq were evaluated using a multi-cohort model. Pan American Health Organization Revolving Fund's vaccine prices were used as tender price, while the recommended retail price for Malaysia was used as market price. We estimate threshold prices defined as prices at which vaccination becomes cost-effective, at various CETs reflecting economic theories of human capital, societal willingness-to-pay and marginal productivity. A budget impact analysis compared programmatic costs with the healthcare budget. At tender prices, both vaccines were cost-saving. At market prices, cost-effectiveness differed with thresholds used. At market price, using 'CMH thresholds', Rotarix programmes were cost-effective and RotaTeq were not cost-effective from the healthcare provider's perspective, while both vaccines were cost-effective from the societal perspective. Using other CETs, both vaccines were not cost-effective at market price, from the healthcare provider's and societal perspectives. At tender and cost-effective prices, rotavirus vaccination cost ∼1 and 3% of the public health budget, respectively. Using locally defined thresholds, rotavirus vaccination is cost-effective at vaccine prices in line

  8. Rotavirus Vaccine will Improve Child Survival by More than Just Preventing Diarrhea: Evidence from Bangladesh.

    Science.gov (United States)

    Saha, Senjuti; Santosham, Mathuram; Hussain, Manzoor; Black, Robert E; Saha, Samir K

    2018-02-01

    Despite the high burden of rotavirus diarrhea, uptake of rotavirus vaccines in Asia remains low. This primarily stems from a perception of rotavirus as a non-life-threatening pathogen amidst a background of competing health priorities and limited resources. In the largest pediatric hospital of Bangladesh, where there is a fierce competition for beds, we found that between November 2015 and October 2016, 12% of 23,064 admissions were due to gastrointestinal infections, 54% of which were caused by rotavirus. One in four cases requiring hospitalization, or 5,879 cases, was refused because of unavailability of beds. Most refused cases were of pneumonia (22%), severe perinatal asphyxia (17%), preterm birth complications (7%), and meningitis (2%), all of which bear high risks of death or disability, if not treated timely. When determining vaccine policies and conducting vaccine impact studies, it would be shortsighted to not consider the impact on morbidity and mortality of cases that are refused admission because of the hospitalization of children with a preventable disease as rotavirus diarrhea. In our hospital, routine use of a rotavirus vaccine with 41% efficacy will release 629 beds per year to accommodate previously refused cases. Based on evidence, we make the case that introduction of this vaccine in Bangladesh and the surrounding region will prevent morbidity and mortality, both directly and indirectly, and help us ensure survival and well-being of all children.

  9. Rotaviruses

    Centers for Disease Control (CDC) Podcasts

    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.

  10. 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

  11. Sustained Effectiveness of Rotavirus Vaccine Against Very Severe Rotavirus Disease Through the Second Year of Life, Bolivia 2013-2014.

    Science.gov (United States)

    Pringle, Kimberly D; Patzi, Maritza; Tate, Jacqueline E; Iniguez Rojas, Volga; Patel, Manish; Inchauste Jordan, Lucia; Montesano, Raul; Zarate, Adolfo; De Oliveira, Lucia; Parashar, Umesh

    2016-05-01

    In Bolivia, monovalent rotavirus vaccine was introduced in 2008 and a previous evaluation reported a vaccine effectiveness (VE) of 77% with 2 doses of vaccine in children aged 5 years after its introduction in Bolivia. Although VE appears to wane in children aged ≥1 year, it still provides significant protection, and does not wane against severe disease. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  12. Public finance of rotavirus vaccination in India and Ethiopia: an extended cost-effectiveness analysis.

    Science.gov (United States)

    Verguet, Stéphane; Murphy, Shane; Anderson, Benjamin; Johansson, Kjell Arne; Glass, Roger; Rheingans, Richard

    2013-10-01

    An estimated 4% of global child deaths (approximately 300,000 deaths) were attributed to rotavirus in 2010. About a third of these deaths occurred in India and Ethiopia. Public finance of rotavirus vaccination in these two countries could substantially decrease child mortality and also reduce rotavirus-related hospitalizations, prevent health-related impoverishment and bring significant cost savings to households. We use a methodology of 'extended cost-effectiveness analysis' (ECEA) to evaluate a hypothetical publicly financed program for rotavirus vaccination in India and Ethiopia. We measure program impact along four dimensions: 1) rotavirus deaths averted; 2) household expenditures averted; 3) financial risk protection afforded; 4) distributional consequences across the wealth strata of the country populations. In India and Ethiopia, the program would lead to a substantial decrease in rotavirus deaths, mainly among the poorer; it would reduce household expenditures across all income groups and it would effectively provide financial risk protection, mostly concentrated among the poorest. Potential indirect benefits of vaccination (herd immunity) would increase program benefits among all income groups, whereas potentially decreased vaccine efficacy among poorer households would reduce the equity benefits of the program. Our approach incorporates financial risk protection and distributional consequences into the systematic economic evaluation of vaccine policy, illustrated here with the case study of public finance for rotavirus vaccination. This enables selection of vaccine packages based on the quantitative inclusion of information on equity and on how much financial risk protection is being bought per dollar expenditure on vaccine policy, in addition to how much health is being bought. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Effect of pentavalent rotavirus vaccine introduction on hospital admissions for diarrhoea and rotavirus in children in Rwanda: a time-series analysis.

    Science.gov (United States)

    Ngabo, Fidele; Tate, Jacqueline E; Gatera, Maurice; Rugambwa, Celse; Donnen, Philippe; Lepage, Philippe; Mwenda, Jason M; Binagwaho, Agnes; Parashar, Umesh D

    2016-02-01

    In May, 2012, Rwanda became the first low-income African country to introduce pentavalent rotavirus vaccine into its routine national immunisation programme. Although the potential health benefits of rotavirus vaccination are huge in low-income African countries that account for more than half the global deaths from rotavirus, concerns remain about the performance of oral rotavirus vaccines in these challenging settings. We conducted a time-series analysis to examine trends in admissions to hospital for non-bloody diarrhoea in children younger than 5 years in Rwanda between Jan 1, 2009, and Dec 31, 2014, using monthly discharge data from the Health Management Information System. Additionally, we reviewed the registries in the paediatric wards at six hospitals from 2009 to 2014 and abstracted the number of total admissions and admissions for diarrhoea in children younger than 5 years by admission month and age group. We studied trends in admissions specific to rotavirus at one hospital that had undertaken active rotavirus surveillance from 2011 to 2014. We assessed changes in rotavirus epidemiology by use of data from eight active surveillance hospitals. Compared with the 2009-11 prevaccine baseline, hospital admissions for non-bloody diarrhoea captured by the Health Management Information System fell by 17-29% from a pre-vaccine median of 4051 to 2881 in 2013 and 3371 in 2014, admissions for acute gastroenteritis captured in paediatric ward registries decreased by 48-49%, and admissions specific to rotavirus captured by active surveillance fell by 61-70%. The greatest effect was recorded in children age-eligible to be vaccinated, but we noted a decrease in the proportion of children with diarrhoea testing positive for rotavirus in almost every age group. The number of admissions to hospital for diarrhoea and rotavirus in Rwanda fell substantially after rotavirus vaccine implementation, including among older children age-ineligible for vaccination, suggesting

  14. Composition of gut microbiota and its influence on the immunogenicity of oral rotavirus vaccines.

    Science.gov (United States)

    Magwira, Cliff A; Taylor, Maureen B

    2018-05-08

    The introduction of oral rotavirus vaccines (ORVVs) has led to a reduction in number of hospitalisations and deaths due to rotavirus (RV) infection. However, the efficacy of the vaccines has been varied with low-income countries showing significantly lower efficacy as compared to high-income countries. The reasons for the disparity are not fully understood but are thought to be multi-factorial. In this review article, we discuss the concept that the disparity in the efficacy of oral rotavirus vaccines between the higher and lower socio-economical countries could be due the nature of the bacteria that colonises and establishes in the gut early in life. We further discuss recent studies that has demonstrated significant correlations between the composition of the gut bacteria and the immunogenicity of oral vaccines, and their implications in the development of novel oral RV vaccines or redesigning the current ones for maximum impact. Copyright © 2018. Published by Elsevier Ltd.

  15. Overcoming perceptions of financial barriers to rotavirus vaccine introduction in Asia.

    Science.gov (United States)

    Nelson, E Anthony S; de Quadros, Ciro A; Santosham, Mathuram; Parashar, Umesh D; Steele, Duncan

    2013-11-01

    Despite a WHO recommendation in 2009, reaffirmed in 2013, that all countries should consider introducing rotavirus vaccines into their National Immunization Programs, as of June 2013 only 45 have done so. One major consideration appears to have been the costs of the vaccine to countries. Of concern, is that Asian countries have been slow to introduce rotavirus vaccines despite having robust data that could inform the decision-making process. Although decisions on new vaccine introduction are very complex and vary by country and region, economic evaluations are often pivotal once vaccine efficacy and safety has been established, and disease burden documented and communicated. Unfortunately, with private sector list prices of vaccines often used in economic evaluations, rather than a potential public health sector pricing structure, policy-makers may defer decisions on rotavirus vaccine introduction based on the belief that "the vaccine price is too high," even though this might be based on erroneous data. The Pan American Health Organization's Revolving Fund provides one example of how vaccine price can be made more competitive and transparent through a regional tendering process. Other mechanisms, such as tiered pricing and UNICEF procurement, also exist that could help Asian and other countries move forward more quickly with rotavirus vaccine introduction.

  16. Overcoming perceptions of financial barriers to rotavirus vaccine introduction in Asia

    Science.gov (United States)

    Nelson, E Anthony S; de Quadros, Ciro A; Santosham, Mathuram; Parashar, Umesh D; Steele, A Duncan

    2013-01-01

    Despite a WHO recommendation in 2009, reaffirmed in 2013, that all countries should consider introducing rotavirus vaccines into their National Immunization Programs, as of June 2013 only 45 have done so. One major consideration appears to have been the costs of the vaccine to countries. Of concern, is that Asian countries have been slow to introduce rotavirus vaccines despite having robust data that could inform the decision-making process. Although decisions on new vaccine introduction are very complex and vary by country and region, economic evaluations are often pivotal once vaccine efficacy and safety has been established, and disease burden documented and communicated. Unfortunately, with private sector list prices of vaccines often used in economic evaluations, rather than a potential public health sector pricing structure, policy-makers may defer decisions on rotavirus vaccine introduction based on the belief that “the vaccine price is too high,” even though this might be based on erroneous data. The Pan American Health Organization’s Revolving Fund provides one example of how vaccine price can be made more competitive and transparent through a regional tendering process. Other mechanisms, such as tiered pricing and UNICEF procurement, also exist that could help Asian and other countries move forward more quickly with rotavirus vaccine introduction. PMID:23955246

  17. Expression and characterization of a novel truncated rotavirus VP4 for the development of a recombinant rotavirus vaccine.

    Science.gov (United States)

    Li, Yijian; Xue, Miaoge; Yu, Linqi; Luo, Guoxing; Yang, Han; Jia, Lianzhi; Zeng, Yuanjun; Li, Tingdong; Ge, Shengxiang; Xia, Ningshao

    2018-04-12

    The outer capsid protein VP4 is an important target for the development of a recombinant rotavirus vaccine because it mediates the attachment and penetration of rotavirus. Due to the poor solubility of full-length VP4, VP8 was explored as candidate rotavirus vaccines in the past years. In previous studies, it has been found that the N-terminal truncated VP8 protein, VP8-1 (aa26-231), could be expressed in soluble form with improved immunogenicity compared to the core of VP8 (aa65-223). However, this protein stimulated only a weak immune response when aluminum hydroxide was used as an adjuvant. In addition, it should be noted that the protective efficacy of VP4 was higher than that of VP8 and VP5. In this study, it was found that when the N-terminal 25 amino acids were deleted, the truncated VP4 ∗ (aa26-476) containing VP8 and the stalk domain of VP5 could be expressed in soluble form in E. coli and purified to homogeneous trimers. Furthermore, the truncated VP4 could induce high titers of neutralizing antibodies when aluminum adjuvant was used and conferred high protective efficacy in reducing the severity of diarrhea and rotavirus shedding in stools in animal models. The immunogenicity of the truncated VP4 was significantly higher than that of VP8 ∗ and VP5 ∗ alone. Taken together, the truncated VP4 ∗ (aa26-476), with enhanced immunogenicity and immunoprotectivity, could be considered as a viable candidate for further development and has the potential to become a parenterally administered rotavirus vaccine. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

    Midgley, Sofie; Gram, N.; Hjulsager, Charlotte Kristiane

    Rotavirus type A infection is a common cause of hospitalisation of children. However, in our laboratory almost 30% of rotavirus positive samples are from adults. Due to this an epidemiological study into the riskfactors for rotavirus infection in adults was set up. All identified rotavirus positive...... 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...... in Denmark as part of the EuroRotaNet vaccine study. Samples positive for rotavirus are type...

  19. 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.

  20. Inactivation of human and simian rotaviruses by ozone

    Energy Technology Data Exchange (ETDEWEB)

    Vaughn, J.M.; Chen, Y.S.; Lindburg, K.; Morales, D.

    1987-09-01

    The inactivation of simian rotavirus Sa-11 and human rotavirus type 2 (Wa) by ozone was compared at 4/sup 0/C by using single-particle virus stocks. Although the human strain was clearly more sensitive, both virus types were rapidly inactivated by ozone concentrations of 0.25 mg/liter or greater at all pH levels tested. Comparison of the virucidal activity of ozone with that of chlorine in identical experiments indicated little significant difference in rotavirus-inactivating efficiencies when the disinfectants were used at concentrations of 0.25 mg/liter or greater.

  1. [Post-licensure passive safety surveillance of rotavirus vaccines: reporting sensitivity for intussusception].

    Science.gov (United States)

    Pérez-Vilar, S; Díez-Domingo, J; Gomar-Fayos, J; Pastor-Villalba, E; Sastre-Cantón, M; Puig-Barberà, J

    2014-08-01

    The aims of this study were to describe the reports of suspected adverse events due to rotavirus vaccines, and assess the reporting sensitivity for intussusception. Descriptive study performed using the reports of suspected adverse events following rotavirus vaccination in infants aged less than 10 months, as registered in the Pharmacovigilance Centre of the Valencian Community during 2007-2011. The reporting rate for intussusception was compared to the intussusception rate in vaccinated infants obtained using the hospital discharge database (CMBD), and the regional vaccine registry. The adverse event reporting rate was 20 per 100,000 administered doses, with the majority (74%) of the reports being classified as non-serious. Fever, vomiting, and diarrhea were the adverse events reported more frequently. Two intussusception cases, which occurred within the first seven days post-vaccination, were reported as temporarily associated to vaccination. The reporting sensitivity for intussusception at the Pharmacovigilance Centre in the 1-7 day interval following rotavirus vaccination was 50%. Our results suggest that rotavirus vaccines have, in general, a good safety profile. Intussusception reporting to the Pharmacovigilance Centre shows sensitivity similar to other passive surveillance systems. The intussusception risk should be further investigated using well-designed epidemiological studies, and evaluated in comparison with the well-known benefits provided by these vaccines. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  2. A systematic review of anti-rotavirus serum IgA antibody titer as a potential correlate of rotavirus vaccine efficacy.

    Science.gov (United States)

    Patel, Manish; Glass, Roger I; Jiang, Baoming; Santosham, Mathuram; Lopman, Ben; Parashar, Umesh

    2013-07-15

    Identifying an immunological correlate of protection for rotavirus vaccines (Rotarix [RV1] and RotaTeq [RV5]) would substantially facilitate testing of interventions for improving efficacy in developing countries and evaluating additional candidate rotavirus vaccines. We accessed PubMed and ClinicalTrials.gov to identify immunogenicity and efficacy trials for RV1 and RV5 to correlate anti-rotavirus serum immunoglobulin A (IgA) antibody titers vs efficacy in regions stratified by all-cause under-5 mortality rates (u5MR). We established a cutoff point for IgA geometric mean concentration or titer (GMC) that predicted lower efficacy and calculated pooled vaccine efficacy among countries with high vs low IgA titers. We observed an inverse correlation between u5MR and IgA titers for RV1 (r(2) = 0.72; P efficacy and IgA titers for both vaccines (r(2) = 0.56; P = .005). Postimmunization anti-rotavirus IgA GMC vaccine efficacy. Efficacy during first 2 years of life was significantly lower among countries with IgA GMC 90 (85%; 95% CI, 82-88). We observed a significant correlation between IgA titers and rotavirus vaccine efficacy and hypothesize that a critical level of IgA antibody titer is associated with a sufficient level of sustained protection after rotavirus vaccination.

  3. 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.

  4. 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 ...

  5. Contribution of Maternal Immunity to Decreased Rotavirus Vaccine Performance in Low- and Middle-Income Countries

    Science.gov (United States)

    Mwila, Katayi; Simuyandi, Michelo; Permar, Sallie R.

    2016-01-01

    ABSTRACT The role of maternal immunity, received by infants either transplacentally or orally from breast milk, in rotavirus vaccine (RV) performance is evaluated here. Breastfeeding withholding has no effect on vaccine responses, but higher levels of transplacental rotavirus-specific IgG antibody contribute to reduced vaccine seroconversion. The gaps in knowledge on the factors associated with low RV efficacy in low- and middle-income countries (LMIC) remain, and further research is needed to shed more light on these issues. PMID:27847365

  6. Real-World Effectiveness of Pentavalent Rotavirus Vaccine Among Bedouin and Jewish Children in Southern Israel.

    Science.gov (United States)

    Leshem, Eyal; Givon-Lavi, Noga; Tate, Jacqueline E; Greenberg, David; Parashar, Umesh D; Dagan, Ron

    2016-05-01

    Pentavalent rotavirus vaccine (RV5) was introduced into the Israeli National Immunization Program in January 2011. We determined RV5 vaccine effectiveness (VE) in southern Israel, a region characterized by 2 distinct populations: Bedouins living in a low- to middle-income, semirural setting, and Jews living in a high-income, urban setting. We enrolled vaccine-eligible children who visited the emergency department (ED) or were hospitalized due to acute gastroenteritis (AGE) during the first 3 rotavirus seasons after RV5 vaccine introduction (2011-2013). Fecal specimens were tested for rotavirus by enzyme immunoassay and genotyped. Vaccination among laboratory-confirmed rotavirus cases was compared with rotavirus-negative AGE controls. Regression models were used to calculate VE estimates by age, clinical setting, and ethnicity. Of 515 enrolled patients, 359 (70%) were Bedouin. Overall, 185 (36%) patients were rotavirus positive; 79 of 119 (66%) were G1P[8] genotype. The adjusted VE for a full 3-dose course of RV5 against ED visit or hospitalization was 63% (95% confidence interval [CI], 38%-78%). RV5 provided G1P[8] genotype-specific effectiveness of 78% (95% CI, 58%-88%). By age, RV5 VE was 64% (95% CI, 21%-84%) and 71% (95% CI, 39%-86%) among children aged 6-11 months and 12-23 months, respectively. By clinical setting, RV5 VE was 59% (95% CI, 23%-78%) against hospitalization, and 67% (95% CI, 11%-88%) against ED visit. The adjusted VE of a full RV5 course among Bedouin children was 62% (95% CI, 29%-79%). RV5 significantly protected against rotavirus-associated ED visits and hospitalizations in a diverse population of vaccine-eligible children living in southern Israel. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  7. A qualitative assessment of factors influencing acceptance of a new rotavirus vaccine among health care providers and consumers

    Energy Technology Data Exchange (ETDEWEB)

    Manish M Patel, Alan P Janssen, Richard Tardif, Mark Herring, Umesh Parashar

    2007-10-18

    In 2006, a new rotavirus vaccine (RotaTeq) was licensed in the US and recommended for routine immunization of all US infants. Because a previously licensed vaccine (Rotashield) was withdrawn from the US for safety concerns, identifying barriers to uptake of RotaTeq will help develop strategies to broaden vaccine coverage. Our qualitative assessment provides complementary data to recent quantitative surveys and suggests that physicians and parents are likely to adopt the newly licensed rotavirus vaccine. Increasing parental awareness of the rotavirus disease burden and providing physicians with timely post-marketing surveillance data will be integral to a successful vaccination program.

  8. 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

  9. 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.

  10. 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 rotaviruses in MA104 cells, primarily through an effect on the virus. Although breastfed infants are directly protected, the addition of specific oligosaccharides to infant formula may confer these benefits to formula-fed infants. © 2017 American Society for Nutrition.

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

    KAUST Repository

    Romero-Maraccini, Ofelia C.; Sadik, Nora J.; Rosado-Lausell, Sahid L.; Pugh, Charles R.; Niu, Xi-Zhi; Croue, Jean-Philippe; Nguyen, Thanh Ha

    2013-01-01

    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

  12. Comparison of 2 Assays for Diagnosing Rotavirus and Evaluating Vaccine Effectiveness in Children with Gastroenteritis

    Science.gov (United States)

    Mijatovic-Rustempasic, Slavica; Tam, Ka Ian; Lyde, Freda C.; Payne, Daniel C.; Szilagyi, Peter; Edwards, Kathryn; Staat, Mary Allen; Weinberg, Geoffrey A.; Hall, Caroline B.; Chappell, James; McNeal, Monica; Gentsch, Jon R.; Bowen, Michael D.; Parashar, Umesh D.

    2013-01-01

    We compared rotavirus detection rates in children with acute gastroenteritis (AGE) and in healthy controls using enzyme immunoassays (EIAs) and semiquantitative real-time reverse transcription PCR (qRT-PCR). We calculated rotavirus vaccine effectiveness using different laboratory-based case definitions to determine which best identified the proportion of disease that was vaccine preventable. Of 648 AGE patients, 158 (24%) were EIA positive, and 157 were also qRT-PCR positive. An additional 65 (10%) were qRT-PCR positive but EIA negative. Of 500 healthy controls, 1 was EIA positive and 24 (5%) were qRT-PCR positive. Rotavirus vaccine was highly effective (84% [95% CI 71%–91%]) in EIA-positive children but offered no significant protection (14% [95% CI −105% to 64%]) in EIA-negative children for whom virus was detected by qRT-PCR alone. Children with rotavirus detected by qRT-PCR but not by EIA were not protected by vaccination, suggesting that rotavirus detected by qRT-PCR alone might not be causally associated with AGE in all patients. PMID:23876518

  13. Strain diversity plays no major role in the varying efficacy of rotavirus vaccines: an overview.

    Science.gov (United States)

    Velasquez, Daniel E; Parashar, Umesh D; Jiang, Baoming

    2014-12-01

    While a monovalent Rotarix® [RV1] and a pentavalent RotaTeq® [RV5] have been extensively tested and found generally safe and equally efficacious in clinical trials, the question still lingers about the evolving diversity of circulating rotavirus strains over time and their relationship with protective immunity induced by rotavirus vaccines. We reviewed data from clinical trials and observational studies that assessed the efficacy or field effectiveness of rotavirus vaccines against different rotavirus strains worldwide. RV1 provided broad clinical efficacy and field effectiveness against severe diarrhea due to all major circulating strains, including the homotypic G1P[8] and the fully heterotypic G2P[4] strains. Similarly, RV5 provided broad efficacy and effectiveness against RV5 and non-RV5 strains throughout different locations. Rotavirus vaccination provides broad heterotypic protection; however continuing surveillance is needed to track the change of circulating strains and monitor the effectiveness and safety of vaccines. Published by Elsevier B.V.

  14. Circulating rotavirus genotypes in the Irish paediatric population prior to the introduction of the vaccination programme.

    Science.gov (United States)

    Yandle, Z; Coughlan, S; Drew, R J; O'Flaherty, N; O'Gorman, J; De Gascun, C

    2017-11-01

    Rotavirus is the leading cause of viral gastroenteritis in children, and it is anticipated that the introduction of the Rotarix™ vaccine (GlaxoSmithKline Biologicals S.A., Rixensart, Belgium) into the Irish immunisation schedule will result in a significant reduction of rotavirus-associated disease. In the pre- and post-vaccination eras, it is important to determine circulating strains of rotavirus to assess vaccine effectiveness, to monitor vaccine failures, and to detect potential emerging strains. This study was a collaboration between the Temple Street Children's University Hospital (TSCUH), Dublin, and the National Virus Reference Laboratory (NVRL), Dublin, to determine the then circulating rotavirus strains in a paediatric hospital. In the 2015/2016 period (July 2015-June 2016) 89 faecal samples from paediatric patients (53 from TSCUH, 36 from other hospitals) were characterised. The results showed G1P[8] to be the predominant genotype (57%), followed by G9P[8] (34%), G4P[8] (6%), G2P[4] (2%), and G12P[8] (1%). This distribution of genotypes is comparable to those found in other European countries prior to vaccination suggesting that the vaccine should be highly efficacious in the Irish population.

  15. Distribution of rotavirus genotypes associated with acute diarrhoea in Zimbabwean children less than five years old before and after rotavirus vaccine introduction.

    Science.gov (United States)

    Mukaratirwa, Arnold; Berejena, Chipo; Nziramasanga, Pasipanodya; Ticklay, Ismail; Gonah, Archebald; Nathoo, Kusum; Manangazira, Portia; Mangwanya, Douglas; Marembo, Joan; Mwenda, Jason M; Weldegebriel, Goitom; Seheri, Mapaseka; Tate, Jacqueline E; Yen, Catherine; Parashar, Umesh; Mujuru, Hilda

    2018-04-05

    Sentinel surveillance for diarrhoea is important to monitor changes in rotavirus epidemiological trends and circulating genotypes among children under 5 years before and after vaccine introduction. The Zimbabwe Ministry of Health and Child Care introduced rotavirus vaccine in national immunization program in May 2014. Active hospital-based surveillance for diarrhoea was conducted at 3 sentinel sites from 2008 to 2016. Children aged less than 5 years, who presented with acute gastroenteritis as a primary illness and who were admitted to a hospital ward or treated at the emergency unit, were enrolled and had a stool specimen collected and tested for rotavirus by enzyme immunoassay (EIA). Genotyping of positive stools was performed using reverse-transcription polymerase chain reaction and genotyping assays. Pre-vaccine introduction, 10% of all positive stool specimens were genotyped and all adequate positive stools were genotyped post-vaccine introduction. During the pre-vaccine period, a total of 6491 acute gastroenteritis stools were collected, of which 3016 (46%) tested positive for rotavirus and 312 (10%) of the rotavirus positive stools were genotyped. During the post-vaccine period, a total of 3750 acute gastroenteritis stools were collected, of which 937 (25%) tested positive for rotavirus and 784 (84%) were genotyped. During the pre-vaccine introduction the most frequent genotype was G9P[8] (21%) followed by G2P[4] (12%), G1P[8] (6%), G2P[6] (5%), G12P[6] (4%), G9P[6] (3%) and G8P[4] (3%). G1P[8] (30%) was most dominant two years after vaccine introduction followed by G9P[6] (20%), G2P[4] (15%), G9P[8] (11%) and G1P[6] (4%). The decline in positivity rate is an indication of early vaccine impact. Diversity of circulating strains underscores the importance of continued monitoring and strain surveillance after vaccine introduction. Copyright © 2018. Published by Elsevier Ltd.

  16. Efficacy of a Low-Cost, Heat-Stable Oral Rotavirus Vaccine in Niger.

    Science.gov (United States)

    Isanaka, Sheila; Guindo, Ousmane; Langendorf, Celine; Matar Seck, Amadou; Plikaytis, Brian D; Sayinzoga-Makombe, Nathan; McNeal, Monica M; Meyer, Nicole; Adehossi, Eric; Djibo, Ali; Jochum, Bruno; Grais, Rebecca F

    2017-03-23

    Each year, rotavirus gastroenteritis is responsible for about 37% of deaths from diarrhea among children younger than 5 years of age worldwide, with a disproportionate effect in sub-Saharan Africa. We conducted a randomized, placebo-controlled trial in Niger to evaluate the efficacy of a live, oral bovine rotavirus pentavalent vaccine (BRV-PV, Serum Institute of India) to prevent severe rotavirus gastroenteritis. Healthy infants received three doses of the vaccine or placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and were graded on the basis of the score on the Vesikari scale (which ranges from 0 to 20, with higher scores indicating more severe disease). The primary end point was the efficacy of three doses of vaccine as compared with placebo against a first episode of laboratory-confirmed severe rotavirus gastroenteritis (Vesikari score, ≥11) beginning 28 days after dose 3. Among the 3508 infants who were included in the per-protocol efficacy analysis, there were 31 cases of severe rotavirus gastroenteritis in the vaccine group and 87 cases in the placebo group (2.14 and 6.44 cases per 100 person-years, respectively), for a vaccine efficacy of 66.7% (95% confidence interval [CI], 49.9 to 77.9). Similar efficacy was seen in the intention-to-treat analyses, which showed a vaccine efficacy of 69.1% (95% CI, 55.0 to 78.7). There was no significant between-group difference in the risk of adverse events, which were reported in 68.7% of the infants in the vaccine group and in 67.2% of those in the placebo group, or in the risk of serious adverse events (in 8.3% in the vaccine group and in 9.1% in the placebo group); there were 27 deaths in the vaccine group and 22 in the placebo group. None of the infants had confirmed intussusception. Three doses of BRV-PV, an oral rotavirus vaccine, had an efficacy of 66.7% against severe rotavirus gastroenteritis among infants in Niger. (Funded by M

  17. Rotavirus vaccines contribute towards universal health coverage in a mixed public-private healthcare system.

    Science.gov (United States)

    Loganathan, Tharani; Jit, Mark; Hutubessy, Raymond; Ng, Chiu-Wan; Lee, Way-Seah; Verguet, Stéphane

    2016-11-01

    To evaluate rotavirus vaccination in Malaysia from the household's perspective. The extended cost-effectiveness analysis (ECEA) framework quantifies the broader value of universal vaccination starting with non-health benefits such as financial risk protection and equity. These dimensions better enable decision-makers to evaluate policy on the public finance of health programmes. The incidence, health service utilisation and household expenditure related to rotavirus gastroenteritis according to national income quintiles were obtained from local data sources. Multiple birth cohorts were distributed into income quintiles and followed from birth over the first five years of life in a multicohort, static model. We found that the rich pay more out of pocket (OOP) than the poor, as the rich use more expensive private care. OOP payments among the poorest although small are high as a proportion of household income. Rotavirus vaccination results in substantial reduction in rotavirus episodes and expenditure and provides financial risk protection to all income groups. Poverty reduction benefits are concentrated amongst the poorest two income quintiles. We propose that universal vaccination complements health financing reforms in strengthening Universal Health Coverage (UHC). ECEA provides an important tool to understand the implications of vaccination for UHC, beyond traditional considerations of economic efficiency. © 2016 John Wiley & Sons Ltd.

  18. Budget impact and cost-utility analysis of universal infant rotavirus vaccination in Spain.

    Science.gov (United States)

    Imaz, Iñaki; Rubio, Beltrán; Cornejo, Ana M; González-Enríquez, Jesús

    2014-04-01

    Rotavirus is not included in the Spanish mass infant vaccination schedule but has also not been economically evaluated for its inclusion. We analysed cost-utility of the universal infant rotavirus vaccination using RotaTeq® versus no vaccination in Spain. We also carried out a budget impact analysis and determined the effect on results of different variables introduced in the model. A deterministic Markov model was built considering loss of quality of life for children and their parents, and introducing direct and indirect costs updated to 2011. The introduction of the vaccination using RotaTeq® as a universal infant vaccination would increase the annual health care budget in 10.43 million euro and would result in a gain of an additional Quality Adjusted Life Year at a cost of 280,338€ from the healthcare system perspective and 210,167€ from the societal perspective. The model was stable to variable modifications. To sum up, according to our model and estimates, the introduction of a universal infant rotavirus vaccination with RotaTeq® in Spain would cause a large impact on the health care budget and would not be efficient unless significant variations in vaccine price, vaccine efficacy and/or utilities took place. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. An update to "The cost-effectiveness of rotavirus vaccination: comparative analyses for five European countries and transferability in Europe".

    Science.gov (United States)

    Jit, Mark; Mangen, Marie-Josée J; Melliez, Hugues; Yazdanpanah, Yazdan; Bilcke, Joke; Salo, Heini; Edmunds, W John; Beutels, Philippe

    2010-11-03

    A cost-effectiveness analysis of rotavirus vaccination in Belgium, England and Wales, Finland, France and the Netherlands published in 2009 was updated based on recent studies on rotavirus burden of disease and vaccine efficacy. All the qualitative conclusions in the previous study were found to remain valid. Vaccination remains cost-effective in Finland only when using plausible tender prices. Copyright © 2010 Elsevier Ltd. All rights reserved.

  20. Subunit Rotavirus Vaccine Administered Parenterally to Rabbits Induces Active Protective Immunity

    Science.gov (United States)

    Ciarlet, Max; Crawford, Sue E.; Barone, Christopher; Bertolotti-Ciarlet, Andrea; Ramig, Robert F.; Estes, Mary K.; Conner, Margaret E.

    1998-01-01

    Virus-like particles (VLPs) are being evaluated as a candidate rotavirus vaccine. The immunogenicity and protective efficacy of different formulations of VLPs administered parenterally to rabbits were tested. Two doses of VLPs (2/6-, G3 2/6/7-, or P[2], G3 2/4/6/7-VLPs) or SA11 simian rotavirus in Freund’s adjuvants, QS-21 (saponin adjuvant), or aluminum phosphate (AlP) were administered. Serological and mucosal immune responses were evaluated in all vaccinated and control rabbits before and after oral challenge with 103 50% infective doses of live P[14], G3 ALA lapine rotavirus. All VLP- and SA11-vaccinated rabbits developed high levels of rotavirus-specific serum and intestinal immunoglobulin G (IgG) antibodies but not intestinal IgA antibodies. SA11 and 2/4/6/7-VLPs afforded similar but much higher mean levels of protection than 2/6/7- or 2/6-VLPs in QS-21. The presence of neutralizing antibodies to VP4 correlated (P < 0.001, r = 0.55; Pearson’s correlation coefficient) with enhanced protection rates, suggesting that these antibodies are important for protection. Although the inclusion of VP4 resulted in higher mean protection levels, high levels of protection (87 to 100%) from infection were observed in individual rabbits immunized with 2/6/7- or 2/6-VLPs in Freund’s adjuvants. Therefore, neither VP7 nor VP4 was absolutely required to achieve protection from infection in the rabbit model when Freund’s adjuvant was used. Our results show that VLPs are immunogenic when administered parenterally to rabbits and that Freund’s adjuvant is a better adjuvant than QS-21. The use of the rabbit model may help further our understanding of the critical rotavirus proteins needed to induce active protection. VLPs are a promising candidate for a parenterally administered subunit rotavirus vaccine. PMID:9765471

  1. Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Armah, George E; Sow, Samba O; Breiman, Robert F; Dallas, Michael J; Tapia, Milagritos D; Feikin, Daniel R; Binka, Fred N; Steele, A Duncan; Laserson, Kayla F; Ansah, Nana A; Levine, Myron M; Lewis, Kristen; Coia, Michele L; Attah-Poku, Margaret; Ojwando, Joel; Rivers, Stephen B; Victor, John C; Nyambane, Geoffrey; Hodgson, Abraham; Schödel, Florian; Ciarlet, Max; Neuzil, Kathleen M

    2010-08-21

    Rotavirus gastroenteritis causes many deaths in infants in sub-Saharan Africa. Because rotavirus vaccines have proven effective in developed countries but had not been tested in developing countries, we assessed efficacy of a pentavalent rotavirus vaccine against severe disease in Ghana, Kenya, and Mali between April, 2007, and March, 2009. In our multicentre, double-blind, placebo-controlled trial, undertaken in rural areas of Ghana and Kenya and an urban area of Mali, we randomly assigned infants aged 4-12 weeks without symptoms of gastrointestinal disorders in a 1:1 ratio to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks, 10 weeks, and 14 weeks of age. Infants with HIV infection were not excluded. Randomisation was done by computer-generated randomisation sequence in blocks of six. We obtained data for gastrointestinal symptoms from parents on presentation to health-care facilities and clinical data were obtained prospectively by clinicians. The primary endpoint was severe rotavirus gastroenteritis (Vesikari score >or=11), detected by enzyme immunoassay, arising 14 days or more after the third dose of placebo or vaccine to end of study (March 31, 2009; around 21 months of age). Analysis was per protocol; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00362648. 5468 infants were randomly assigned to receive pentavalent rotavirus vaccine (n=2733) or placebo (n=2735). 2357 infants assigned to vaccine and 2348 assigned to placebo were included in the per-protocol analysis. 79 cases of severe rotavirus gastroenteritis were reported in 2610.6 person-years in the vaccine group, compared with 129 cases in 2585.9 person-years in the placebo group, resulting

  2. Efficacy, immunogenicity, and safety of two doses of a tetravalent rotavirus vaccine RRV-TV in Ghana with the first dose administered during the neonatal period.

    Science.gov (United States)

    Armah, George E; Kapikian, Albert Z; Vesikari, Timo; Cunliffe, Nigel; Jacobson, Robert M; Burlington, D Bruce; Ruiz, Leonard P

    2013-08-01

    Oral rhesus/rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) was licensed in 1998 but withdrawn in 1999 due to a rare association with intussusception, which occurred disproportionately in infants receiving their first dose at ≥90 days of age. This study examined RRV-TV for the prevention of rotavirus gastroenteritis (RV-GE) in Ghana, West Africa, with infants receiving the first dose during the neonatal period and the second before 60 days of age. In a double-blinded, randomized, placebo-controlled trial in Navrongo, Ghana, we recruited neonates to receive 2 doses of RRV-TV or placebo and followed them to age 12 months. In the intention-to-treat population of 998 infants, we measured a vaccine efficacy of 63.1% against RV-GE of any severity associated with any of the 4 serotypes represented in the vaccine and 60.7% against RV-GE associated with any rotavirus serotype. RRV-TV in a 2-dose schedule with the first dose during the neonatal period is efficacious in preventing RV-GE in rural Ghana. Neonatal dosing results in early protection and may be the optimum schedule to avoid or significantly reduce intussusception, now reported to be associated in international settings with the 2 most widely marketed, licensed, live virus, oral rotavirus vaccines.

  3. Significant Correlation Between the Infant Gut Microbiome and Rotavirus Vaccine Response in Rural Ghana

    NARCIS (Netherlands)

    Harris, Vanessa C.; Armah, George; Fuentes Enriquez de Salamanca, Susana; Korpela, Katri E.; Parashar, Umesh; Victor, John C.; Tate, Jacqueline; Weerth, de Carolina; Giaquinto, Carlo; Wiersinga, Willem Joost; Lewis, Kristen D.C.; Vos, de Willem M.

    2017-01-01

    BACKGROUND:  Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and 95% of RV-associated deaths occur in Africa and Asia where RV vaccines (RVVs) have lower efficacy. We hypothesize that differences in intestinal microbiome composition correlate with the decreased

  4. Efficacy and immunogenicity of two or three dose rotavirus-vaccine regimen in South African children over two consecutive rotavirus-seasons: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Madhi, S A; Kirsten, M; Louw, C; Bos, P; Aspinall, S; Bouckenooghe, A; Neuzil, K M; Steele, A D

    2012-04-27

    Human rotavirus vaccine (HRV; i.e., Rotarix) reduced the incidence of severe rotavirus gastroenteritis (RVGE) by 77% (95% Confidence interval: 56-88%) during the first year of life in South Africa. Persistence of HRV-derived protection against RVGE during subsequent rotavirus seasons, although evident in industrialized settings, remains to be established in African settings. This study reports on the efficacy of HRV against severe RVGE over two consecutive rotavirus seasons in South African children. A prospective, double-blind, placebo controlled multi-centered trial in South Africa and Malawi randomly assigned infants in a 1:1:1 ratio to receive either two (10 and 14 weeks; HRV_2D) or three (6, 10 and 14 weeks; HRV_3D) doses of HRV or placebo. The primary analysis involved pooling of HRV_2D and HRV_3D arms. Episodes of gastroenteritis caused by wild-type rotavirus were identified through active follow-up surveillance and graded by the Vesikari scale. 1339 infants (447 in the HRV_2D group, 447 in the HRV_3D group and 445 in the placebo group) were enrolled in Year 2 of the study, including 1035 (77.3%) who were followed up over two consecutive rotavirus seasons (i.e., Cohort 2 subjects). Rotarix was associated with ongoing protection against severe RVGE, preventing 2.5 episodes per 100 vaccinated children over two consecutive rotavirus seasons; vaccine efficacy: 59% (95% Confidence interval: 1-83%). An exploratory analysis indicated better immunogenicity (among Cohort 1 subjects) and a higher point-efficacy estimate over two seasons in the HRV_3D compared to HRV_2D arms of the study in Cohort 2 subjects. Rotarix is associated with significant reductions in severe gastroenteritis episodes through 2 years of life among South African children. Further research is needed to determine the optimal dosing schedule of Rotarix in providing long-term protection against rotavirus illness in African children. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Rotavirus epidemiology and surveillance before vaccine introduction in Argentina, 2012-2014.

    Science.gov (United States)

    Degiuseppe, Juan Ignacio; Reale, Ezequiel Agustín; Stupka, Juan Andrés

    2017-03-01

    Group A Rotavirus has been widely described as one of the most important infantile diarrheal pathogens worldwide. In Argentina, it is responsible for over 200,000 acute diarrhea cases and from 30 to 50 deaths annually in children under 5 years. The aim of this study is to analyze frequency, seasonality, age group distribution, and circulating genotypes based on data notified in the 2012-2014 period and in turn to assess the pre-vaccine scenario, considering that rotavirus vaccine was introduced in 2015. Data were taken from the Viral Diarrhea Notification module of the Argentine SNVS-SIVILA surveillance tool. Analyses of circulating genotypes were performed on rotavirus-positive stool specimens by conventional binary characterization of the outermost capsid genes. Overall data showed rotavirus detection in about 25% of samples tested, and higher rates in children under 2 years old were observed. Rotavirus positive cases were distributed according to a typical winter seasonal pattern. A heterogeneous regional pattern of prevalence was also observed, with higher rates detected in the North region. Genotype co-circulation and annual fluctuation were observed. In general, G1P[8], G2P[4], G3P[8], and G12P[8] were the most frequently detected genotypes. This study represents the last survey taken of a population considered to be naïve. J. Med. Virol. 89:423-428, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. The composition of demand for newly launched vaccines: results from the pneumococcal and rotavirus vaccine introductions in Ethiopia and Malawi.

    Science.gov (United States)

    Williams, B Adam; Kidane, Teklay; Chirwa, Geoffrey; Tesfaye, Neghist; Prescott, Marta R; Scotney, Soleine T; Valle, Moussa; Abebe, Sintayehu; Tambuli, Adija; Malewezi, Bridget; Mohammed, Tahir; Kobayashi, Emily; Wootton, Emily; Wong, Renee; Dosani, Rahima; Subramaniam, Hamsa; Joseph, Jessica; Yavuz, Elif; Apple, Aliza; Le Tallec, Yann; Kang'ethe, Alice

    2016-06-01

    Understanding post-launch demand for new vaccines can help countries maximize the benefits of immunization programmes. In particular, low- and middle-income countries (LMICs) should ensure adequate resource planning with regards to stock consumption and service delivery for new vaccines, whereas global suppliers must produce enough vaccines to meet demand. If a country underestimates the number of children seeking vaccination, a stock-out of commodities will create missed opportunities for saving lives. We describe the post-launch demand for the first dose of pneumococcal conjugate vaccine (PCV1) in Ethiopia and Malawi and the first dose of rotavirus vaccine (Rota1) in Malawi, with focus on the new birth cohort and the 'backlog cohort', comprised of older children who are still eligible for vaccination at the time of launch. PCV1 and Rota1 uptake were compared with the demand for the first dose of pentavalent vaccine (Penta1), a routine immunization that targets the same age group and immunization schedule. In the first year, the total demand for PCV1 was 37% greater than that of Penta1 in Ethiopia and 59% greater in Malawi. In the first 6 months, the demand of Rota1 was only 5.9% greater than Penta1 demand in Malawi. Over the first three post-introduction months, 70.7% of PCV1 demand in Ethiopia and 71.5% of demand in Malawi came from children in the backlog cohort, whereas only 28.0% of Rota1 demand in Malawi was from the backlog cohort. The composition of demand was impacted by time elapsed since vaccine introduction and age restrictions. Evidence suggests that countries' plans should account for the impact of backlog demand, especially in the first 3 months post-introduction. LMICs should request for higher stock volumes when compared with routine needs, plan social mobilization activities to reach the backlog cohort and allocate human resources and cold chain capacity to accommodate high demand following vaccine introduction. © The Author 2016. Published by

  7. Immunogenicity of the pentavalent rotavirus vaccine among infants in two developing countries in Asia, Bangladesh and Vietnam.

    Science.gov (United States)

    Shin, Sunheang; Anh, Dang Duc; Zaman, K; Yunus, M; Mai, Le Thi Phuong; Thiem, Vu Dinh; Azim, Tasnim; Victor, John C; Dallas, Michael J; Steele, A Duncan; Neuzil, Kathleen M; Ciarlet, Max

    2012-04-27

    We evaluated the immunogenicity of the pentavalent rotavirus vaccine (PRV) in two GAVI-eligible Asian countries, Bangladesh and Vietnam, nested in a larger randomized, double-blind, placebo-controlled efficacy trial conducted over a two-year period from 2007 through 2009. 2036 infants were randomly assigned, in a 1:1 ratio, to receive three oral doses of PRV or placebo approximately at 6, 10, and 14 weeks of age. Concomitant use of EPI vaccines, including oral poliovirus vaccine (OPV) and diphtheria-tetanus-whole cell pertussis (DTwP) vaccine, was encouraged in accordance to the local EPI schedule. A total of 303 infants were evaluated for immunogenicity and blood samples were collected before the first dose (pD1) and approximately 14 days following the third dose (PD3). The seroresponse rates (≥3-fold rise from pD1 to PD3) and geometric mean titers (GMTs) were measured for anti-rotavirus immunoglobulin A (IgA) and serum neutralizing antibody (SNA) to human rotavirus serotypes G1, G2, G3, G4, and P1A[8], respectively. Nearly 88% of the subjects showed a ≥3-fold increase in serum anti-rotavirus IgA response in the analysis of the two countries combined. When analyzed separately, the IgA response was lower in Bangladeshi children (78.1% [95% CI: 66.0, 87.5]) than in Vietnamese children (97.0% [95% CI: 89.6, 99.6]), with a PD3 GMT of 29.1 (units/mL) and 158.5 (units/mL), respectively. In the combined population, the SNA responses to the individual serotypes tested ranged from 10 (G3) to 50 (G1) percentage points lower than the responses shown in the developed countries. However, the SNA response to G3 in Vietnamese subjects was 37.3% (95% CI: 25.8, 50.0), which was similar to the G3 response rate in developed countries. Three oral doses of PRV were immunogenic in two GAVI-eligible Asian countries: Bangladesh and Vietnam. The GMTs of both the serum anti-rotavirus IgA and SNA responses were generally higher in Vietnamese than in Bangladeshi children. The SNA

  8. Removing the age restrictions for rotavirus vaccination: a benefit-risk modeling analysis.

    Directory of Open Access Journals (Sweden)

    Manish M Patel

    Full Text Available BACKGROUND: To minimize potential risk of intussusception, the World Health Organization (WHO recommended in 2009 that rotavirus immunization should be initiated by age 15 weeks and completed before 32 weeks. These restrictions could adversely impact vaccination coverage and thereby its health impact, particularly in developing countries where delays in vaccination often occur. METHODS AND FINDINGS: We conducted a modeling study to estimate the number of rotavirus deaths prevented and the number of intussusception deaths caused by vaccination when administered on the restricted schedule versus an unrestricted schedule whereby rotavirus vaccine would be administered with DTP vaccine up to age 3 years. Countries were grouped on the basis of child mortality rates, using WHO data. Inputs were estimates of WHO rotavirus mortality by week of age from a recent study, intussusception mortality based on a literature review, predicted vaccination rates by week of age from USAID Demographic and Health Surveys, the United Nations Children's Fund (UNICEF Multiple Indicator Cluster Surveys (MICS, and WHO-UNICEF 2010 country-specific coverage estimates, and published estimates of vaccine efficacy and vaccine-associated intussusception risk. On the basis of the error estimates and distributions for model inputs, we conducted 2,000 simulations to obtain median estimates of deaths averted and caused as well as the uncertainty ranges, defined as the 5th-95th percentile, to provide an indication of the uncertainty in the estimates. We estimated that in low and low-middle income countries a restricted schedule would prevent 155,800 rotavirus deaths (5th-95th centiles, 83,300-217,700 while causing potentially 253 intussusception deaths (76-689. In contrast, vaccination without age restrictions would prevent 203,000 rotavirus deaths (102,000-281,500 while potentially causing 547 intussusception deaths (237-1,160. Thus, removing the age restrictions would avert an

  9. Cost-effectiveness of introducing a rotavirus vaccine in developing countries: The case of Mexico

    Science.gov (United States)

    Valencia-Mendoza, Atanacio; Bertozzi, Stefano M; Gutierrez, Juan-Pablo; Itzler, Robbin

    2008-01-01

    Background In developing countries rotavirus is the leading cause of severe diarrhoea and diarrhoeal deaths in children under 5. Vaccination could greatly alleviate that burden, but in Mexico as in most low- and middle-income countries the decision to add rotavirus vaccine to the national immunisation program will depend heavily on its cost-effectiveness and affordability. The objective of this study was to assess the cost-effectiveness of including the pentavalent rotavirus vaccine in Mexico's national immunisation program. Methods A cost-effectiveness model was developed from the perspective of the health system, modelling the vaccination of a hypothetical birth cohort of 2 million children monitored from birth through 60 months of age. It compares the cost and disease burden of rotavirus in an unvaccinated cohort of children with one vaccinated as recommended at 2, 4, and 6 months. Results Including the pentavalent vaccine in the national immunisation program could prevent 71,464 medical visits (59%), 5,040 hospital admissions (66%), and 612 deaths from rotavirus gastroenteritis (70%). At US$10 per dose and a cost of administration of US$13.70 per 3-dose regimen, vaccination would cost US$122,058 per death prevented, US$4,383 per discounted life-year saved, at a total net cost of US$74.7 million dollars to the health care system. Key variables influencing the results were, in order of importance, case fatality, vaccine price, vaccine efficacy, serotype prevalence, and annual loss of efficacy. The results are also very sensitive to the discount rate assumed when calculated per life-year saved. Conclusion At prices below US $15 per dose, the cost per life-year saved is estimated to be lower than one GNP per capita and hence highly cost effective by the WHO Commission on Macroeconomics and Health criteria. The cost-effectiveness estimates are highly dependent upon the mortality in the absence of the vaccine, which suggests that the vaccine is likely to be

  10. Cost-effectiveness of introducing a rotavirus vaccine in developing countries: The case of Mexico

    Directory of Open Access Journals (Sweden)

    Gutierrez Juan-Pablo

    2008-07-01

    Full Text Available Abstract Background In developing countries rotavirus is the leading cause of severe diarrhoea and diarrhoeal deaths in children under 5. Vaccination could greatly alleviate that burden, but in Mexico as in most low- and middle-income countries the decision to add rotavirus vaccine to the national immunisation program will depend heavily on its cost-effectiveness and affordability. The objective of this study was to assess the cost-effectiveness of including the pentavalent rotavirus vaccine in Mexico's national immunisation program. Methods A cost-effectiveness model was developed from the perspective of the health system, modelling the vaccination of a hypothetical birth cohort of 2 million children monitored from birth through 60 months of age. It compares the cost and disease burden of rotavirus in an unvaccinated cohort of children with one vaccinated as recommended at 2, 4, and 6 months. Results Including the pentavalent vaccine in the national immunisation program could prevent 71,464 medical visits (59%, 5,040 hospital admissions (66%, and 612 deaths from rotavirus gastroenteritis (70%. At US$10 per dose and a cost of administration of US$13.70 per 3-dose regimen, vaccination would cost US$122,058 per death prevented, US$4,383 per discounted life-year saved, at a total net cost of US$74.7 million dollars to the health care system. Key variables influencing the results were, in order of importance, case fatality, vaccine price, vaccine efficacy, serotype prevalence, and annual loss of efficacy. The results are also very sensitive to the discount rate assumed when calculated per life-year saved. Conclusion At prices below US $15 per dose, the cost per life-year saved is estimated to be lower than one GNP per capita and hence highly cost effective by the WHO Commission on Macroeconomics and Health criteria. The cost-effectiveness estimates are highly dependent upon the mortality in the absence of the vaccine, which suggests that the vaccine

  11. Use of Internet Search Data to Monitor Rotavirus Vaccine Impact in the United States, United Kingdom, and Mexico.

    Science.gov (United States)

    Shah, Minesh P; Lopman, Benjamin A; Tate, Jacqueline E; Harris, John; Esparza-Aguilar, Marcelino; Sanchez-Uribe, Edgar; Richardson, Vesta; Steiner, Claudia A; Parashar, Umesh D

    2018-02-19

    Previous studies have found a strong correlation between internet search and public health surveillance data. Less is known about how search data respond to public health interventions, such as vaccination, and the consistency of responses in different countries. In this study, we aimed to study the correlation between internet searches for "rotavirus" and rotavirus disease activity in the United States, United Kingdom, and Mexico before and after introduction of rotavirus vaccine. We compared time series of internet searches for "rotavirus" from Google Trends with rotavirus laboratory reports from the United States and United Kingdom and with hospitalizations for acute gastroenteritis in the United States and Mexico. Using time and location parameters, Google quantifies an internet query share (IQS) to measure the relative search volume for specific terms. We analyzed the correlation between IQS and laboratory and hospitalization data before and after national vaccine introductions. There was a strong positive correlation between the rotavirus IQS and laboratory reports in the United States (R2 = 0.79) and United Kingdom (R2 = 0.60) and between the rotavirus IQS and acute gastroenteritis hospitalizations in the United States (R2 = 0.87) and Mexico (R2 = 0.69) (P United States and by 70% (95% CI, 55%-86%) in Mexico. In the United Kingdom, there was a loss of seasonal variation after vaccine introduction. Rotavirus internet search data trends mirrored national rotavirus laboratory trends in the United States and United Kingdom and gastroenteritis-hospitalization data in the United States and Mexico; lower correlations were found after rotavirus vaccine introduction. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  12. MATHEMATICAL MODELING AS A MODERN TOOL OF PROJECTING THE EFFICACY OF ROTAVIRUS VACCINES

    Directory of Open Access Journals (Sweden)

    S. O. Solovyov

    2012-11-01

    Full Text Available With the use of molecular biological studies there were estimated the peculiarities of the circulation of rotavirus genotypes on the territory of Ukraine. It was estimated predictive genotype-specific efficacy of the vaccine based on rotavirus strain RIX4114 with genotype G1P, based on the methods of distribution and multiplicative synthesis, which were used for the first time in such calculations. This allows obtaining a preliminary evaluation of its efficacy prior to clinical trials. It was established that the calculated value is sufficiently high (80,4% in conditions of its mass use among population of Ukraine.

  13. Human Papillomavirus (HPV) Vaccine

    Science.gov (United States)

    Why get vaccinated?HPV vaccine prevents infection with human papillomavirus (HPV) types that are associated with cause ... at http://www.cdc.gov/hpv. HPV Vaccine (Human Papillomavirus) Information Statement. U.S. Department of Health and ...

  14. 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.

  15. Human rotavirus group a serotypes causing gastroenteritis in children less than 5 years and HIV-infected adults in Viwandani slum, Nairobi.

    Science.gov (United States)

    Raini, S K; Nyangao, J; Kombich, J; Sang, C; Gikonyo, J; Ongus, J R; Odari, E O

    2015-01-01

    Rotavirus remains a leading cause of acute gastroenteritis in children worldwide with an estimated 2000 deaths each day in developing countries. 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. A cross-sectional study was conducted to document human rotavirus group A serotypes in children below 5 years and HIV-infected adults in Viwandani slum in Nairobi, Kenya. A total of 260 (128 from children and 132 from HIV infected adults) fecal specimen samples were analyzed from August 2012 to July 2013. Screening for rotavirus was done by antigen based enzyme immune-sorbent assay (ELISA), Polyacrylamide gel electrophoresis (PAGE) was used to detect rotavirus electropherotypes and finally genotyping was done by RT-PCR using genotype-specific primer sets targeting VP4 and VP7 genes. Rotavirus was detected in 23% and 8% of children and adult, respectively. Prevalence was high in children of 48 years. Long electropherotypes accounted for 80% and 60% while short electropherotypes accounted for 20% and 40% in children and adult, respectively. The common globally distributed strains, G1 and G3, accounted for 60% detections while the unusual G9 strain accounted for 80% infection in adults. G1P[8] was the common genotypic combination in children, accounting for 40% infection, whereas G9 [P8] accounted for 60% of the infections in adults. This study shows the existence of strain diversity between rotavirus circulating in children and adults within this study group. It further shows that as currently constituted, the 2 vaccines recommended for rotavirus would cover the circulating strain in Viwandani slum. Finally, there is a need for continuous rotavirus strain surveillance in children and a further focus on HIV

  16. An ensemble approach to predicting the impact of vaccination on rotavirus disease in Niger.

    Science.gov (United States)

    Park, Jaewoo; Goldstein, Joshua; Haran, Murali; Ferrari, Matthew

    2017-10-13

    Recently developed vaccines provide a new way of controlling rotavirus in sub-Saharan Africa. Models for the transmission dynamics of rotavirus are critical both for estimating current burden from imperfect surveillance and for assessing potential effects of vaccine intervention strategies. We examine rotavirus infection in the Maradi area in southern Niger using hospital surveillance data provided by Epicentre collected over two years. Additionally, a cluster survey of households in the region allows us to estimate the proportion of children with diarrhea who consulted at a health structure. Model fit and future projections are necessarily particular to a given model; thus, where there are competing models for the underlying epidemiology an ensemble approach can account for that uncertainty. We compare our results across several variants of Susceptible-Infectious-Recovered (SIR) compartmental models to quantify the impact of modeling assumptions on our estimates. Model-specific parameters are estimated by Bayesian inference using Markov chain Monte Carlo. We then use Bayesian model averaging to generate ensemble estimates of the current dynamics, including estimates of R 0 , the burden of infection in the region, as well as the impact of vaccination on both the short-term dynamics and the long-term reduction of rotavirus incidence under varying levels of coverage. The ensemble of models predicts that the current burden of severe rotavirus disease is 2.6-3.7% of the population each year and that a 2-dose vaccine schedule achieving 70% coverage could reduce burden by 39-42%. Copyright © 2017. Published by Elsevier Ltd.

  17. Effectiveness of Pentavalent Rotavirus Vaccine Against a Diverse Range of Circulating Strains in Nicaragua.

    Science.gov (United States)

    Patel, Manish; Pedreira, Cristina; De Oliveira, Lúcia Helena; Tate, Jacqueline; Leshem, Eyal; Mercado, Juan; Umaña, Jazmina; Balmaceda, Angel; Reyes, Martha; Kerin, Tara; McDonald, Sharla; Gentsch, Jon; Bowen, Michael D; Parashar, Umesh

    2016-05-01

    Because >60 rotavirus strains have been reported worldwide, concerns exist about strain replacement after the introduction of rotavirus vaccines, particularly in developing countries with diverse strains and lower efficacy. We used the case-control design in 4 hospitals in Nicaragua to assess strain-specific vaccine effectiveness (VE) of a pentavalent rotavirus vaccine (RotaTeq) against rotavirus diarrhea. Cases were identified through prospective strain surveillance with reverse transcription-polymerase chain reaction for 3 years among children hospitalized for diarrhea, and controls were children negative for rotavirus. We enrolled 1178 case-patients, 1082 (92%) with G and P typing, and 4927 controls. A different strain predominated each year with increasing age of the vaccine-eligible cohort during the study period: G2P[4] in 2008 (97%; mean age, 11.9 months), G1P[8] in 2009 (55%; mean age, 17.0 months), and G3P[8] in 2010 (78%; mean age, 17.3 months). Overall VE was 45% (95% confidence interval, 25%-59%). Regardless of the strain, VE estimates were 12%-79% lower among children aged ≥12 months relative to those 6-11 months of age. The lower VE for G3P[8] was related to the higher mean age of cases (17.3 months) compared with the G2P[4] strains (11.9 months), with a significant trend (R(2)= 0.819;P< .001) of declining effectiveness with increasing mean age of the cases. Introduction of RotaTeq did not result in sustained emergence of any particular strain in Nicaragua. Variation in strain-specific effectiveness was due to an age-related decline in effectiveness rather than differences in protection against the observed strains. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  18. Cost-effectiveness analysis of the introduction of rotavirus vaccine in Iran.

    Science.gov (United States)

    Javanbakht, Mehdi; Moradi-Lakeh, Maziar; Yaghoubi, Mohsen; Esteghamati, Abdoulreza; Mansour Ghanaie, Roxana; Mahmoudi, Sussan; Shamshiri, Ahmad-Reza; Zahraei, Seyed Mohsen; Baxter, Louise; Shakerian, Sareh; Chaudhri, Irtaza; Fleming, Jessica A; Munier, Aline; Baradaran, Hamid R

    2015-05-07

    Although the mortality from diarrheal diseases has been decreasing dramatically in Iran, it still represents an important proportion of disease burden in children Rotavirus vaccines are among the most effective strategies against diarrheal diseases in specific epidemiological conditions. This study aimed to evaluate the cost-effectiveness of the introduction of rotavirus vaccine (3 doses of pentavalent RotaTeq (RV5)) in Iran, from the viewpoints of Iran's health system and society. The TRIVAC decision support model was used to calculate total incremental costs, life years (LYs) gained, and disability-adjusted life years (DALYs) averted due to the vaccination program. Necessary input data were collected from the most valid accessible sources as well as a systematic review and meta-analysis on epidemiological studies. We used WHO guidelines to estimate vaccination cost. An annual discount rate of 3% was considered for both health gain and costs. A deterministic sensitivity analysis was performed for testing the robustness of the models results. Our results indicated that total DALYs potentially lost due to rotavirus diarrhea within 10 years would be 138,161, of which 76,591 could be prevented by rotavirus vaccine. The total vaccination cost for 10 cohorts was estimated to be US$ 499.91 million. Also, US$ 470.61 million would be saved because of preventing outpatient visits and inpatient admissions (cost-saving from the society perspective). We estimated a cost per DALY averted of US$ 2868 for RV5 vaccination, which corresponds to a highly cost-effective strategy from the government perspective. In the sensitivity analysis, all scenarios tested were still cost-saving or highly cost-effective from the society perspective, except in the least favorable scenario and low vaccine efficacy and disease incidence scenario. Based on the findings, introduction of rotavirus vaccine is a highly cost-effective strategy from the government perspective. Introducing the vaccine to

  19. Estimated impact and cost-effectiveness of rotavirus vaccination in Senegal: A country-led analysis.

    Science.gov (United States)

    Diop, Abdou; Atherly, Deborah; Faye, Alioune; Lamine Sall, Farba; Clark, Andrew D; Nadiel, Leon; Yade, Binetou; Ndiaye, Mamadou; Fafa Cissé, Moussa; Ba, Mamadou

    2015-05-07

    Rotavirus is the leading cause of acute severe diarrhea among children under 5 globally and one of the leading causes of death attributable to diarrhea. Among African children hospitalized with diarrhea, 38% of the cases are due to rotavirus. In Senegal, rotavirus deaths are estimated to represent 5.4% of all deaths among children under 5. Along with the substantial disease burden, there is a growing awareness of the economic burden created by diarrheal disease. This analysis aims to provide policymakers with more consistent and reliable economic evidence to support the decision-making process about the introduction and maintenance of a rotavirus vaccine program. The study was conducted using the processes and tools first established by the Pan American Health Organization's ProVac Initiative in the Latin American region. TRIVAC version 2.0, an Excel-based model, was used to perform the analysis. The costs and health outcomes were calculated for 20 successive birth cohorts (2014-2033). Model inputs were gathered from local, national, and international sources with the guidance of a Senegalese group of experts including local pediatricians, personnel from the Ministry of Health and the World Health Organization, as well as disease-surveillance and laboratory specialists. The cost per disability-adjusted life-year (DALY) averted, discounted at 3%, is US$ 92 from the health care provider perspective and US$ 73 from the societal perspective. For the 20 cohorts, the vaccine is projected to prevent more than 2 million cases of rotavirus and to avert more than 8500 deaths. The proportion of rotavirus deaths averted is estimated to be 42%. For 20 cohorts, the discounted net costs of the program were estimated to be US$ 17.6 million from the healthcare provider perspective and US$ 13.8 million from the societal perspective. From both perspectives, introducing the rotavirus vaccine is highly cost-effective compared to no vaccination. The results are consistent with those

  20. Cost-effectiveness analysis of rotavirus vaccination among Libyan ...

    African Journals Online (AJOL)

    Methods: We used a published decision tree model that has been adapted to the Libyan situation to analyze a birth cohort of 160,000 children. The evaluation of diarrhea events in three public hospitals helped to estimate the rotavirus burden. The economic analysis was done from two perspectives: health care provider and ...

  1. Cost-effectiveness analysis of rotavirus vaccination in China: Projected possibility of scale-up from the current domestic option.

    Science.gov (United States)

    Cui, Shuhui; Tobe, Ruoyan Gai; Mo, Xiuting; Liu, Xiaoyan; Xu, Lingzhong; Li, Shixue

    2016-11-15

    Rotavirus infection causes considerable disease burden of acute gastroenteritis (AGE) hospitalization and death among children less than 5 years in China. Although two rotavirus vaccines (Rotarix and RotaTeq) have been licensed in more than 100 countries in the world, the Lanzhou Lamb rotavirus vaccine (LLR) is the only vaccine licensed in China. This study aims to forecast the potential impacts of the two international vaccines compared to domestic LLR. An economic evaluation was performed using a Markov simulation model. We compared costs at the societal aspect and health impacts with and without a vaccination program by LLR, Rotarix or RotaTeq. Parameters including demographic, epidemiological data, costs and efficacy of vaccines were obtained from literature review. The model incorporated the impact of vaccination on reduction of incidence of rotavirus infection and severity of AGE indicated by hospitalization, inpatient visits and deaths. Outcomes are presented in terms of quality-adjusted life years (QALYs) gained and incremental cost-effectiveness ratio (ICER) compared to status quo. In a hypothetical cohort of 100,000 infants, the two international vaccines showed very good cost-effectiveness, with ICER of Rotateq and Rotarix shifting from LLR of $1715.11/QALY and $2105.66/QALY, respectively. Rotateq and Rotarix had significantly decreased incidence compared to LLR, particularly among infants aged 6 months to 2 years. RotaTeq is expected to introduce in the national routine immunization program to reduce disease burden of rotavirus infection with universal coverage.

  2. Immunogenicity of rotavirus vaccine (RotarixTM in infants with environmental enteric dysfunction.

    Directory of Open Access Journals (Sweden)

    Innocent Mwape

    Full Text Available Deployment of rotavirus vaccines has contributed to significant declines in diarrheal morbidity and mortality globally. Unfortunately, vaccine performance in low-middle income countries (LMICs is generally lower than in developed countries. The cause for this has been associated with several host and maternal factors including poor water sanitation and hygiene (WASH status, which are predominant in LMICs. More recently, environmental enteric dysfunction (EED has specifically been hypothesized to contribute to poor vaccine uptake and response. The aim of this study was to examine the association between serological biomarkers of EED and seroconversion to rotavirus vaccine in Zambian infants.This was a retrospective cohort study of 142 infants who had been fully immunized with Rotarix™, and had known seroconversion status. Seroconversion was defined as 4-fold or more increase in rotavirus-specific IgA titres between pre-vaccination and one month post-dose two vaccination. We performed ELISA assays to assess soluble CD14 (sCD14, Endotoxin Core IgG Antibodies (EndoCAb, intestinal fatty acid binding protein (i-FABP and Zonulin according to the manufacturers protocols. Generalised linear model with family-poisson, link-log and robust standard error was used to estimate the independent effects of biomarkers on seroconversion adjusting for important cofounders.The median concentration of Zonulin, Soluble CD14, EndoCaB, and IFABP were 209.3 (IQR = 39.7, 395.1, 21.5 (IQR = 21.5, 21.5, 0.3 (IQR = 0.3, 0.3, and 107.7 (IQR = 6.4, 1141.4 respectively. In multivariable analyses adjusting for the independent effect of other biomarkers and confounders (i.e. age of child at vaccination, breast-milk anti-rotavirus IgA, infant serum anti-rotavirus IgG, and IgA seropositivity at baseline, there was strong evidence of about 24% increase in seroconversion due to doubling Zonulin concentration (Adjusted risk ratio (aRR = 1.24; 95% CI = 1.12 to1.37; p<0

  3. Cost-effectiveness analysis of vaccination against rotavirus with RIX4414 in France.

    Science.gov (United States)

    Standaert, Baudouin; Parez, Nathalie; Tehard, Bertrand; Colin, Xavier; Detournay, Bruno

    2008-01-01

    It is estimated that annually 300 000 cases of rotavirus-induced gastroenteritis (RVGE) occur in children aged up to 5 years in France. A two-dose vaccine against rotavirus infection (RIX4414; Rotarix, GlaxoSmithKline), has been shown to be highly effective against severe RVGE. This study evaluated the cost effectiveness of general vaccination against rotavirus using RIX4414 in France. A Markov model simulated RVGE events and the associated outcomes and costs relating to general vaccination of infants against rotavirus infection using RIX4414 (Rotarix) in a birth cohort of children aged up to 5 years in France with a combined adjustment for age distribution with the seasonality of the infection. Costs and outcomes were estimated from a limited societal perspective, including direct medical costs paid out of pocket or by third-party payers, as well as the proportion of direct medical costs reimbursed by the health authorities. Indirect costs were not included in the base-case analysis. The primary outcome measure was the incremental cost per QALY. Vaccination with RIX4414 incurred an incremental cost of 44 583 Euro per QALY at a public price of 57 Euro per vaccine dose. Univariate sensitivity analyses showed that the parameters with the largest influence on the results were the transition probabilities of severe diarrhoea, seeking medical advice and emergency visits, utility scores of diarrhoea (mild) in children and infants, and the discount rate for benefits. Probabilistic multivariate sensitivity analysis confirmed these results. The acceptability curve indicated that 94% of the results were under an informal threshold of 50 000 Euro per QALY. Comparing our results with those of a recently published study using pooled data for two rotavirus vaccine products in France, the main differences are explained by differences in model structure and in data input values. They include a different age distribution of the infection, shorter duration of the at-risk period (3

  4. Immunogenicity of rotavirus vaccine (RotarixTM) in infants with environmental enteric dysfunction.

    Science.gov (United States)

    Mwape, Innocent; Bosomprah, Samuel; Mwaba, John; Mwila-Kazimbaya, Katayi; Laban, Natasha Makabilo; Chisenga, Caroline Cleopatra; Sijumbila, Gibson; Simuyandi, Michelo; Chilengi, Roma

    2017-01-01

    Deployment of rotavirus vaccines has contributed to significant declines in diarrheal morbidity and mortality globally. Unfortunately, vaccine performance in low-middle income countries (LMICs) is generally lower than in developed countries. The cause for this has been associated with several host and maternal factors including poor water sanitation and hygiene (WASH) status, which are predominant in LMICs. More recently, environmental enteric dysfunction (EED) has specifically been hypothesized to contribute to poor vaccine uptake and response. The aim of this study was to examine the association between serological biomarkers of EED and seroconversion to rotavirus vaccine in Zambian infants. This was a retrospective cohort study of 142 infants who had been fully immunized with Rotarix™, and had known seroconversion status. Seroconversion was defined as 4-fold or more increase in rotavirus-specific IgA titres between pre-vaccination and one month post-dose two vaccination. We performed ELISA assays to assess soluble CD14 (sCD14), Endotoxin Core IgG Antibodies (EndoCAb), intestinal fatty acid binding protein (i-FABP) and Zonulin according to the manufacturers protocols. Generalised linear model with family-poisson, link-log and robust standard error was used to estimate the independent effects of biomarkers on seroconversion adjusting for important cofounders. The median concentration of Zonulin, Soluble CD14, EndoCaB, and IFABP were 209.3 (IQR = 39.7, 395.1), 21.5 (IQR = 21.5, 21.5), 0.3 (IQR = 0.3, 0.3), and 107.7 (IQR = 6.4, 1141.4) respectively. In multivariable analyses adjusting for the independent effect of other biomarkers and confounders (i.e. age of child at vaccination, breast-milk anti-rotavirus IgA, infant serum anti-rotavirus IgG, and IgA seropositivity at baseline), there was strong evidence of about 24% increase in seroconversion due to doubling Zonulin concentration (Adjusted risk ratio (aRR) = 1.24; 95% CI = 1.12 to1.37; pzonulin and IFABP

  5. Molecular characterization of rotavirus strains from pre- and post-vaccination periods in a country with low vaccination coverage: the case of Slovenia.

    Science.gov (United States)

    Steyer, Andrej; Sagadin, Martin; Kolenc, Marko; Poljšak-Prijatelj, Mateja

    2014-12-01

    Rotavirus vaccination started in Slovenia in 2007 on a voluntarily basis. The vaccination rate is relatively low (up to 27%) and no increasing trend is observed. We present rotavirus genotype distribution among children hospitalized for rotavirus gastroenteritis in Slovenia. Eight consecutive rotavirus seasons were followed, from 2005/06 to 2012/13, and 113 strains of the most common rotavirus genotypes were randomly selected for molecular characterization of rotavirus VP7 and VP4 (VP8(∗)) genome segments. During the vaccine introduction period, from 2007 to 2013, rotavirus genotype prevalences changed, with G1P[8] decreasing from 74.1% to 8.7% between 2007/08 and 2010/11 seasons, replaced by G4P[8] and G2P[4], with up to 52.0% prevalence. Comparable analysis of VP7 and VP8(∗) genome fragments within G1P[8] genotype lineages revealed considerable differences for rotavirus strains circulating before and during the vaccination period. The G1P[8] rotavirus strains from the pre-vaccination period clustered in a phylogenetic tree within Rotarix®-like VP7 and VP8(∗) lineages. However, since 2007, the majority of G1P[8] strains have shifted to distant genetic lineages with lower nucleotide (88.1-94.0% for VP7 and 86.6-91.1% for VP8(∗)) and amino acid (93.8-95.2% for VP7 and 85.3-94.6% for VP8(∗)) identities to the vaccine Rotarix® strain. This change also resulted in a different deduced amino acid profile at the major VP7 and VP8(∗) antigenic epitopes. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Protein-energy malnutrition alters IgA responses to rotavirus vaccination and infection but does not impair vaccine efficacy in mice.

    Science.gov (United States)

    Maier, Elizabeth A; Weage, Kristina J; Guedes, Marjorie M; Denson, Lee A; McNeal, Monica M; Bernstein, David I; Moore, Sean R

    2013-12-17

    Conflicting evidence links malnutrition to the reduced efficacy of rotavirus vaccines in developing countries, where diarrhea and undernutrition remain leading causes of child deaths. Here, we adapted mouse models of rotavirus vaccination (rhesus rotavirus, RRV), rotavirus infection (EDIM), and protein-energy malnutrition (PEM) to test the hypothesis that undernutrition reduces rotavirus vaccine immunogenicity and efficacy. We randomized wild type Balb/C dams with 3-day-old pups to a control diet (CD) or an isocaloric, multideficient regional basic diet (RBD) that produces PEM. At 3 weeks of age, we weaned CD and RBD pups to their dams' diet and subrandomized weanlings to receive a single dose of either live oral rotavirus vaccine (RRV) or PBS. At 6 weeks of age, we orally challenged all groups with murine rotavirus (EDIM). Serum and stool specimens were collected before and after RRV and EDIM administration to measure viral shedding and antibody responses by ELISA. RBD pups and weanlings exhibited significant failure to thrive compared to age-matched CD mice (Pvaccination induced higher levels of serum anti-RV IgA responses in RBD vs. CD mice (PVaccination protected CD and RBD mice equally against EDIM infection, as measured by viral shedding. In unvaccinated RBD mice, EDIM shedding peaked 1 day earlier (Pvaccination (Pvaccination mitigated stool IgA responses to EDIM more in CD vs. RBD mice (Pvaccination and infection, undernutrition does not impair rotavirus vaccine efficacy nor exacerbate infection in this mouse model of protein-energy malnutrition. Alternative models are needed to elucidate host-pathogen factors undermining rotavirus vaccine effectiveness in high-risk global settings. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Rotavirus Vaccination and the Risk of Celiac Disease or Type 1 Diabetes in Finnish Children at Early Life.

    Science.gov (United States)

    Vaarala, Outi; Jokinen, Jukka; Lahdenkari, Mika; Leino, Tuija

    2017-07-01

    Rotavirus infection has been suggested as a trigger of type 1 diabetes (T1D)-related autoimmunity and celiac disease (CD)-related autoimmunity. We carried out a nationwide, population-based cohort study evaluating whether prevention of rotavirus infection with vaccination affects the risk of CD and T1D diagnosed during 2009-2014 in Finnish children by comparing vaccinated and unvaccinated children in a cohort born in 2009-2010. Nationwide rotavirus vaccination records were collected from healthcare databases during 2009-2011 and validated for a sample of 495 children born from July 2009 to December 2009. Incident diagnoses of CD and T1D during 2009-2014 in the cohort were identified in the National Care Register. The adjusted relative risks (with 95% confidence intervals) were 0.91 (0.69-1.20) for T1D and 0.87 (0.65-1.17) for CD in vaccinated children compared with unvaccinated, suggesting that oral rotavirus vaccination does not alter the risk of CD or T1D during 4-6 years follow-up after vaccination. Our results suggest that oral rotavirus vaccination is considered safe in the individuals at risk of CD and T1D.

  8. Cost-effectiveness of rotavirus vaccination in Turkey

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    Tulin Koksal

    2017-10-01

    Conclusion: At a cost per vaccine course of US$31.5 for monovalent and US$38 for pentavalent vaccine, routine RV vaccination could be potentially cost effective and also cost saving in Turkey. National RV vaccinations will play a significant role in preventing RV infections.

  9. Correlates of protection for rotavirus vaccines: Possible alternative trial endpoints, opportunities, and challenges.

    Science.gov (United States)

    Angel, Juana; Steele, A Duncan; Franco, Manuel A

    2014-01-01

    Rotavirus (RV) is a major vaccine-preventable killer of young children worldwide. Two RV vaccines are globally commercially available and other vaccines are in different stages of development. Due to the absence of a suitable correlate of protection (CoP), all RV vaccine efficacy trials have had clinical endpoints. These trials represent an important challenge since RV vaccines have to be introduced in many different settings, placebo-controlled studies are unethical due to the availability of licensed vaccines, and comparator assessments for new vaccines with clinical endpoints are very large, complex, and expensive to conduct. A CoP as a surrogate endpoint would allow predictions of vaccine efficacy for new RV vaccines and enable a regulatory pathway, contributing to the more rapid development of new RV vaccines. The goal of this review is to summarize experiences from RV natural infection and vaccine studies to evaluate potential CoP for use as surrogate endpoints for assessment of new RV vaccines, and to explore challenges and opportunities in the field.

  10. The Impact of Rotavirus Vaccination on Discounted Net Tax Revenue in Egypt: A Government Perspective Analysis

    OpenAIRE

    Mark P. Connolly; Oleksandr Topachevskyi; Baudouin Standaert; Omayra Ortega; Maarten Postma

    2012-01-01

    Background:Background: We evaluated national rotavirus (RV) immunization programme costs to estimate how resulting changes in morbidity and mortality will influence government fiscal accounts over time. The assumption was that increased childhood survival in vaccinated cohorts leads to increased numbers of children consuming government resource, and an increased number of future tax payers. Abstract: Objective:Objective: Our objective was to evaluate the difference in lifetime discounted net ...

  11. Prenatal vitamin A deficiency impairs adaptive immune responses to pentavalent rotavirus vaccine (RotaTeq®) in a neonatal gnotobiotic pig model.

    Science.gov (United States)

    Kandasamy, Sukumar; Chattha, Kuldeep S; Vlasova, Anastasia N; Saif, Linda J

    2014-02-07

    Vitamin A deficiency (VAD) is associated with increased childhood mortality and morbidity in impoverished Asian and African countries, but the impact of VAD on rotavirus (RV) vaccine or infection is poorly understood. We assessed effects of gestational and dietary induced pre- and post-natal VAD and vitamin A supplementation on immune responses to a pentavalent rotavirus vaccine, RotaTeq(®) in a neonatal gnotobiotic pig model. Vaccine efficacy was assessed against virulent G1P[8] human rotavirus (HRV) challenge. VAD and vitamin A sufficient (VAS) piglets were derived from dietary VAD and VAS sows, respectively. VAD piglets had significantly lower levels of hepatic vitamin A compared to that of VAS piglets. RotaTeq(®)-vaccinated VAD piglets had 350-fold higher fecal virus shedding titers compared to vaccinated VAS piglets post-challenge. Only 25% of vaccinated non-vitamin A supplemented VAD piglets were protected against diarrhea compared with 100% protection rate in vaccinated non-supplemented VAS piglets post-challenge. Intestinal HRV specific immune responses were compromised in VAD piglets. Vaccinated VAD piglets had significantly lower ileal HRV IgG antibody secreting cell (ASC) responses (pre-challenge) and duodenal HRV IgA ASC responses (post-challenge) compared to vaccinated VAS piglets. Also, intestinal HRV IgA antibody titers were 11-fold lower in vaccinated VAD compared to vaccinated VAS piglets post-challenge. Persistently elevated levels of IL-8, a pro-inflammatory mediator, and lower IL-10 responses (anti-inflammatory) in vaccinated VAD compared to VAS piglets suggest more severe inflammatory responses in VAD piglets post-challenge. Moreover higher IFN-γ responses pre-challenge were observed in VAD compared to VAS piglets. The impaired vaccine-specific intestinal antibody responses and decreased immunoregulatory cytokine responses coincided with reduced protective efficacy of the RV vaccine against virulent HRV challenge in VAD piglets. In

  12. Inclusion of a universal tetanus toxoid CD4(+) T cell epitope P2 significantly enhanced the immunogenicity of recombinant rotavirus ΔVP8* subunit parenteral vaccines.

    Science.gov (United States)

    Wen, Xiaobo; Wen, Ke; Cao, Dianjun; Li, Guohua; Jones, Ronald W; Li, Jianping; Szu, Shousun; Hoshino, Yasutaka; Yuan, Lijuan

    2014-07-31

    Currently available live oral rotavirus vaccines, Rotarix(®) and RotaTeq(®), are highly efficacious in developed countries. However, the immunogenicity and efficacy of such vaccines in some developing countries are low. We reported previously that bacterially-expressed rotavirus ΔVP8* subunit vaccine candidates with P[8], P[4] or P[6] specificity elicited high-titer virus neutralizing antibodies in animals immunized intramuscularly. Of note was the finding that antibodies induced with the P[8]ΔVP8* vaccine neutralized both homotypic P[8] and heterotypic P[4] rotavirus strains to high titer. To further improve its vaccine potential, a tetanus toxoid universal CD4(+) T cell epitope P2 was introduced into P[8] or P[6]ΔVP8* construct. The resulting recombinant fusion proteins expressed in Escherichia coli were of high solubility and were produced with high yield. Two doses (10 or 20 μg/dose) of the P2-P[8]ΔVP8* vaccine or P2-P[6]ΔVP8* vaccine with aluminum phosphate adjuvant elicited significantly higher geometric mean homologous neutralizing antibody titers than the vaccines without P2 in intramuscularly immunized guinea pigs. Interestingly, high levels of neutralizing antibody responses induced in guinea pigs with 3 doses of the P2-P[8]ΔVP8* vaccine persisted for at least 6 months. Furthermore, in the gnotobiotic piglet challenge study, three intramuscular doses (50 μg/dose) of the P2-P[8]ΔVP8* vaccine with aluminum phosphate adjuvant significantly delayed the onset of diarrhea and significantly reduced the duration of diarrhea and the cumulative diarrhea score after oral challenge with virulent human rotavirus Wa (G1P[8]) strain. The P2-P[8]ΔVP8* vaccine induced serum virus neutralizing antibody and VP4-specific IgG antibody production prechallenge, and primed the pigs for higher antibody and intestinal and systemic virus-specific IFN-γ producing CD4(+) T cell responses postchallenge. These two subunit vaccines could be used at a minimum singly or

  13. A qualitative assessment of factors influencing acceptance of a new rotavirus vaccine among health care providers and consumers

    Directory of Open Access Journals (Sweden)

    Herring Mark

    2007-10-01

    Full Text Available Abstract Background In 2006, a new rotavirus vaccine (RotaTeq was licensed in the US and recommended for routine immunization of all US infants. Because a previously licensed vaccine (Rotashield was withdrawn from the US for safety concerns, identifying barriers to uptake of RotaTeq will help develop strategies to broaden vaccine coverage. Methods We explored beliefs and attitudes of parents (n = 57 and providers (n = 10 towards rotavirus disease and vaccines through a qualitative assessment using focus groups and in-depth interviews. Results All physicians were familiar with safety concerns about rotavirus vaccines, but felt reassured by RotaTeq's safety profile. When asked about likelihood of using RotaTeq on a scale of one to seven (1 = "absolutely not;" 7 = "absolutely yes" the mean score was 5 (range = 3–6. Physicians expressed a high likelihood of adopting RotaTeq, particularly if recommended by their professional organizations and expressed specific interest in post-marketing safety data. Similarly, consumers found the RotaTeq safety profile to be favorable and would rely on their physician's recommendation for vaccination. However, when asked to rank likelihood of having their child vaccinated against rotavirus (1 = "definitely not get;" 7 = "definitely get", 29% ranked 1 or 2, 36% 3 or 4, and 35% 5 to 7. Conclusion Our qualitative assessment provides complementary data to recent quantitative surveys and suggests that physicians and parents are likely to adopt the newly licensed rotavirus vaccine. Increasing parental awareness of the rotavirus disease burden and providing physicians with timely post-marketing surveillance data will be integral to a successful vaccination program.

  14. Significant Correlation Between the Infant Gut Microbiome and Rotavirus Vaccine Response in Rural Ghana.

    Science.gov (United States)

    Harris, Vanessa C; Armah, George; Fuentes, Susana; Korpela, Katri E; Parashar, Umesh; Victor, John C; Tate, Jacqueline; de Weerth, Carolina; Giaquinto, Carlo; Wiersinga, Willem Joost; Lewis, Kristen D C; de Vos, Willem M

    2017-01-01

    Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and 95% of RV-associated deaths occur in Africa and Asia where RV vaccines (RVVs) have lower efficacy. We hypothesize that differences in intestinal microbiome composition correlate with the decreased RVV efficacy observed in poor settings.  We conducted a nested, case-control study comparing prevaccination, fecal microbiome compositions between 6-week old, matched RVV responders and nonresponders in rural Ghana. These infants' microbiomes were then compared with 154 age-matched, healthy Dutch infants' microbiomes, assumed to be RVV responders. Fecal microbiome analysis was performed in all groups using the Human Intestinal Tract Chip.  We analyzed findings in 78 Ghanaian infants, including 39 RVV responder and nonresponder pairs. The overall microbiome composition was significantly different between RVV responders and nonresponders (FDR, 0.12), and Ghanaian responders were more similar to Dutch infants than nonresponders (P = .002). RVV response correlated with an increased abundance of Streptococcus bovis and a decreased abundance of the Bacteroidetes phylum in comparisons between both Ghanaian RVV responders and nonresponders (FDR, 0.008 vs 0.003) and Dutch infants and Ghanaian nonresponders (FDR, 0.002 vs 0.009).  The intestinal microbiome composition correlates significantly with RVV immunogenicity and may contribute to the diminished RVV immunogenicity observed in developing countries. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  15. Intervention analysis of introduction of rotavirus vaccine on hospital admissions rates due to acute diarrhea

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    Maria de Lourdes Teixeira Masukawa

    2014-10-01

    Full Text Available The aim of this study is to investigate the impact of rotavirus vaccine on hospitalization rates for acute diarrhea in children younger than 5 years old after the introduction of the vaccine in 2006. A descriptive analytical observational study was carried out of the hospitalization rates occurred between 2000 and 2011 in 22 Regional Health Centers of Paraná State, Brazil. The effect of the vaccine was assessed by applying the SARIMA/Box-Jenkins time series methodology of intervention analysis, which allows verifying the slopes of the series are different after the introduction of the vaccine and estimating the magnitude of these effects for children younger than five years of age, by age group, for each region center. It was verified a statistically significant reduction by center/month on hospitalization rates for children 1 year old and younger, with averages of 47% and 58%, respectively, in December 2011.

  16. Estimating the costs of implementing the rotavirus vaccine in the national immunisation programme: the case of Malawi

    DEFF Research Database (Denmark)

    Madsen, Lizell Bustamante; Ustrup, Marte; Hansen, Karsten S.

    2014-01-01

    in the national immunisation programme of a low-income country. Furthermore, the aim was to examine the relative contribution of different components to the total cost. methods Following the World Health Organization guidelines, we estimated the resource use and costs associated with rotavirus vaccine...... implementation, using Malawi as a case. The cost analysis was undertaken from a governmental perspective. All costs were calculated for a 5-years period (2012–2016) and discounted at 5%. The value of key input parameters was varied in a sensitivity analysis. results The total cost of rotavirus vaccine...... purchase, while 17% was attributed to system costs, with personnel, transportation and cold chain as the main cost components. conclusion The total cost of rotavirus vaccine implementation in Malawi is high compared with the governmental health budget of US$ 26 per capita per year. This highlights the need...

  17. Economic impact of a rotavirus vaccination program in Mexico Impacto económico de un programa de vacunación contra rotavirus en México

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    Dagna Constenla

    2009-06-01

    Full Text Available OBJECTIVES: To evaluate the cost and benefits of a national rotavirus childhood vaccination program in Mexico. METHODS: A decision-analysis model was designed to take the Mexican health care system's perspective on a comparison of two alternatives: to vaccinate against rotavirus or not. Using published, national data, estimations were calculated for the rotavirus illnesses, deaths, and disability-adjusted life years (DALYs that would be averted and the incremental costeffectiveness ratios (US$/DALY of a hypothetical annual birth cohort of 2 285 000 children, with certain assumptions made for cost, coverage, and efficacy rates. RESULTS: With 93% coverage and a vaccine price of US$ 16 per course (2 doses, a rotavirus vaccination program in Mexico would prevent an estimated 651 deaths (or 0.28 deaths per 1 000 children; 13 833 hospitalizations (6.05 hospitalizations per 1 000 children; and 414 927 outpatient visits (182 outpatient visits per 1 000 children for rotavirus-related acute gastroenteritis (AGE. Vaccination is likely to reduce the economic burden of rotavirus AGE in Mexico by averting US$ 14 million (71% of the overall health care burden. At a vaccine price of US$ 16 per course, the cost-effectiveness ratio would be US$ 1 139 per DALY averted. A reduction in the price of the rotavirus vaccination program (US$ 8 per course would yield a lower incremental cost-effectiveness ratio of US$ 303 per DALY averted. CONCLUSIONS: A national rotavirus vaccination program in Mexico is projected to reduce childhood incidence and mortality and to be highly cost-effective based on the World Health Organization's thresholds for cost-effective interventions.OBJETIVOS: Evaluar el costo y los beneficios de un programa nacional de vacunación infantil contra el rotavirus en México. MÉTODOS: Se diseñó un modelo de análisis de decisión, desde la perspectiva del sistema de salud mexicano, para comparar dos alternativas: vacunar contra el rotavirus o no

  18. Rotavirus diarrhea disease burden in Peru: the need for a rotavirus vaccine and its potential cost savings Carga de morbilidad de la diarrea por rotavirus en Perú: la necesidad de una vacuna y su potencial de ahorro

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    Peter Ehrenkranz

    2001-10-01

    Full Text Available Objective. To assess the disease burden of rotavirus diarrhea in Peru as well the need for and the potential cost savings with a rotavirus vaccine in that country. Methods. To assess the burden of rotavirus diarrhea in Peru, we reviewed published and unpublished reports where rotavirus was sought as the etiologic agent of diarrhea in children. Rotavirus detection rates obtained from these studies were combined with diarrhea incidence rates from a number of national surveys in order to estimate both the burden of rotavirus diarrhea in the country and its associated medical costs. Results. Rotavirus is a significant cause of morbidity and mortality in Peruvian children. In their first 5 years of life, an estimated 1 in 1.6 children will experience an episode of rotavirus diarrhea, 1 in 9.4 will seek medical care, 1 in 19.7 will require hospitalization, and 1 in 375 will die of the disease. Per year, this represents approximately 384 000 cases, 64 000 clinic visits, 30 000 hospitalizations, and 1 600 deaths. The annual cost of medical care alone for these children is approximately US$ 2.6 million--and that does not take into account the indirect or societal costs of the illness and the deaths. Conclusions. Rotavirus immunization provides the prospect of decreasing the morbidity and mortality from diarrhea in Peru, but a vaccine regimen would have to be relatively inexpensive, a few dollars or less per child. Future cost-effectiveness analyses should explore the total costs (medical as well as indirect or societal associated with rotavirus diarrhea. Newly licensed vaccines should be tested according to both their ability to avert deaths and their efficacy with fewer than three doses. All three of these factors could increase the cost savings associated with a rotavirus vaccine.Objetivos. Evaluar la carga de morbilidad de la diarrea por rotavirus en Perú, la necesidad de una vacuna y el ahorro que esta podría proporcionar en este país. M

  19. Cost-effectiveness analysis of rotavirus vaccination in China: Projected possibility of scale-up from the current domestic option

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    Shuhui Cui

    2016-11-01

    Full Text Available Abstract Background Rotavirus infection causes considerable disease burden of acute gastroenteritis (AGE hospitalization and death among children less than 5 years in China. Although two rotavirus vaccines (Rotarix and RotaTeq have been licensed in more than 100 countries in the world, the Lanzhou Lamb rotavirus vaccine (LLR is the only vaccine licensed in China. This study aims to forecast the potential impacts of the two international vaccines compared to domestic LLR. Methods An economic evaluation was performed using a Markov simulation model. We compared costs at the societal aspect and health impacts with and without a vaccination program by LLR, Rotarix or RotaTeq. Parameters including demographic, epidemiological data, costs and efficacy of vaccines were obtained from literature review. The model incorporated the impact of vaccination on reduction of incidence of rotavirus infection and severity of AGE indicated by hospitalization, inpatient visits and deaths. Outcomes are presented in terms of quality-adjusted life years (QALYs gained and incremental cost-effectiveness ratio (ICER compared to status quo. Results In a hypothetical cohort of 100,000 infants, the two international vaccines showed very good cost-effectiveness, with ICER of Rotateq and Rotarix shifting from LLR of $1715.11/QALY and $2105.66/QALY, respectively. Rotateq and Rotarix had significantly decreased incidence compared to LLR, particularly among infants aged 6 months to 2 years. Conclusions RotaTeq is expected to introduce in the national routine immunization program to reduce disease burden of rotavirus infection with universal coverage.

  20. Evidence for presumable feline origin of sporadic G6P[9] rotaviruses in humans.

    Science.gov (United States)

    Pietsch, Corinna; Liebert, Uwe G

    2018-05-31

    Species A rotaviruses are highly diverse and impose a substantial burden to human and animal health. Interspecies transmission between livestock, domestic animals and humans is commonly observed, but spread of animal-like rotaviruses within the human population is limited. During the continued monitoring of rotavirus strains in Germany, an unusual G6P[9] rotavirus strain was detected in feces of a child. The complete rotavirus coding sequences revealed a unique G6-P[9]-I2-R2-C2-M2-A3-N2-T3-E2-H3 genotype constellation. The virus was phylogenetically related to feline G3P[9] strains and other human G6P[9] rotaviruses of presumable zoonotic origin. Analysis of primer binding sites of G6 specific genotyping revealed further evidence of a G6P[9] feline reservoir. Moreover, substantial deficits of conventional semi-nested PCR genotyping approaches in detecting contemporary G6P[9] were revealed. Rotavirus strain GER29-14 most likely resulted from a direct or recent interspecies transmission from a cat to human. Further studies could assess nucleic acid sequences and genotype constellations of feline rotavirus to confirm the likely feline origin of sporadic human G6P[9] strains. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Secondary efficacy endpoints of the pentavalent rotavirus vaccine against gastroenteritis in sub-Saharan Africa.

    Science.gov (United States)

    Tapia, Milagritos D; Armah, George; Breiman, Robert F; Dallas, Michael J; Lewis, Kristen D C; Sow, Samba O; Rivers, Stephen B; Levine, Myron M; Laserson, Kayla F; Feikin, Daniel R; Victor, John C; Ciarlet, Max; Neuzil, Kathleen M; Steele, A Duncan

    2012-04-27

    The efficacy of the pentavalent rotavirus vaccine (PRV), RotaTeq(®), was evaluated in a double-blind, placebo-controlled, multicenter Phase III clinical trial conducted (April 2007-March 2009) in 3 low-income countries in Africa: Ghana, Kenya, and Mali. In total, 5468 infants were randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6, 10, and 14 weeks of age; concomitant administration with routine EPI vaccines, including OPV, was allowed. HIV-infected infants were not excluded. The primary endpoint, vaccine efficacy (VE) against severe-rotavirus gastroenteritis (RVGE), as measured by Vesikari scoring system (VSS, score ≥11), from ≥14 days following Dose 3 through a follow-up period of nearly 2 years in the combined 3 African countries, and secondary endpoints by total follow-up period have been previously reported. In this study, we report post hoc subgroup analyses on secondary endpoints of public health importance. VE against RVGE of any severity was 49.2% (95%CI: 29.9, 63.5) through the first year of life and 30.5% (95%CI: 16.7, 42.2) through the complete follow-up period. VE against severe-gastroenteritis of any etiology was 21.5% (95%CI: vaccine-contained G and P types (G1-G4, P1A[8]), (ii) non-vaccine G types (G8, G9, G10), and (iii) non-vaccine P types (P1B[4], P2A[6]) was 34.0% (95%CI:11.2, 51.2), 81.8% (95%CI:16.5, 98.0) and 40.7% (95%CI:8.4, 62.1), respectively. There was a trend towards higher VE with higher disease severity, although in some cases the numbers were small. In African countries with high under-5 mortality rates, PRV significantly reduced RVGE through nearly 2 years of follow-up; more modest reductions were observed against gastroenteritis of any etiology. PRV provides protection against severe-RVGE caused by diverse rotavirus genotypes, including those not contained in the vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Molecular characterization of a human G20P[28] rotavirus a strain with multiple genes related to bat rotaviruses.

    Science.gov (United States)

    Esona, Mathew D; Roy, Sunando; Rungsrisuriyachai, Kunchala; Gautam, Rashi; Hermelijn, Sandra; Rey-Benito, Gloria; Bowen, Michael D

    2018-01-01

    Group A rotaviruses are the major cause of severe gastroenteritis in the young of mammals and birds. This report describes characterization of an unusual G20P[28] rotavirus strain detected in a 24month old child from Suriname. Genomic sequence analyses revealed that the genotype constellation of the Suriname strain RVA/Human-wt/SUR/2014735512/2013/G20P[28] was G20-P[28]-I13-R13-C13-M12-A23-N13-T15-E20-H15. Genes VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5 were recently assigned novel genotypes by the Rotavirus Classification Working Group (RCWG). Three of the 11 gene segments (VP7, VP4, VP6) were similar to cognate gene sequences of bat-like human rotavirus strain Ecu534 from Ecuador and the VP7, NSP3 and NSP5 gene segments of strain RVA/Human-wt/SUR/2014735512/2013/G20P[28] were found to be closely related to gene sequences of bat rotavirus strain 3081/BRA detected in Brazil. Although distantly related, the VP1 gene of the study strain and bat strain BatLi09 detected in Cameroon in 2014 are monophyletic. The NSP1 gene was found to be most closely related to human strain QUI-35-F5 from Brazil. These findings suggest that strain RVA/Human-wt/SUR/2014735512/2013/G20P[28] represents a zoonotic infection from a bat host. Published by Elsevier B.V.

  3. Ecological assessment of the direct and indirect effects of routine rotavirus vaccination in Merseyside, UK using data from multiple health systems: a study protocol.

    Science.gov (United States)

    Hungerford, Daniel; Vivancos, Roberto; French, Neil; Iturriza-Gomara, Miren; Cunliffe, Nigel

    2014-11-25

    Rotavirus is the most common cause of severe gastroenteritis in infants and young children worldwide. Currently 67 countries include rotavirus vaccine in childhood immunisation programmes, but uptake in Western Europe has been slow. In July 2013, rotavirus vaccine was introduced into the UK's routine childhood immunisation programme. Prior to vaccine introduction in the UK, rotavirus was estimated to result in 750,000 diarrhoea episodes and 80,000 general practice (GP) consultations each year, together with 45% and 20% of hospital admissions and emergency department attendances for acute gastroenteritis, in children under 5 years of age. This paper describes a protocol for an ecological study that will assess rotavirus vaccine impact in the UK, to inform rotavirus immunisation policy in the UK and in other Western European countries. In Merseyside, UK, we will conduct an ecological study using a 'before and after' approach to examine changes in gastroenteritis and rotavirus incidence following the introduction of rotavirus vaccination. Data will be collected on mortality, hospital admissions, nosocomial infection, emergency department attendances, GP consultations and community health consultations to capture all healthcare providers in the region. We will assess both the direct and indirect effects of the vaccine on the study population. Comparisons of outcome indicator rates will be made in relation to vaccine uptake and socioeconomic status. The study has been approved by NHS Research Ethics Committee, South Central-Berkshire REC Reference: 14/SC/1140. Study outputs will be disseminated through scientific conferences and peer-reviewed publications. The study will demonstrate the impact of rotavirus vaccination on the burden of disease from a complete health system perspective. It will identify key areas that require improved data collection tools to maximise the usefulness of this surveillance approach and will provide a template for vaccine evaluations using

  4. Human rotavirus strain Wa downregulates NHE1 and NHE6 expressions in rotavirus-infected Caco-2 cells.

    Science.gov (United States)

    Chen, Honglang; Song, Lijun; Li, Guixian; Chen, Wenfeng; Zhao, Shumin; Zhou, Ruoxia; Shi, Xiaoying; Peng, Zhenying; Zhao, Wenchang

    2017-06-01

    Rotavirus (RV) is the most common cause of severe gastroenteritis and fatal dehydration in human infants and neonates of different species. However, the pathogenesis of rotavirus-induced diarrhea is poorly understood. Secretory diarrhea caused by rotavirus may lead to a combination of excessive secretion of fluid and electrolytes into the intestinal lumen. Fluid absorption in the small intestine is driven by Na + -coupled transport mechanisms at the luminal membrane, including Na + /H + exchanger (NHE). Here, we performed qRT-PCR to detect the transcription of NHEs. Western blotting was employed for protein detection. Furthermore, immunocytochemistry was used to validate the NHE's protein expression. Finally, intracellular Ca 2+ concentration was detected by confocal laser scanning microscopy. The results demonstrated that the NHE6 mRNA and protein expressed in the human colon adenocarcinoma cell line (Caco-2). Furthermore, RV-Wa induced decreased expression of the NHE1 and NHE6 in Caco-2 cell in a time-dependent manner. In addition, intracellular Ca 2+ concentration in RV-Wa-infected Caco-2 cells was higher than that in the mock-infected cells. Furthermore, RV-Wa also can downregulate the expression of calmodulin (CaM) and calmodulin kinase II (CaMKII) in Caco-2 cells. These findings provides important insights into the mechanisms of rotavirus-induced diarrhea. Further studies on the underlying pathophysiological mechanisms that downregulate NHEs in RV-induced diarrhea are required.

  5. Active surveillance for intussusception in a phase III efficacy trial of an oral monovalent rotavirus vaccine in India.

    Science.gov (United States)

    John, Jacob; Kawade, Anand; Rongsen-Chandola, Temsunaro; Bavdekar, Ashish; Bhandari, Nita; Taneja, Sunita; Antony, Kalpana; Bhatnagar, Veereshwar; Gupta, Arun; Kabra, Madhulika; Kang, Gagandeep

    2014-08-11

    Post licensure studies have identified an increased risk of intussusception following vaccination with currently licensed rotavirus vaccines, raising safety concerns generic to all rotavirus vaccines. We describe the surveillance for intussusception in a phase III clinical trial with an oral monovalent rotavirus vaccine developed from the neonatal 116E strain. Using broad screening criteria and active surveillance, the incidence of intussusception between 6 weeks and 2 years of age was measured in 4532 children who received three doses of vaccine and 2267 children who received a placebo in the clinical trial. Possible intussusceptions were evaluated with a screening ultrasonogram. An independent intussusception case adjudication committee reviewed all intussusceptions and graded them on Brighton Collaboration criteria for diagnostic certainty. We identified twenty-three intussusceptions on ultrasound from 1361 evaluated sentinel events. Eleven were of level 1 diagnostic certainty as determined by the independent intussusception case adjudication committee. None required surgical intervention, and the earliest identified intussusception was at 36 days following the third dose in a placebo recipient. Among vaccine recipients the first event of intussusception occurred 112 days after the third dose. The incidence of ultrasound-diagnosed intussusception was 200/100,000 child-years (95% CI, 120, 320) among those receiving the vaccine and 141/100,000 child-years (95% CI, 50, 310) among those receiving the placebo. The incidence rate of confirmed intussusception among vaccine recipients was 94/100,000 child-years (95% CI, 41, 185) and 71/100,000 child-years (95% CI, 15, 206) among those receiving the placebo. In this licensure study, 23 cases of intussusception were identified through an active surveillance system, but there was no temporal association with rotavirus vaccination. The use of active surveillance with broad criteria intended for ensuring safety of children

  6. Rotavirus infection in Saudi Arabia

    International Nuclear Information System (INIS)

    Kheyami, Ali M.; Cunliffe, Nigel A.; Hart, C. Anthony

    2006-01-01

    Human rotavirus, an important causative agent of severe gastroenteritis in infants and young children worldwide, leads to high morbidity in both developing and developed countries. Effective control depends upon an accurate understanding of disease burden and the relative importance of circulating serotypes. We examined the epidemiology and disease burden of rotavirus in Saudi Arabia through a review of 22 published studies of rotavirus and the antilogy diarrhea carried out from 1982 to 2003. The prevalence of rotavirus ranged between 10% to 46% with a median of 30%. Most cases were among children less than 2 years of age, and particularly in first year of life. There were significant differences in the seasonability within Saudi Arabia with increased infection during winter in some cities and during summer in others. G1 was the predominant serotype followed by G4, G3 and G2, in 4 studies where strains have been G-typed. The prevalence of noticeable strains ranged from 11.0% to 31.3%. No data were available on P types... Results of electropherotyping in 4 studies revealed that the long elctropherotype was predominant. Rotavirus is an important cause of severe diarrhea in Saudi children. However, the available data on rotavirus strains in circulation are limited. And there is an urgent need for up-to-date and comprehensive studies to evaluate rotavirus strains in circulation and identify unusual types that could be incorporated into future vaccines. (author)

  7. Baseline incidence of intussusception in early childhood before rotavirus vaccine introduction, the netherlands, january 2008 to december 2012

    NARCIS (Netherlands)

    Gadroen, Kartini; Kemmeren, Jeanet M.; Bruijning-Verhagen, P. C.; Straus, Sabine M J M; Weibel, Daniel; de Melker, Hester E.; Sturkenboom, M. C.

    2017-01-01

    Intussusception is a rare, potentially life-threatening condition in early childhood. It gained attention due to an unexpected association with the first rotavirus vaccine, RotaShield, which was subsequently withdrawn from the market. Across Europe, broad variations in intussusception incidence

  8. Baseline incidence of intussusception in early childhood before rotavirus vaccine introduction, the Netherlands, January 2008 to December 2012.

    NARCIS (Netherlands)

    Gadroen, Kartini; Kemmeren, Jeanet M; Bruijning-Verhagen, Patricia Cj; Straus, Sabine Mjm; Weibel, Daniel; de Melker, Hester E; Sturkenboom, Miriam Cjm

    2017-01-01

    Intussusception is a rare, potentially life-threatening condition in early childhood. It gained attention due to an unexpected association with the first rotavirus vaccine, RotaShield, which was subsequently withdrawn from the market. Across Europe, broad variations in intussusception incidence

  9. Subunit Vaccine Preparation of Bovine Rotavirus and Its Efficacy in Mice.

    Science.gov (United States)

    Suocheng, Wei; Tuanjie, Che; Changjun, Song; Fengling, Tian; Zhongren, Ma

    2015-09-01

    Rotaviruses (RV) are important viral diarrheal agents in calves. Vaccination is an optimum measure to prevent bovine rotaviruses (BRV) infection. However, little research on BRV VP7 vaccine has been done and currently there is no BRV vaccine. To prepare a subunit vaccine of BRV and investigate its efficacy. Total RNA was extracted from MA104 cells infected with bovine rotavirus (BRV) strain GSB01. BRV VP7 gene was amplified using real time fluorescence quantitative PCR (qPCR). The pEASY-T3-VP7 plasmid was digested using HindⅢ and BamHI restriction endonucleases, then recombined into the prokaryotic expression vector pET32a. The pET32a-VP7 and pET32a-VP7-LTB (heat-labile enterotoxin B subunit) were transformed into BL21 (DE3) competent cells of Escherichia coli, respectively, and induced with IPTG, then analyzed using SDS-PAGE. Sixty mice were randomly divided into three groups (n=20). Group A mice was used as His-tag control and mice in group B and C were inoculated with pET32a-VP7 and pET32a-VP7-LTB, respectively. VP7 IgG antibody titers and protection efficiency of pET32a-VP7-LTB were further determined in neonatal mice challenged with GSB01 BRV strain. SDS-PAGE analysis showed that the pET32a-VP7 was highly expressed in the BL21 (DE3) cells. PET32a-VP7 and pET32a-VP7-LTB protein could promote VP7 IgG antibody titer(8.33×103 vs. 17.26×103)in mice. Immunization protection ratios of pET32a-VP7 and pET32a-VP7-LTB proteins in the neonatal mice were 86.4% and 91.7%, respectively. The fusion protein of pET32a-VP7-LTB had excellent immunogenicity and protected mice from BRV infection. Our findings can be used for further developing of a high-efficiency subunit vaccine of BRV.

  10. Anticipating rotavirus vaccines: review of epidemiologic studies of rotavirus diarrhea in Argentina En anticipación de una vacuna antirrotavirus: revisión de estudios epidemiológicos sobre la diarrea por rotavirus en la Argentina

    Directory of Open Access Journals (Sweden)

    Jorge A. Gómez

    1998-02-01

    Full Text Available Rotavirus is the most common cause of severe diarrhea in children worldwide, and vaccines currently being field-tested could be available for childhood immunization in several years. To assess the rotavirus disease burden in Argentina and the value of future national surveillance for the disease, we reviewed available data on rotavirus detections reported by published and unpublished studies conducted in nine Argentine cities and by a multicenter study. Data from these studies indicated that rotavirus was detected in 20% of 5 226 specimens (within a range of 6% to 54% for different studies from children hospitalized for diarrhea and in 9% of 6 587 specimens (within a range of 5% to 22% for different studies from children who were outpatients, members of mixed populations (hospitalized patients and outpatients, or survey subjects in community-based studies. The hospital data showed that while rotavirus was detected throughout the year, a peak occurred during the winter months (May­July, when up to half of the children with diarrhea were found positive for rotavirus. Attempted serotyping of 294 rotavirus-positive specimens for G-protein by three laboratories was successful in 230 cases (78%; the resulting data indicated that serotype G1 was the most common (being present in 60% of the successfully serotyped specimens, followed by G2 (in 20%, G4 (in 14%, and G3 (in 5%. Based on national data for Argentina, we estimate that in 1991 there were roughly 84 500 rotavirus-associated outpatient visits (1 for every 8 births and 21 000 hospitalizations averaging 4 days in length (1 for every 31 births, all of which entailed direct medical costs estimated at US$ 27.7 million. These preliminary data show that the rotavirus disease burden in Argentine children is extensive and could be decreased by a safe and effective vaccine. Further surveillance is needed to improve our understanding of the epidemiology and distribution of rotavirus strains in Argentina

  11. Effectiveness of rotavirus pentavalent vaccine under a universal immunization programme in Israel, 2011-2015: a case-control study.

    Science.gov (United States)

    Muhsen, K; Anis, E; Rubinstein, U; Kassem, E; Goren, S; Shulman, L M; Ephros, M; Cohen, D

    2018-01-01

    The use of rotavirus pentavalent vaccine (RotaTeq ® ) as a sole vaccine within rotavirus universal immunization programmes remains limited. We examined the effectiveness of RotaTeq in preventing rotavirus gastroenteritis (RVGE) hospitalization in Israel, after the introduction of universal immunization against the disease. A test-negative case-control study included age-eligible children for universal RotaTeq immunization (aged 2-59 months, born in 2011-2015). Cases (n = 98) were patients who tested positive for rotavirus by immunochromatography; those who tested negative (n = 628) comprised the control group. Information on rotavirus immunization history was obtained through linkage with a national immunization registry. Vaccination status was compared between cases and controls, adjusted odds ratios (aORs) were obtained from logistic regression models, and vaccine effectiveness calculated as (1 - aOR)*100. Immunization with RotaTeq was less frequent in RVGE cases (73.5%) than in controls (90.1%), p < 0.001; this association persisted after controlling for potential confounders. Effectiveness of the complete vaccine series was estimated at 77% (95% confidence interval (CI): 49-90) in children aged 6-59 months, and 86% (95% CI: 65-94) in children aged 6-23 months; whereas for the incomplete series, the respective estimates were 72% (95% CI: 28-89) and 75% (95% CI: 30-91). Vaccine effectiveness was estimated at 79% (95% CI: 45-92) against G1P[8]-associated RVGE hospitalizations and 69% (95% CI: 11-89) against other genotype-RVGE hospitalizations. High effectiveness of RotaTeq as the sole rotavirus vaccine in a universal immunization programme was demonstrated in a high-income country. Although partial vaccination conferred protection, completing the vaccine series is warranted to maximize the benefit. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  12. Inactivation of human and simian rotaviruses by chlorine dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yu-Shiaw (Brookhaven National Lab., Upton, NY (USA)); Vaughn, J.M. (Univ. of New England College of Medicine, Biddeford, ME (USA))

    1990-05-01

    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{degree}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{sup 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 a 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.

  13. Efficacy of pentavalent rotavirus vaccine in a high HIV prevalence population in Kenya.

    Science.gov (United States)

    Feikin, Daniel R; Laserson, Kayla F; Ojwando, Joel; Nyambane, Geoffrey; Ssempijja, Victor; Audi, Allan; Nyakundi, Daveline; Oyieko, Janet; Dallas, Michael J; Ciarlet, Max; Neuzil, Kathleen M; Breiman, Robert F

    2012-04-27

    Rotavirus gastroenteritis (RVGE) is a leading cause of death in African children. The efficacy of pentavalent rotavirus vaccine (PRV) against severe RVGE evaluated in Ghana, Kenya, and Mali in a randomized, double-blind, placebo-controlled trial, showed a combined regional efficacy of 39.3% (95% confidence interval [CI]: 19.1,54.7) in nearly 2 years of follow-up. This report concentrates on the Kenya findings. Infants received 3 doses of PRV/placebo at approximately 6-, 10-, and 14-weeks of age. HIV testing was offered to all participants. Data on illness symptoms and signs were collected upon presentation to healthcare facilities, where stools were collected, and analyzed by rotavirus-specific enzyme-linked immunosorbent assay. The primary endpoint was severe RVGE (Vesikari score ≥ 11), occurring ≥ 14 days following the third dose. At monthly home visits, symptoms of illnesses during the past 2 weeks were solicited and limited physical exams were performed; dehydration was defined by WHO's Integrated Management of Childhood Illness. Vaccine efficacy (VE) against severe RVGE through nearly 2 years of follow-up among 1308 Kenyan children was 63.9% (95% CI: -5.9,89.8). Through the first year of life, VE against severe RVGE was 83.4% (95% CI: 25.5,98.2). From home visits, VE against all-cause gastroenteritis with severe dehydration was 34.4% (95% CI: 5.3,54.6) through the first year and 29.7% (95% CI: 2.5,49.3) through the entire follow-up period. The reduction in incidence of gastroenteritis with severe dehydration in the community during the first year of life (19.0 cases/100 person-years) was almost six times greater than the reduction in severe RVGE presenting to the clinic (3.3/100 person-years). Oral rehydration solution use was lower among PRV recipients (VE 23.1%, 95% CI: 8.8,35.1). An estimated 41% of gastroenteritis with severe dehydration in the first year reported at home was rotavirus-related. PRV significantly reduced severe RVGE in Kenya. The impact

  14. Correlates of protection against human rotavirus disease and the factors influencing protection in low-income settings.

    Science.gov (United States)

    Clarke, E; Desselberger, U

    2015-01-01

    Rotaviruses (RV) are the leading cause of gastroenteritis in infants and children worldwide and are associated with high mortality predominately in low-income settings. The virus is classified into G and P serotypes and further into P genotypes based on differences in the surface-exposed proteins VP7 and VP4, respectively. Infection results in a variable level of protection from subsequent reinfection and disease. This protection is predominantly homotypic in some settings, whereas broader heterotypic protection is reported in other cohorts. Two antigenically distinct oral RV vaccines are licensed and are being rolled out widely, including in resource-poor setting, with funding provided by the GAVI alliance. First is a monovalent vaccine derived from a live-attenuated human RV strain, whereas the second is a pentavalent bovine-human reassortment vaccine. Both vaccines are highly efficacious in high-income settings, but greatly reduced levels of protection are reported in low-income countries. Here, the current challenges facing mucosal immunologists and vaccinologists aiming to define immunological correlates and to understand the variable levels of protection conferred by these vaccines in humans is considered. Such understanding is critical to maximize the public health impact of the current vaccines and also to the development of the next generation of RV vaccines, which are needed.

  15. 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

  16. Impact of enterovirus and other enteric pathogens on oral polio and rotavirus vaccine performance in Bangladeshi infants.

    Science.gov (United States)

    Taniuchi, Mami; Platts-Mills, James A; Begum, Sharmin; Uddin, Md Jashim; Sobuz, Shihab U; Liu, Jie; Kirkpatrick, Beth D; Colgate, E Ross; Carmolli, Marya P; Dickson, Dorothy M; Nayak, Uma; Haque, Rashidul; Petri, William A; Houpt, Eric R

    2016-06-08

    Oral polio vaccine (OPV) and rotavirus vaccine (RV) exhibit poorer performance in low-income settings compared to high-income settings. Prior studies have suggested an inhibitory effect of concurrent non-polio enterovirus (NPEV) infection, but the impact of other enteric infections has not been comprehensively evaluated. In urban Bangladesh, we tested stools for a broad range of enteric viruses, bacteria, parasites, and fungi by quantitative PCR from infants at weeks 6 and 10 of life, coincident with the first OPV and RV administration respectively, and examined the association between enteropathogen quantity and subsequent OPV serum neutralizing titers, serum rotavirus IgA, and rotavirus diarrhea. Campylobacter and enterovirus (EV) quantity at the time of administration of the first dose of OPV was associated with lower OPV1-2 serum neutralizing titers, while enterovirus quantity was also associated with diminished rotavirus IgA (-0.08 change in log titer per tenfold increase in quantity; P=0.037), failure to seroconvert (OR 0.78, 95% CI: 0.64-0.96; P=0.022), and breakthrough rotavirus diarrhea (OR 1.34, 95% CI: 1.05-1.71; P=0.020) after adjusting for potential confounders. These associations were not observed for Sabin strain poliovirus quantity. In this broad survey of enteropathogens and oral vaccine performance we find a particular association between EV carriage, particularly NPEV, and OPV immunogenicity and RV protection. Strategies to reduce EV infections may improve oral vaccine responses. ClinicalTrials.gov Identifier: NCT01375647. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Monitoring of children with acute gastroenteritis in Madrid, Spain, during 2010-2011: rotavirus genotype distribution after the vaccines introduction.

    Science.gov (United States)

    Sánchez-Fauquier, Alicia; González-Galán, Verónica; Arroyo, Sandra; Cabornero, Ana; Ruiz-Burruecos, Ana; Wilhelmi-De Cal, Isabel

    2014-05-01

    A structured surveillance study was conducted on children with diarrhea who were hospitalized in Madrid (Spain) during 2010-2011, in order to describe temporal, geographic, and age-related trends in rotavirus (RV) strains after the introduction of the RV vaccines in our country. A total of 370 children were enrolled, with RV being detected in 117 (31.6%) cases. Coinfections were detected mainly with rotavirus, astrovirus and norovirus. The most prevalent rotavirus G type was G1 (60.7%) followed by G2 (16.09%), G9 (5.9%), and G12 (5.1%). The G12 genotype appeared for the first time in 2008 in Spain, and it has increased to 5.1% of the cases in this report. Some uncommon P genotypes, such as P[14] and P[6], both with a low percentage, were found. The samples with G1 G2, G9 and G12 genotypes appeared in all ages, but were significantly higher in children under 2 years old. A long-term structured surveillance is required in the Spanish post vaccine era, in order to determine the prevalence and variability of RV genotypes. This will especially be needed to distinguish between changes occurring as a result of natural fluctuation in genotype or those (changes) that could be mediated by population immunity to the vaccines. In addition, it will be necessary to study the impact of the current vaccines on the circulating rotavirus strains and on the overall reduction in the prevalence of rotavirus disease among children in Spain. Copyright © 2013 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  18. Impact of self-financed rotavirus vaccines on hospital stays and costs in Spain after a 3-year introductory period.

    Science.gov (United States)

    Redondo-González, O; Tenías-Burillo, J M; Ruiz-Gonzalo, J

    2017-07-01

    Vaccination has reduced rotavirus hospitalizations by 25% in European regions with low-moderate vaccine availability. We aimed to quantify the reduction in hospital costs after the longest period in which Rotarix® and Rotateq® were simultaneously commercially available in Spain. Cases, length of stay (LOS), and diagnosis-related groups (DRGs) were retrieved from the Minimum Basic Data Set. Healthcare expenditure was estimated through the cost accounting system Gescot®. DRGs were clustered: I, non-bacterial gastroenteritis with complications; II, without complications; III, requiring surgical/other procedures or neonatal cases (highest DRG weights). Comparisons between pre (2003-2005)- and post-vaccine (2007-2009) hospital stays and costs by DRG group were made. Rotaviruses were the most common agents of specific-coded gastroenteritis (N = 1657/5012). LOS and extended LOS of rotaviruses fell significantly in 2007-2009 (β-coefficient = -0·43, 95% confidence intervals (95% CI) -0·68 to -0·17; and odds ratio 0·62, 95% CI 0·50-0·76, respectively). Overall, costs attributable to rotavirus hospitalizations fell approximately €244 per patient (95% CI -365 to -123); the decrease in DRG group III was €2269 per patient (95% CI -4098 to -380). We concluded modest savings in hospital costs, largely attributable to cases with higher DRG weights, and a faster recovery. A universal rotavirus vaccination program deserves being re-evaluated, regarding its potential high impact on both at-risk children and societal costs.

  19. Impact of Rotavirus Vaccine Introduction and Postintroduction Etiology of Diarrhea Requiring Hospital Admission in Haydom, Tanzania, a Rural African Setting

    Science.gov (United States)

    Platts-Mills, James A.; Amour, Caroline; Gratz, Jean; Nshama, Rosemary; Walongo, Thomas; Mujaga, Buliga; Maro, Athanasia; McMurry, Timothy L; Liu, Jie; Mduma, Estomih; Houpt, Eric R

    2017-01-01

    Abstract Background No data are available on the etiology of diarrhea requiring hospitalization after rotavirus vaccine introduction in Africa. The monovalent rotavirus vaccine was introduced in Tanzania on 1 January 2013. We performed a vaccine impact and effectiveness study as well as a quantitative polymerase chain reaction (qPCR)–based etiology study at a rural Tanzanian hospital. Methods We obtained data on admissions among children <5 years to Haydom Lutheran Hospital between 1 January 2010 and 31 December 2015 and estimated the impact of vaccine introduction on all-cause diarrhea admissions. We then performed a vaccine effectiveness study using the test-negative design. Finally, we tested diarrheal specimens during 2015 by qPCR for a broad range of enteropathogens and calculated pathogen-specific attributable fractions (AFs). Results Vaccine introduction was associated with a 44.9% (95% confidence interval [CI], 17.6%–97.4%) reduction in diarrhea admissions in 2015, as well as delay of the rotavirus season. The effectiveness of 2 doses of vaccine was 74.8% (95% CI, –8.2% to 94.1%) using an enzyme immunoassay–based case definition and 85.1% (95% CI, 26.5%–97.0%) using a qPCR-based case definition. Among 146 children enrolled in 2015, rotavirus remained the leading etiology of diarrhea requiring hospitalization (AF, 25.8% [95% CI, 24.4%–26.7%]), followed by heat-stable enterotoxin-producing Escherichia coli (AF, 18.4% [95% CI, 12.9%–21.9%]), Shigella/enteroinvasive E. coli (AF, 14.5% [95% CI, 10.2%–22.8%]), and Cryptosporidium (AF, 7.9% [95% CI, 6.2%–9.3%]). Conclusions Despite the clear impact of vaccine introduction in this setting, rotavirus remained the leading etiology of diarrhea requiring hospitalization. Further efforts to maximize vaccine coverage and improve vaccine performance in these settings are warranted. PMID:28575304

  20. Quantifying Parameter and Structural Uncertainty of Dynamic Disease Transmission Models Using MCMC: An Application to Rotavirus Vaccination in England and Wales.

    Science.gov (United States)

    Bilcke, Joke; Chapman, Ruth; Atchison, Christina; Cromer, Deborah; Johnson, Helen; Willem, Lander; Cox, Martin; Edmunds, William John; Jit, Mark

    2015-07-01

    Two vaccines (Rotarix and RotaTeq) are highly effective at preventing severe rotavirus disease. Rotavirus vaccination has been introduced in the United Kingdom and other countries partly based on modeling and cost-effectiveness results. However, most of these models fail to account for the uncertainty about several vaccine characteristics and the mechanism of vaccine action. A deterministic dynamic transmission model of rotavirus vaccination in the United Kingdom was developed. This improves on previous models by 1) allowing for 2 different mechanisms of action for Rotarix and RotaTeq, 2) using clinical trial data to understand these mechanisms, and 3) accounting for uncertainty by using Markov Chain Monte Carlo. In the long run, Rotarix and RotaTeq are predicted to reduce the overall rotavirus incidence by 50% (39%-63%) and 44% (30%-62%), respectively but with an increase in incidence in primary school children and adults up to 25 y of age. The vaccines are estimated to give more protection than 1 or 2 natural infections. The duration of protection is highly uncertain but has only impact on the predicted reduction in rotavirus burden for values lower than 10 y. The 2 vaccine mechanism structures fit equally well with the clinical trial data. Long-term postvaccination dynamics cannot be predicted reliably with the data available. Accounting for the joint uncertainty of several vaccine characteristics resulted in more insight into which of these are crucial for determining the impact of rotavirus vaccination. Data for up to at least 10 y postvaccination and covering older children and adults are crucial to address remaining questions on the impact of widespread rotavirus vaccination. © The Author(s) 2015.

  1. 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.

  2. The impact of rotavirus vaccination on discounted net tax revenue in Egypt: a government perspective analysis.

    Science.gov (United States)

    Connolly, Mark P; Topachevskyi, Oleksandr; Standaert, Baudouin; Ortega, Omayra; Postma, Maarten

    2012-08-01

    We evaluated national rotavirus (RV) immunization programme costs to estimate how resulting changes in morbidity and mortality will influence government fiscal accounts over time. The assumption was that increased childhood survival in vaccinated cohorts leads to increased numbers of children consuming government resource, and an increased number of future tax payers. Our objective was to evaluate the difference in lifetime discounted net tax revenue generated by RV vaccinated and unvaccinated cohorts from the Egyptian government perspective. The model framework adopts the Egyptian government perspective for RV immunization costs (year 2009 values) and all government transfers (e.g. education costs, health costs, pensions). To reflect the government tax revenue, we applied a fixed income tax burden to earnings over the lifetime of vaccinated and unvaccinated cohorts. At each year of the model, we derive net taxes (gross taxes less transfers) discounted to the immunization year to reflect the present value of RV vaccination investment costs. Projected incremental net present values of the vaccinated cohort versus the unvaccinated cohort are $US6.1 million, $US58.1 million and $US55.7 million at 25-, 50- and 72-year time horizons, respectively. The internal rate of return for the government based on RV vaccination at years 25, 50 and 72 was 10.8%, 15.1% and 14.9, respectively. Within the first 5 years of vaccination, 76% of vaccine acquisition costs were offset due to direct and indirect cost savings attributed to a reduction in RV-related disease burden. Investments in RV vaccination in a single year are entirely offset when the vaccinated cohort of newborns reach 22 years of age. The government perspective is useful for evaluating investments in RV vaccination because of ongoing government transfers and tax receipts attributed to changes in RV-attributed morbidity and mortality. The analysis described here illustrates that investing in RV offers tangible long

  3. Human rotavirus subgroups and severity of associated diarrhoea in Ghana.

    Science.gov (United States)

    Armah, George E.; Hori, Hiroki; Anyanful, Akwasi; Addo, Julius A.; Commey, Joseph O.; Kamiya, Hitoshi; Nkrumah, Francis K.

    1995-11-01

    In a 12 month study of children with acute diarrhoea seeking medical care in 2 hospitals in Accra, Ghana, 16.3% were found to be infected with human rotaviruses (HRV). Vomiting and diarrhoea were the main symptoms observed. HRV infection was frequently associated with severe diarrhoea. Vomiting was however less frequent in HRV associated diarrhoea than in non HRV diarrhoea. No significant association was observed between the severity of dehydration and HRV infection. Subgroup II HRV was the predominant subgroup identified with the dominant serotypes being HRV serotypes 1 and 4. Poly-acrylamide gel electrophoresis of HRV RNAs isolated from 40 positive stool samples revealed the existence of 7 distinct electrophoretic migration patterns in the study population.

  4. Trivalent combination vaccine induces broad heterologous immune responses to norovirus and rotavirus in mice.

    Directory of Open Access Journals (Sweden)

    Kirsi Tamminen

    Full Text Available Rotavirus (RV and norovirus (NoV are the two major causes of viral gastroenteritis (GE in children worldwide. We have developed an injectable vaccine design to prevent infection or GE induced with these enteric viruses. The trivalent combination vaccine consists of NoV capsid (VP1 derived virus-like particles (VLPs of GI-3 and GII-4 representing the two major NoV genogroups and tubular RV recombinant VP6 (rVP6, the most conserved and abundant RV protein. Each component was produced in insect cells by a recombinant baculovirus expression system and combined in vitro. The vaccine components were administered intramuscularly to BALB/c mice either separately or in the trivalent combination. High levels of NoV and RV type specific serum IgGs with high avidity (>50% as well as intestinal IgGs were detected in the immunized mice. Cross-reactive IgG antibodies were also elicited against heterologous NoV VLPs not used for immunization (GII-4 NO, GII-12 and GI-1 VLPs and to different RVs from cell cultures. NoV-specific serum antibodies blocked binding of homologous and heterologous VLPs to the putative receptors, histo-blood group antigens, suggesting broad NoV neutralizing activity of the sera. Mucosal antibodies of mice immunized with the trivalent combination vaccine inhibited RV infection in vitro. In addition, cross-reactive T cell immune responses to NoV and RV-specific antigens were detected. All the responses were sustained for up to six months. No mutual inhibition of the components in the trivalent vaccine combination was observed. In conclusion, the NoV GI and GII VLPs combination induced broader cross-reactive and potentially neutralizing immune responses than either of the VLPs alone. Therefore, trivalent vaccine might induce protective immune responses to the vast majority of circulating NoV and RV genotypes.

  5. 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.

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

    African Journals Online (AJOL)

    Background: Rotavirus remains a leading cause of acute gastroenteritis in children worldwide with an estimated 2000 deaths each day in developing countries. 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 ...

  7. Rotavirus vaccine coverage and factors associated with uptake using linked data: Ontario, Canada.

    Science.gov (United States)

    Wilson, Sarah E; Chung, Hannah; Schwartz, Kevin L; Guttmann, Astrid; Deeks, Shelley L; Kwong, Jeffrey C; Crowcroft, Natasha S; Wing, Laura; Tu, Karen

    2018-01-01

    In August 2011, Ontario, Canada introduced a rotavirus immunization program using Rotarix™ vaccine. No assessments of rotavirus vaccine coverage have been previously conducted in Ontario. We assessed vaccine coverage (series initiation and completion) and factors associated with uptake using the Electronic Medical Record Administrative data Linked Database (EMRALD), a collection of family physician electronic medical records (EMR) linked to health administrative data. Series initiation (1 dose) and series completion (2 doses) before and after the program's introduction were calculated. To identify factors associated with series initiation and completion, adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) were calculated using logistic regression. A total of 12,525 children were included. Series completion increased each year of the program (73%, 79% and 84%, respectively). Factors associated with series initiation included high continuity of care (aOR = 2.15; 95%CI, 1.61-2.87), maternal influenza vaccination (aOR = 1.55; 95%CI,1.24-1.93), maternal immmigration to Canada in the last five years (aOR = 1.47; 95% CI, 1.05-2.04), and having no siblings (aOR = 1.62; 95%CI,1.30-2.03). Relative to the first program year, infants were more likely to initiate the series in the second year (aOR = 1.71; 95% CI 1.39-2.10) and third year (aOR = 2.02; 95% CI 1.56-2.61) of the program. Infants receiving care from physicians with large practices were less likely to initiate the series (aOR 0.91; 95%CI, 0.88-0.94, per 100 patients rostered) and less likely to complete the series (aOR 0.94; 95%CI, 0.91-0.97, per 100 patients rostered). Additional associations were identified for series completion. Family physician delivery achieved moderately high coverage in the program's first three years. This assessment demonstrates the usefulness of EMR data for evaluating vaccine coverage. Important insights into factors associated with initiation or completion (i.e. high

  8. Human Papillomavirus (HPV) Vaccines

    Science.gov (United States)

    ... factors for developing them, such as taking oral contraceptives . A safety review of Gardasil in Denmark and ... and venous thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark ...

  9. How can a multilevel promotion of breastfeeding reduce the required budget for rotavirus vaccination in Indonesia?

    NARCIS (Netherlands)

    Zakiyah, N.; Suwantika, A.A.; Postma, M.J.

    2014-01-01

    Objectives: Breast milk is considered to give protection against rotavirus infection since it contains anti-rotavirus maternal antibodies and other nonspecific inhibitors. Multilevel promotion of breastfeeding is a complex intervention that modifies behavioral determinants through multiple levels of

  10. Rotavirus Strain Trends During the Postlicensure Vaccine Era: United States, 2008–2013

    Science.gov (United States)

    Bowen, Michael D.; Mijatovic-Rustempasic, Slavica; Esona, Mathew D.; Teel, Elizabeth N.; Gautam, Rashi; Sturgeon, Michele; Azimi, Parvin H.; Baker, Carol J.; Bernstein, David I.; Boom, Julie A.; Chappell, James; Donauer, Stephanie; Edwards, Kathryn M.; Englund, Janet A.; Halasa, Natasha B.; Harrison, Christopher J.; Johnston, Samantha H.; Klein, Eileen J.; McNeal, Monica M.; Moffatt, Mary E.; Rench, Marcia A.; Sahni, Leila C.; Selvarangan, Rangaraj; Staat, Mary A.; Szilagyi, Peter G.; Weinberg, Geoffrey A.; Wikswo, Mary E.; Parashar, Umesh D.; Payne, Daniel C.

    2016-01-01

    Background Group A rotaviruses (RVA) are a significant cause of pediatric gastroenteritis worldwide. The New Vaccine Surveillance Network (NVSN) has conducted active surveillance for RVA at pediatric hospitals and emergency departments at 3–7 geographically diverse sites in the United States since 2006. Methods Over 6 consecutive years, from 2008 to 2013, 1523 samples from NVSN sites that were tested positive by a Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention for genotyping. Results In the 2009, 2010, and 2011 seasons, genotype G3P[8] was the predominant genotype throughout the network, with a 46%–84% prevalence. In the 2012 season, G12P[8] replaced G3P[8] as the most common genotype, with a 70% prevalence, and this trend persisted in 2013 (68.0% prevalence). Vaccine (RotaTeq; Rotarix) strains were detected in 0.6%–3.4% of genotyped samples each season. Uncommon and unusual strains (eg, G8P[4], G3P[24], G2P[8], G3P[4], G3P[6], G24P[14], G4P[6], and G9P[4]) were detected sporadically over the study period. Year, study site, and race were found to be significant predictors of genotype. Conclusions Continued active surveillance is needed to monitor RVA genotypes in the United States and to detect potential changes since vaccine licensure. PMID:27302190

  11. Evaluation of a Booster Dose of Pentavalent Rotavirus Vaccine Co-Administered with Measles, Yellow Fever and Meningitis A Vaccines in 9-month-old Malian Infants.

    Science.gov (United States)

    Haidara, Fadima C; Tapia, Milagritos D; Sow, Samba O; Doumbia, Moussa; Coulibaly, Flanon; Diallo, Fatoumata; Traoré, Awa; Kodio, Mamoudou; Kelly, Corey L; Fitzpatrick, Meagan; Kotloff, Karen; Victor, John C; Neuzil, Kathleen

    2018-04-12

    Rotavirus vaccines given to infants are safe and efficacious. A booster dose of rotavirus vaccine could extend protection into the second year of life in low resource countries. We conducted an open-label, individual-randomized trial in Bamako, Mali. We assigned 600 9- to 11-month old infants to measles (MV), yellow fever (YFV), and meningococcal A conjugate vaccines with or without pentavalent rotavirus vaccine (PRV). We assessed non-inferiority of seroconversion and seroresponse rates (<10% difference) to MV, YFV and MenAV. We compared the seroresponse to PRV. Seroconversion to measles occurred in 255/261 (97.7%) and 246/252 (97.6%) of the PRV and control group; difference, 0.1% (95% CI, - 4.0 to 4.2). Seroresponse to YFV occurred in 48.1% (141/293) of the PRV group compared to 52.2% (153/293) of the control group; difference - 4.1% (95% CI, -12.2 to 4.0). A 4-fold rise in meningococcal A bactericidal titer was observed in 273/292 (93.5%) PRV recipients and 276/293 (94.2%) controls; difference, -0.7% (95% CI, - 5.2 to 3.8). Rises in anti-rotavirus IgA and IgG geometric mean concentrations were higher among PRV recipients (118 [95% CI, 91 to 154] and 364 [95% CI, 294 to 450]) compared to controls (68 [95% CI, 50 to 92] and 153 [95% CI, 114 to 207]. PRV did not interfere with MV and MenAV; this study could not rule out interference with YFV. PRV increased serum rotavirus antibody levels. NCT02286895.

  12. Determinants of Parents' Decision to Vaccinate Their Children against Rotavirus: Results of a Longitudinal Study

    Science.gov (United States)

    Dube, E.; Bettinger, J. A.; Halperin, B.; Bradet, R.; Lavoie, F.; Sauvageau, C.; Gilca, V.; Boulianne, N.

    2012-01-01

    Rotavirus disease is a common cause of health care utilization and almost all children are affected by the age of 5 years. In Canada, at the time of this survey (2008-09), immunization rates for rotavirus were less than 20%. We assessed the determinants of a parent's acceptance to have their child immunized against rotavirus. The survey…

  13. Concomitant administration of diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine derived from Sabin strains (DTaP-sIPV) with pentavalent rotavirus vaccine in Japanese infants.

    Science.gov (United States)

    Tanaka, Yoshiyuki; Yokokawa, Ruriko; Rong, Han Shi; Kishino, Hiroyuki; Stek, Jon E; Nelson, Margaret; Lawrence, Jody

    2017-06-03

    Rotavirus is the leading cause of severe acute gastroenteritis in infants and young children. Most children are infected with rotavirus, and the health and economic burdens of rotavirus gastroenteritis on healthcare systems and families are considerable. In 2012 pentavalent rotavirus vaccine (RV5) and diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine derived from Sabin strains (DTaP-sIPV) were licensed in Japan. We examined the immunogenicity and safety of DTaP-sIPV when administrated concomitantly with RV5 in Japanese infants. A total of 192 infants 6 to 11 weeks of age randomized to Group 1 (N = 96) received DTaP-sIPV and RV5 concomitantly, and Group 2 (N = 96) received DTaP-sIPV and RV5 separately. Antibody titer to diphtheria toxin, pertussis antigens (PT and FHA), tetanus toxin, and poliovirus type 1, 2, and 3 were measured at 4 to 6 weeks following 3-doses of DTaP-sIPV. Seroprotection rates for all components of DTaP-sIPV were 100% in both groups, and the geometric mean titers for DTaP-sIPV in Group 1 were comparable to Group 2. Incidence of systemic AEs (including diarrhea, vomiting, fever, and nasopharyngitis) were lower in Group 1 than in Group 2. All vaccine-related AEs were mild or moderate in intensity. There were no vaccine-related serious AEs, no deaths, and no cases of intussusception during the study. Concomitant administration of DTaP-sIPV and RV5 induced satisfactory immune responses to DTaP-sIPV and acceptable safety profile. The administration of DTaP-sIPV given concomitantly with RV5 is expected to facilitate compliance with the vaccination schedule and improve vaccine coverage in Japanese infants.

  14. The Human Hookworm Vaccine.

    Science.gov (United States)

    Hotez, Peter J; Diemert, David; Bacon, Kristina M; Beaumier, Coreen; Bethony, Jeffrey M; Bottazzi, Maria Elena; Brooker, Simon; Couto, Artur Roberto; Freire, Marcos da Silva; Homma, Akira; Lee, Bruce Y; Loukas, Alex; Loblack, Marva; Morel, Carlos Medicis; Oliveira, Rodrigo Correa; Russell, Philip K

    2013-04-18

    Hookworm infection is one of the world's most common neglected tropical diseases and a leading cause of iron deficiency anemia in low- and middle-income countries. A Human Hookworm Vaccine is currently being developed by the Sabin Vaccine Institute and is in phase 1 clinical testing. The candidate vaccine is comprised of two recombinant antigens known as Na-GST-1 and Na-APR-1, each of which is an important parasite enzyme required for hookworms to successfully utilize host blood as a source of energy. The recombinant proteins are formulated on Alhydrogel(®) and are being tested in combination with a synthetic Toll-like receptor 4 agonist. The aim of the vaccine is to induce anti-enzyme antibodies that will reduce both host blood loss and the number of hookworms attached to the gut. Transfer of the manufacturing technology to the Oswaldo Cruz Foundation (FIOCRUZ)/Bio-Manguinhos (a Brazilian public sector developing country vaccine manufacturer) is planned, with a clinical development plan that could lead to registration of the vaccine in Brazil. The vaccine would also need to be introduced in the poorest regions of Africa and Asia, where hookworm infection is highly endemic. Ultimately, the vaccine could become an essential tool for achieving hookworm control and elimination, a key target in the 2012 London Declaration on Neglected Tropical Diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Physicochemical stability and inactivation of human and simian rotaviruses

    International Nuclear Information System (INIS)

    Meng, Z.D.; Birch, C.; Heath, R.; Gust, I.

    1987-01-01

    The effects of various physical and chemical treatments on the stability of a human serotype 1 rotavirus and simian agent 11 (SA11) were compared by using a fluorescence focus assay. The infectivity of both strains was retained after storage at room temperature for 14 days, 4 degree C for 22 days, and -20 degree C for 32 days; lyophilization; and treatment at pH 3 to 11. Both viruses were inactivated at pH 12, as was the human virus at pH 2, although this pH resulted in only partial inactivation of SA11. The human virus also appeared to be more sensitive than SA11 to the action of ether and chloroform. The infectivity of both viruses was lost after UV irradiation for 15 min and after treatment with 8% formaldehyde for 5 min, 70% (vol/vol) ethanol for 30 min, and 2% lysol, 2% phenol, and 1% H 2 O 2 for 1 h each

  16. Physicochemical stability and inactivation of human and simian rotaviruses

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Z.D.; Birch, C.; Heath, R.; Gust, I.

    1987-04-01

    The effects of various physical and chemical treatments on the stability of a human serotype 1 rotavirus and simian agent 11 (SA11) were compared by using a fluorescence focus assay. The infectivity of both strains was retained after storage at room temperature for 14 days, 4 degree C for 22 days, and -20 degree C for 32 days; lyophilization; and treatment at pH 3 to 11. Both viruses were inactivated at pH 12, as was the human virus at pH 2, although this pH resulted in only partial inactivation of SA11. The human virus also appeared to be more sensitive than SA11 to the action of ether and chloroform. The infectivity of both viruses was lost after UV irradiation for 15 min and after treatment with 8% formaldehyde for 5 min, 70% (vol/vol) ethanol for 30 min, and 2% lysol, 2% phenol, and 1% H/sub 2/O/sub 2/ for 1 h each.

  17. Epidemiology of group A rotavirus infection after the introduction of monovalent vaccine in the National Immunization Program of Saudi Arabia.

    Science.gov (United States)

    Al-Ayed, Mohammed Saeed Zayed; Asaad, Ahmed Morad; Qureshi, Mohamed Ansar; Hawan, Ali Abdullah

    2017-03-01

    This study aimed to investigate the prevalence of group A rotavirus (RVA) gastroenteritis and the distribution of the RVA genotypes as well as to determine a possible change in the age of occurrence of the RVA infection in the first 2 years after Rotarix® vaccine introduction in Saudi Arabia. This descriptive study included 850 hospitalized children vaccine introduction, especially in the age group between 1 and 12 months, and a reduction in the circulation of G1P[6]. The parallel rise and spread of G2P[4] in post-vaccination period might pose an impact to long-term vaccine efficacy. Continued surveillance studies in different Saudi regions are crucial to document the effectiveness of Rotarix® vaccine and evaluate the potential emergence of rare/novel RVA genotypes. J. Med. Virol. 89:429-434, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Quantifying the Impact of Natural Immunity on Rotavirus Vaccine Efficacy Estimates: A Clinical Trial in Dhaka, Bangladesh (PROVIDE) and a Simulation Study.

    Science.gov (United States)

    Rogawski, Elizabeth T; Platts-Mills, James A; Colgate, E Ross; Haque, Rashidul; Zaman, K; Petri, William A; Kirkpatrick, Beth D

    2018-03-05

    The low efficacy of rotavirus vaccines in clinical trials performed in low-resource settings may be partially explained by acquired immunity from natural exposure, especially in settings with high disease incidence. In a clinical trial of monovalent rotavirus vaccine in Bangladesh, we compared the original per-protocol efficacy estimate to efficacy derived from a recurrent events survival model in which children were considered naturally exposed and potentially immune after their first rotavirus diarrhea (RVD) episode. We then simulated trial cohorts to estimate the expected impact of prior exposure on efficacy estimates for varying rotavirus incidence rates and vaccine efficacies. Accounting for natural immunity increased the per-protocol vaccine efficacy estimate against severe RVD from 63.1% (95% confidence interval [CI], 33.0%-79.7%) to 70.2% (95% CI, 44.5%-84.0%) in the postvaccination period, and original year 2 efficacy was underestimated by 14%. The simulations demonstrated that this expected impact increases linearly with RVD incidence, will be greatest for vaccine efficacies near 50%, and can reach 20% in settings with high incidence and low efficacy. High rotavirus incidence leads to predictably lower vaccine efficacy estimates due to the acquisition of natural immunity in unvaccinated children, and this phenomenon should be considered when comparing efficacy estimates across settings. NCT01375647.

  19. Rotavirus Immunization in Africa: A Perspective Re-visited

    African Journals Online (AJOL)

    trials in developed countries, the history of rotavirus vaccine in Africa has not been good. The earlier rotavirus vaccine candidates, based on bovine rotavirus strains, were ... trials in Peru and Brazil [19,20]. Other more obvious reasons may include vaccine-related issues (such as the antigenic make-up of the bovine rotavirus ...

  20. Immunogenicity and efficacy in mice of an adenovirus-based bicistronic rotavirus vaccine expressing NSP4 and VP7.

    Science.gov (United States)

    Xie, Li; Yan, Min; Wang, Xiaonan; Ye, Jing; Mi, Kai; Yan, Shanshan; Niu, Xianglian; Li, Hongjun; Sun, Maosheng

    2015-12-02

    NSP4 and VP7 are important functional proteins of rotavirus. Proper combination of viral gene expression is favorable to improving the protection effect of subunit vaccine. In the present study, We evaluated the immunogenicity and efficacy of the bicistronic recombinant adenovirus (rAd-NSP4-VP7) and two single-gene expressing adenoviruses (rAd-NSP4, rAd-VP7). The three adenovirus vaccines were used to immunize mice by intramuscular or intranasal administration. The data showed significant increases in serum antibodies, T lymphocyte subpopulations proliferation, and cytokine secretions of splenocyte in all immunized groups. However, the serum IgA and neutralizing antibody levels of the rAd-NSP4-VP7 or rAd-VP7 groups were significantly higher than those of the rAd-NSP4, while the splenocyte numbers of IFN-γ secretion in the rAd-NSP4-VP7 or rAd-NSP4 groups was greater than that of the rAd-VP7. Furthermore, the efficacy evaluation in a suckling mice model indicated that only rAd-NSP4-VP7 conferred significant protection against rotavirus shedding challenge. These results suggest that the co-expression of NSP4 and VP7 in an adenovirus vector induce both humoral and cell-mediated immune responses efficiently, and provide potential efficacy for protection against rotavirus disease. It is possible to represent an efficacious subunits vaccine strategy for control of rotavirus infection and transmission. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Efficacy of the pentavalent rotavirus vaccine, RotaTeq®, in Finnish infants up to 3 years of age: the Finnish Extension Study.

    Science.gov (United States)

    Vesikari, Timo; Karvonen, Aino; Ferrante, Shannon Allen; Ciarlet, Max

    2010-11-01

    Rotavirus Efficacy and Safety Trial (REST) enrolled nearly 70,000 infants, of whom more than 23,000 were from Finland. REST determined the efficacy of the pentavalent rotavirus vaccine (RV5) against rotavirus-related hospitalisations and emergency department (ED) visits in the first year after vaccination. Finnish infants initially in REST transitioned into the Finnish Extension Study (FES), where they were followed for rotavirus-related hospitalisations and ED visits through their second year of life and beyond. FES identified 150 (31%) additional rotavirus gastroenteritis (RVGE) cases beyond those identified in REST in the Finnish participants. Overall, RV5 reduced RVGE hospitalisations and ED visits, regardless of the rotavirus serotype, by 93.8% (95% confidence interval [CI]: 90.8-95.9%) for up to 3.1 years following the last vaccine dose. Vaccine efficacy against combined hospitalisations and ED visits between ages 4 months to 11 months, 12 months to 23 months, and 24 months to 35 months was 93.9% (95% CI: 89.1-96.9%), 94.4% (95% CI: 90.2-97.0%), and 85.9% (95% CI: 51.6-97.2%), respectively. The reduction of hospitalisations and ED visits due to any acute gastroenteritis, rotavirus or not, was 62.4% (95% CI: 57.6-66.6%) over the entire follow-up period. The results from FES confirm that RV5 induces high and sustained protection against rotavirus-related hospitalisations and ED visits, and has a very substantial impact on all gastroenteritis-related hospitalisations and ED visits into the third year of life in Finnish children.

  2. Genetic diversity of G1P[8] rotavirus VP7 and VP8* antigens in Finland over a 20-year period: No evidence for selection pressure by universal mass vaccination with RotaTeq® vaccine.

    Science.gov (United States)

    Hemming, Maria; Vesikari, Timo

    2013-10-01

    Two live-attenuated oral vaccines (Rotarix™ and Rotateq®) against rotavirus gastroenteritis were licensed in 2006 and have been introduced into National Immunization Programs (NIPs) of several countries. Large scale use of rotavirus vaccines might cause antigenic pressure on circulating rotavirus types or lead to selection of new rotaviruses thus decreasing vaccine efficacy. We examined the nucleotide and amino acid sequences of the surface proteins VP7 and VP4 (cleaved to VP8(*) and VP5(*)) of a total of 108 G1P[8] rotavirus strains collected over a 20-year period from 1992, including the years 2006-2009 when rotavirus vaccine (mainly Rotarix™) was available, and the years 2009-2012 after implementation of RotaTeq® vaccine into the NIP of Finland. In G1 VP7 no changes at amino acid level were observed. In VP8(*) periodical fluctuation of the sublineage over the study period was found with multiple changes both at nucleotide and amino acid levels. Most amino acid changes were in the dominant antigenic epitopes of VP8(*). A change in VP8(*) sublineage occurred between 2008 and 2009, with a temporal correlation to the use of Rotarix™ up to 30% coverage in the period. In contrast, no antigenic changes in the VP8(*) protein appeared to be correlated to the exclusive use of RotaTeq® vaccine after 2009. Nevertheless, long-term surveillance of antigenic changes in VP4 and also VP7 proteins in wild-type rotavirus strains is warranted in countries with large scale use of the currently licensed live oral rotavirus vaccines. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Rotavirus Strain Trends During the Postlicensure Vaccine Era: United States, 2008-2013.

    Science.gov (United States)

    Bowen, Michael D; Mijatovic-Rustempasic, Slavica; Esona, Mathew D; Teel, Elizabeth N; Gautam, Rashi; Sturgeon, Michele; Azimi, Parvin H; Baker, Carol J; Bernstein, David I; Boom, Julie A; Chappell, James; Donauer, Stephanie; Edwards, Kathryn M; Englund, Janet A; Halasa, Natasha B; Harrison, Christopher J; Johnston, Samantha H; Klein, Eileen J; McNeal, Monica M; Moffatt, Mary E; Rench, Marcia A; Sahni, Leila C; Selvarangan, Rangaraj; Staat, Mary A; Szilagyi, Peter G; Weinberg, Geoffrey A; Wikswo, Mary E; Parashar, Umesh D; Payne, Daniel C

    2016-09-01

    Group A rotaviruses (RVA) are a significant cause of pediatric gastroenteritis worldwide. The New Vaccine Surveillance Network (NVSN) has conducted active surveillance for RVA at pediatric hospitals and emergency departments at 3-7 geographically diverse sites in the United States since 2006. Over 6 consecutive years, from 2008 to 2013, 1523 samples from NVSN sites that were tested positive by a Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention for genotyping. In the 2009, 2010, and 2011 seasons, genotype G3P[8] was the predominant genotype throughout the network, with a 46%-84% prevalence. In the 2012 season, G12P[8] replaced G3P[8] as the most common genotype, with a 70% prevalence, and this trend persisted in 2013 (68.0% prevalence). Vaccine (RotaTeq; Rotarix) strains were detected in 0.6%-3.4% of genotyped samples each season. Uncommon and unusual strains (eg, G8P[4], G3P[24], G2P[8], G3P[4], G3P[6], G24P[14], G4P[6], and G9P[4]) were detected sporadically over the study period. Year, study site, and race were found to be significant predictors of genotype. Continued active surveillance is needed to monitor RVA genotypes in the United States and to detect potential changes since vaccine licensure. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  4. Methodology and lessons-learned from the efficacy clinical trial of the pentavalent rotavirus vaccine in Bangladesh.

    Science.gov (United States)

    Zaman, K; Yunus, M; El Arifeen, Shams; Azim, Tasnim; Faruque, A S G; Huq, Ehsanul; Hossain, Ilias; Luby, Stephen P; Victor, John C; Dallas, Michael J; Lewis, Kristen D C; Rivers, Stephen B; Steele, A Duncan; Neuzil, Kathleen M; Ciarlet, Max; Sack, David A

    2012-04-27

    An efficacy clinical trial with pentavalent rotavirus vaccine (PRV), RotaTeq(®), was conducted at Matlab field site of ICDDR,B, Bangladesh from March 2007 to March 2009. The methodology, including operation logistics, and lessons-learned are described in this report. Vaccination was organized at 41 fixed-site clinics twice/month. A total of 1136 infants were randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6-, 10-, and 14-weeks of age with routine vaccines of the Expanded Programme on Immunization (EPI) schedule. Twelve field-workers routinely visited study participants for safety and efficacy follow-up. The study was conducted following good clinical practices and maintaining cold-chain requirements. There were no temperature deviations of clinical vaccine supplies. Data entry was done using the source documents to a central database developed by the sponsor which was linked to web. Among enrolled infants, 1128 (99.3%) received 3 doses of PRV/placebo and efficacy follow-up was conducted for a median of 554 days. For the evaluation of immunogenicity, blood samples were collected from 150 participants predose 1 and from 147 (98%) of the same participants post dose 3. Stool samples were collected from 778 (99.9%) acute gastroenteritis episodes among children who reported to diarrhoea treatment centres. Thirty-nine serious adverse events, including 6 deaths, occurred among study participants. The efficacy of PRV against severe rotavirus gastroenteritis was 42.7% through the entire follow-up period; serum anti-rotavirus IgA response was 78.1%. Inclement weather, difficult transportation, and movement of study participants were some of the challenges identified. This is the first vaccine trial in rural Bangladesh with online data entry. The study was well accepted in the community and was completed successfully. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Impact of rotavirus vaccine introduction and post-introduction etiology of diarrhea requiring hospital admission in Haydom, Tanzania, a rural African setting.

    Science.gov (United States)

    Platts-Mills, James A; Amour, Caroline; Gratz, Jean; Nshama, Rosemary; Walongo, Thomas; Mujaga, Buliga; Maro, Athanasia; McMurry, Timothy L; Liu, Jie; Mduma, Estomih; Houpt, Eric R

    2017-05-29

    No data are available on the etiology of diarrhea requiring hospitalization after rotavirus vaccine introduction in Africa. The monovalent rotavirus vaccine was introduced in Tanzania on January 1, 2013. We performed a vaccine impact and effectiveness study as well as a qPCR-based etiology study at a rural Tanzanian hospital. We obtained data on admissions among children under 5 years to Haydom Lutheran Hospital between January 1, 2010 and December 31, 2015, and estimated the impact of vaccine introduction on all-cause diarrhea admissions. We then performed a vaccine effectiveness study using the test-negative design. Finally, we tested diarrheal specimens during 2015 by qPCR for a broad range of enteropathogens and calculated pathogen-specific attributable fractions. Vaccine introduction was associated with a 44.9% (95% CI 17.6 - 97.4) reduction in diarrhea admissions in 2015, as well as delay of the rotavirus season. The effectiveness of two doses of vaccine was 74.8% (-8.2 - 94.1) using an enzyme immunoassay-based case definition and 85.1% (26.5 - 97.0) using a qPCR-based case definition. Among 146 children enrolled in 2015, rotavirus remained the leading etiology of diarrhea requiring hospitalization (AF 25.8%, 95% CI: 24.4 - 26.7), followed by heat-stabile enterotoxin-producing E. coli (18.4%, 12.9 - 21.9), Shigella/enteroinvasive E. coli (14.5%, 10.2 - 22.8), and Cryptosporidium (7.9%, 6.2 - 9.3). Despite the clear impact of vaccine introduction in this setting, rotavirus remained the leading etiology of diarrhea requiring hospitalization. Further efforts to maximize vaccine coverage and improve vaccine performance in these settings are warranted. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  6. Rotavirus vaccine impact and socioeconomic deprivation: an interrupted time-series analysis of gastrointestinal disease outcomes across primary and secondary care in the UK.

    Science.gov (United States)

    Hungerford, Daniel; Vivancos, Roberto; Read, Jonathan M; Iturriza-Gόmara, Miren; French, Neil; Cunliffe, Nigel A

    2018-01-29

    Rotavirus causes severe gastroenteritis in infants and young children worldwide. The UK introduced the monovalent rotavirus vaccine (Rotarix®) in July 2013. Vaccination is free of charge to parents, with two doses delivered at 8 and 12 weeks of age. We evaluated vaccine impact across a health system in relation to socioeconomic deprivation. We used interrupted time-series analyses to assess changes in monthly health-care attendances in Merseyside, UK, for all ages, from July 2013 to June 2016, compared to predicted counterfactual attendances without vaccination spanning 3-11 years pre-vaccine. Outcome measures included laboratory-confirmed rotavirus gastroenteritis (RVGE) hospitalisations, acute gastroenteritis (AGE) hospitalisations, emergency department (ED) attendances for gastrointestinal conditions and consultations for infectious gastroenteritis at community walk-in centres (WIC) and general practices (GP). All analyses were stratified by age. Hospitalisations were additionally stratified by vaccine uptake and small-area-level socioeconomic deprivation. The uptake of the first and second doses of rotavirus vaccine was 91.4% (29,108/31,836) and 86.7% (27,594/31,836), respectively. Among children aged impact was greatest during the rotavirus season and for vaccine-eligible age groups. In adults aged 65+ years, AGE hospitalisations fell by 25% (95% CI 19-30%; p socioeconomically deprived communities (adjusted incident rate ratio 1.57; 95% CI 1.51-1.64; p impact was greatest among the most deprived populations, despite lower vaccine uptake. Prioritising vaccine uptake in socioeconomically deprived communities should give the greatest health benefit in terms of population disease burden.

  7. Impact of maternal antibodies and infant gut microbiota on the immunogenicity of rotavirus vaccines in African, Indian and European infants: protocol for a prospective cohort study.

    Science.gov (United States)

    Sindhu, Kuladaipalayam Natarajan C; Cunliffe, Nigel; Peak, Matthew; Turner, Mark; Darby, Alistair; Grassly, Nicholas; Gordon, Melita; Dube, Queen; Babji, Sudhir; Praharaj, Ira; Verghese, Valsan; Iturriza-Gómara, Miren; Kang, Gagandeep

    2017-03-29

    Gastroenteritis is the leading cause of morbidity and mortality among young children living in resource-poor settings, majority of which is attributed to rotavirus. Rotavirus vaccination can therefore have a significant impact on infant mortality. However, rotavirus vaccine efficacy in Sub-Saharan Africa and Southeast Asia is significantly lower than in high-income countries. Maternally derived antibodies, infant gut microbiota and concomitant oral polio vaccination have been proposed as potential reasons for poor vaccine performance in low-income settings. The overall aim of this study is to compare the role of maternally derived antibodies and infant gut microbiota in determining immune response to rotavirus vaccine in high-income and low-income settings, using the same vaccine and a similar study protocol. The study is an observational cohort in three countries-Malawi, India and UK. Mothers will be enrolled in third trimester of pregnancy and followed up, along with infants after delivery, until the infant completes two doses of oral rotavirus vaccine (along with routine immunisation). The levels of prevaccination maternally derived rotavirus-specific antibodies (IgG) will be correlated with infant seroconversion and antibody titres, 4 weeks after the second dose of rotavirus vaccine. Both within-country and between-country comparisons of gut microbiome will be carried out between children who seroconvert and those who do not. The impact of oral polio vaccine coadministration on rotavirus vaccine response will be studied in Indian infants. Ethical approvals have been obtained from Integrated Research Application System (IRAS, NHS ethics) in UK, College of Medicine Research and Ethics Committee (COMREC) in Malawi and Institutional Review Board (IRB), Christian Medical College, Vellore in India. Participant recruitment and follow-up is ongoing at all three sites. Analysis of data, followed by publication of the results, is expected in 2018. Published by the BMJ

  8. Retrospective hospital based surveillance of intussusception in children in a sentinel paediatric hospital: benefits and pitfalls for use in post-marketing surveillance of rotavirus vaccines.

    Science.gov (United States)

    Lloyd-Johnsen, C; Justice, F; Donath, S; Bines, J E

    2012-04-27

    Evaluation of the safety of rotavirus vaccines, particularly with respect to the risk of intussusception, is recommended for countries planning to introduce rotavirus vaccines into the National Immunisation Program. However, as prospective studies are costly, require time to conduct and may be difficult to perform in some settings, retrospective hospital based surveillance at sentinel sites has been suggested as an option for surveillance for intussusception following introduction of rotavirus vaccines. To assess the value of retrospective hospital based surveillance to describe clinical and epidemiological features of intussusception in children aged <24 months and to investigate any temporal association between receipt of a rotavirus vaccine and intussusception. A retrospective chart review of all patients diagnosed with intussusception at Royal Children's Hospital, Melbourne, Australia over an 8-year period including before and after rotavirus vaccine introduction into the National Immunisation Program, was conducted using patients identified by a medical record database (ICD-10-CM 56.1). Patient profile, clinical presentation, treatment and outcome were analysed along with records of immunisation status obtained using the Australian Childhood Immunisation Register. A 9% misclassification rate of discharge diagnosis of intussusception was identified on critical chart review. The incidence rate of intussusception at the Royal Children's Hospital over the study period was 1.91 per 10,000 infants <24 months (95% CI 1.65-2.20). Intestinal resection was required in 6.5% of infants (95% CI 3.6%, 11.0%). Intussusception occurred within 30 days after vaccination in 2 of 27 patients who had received at least 1 dose of a rotavirus vaccine. Valuable data on the incidence, clinical presentation and treatment outcomes of intussusception can be obtained from data retrieved from hospital medical records in a sentinel paediatric hospital using standardised methodology. However

  9. Efficacy and safety of pentavalent rotavirus vaccine in Japan: a randomized, double-blind, placebo-controlled, multicenter trial.

    Science.gov (United States)

    Iwata, Satoshi; Nakata, Shuji; Ukae, Susumu; Koizumi, Yoshitugu; Morita, Yasuyuki; Kuroki, Haruo; Tanaka, Yoshiyuki; Shizuya, Toshiyuki; Schödel, Florian; Brown, Michelle L; Lawrence, Jody

    2013-08-01

    Rotavirus is the most common cause of severe gastroenteritis in children under 5 y of age. Estimates of disease burden in Japan suggest that between 26,500 and 78,000 children in this age group need hospitalization each year, resulting in a direct medical cost of 10 to 24 billion Yen. Since being introduced in routine infant immunization schedules in the United States in 2006, the oral live pentavalent rotavirus vaccine RV5 (RotaTeq™) has contributed to dramatic reductions in the incidence of rotavirus gastroenteritis (RVGE) and in health care resource utilization. This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of a 3-dose regimen of RV5 in healthy infants, age 6 to 12 weeks, at 32 sites across Japan. The results indicate that RV5 was significantly efficacious in preventing any severity [74.5% (95% confidence interval [CI]: 39.9%, 90.6%; pvaccine. The observed cases of RVGE included rotavirus types G1 (n=19), G3 (n=9), G9 (n=5) and one unspecified G serotype with P1A[8]. No G2 or G4 RVGE cases were observed, and this study was not powered to evaluate efficacy against individual serotypes. RV5 was generally safe and well tolerated in Japanese infants. These results are comparable to those observed in clinical studies conducted in other developed countries. Introduction of the vaccine in Japan may reduce disease burden and associated health care costs.

  10. Predictors of Uptake and Timeliness of Newly Introduced Pneumococcal and Rotavirus Vaccines, and of Measles Vaccine in Rural Malawi: A Population Cohort Study.

    Directory of Open Access Journals (Sweden)

    Hazzie Mvula

    Full Text Available Malawi introduced pneumococcal conjugate vaccine (PCV13 and monovalent rotavirus vaccine (RV1 in 2011 and 2012 respectively, and is planning the introduction of a second-dose measles vaccine (MV. We assessed predictors of availability, uptake and timeliness of these vaccines in a rural Malawian setting.Commencing on the first date of PCV13 eligibility we conducted a prospective population-based birth cohort study of 2,616 children under demographic surveillance in Karonga District, northern Malawi who were eligible for PCV13, or from the date of RV1 introduction both PCV13 and RV1. Potential predictors of vaccine uptake and timeliness for PCV13, RV1 and MV were analysed respectively using robust Poisson and Cox regression.Vaccine coverage was high for all vaccines, ranging from 86.9% for RV1 dose 2 to 95.4% for PCV13 dose 1. Median time delay for PCV13 dose 1 was 17 days (IQR 7-36, 19 days (IQR 8-36 for RV1 dose 1 and 20 days (IQR 3-46 for MV. Infants born to lower educated or farming mothers and those living further away from the road or clinic were at greater risk of being not fully vaccinated and being vaccinated late. Delays in vaccination were also associated with non-facility birth. Vaccine stock-outs resulted in both a delay in vaccine timeliness and in a decrease in completion of schedule.Despite high vaccination coverage in this setting, delays in vaccination were common. We identified programmatic and socio-demographic risk factors for uptake and timeliness of vaccination. Understanding who remains most vulnerable to be unvaccinated allows for focussed delivery thereby increasing population coverage and maximising the equitable benefits of universal vaccination programmes.

  11. 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.

  12. Predominance of norovirus and sapovirus in Nicaragua after implementation of universal rotavirus vaccination.

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    Filemón Bucardo

    Full Text Available BACKGROUND: Despite significant reduction of rotavirus (RV infections following implementation of RotaTeq vaccination in Nicaragua, a large burden of patients with diarrhea persists. METHODS: We conducted a community- and hospital-based study of the burden of RV, norovirus (NV and sapovirus (SV infections as cause of sporadic acute gastroenteritis (GE among 330 children ≤ 5 years of age between September 2009 and October 2010 in two major cities of Nicaragua with a RotaTeq coverage rate of 95%. RESULTS: We found that NV, SV and RV infections altogether accounted for 45% of cases of GE. Notably, NV was found in 24% (79/330 of the children, followed by SV (17%, 57/330 and RV (8%, 25/330. The detection rate in the hospital setting was 27%, 15% and 14% for NV, SV and RV respectively, whereas in the community setting the detection rate of RV was < 1%. Among each of the investigated viruses one particular genogroup or genotype was dominant; GII.4 (82% for NV, GI (46% for SV and G1P[8] (64% in RV. These variants were also found in higher proportions in the hospital setting compared to the community setting. The GII.4.2006 Minerva strain circulating globally since 2006 was the most common among genotyped NV in this study, with the GII.4-2010 New Orleans emerging in 2010. CONCLUSIONS: This study shows that NV has become the leading viral cause of gastroenteritis at hospital and community settings in Nicaragua after implementation of RV vaccination.

  13. Beta 3 and PDI proteins isolated from human platelets bind with ECwt rotavirus in vitro

    International Nuclear Information System (INIS)

    Mayorga, Diana; Rubio, Linda; Guerrero-Fonseca, Carlos A; Acosta-Losada, Orlando

    2010-01-01

    Commercial integrin Beta 3 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 Beta 3 and PDI and wild type rotavirus strains. Objective. To explore a methodology allowing isolation of proteins Beta 3 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 Beta 3 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 Beta 3 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 electro elution from a gel slice. Polyclonal antibodies against protein Beta 3 were generated in rabbit. Incubation of eluted proteins Beta 3 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 Beta 3 and PDI were partially purified from human platelets by preparative electrophoresis. The isolation of these proteins allowed the generation of polyclonal antibodies against Beta 3 in addition to the establishment of the in vitro interaction of proteins Beta 3 and PDI with rotavirus ECwt. This interaction was also demonstrated in vivo after incubating the virus with isolated small

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

    African Journals Online (AJOL)

    Subjects and Methods:Faecal samples were collected from 119 infants and young children with diarrhoea and were analysed by commercial ELISA and polyacrylamide gel electrophoresis (SDS-PAGE) to identify possible non-group A rotaviruses. Extraction of any potential rrotavirus double-stranded RNA from faeces amd ...

  15. Efficacy, safety and effectiveness of licensed rotavirus vaccines: a systematic review and meta-analysis for Latin America and the Caribbean.

    Science.gov (United States)

    Velázquez, Raúl F; Linhares, Alexandre C; Muñoz, Sergio; Seron, Pamela; Lorca, Pedro; DeAntonio, Rodrigo; Ortega-Barria, Eduardo

    2017-01-13

    RotaTeq™ (RV5; Merck & Co. Inc., USA) and Rotarix™ (RV1, GlaxoSmithKline, Belgium) vaccines, developed to prevent rotavirus diarrhea in children under five years old, were both introduced into national immunization programs in 2006. As many countries in Latin America and the Caribbean have included either RV5 or RV1 in their routine childhood vaccination programs, we conducted a systematic review and meta-analysis to analyze efficacy, safety and effectiveness data from the region. We conducted a systematic search in PubMed, EMBASE, Scielo, Lilacs and the Cochrane Central Register, for controlled efficacy, safety and effectiveness studies published between January 2000 until December 2011, on RV5 and RV1 across Latin America (where both vaccines are available since 2006). The primary outcome measures were: rotavirus-related gastroenteritis of any severity; rotavirus emergency department visits and hospitalization; and severe adverse events. The results of the meta-analysis for efficacy show that RV1 reduced the risk of any-severity rotavirus-related gastroenteritis by 65% (relative risk (RR) 0.35, 95% confidence interval (CI) 0.25; 0.50), and of severe gastroenteritis by 82% (RR 0.18, 95%CI 0.12; 0.26) versus placebo. In trials, both vaccines significantly reduced the risk of hospitalization and emergency visits by 85% (RR 0.15, 95%CI 0.09; 0.25) for RV1 and by 90% (RR 0.099, 95%CI 0.012; 0.77) for RV5. Vaccination with RV5 or RV1 did not increase the risk of death, intussusception, or other severe adverse events which were previously associated with the first licensed rotavirus vaccine. Real-world effectiveness studies showed that both vaccines reduced rotavirus hospitalization in the region by around 45-50% for RV5 (for 1 to 3 doses, respectively), and, by around 50-80% for RV1 (for 1 to 2 doses, respectively). For RV1, effectiveness against hospitalization was highest (around 80-96%) for children vaccinated before 12 months of age, compared with 5

  16. The impact of rotavirus vaccination on emergency department visits and hospital admissions for acute diarrhea in children under 5 years

    Directory of Open Access Journals (Sweden)

    Rodrigo Locatelli Pedro Paulo

    Full Text Available Summary Introduction: Acute diarrheal disease is the second cause of death in children under 5 years. In Brazil, from 2003 to 2009, acute diarrhea was responsible for nearly 100,000 hospital admissions per year and 4% of the deaths in children under 5 years. Rotavirus is the leading cause of severe acute diarrhea worldwide. In 2006, the rotavirus monovalent vaccine (RV1 was added to the Brazilian National Immunization Program. Objectives: To analyze the impact of the RV1 on emergency department (ED visits and hospital admissions for acute diarrhea. Method: A retrospective ecologic study at the University Hospital, University of São Paulo. The study analyzed the pre-vaccine (2003–2005 and the post-vaccine (2007–2009 periods. We screened the main diagnosis of all ED attendances and hospital admissions of children under 5 years in an electronic registry system database and calculated the rates of ED visits and hospital admissions. The reduction rate was analyzed according to the following formula: reduction (% = (1 - odds ratio x 100. Results: The rates of ED visits for acute diarrhea was 85.8 and 80.9 per 1,000 total ED visits in the pre and post vaccination periods, respectively, resulting in 6% reduction (95CI 4 to 9%, p<0.001. The rates of hospital admissions for acute diarrhea was 40.8 per 1,000 in the pre-vaccine period and dropped to 24.9 per 1,000 hospitalizations, resulting in 40% reduction (95CI 22 to 54%, p<0.001. Conclusion: The introduction of the RV1 vaccine resulted in 6% reduction in the ED visits and 40% reduction in hospital admissions for acute diarrhea.

  17. The impact of rotavirus vaccination on emergency department visits and hospital admissions for acute diarrhea in children under 5 years.

    Science.gov (United States)

    Paulo, Rodrigo Locatelli Pedro; Rodrigues, André Broggin Dutra; Machado, Beatriz Marcondes; Gilio, Alfredo Elias

    2016-09-01

    Acute diarrheal disease is the second cause of death in children under 5 years. In Brazil, from 2003 to 2009, acute diarrhea was responsible for nearly 100,000 hospital admissions per year and 4% of the deaths in children under 5 years. Rotavirus is the leading cause of severe acute diarrhea worldwide. In 2006, the rotavirus monovalent vaccine (RV1) was added to the Brazilian National Immunization Program. To analyze the impact of the RV1 on emergency department (ED) visits and hospital admissions for acute diarrhea. A retrospective ecologic study at the University Hospital, University of São Paulo. The study analyzed the pre-vaccine (2003-2005) and the post-vaccine (2007-2009) periods. We screened the main diagnosis of all ED attendances and hospital admissions of children under 5 years in an electronic registry system database and calculated the rates of ED visits and hospital admissions. The reduction rate was analyzed according to the following formula: reduction (%) = (1 - odds ratio) x 100. The rates of ED visits for acute diarrhea was 85.8 and 80.9 per 1,000 total ED visits in the pre and post vaccination periods, respectively, resulting in 6% reduction (95CI 4 to 9%, p<0.001). The rates of hospital admissions for acute diarrhea was 40.8 per 1,000 in the pre-vaccine period and dropped to 24.9 per 1,000 hospitalizations, resulting in 40% reduction (95CI 22 to 54%, p<0.001). The introduction of the RV1 vaccine resulted in 6% reduction in the ED visits and 40% reduction in hospital admissions for acute diarrhea.

  18. The cost-effectiveness of rotavirus vaccination: Comparative analyses for five European countries and transferability in Europe.

    Science.gov (United States)

    Jit, Mark; Bilcke, Joke; Mangen, Marie-Josée J; Salo, Heini; Melliez, Hugues; Edmunds, W John; Yazdan, Yazdanpanah; Beutels, Philippe

    2009-10-19

    Cost-effectiveness analyses are usually not directly comparable between countries because of differences in analytical and modelling assumptions. We investigated the cost-effectiveness of rotavirus vaccination in five European Union countries (Belgium, England and Wales, Finland, France and the Netherlands) using a single model, burden of disease estimates supplied by national public health agencies and a subset of common assumptions. Under base case assumptions (vaccination with Rotarix, 3% discount rate, health care provider perspective, no herd immunity and quality of life of one caregiver affected by a rotavirus episode) and a cost-effectiveness threshold of euro30,000, vaccination is likely to be cost effective in Finland only. However, single changes to assumptions may make it cost effective in Belgium and the Netherlands. The estimated threshold price per dose for Rotarix (excluding administration costs) to be cost effective was euro41 in Belgium, euro28 in England and Wales, euro51 in Finland, euro36 in France and euro46 in the Netherlands.

  19. Epidemiological and Economic Impact of Monovalent and Pentavalent Rotavirus Vaccines in Low and Middle Income Countries: A Cost-effectiveness Modeling Analysis.

    Science.gov (United States)

    Paternina-Caicedo, Angel; De la Hoz-Restrepo, Fernando; Alvis-Guzmán, Nelson

    2015-07-01

    The competing choices of vaccination with either RV1 or RV5, the potential budget impact of vaccines on the EPI with different prices and new evidence make important an updated analysis for health decision makers in each country. The objective of this study is to assess cost-effectiveness of the monovalent and pentavalent rotavirus vaccines and impact on children deaths, inpatient and outpatient visits in 116 low and middle income countries that represent approximately 99% of rotavirus mortality. A decision tree model followed hypothetical cohorts of children from birth up to 5 years of age for each country in 2010. Inputs were gathered from international databases and previous research on incidence and effectiveness of monovalent and pentavalent vaccines. Costs were expressed in 2010 international dollars. Outcomes were reported in terms of cost per disability-adjusted life-year averted, comparing no vaccination with either monovalent or pentavalent mass introduction. Vaccine price was assumed fixed for all world low-income and middle-income countries. Around 292,000 deaths, 3.34 million inpatient cases and 23.09 million outpatient cases would occur with no vaccination. In the base-case scenario, monovalent vaccination would prevent 54.7% of inpatient cases and 45.4% of deaths. Pentavalent vaccination would prevent 51.4% of inpatient cases and 41.1% of deaths. The vaccine was cost-effective in all world countries in the base-case scenario for both vaccines. Cost per disability-adjusted life-year averted in all selected countries was I$372 for monovalent, and I$453 for pentavalent vaccination. Rotavirus vaccine is cost-effective in most analyzed countries. Despite cost-effectiveness analysis is a useful tool for decision making in middle-income countries, for low-income countries health decision makers should also assess the impact of introducing either vaccine on local resources and budget impact analysis of vaccination.

  20. Oral Vaccination with the Porcine Rotavirus VP4 Outer Capsid Protein Expressed by Lactococcus lactis Induces Specific Antibody Production

    Directory of Open Access Journals (Sweden)

    Yi-jing Li

    2010-01-01

    Full Text Available The objective of this study to design a delivery system resistant to the gastrointestinal environment for oral vaccine against porcine rotavirus. Lactococcus lactis NZ9000 was transformed with segments of vP4 of the porcine rotavirus inserted into the pNZ8112 surface-expression vector, and a recombinant L. lactis expressing VP4 protein was constructed. An approximately 27 kDa VP4 protein was confirmed by SDS-PAGE , Western blot and immunostaining analysis. BALB/c mice were immunized orally with VP4-expression recombinant L. lactis and cellular, mucosal and systemic humoral immune responses were examined. Specific anti-VP4 secretory IgA and IgG were found in feces, ophthalmic and vaginal washes and in serum. The induced antibodies demonstrated neutralizing effects on porcine rotavirus infection on MA104 cells. Our findings suggest that oral immunization with VP4-expressing L. lactis induced both specific local and systemic humoral and cellular immune responses in mice.

  1. 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 ...

  2. Nutritional status in relation to the efficacy of the rhesus-human reassortant, tetravalent rotavirus vaccine (RRV-TV in infants from Belém, Pará State, Brazil Relação entre o estado nutricional e a eficácia da vacina tetravalente contra rotavírus de origem símio-humana, geneticamente rearranjada (RRV-TV, em crianças de Belém, Pará, Brasil

    Directory of Open Access Journals (Sweden)

    Alexandre C. LINHARES

    2002-02-01

    Full Text Available The rhesus-human reassortant, tetravalent rotavirus vaccine (RRV-TV was licensed for routine use in the United States of America but it was recently withdrawn from the market because of its possible association with intussusception as an adverse event. The protective efficacy of 3 doses of RRV-TV, in its lower-titer (4 x 10(4 pfu/dose formulation, was evaluated according to the nutritional status of infants who participated in a phase III trial in Belém, Northern Brazil. A moderate protection conferred by RRV-TV was related to weight-for-age Z-scores (WAZ greater than -1 only, with rates of 38% (p = 0.04 and 40% (p = 0.04 for all- and- pure rotavirus diarrhoeal cases, respectively. In addition, there was a trend for greater efficacy (43%, p = 0.05 among infants reaching an height-for-age Z-score (HAZ of > -1. Taking WAZ, HAZ and weight-for-height Z-score (WHZ indices 0.05 if both placebo and vaccine groups are compared. There was no significant difference if rates of mixed and pure rotavirus diarrhoeal cases are compared in relation to HAZ, WAZ and weight-for-height Z-score (WHZ indices. Although a low number of malnourished infants could be identified in the present study, our data show some evidence that malnutrition may interfere with the efficacy of rotavirus vaccines in developing countries.A vacina tetravalente contra rotavírus de origem símio-humana, geneticamente rearranjada (RRV-TV, foi licenciada para uso rotineiro nos Estados Unidos da América do Norte; entretanto, tal imunizante foi removido do mercado, uma vez que a intussuscepção emergiu como possível evento adverso vacinal. A eficácia da RRV-TV - em sua formulação menos concentrada (10 x 10(4 pfu/dose - foi avaliada no tocante ao estado nutricional das crianças que integraram estudo caracterizado como de fase III, levado a efeito em Belém, região norte do Brasil. Observou-se proteção (moderada apenas entre os indivíduos com escore "Z" (peso-por-idade, WAZ superior

  3. Predictors of administration and attitudes about pneumococcal, Haemophilus influenzae type b and rotavirus vaccines among pediatricians in India: a national survey.

    Science.gov (United States)

    Gargano, Lisa M; Thacker, Naveen; Choudhury, Panna; Weiss, Paul S; Pazol, Karen; Bahl, Sunil; Jafari, Hamid S; Arora, Manisha; Orenstein, Walter A; Hughes, James M; Omer, Saad B

    2012-05-21

    According to the World Health Organization in 2008, pneumonia accounted for 20% of deaths and diarrheal diseases accounted for 13% of deaths among children under 5 in India. Vaccines are available for Streptococcus pneumoniae (pneumococcal conjugate vaccine (PCV)), Haemophilus influenzae type b (Hib vaccine), and rotavirus. Barriers to including these vaccines in routine immunization schedule in India include potential negative impacts on fragile existing immunization programs and cost. Pediatricians who are members of the Indian Academy of Pediatrics (IAP) are important stakeholders for vaccine delivery and maintaining public confidence in vaccines. A random sample of 785 pediatricians belonging to IAP was selected for the survey conducted from June 2009 to June 2010. Descriptive analyses using sampling weights were performed to evaluate the distributions of variables assessing vaccine-related attitudes and behaviors among pediatricians. Logistic regression was used to assess factors associated with routine vaccine use. The majority of pediatricians reported administering PCV (85.6%), Hib (95.9%), and rotavirus (80.2%) vaccine selectively or routinely. Pediatricians who had high perceived disease susceptibility were 2.42 times more likely to report routine administration of Hib vaccine (OR 2.42, 95% CI 1.24, 4.74). Pediatricians who had high perceived Hib vaccine efficacy were 4.74 times more likely to administer Hib vaccine routinely (OR 4.74, 95% CI 2.09, 10.74). Perceptions of disease susceptibility and severity or of vaccine safety and efficacy were not associated with routine administration of PCV or rotavirus vaccine. Understanding predictors of routine use of a new vaccine could help focus interventions to improve the routine use of other vaccines. The importance of perceived susceptibility to and severity of diseases caused by S. pneumoniae, Hib, and rotavirus and perceived efficacy and safety of the vaccines by pediatricians presents an opportunity to

  4. Characterization and protective efficacy in an animal model of a novel truncated rotavirus VP8 subunit parenteral vaccine candidate.

    Science.gov (United States)

    Xue, Miaoge; Yu, Linqi; Che, Yaojian; Lin, Haijun; Zeng, Yuanjun; Fang, Mujin; Li, Tingdong; Ge, Shengxiang; Xia, Ningshao

    2015-05-21

    The cell-attachment protein VP8* of rotavirus is a potential candidate parenteral vaccine. However, the yield of full-length VP8 protein (VP8*, residues 1-231) expressed in Escherichia coli was low, and a truncated VP8 protein (ΔVP8*, residues 65-231) cannot elicit efficient protective immunity in a mouse model. In this study, tow novel truncated VP8 proteins, VP8-1 (residues 26-231) and VP8-2 (residues 51-231), were expressed in E. coli and evaluated for immunogenicity and protective efficacy, compared with VP8* and ΔVP8*. As well as ΔVP8*, the protein VP8-1 and VP8-2 were successfully expressed in high yield and purified in homogeneous dimeric forms, while the protein VP8* was expressed with lower yield and prone to aggregation and degradation in solution. Although the immunogenicity of the protein VP8*, VP8-1, VP8-2 and ΔVP8* was comparable, immunization of VP8* and VP8-1 elicited significantly higher neutralizing antibody titers than that of VP8-2 and ΔVP8* in mice. Furthermore, when assessed using a mouse maternal antibody model, the efficacy of VP8-1 to protect against rotavirus-induced diarrhea in pups was comparable to that of VP8*, both were dramatically higher than that of VP8-2 and ΔVP8*. Taken together, the novel truncated protein VP8-1, with increased yield, improved homogeneity and high protective efficacy, is a viable candidate for further development of a parenterally administrated prophylactic vaccine against rotavirus infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Impacto de la introducción de la vacuna contra el rotavirus en la hospitalización por gastroenteritis aguda grave en el Hospital del Niño de la Ciudad de Panamá Impact of rotavirus vaccine introduction on hospital admissions for severe acute gastroenteritis at the Children's Hospital in Panama City

    Directory of Open Access Journals (Sweden)

    Javier Nieto Guevara

    2008-09-01

    < 0.05. RESULTS: There was a total of 1 240 episodes of severe acute gastroenteritis in 1 222 children. No significant differences were found between the two study periods regarding the number of complications (P = 0.92 and deaths (P = 1.00. Although there were more episodes of severe acute gastroenteritis after initiating vaccination against human rotavirus than there were in the period prior, the difference was not statistically significant (RR = 1.12; 95%CI: 087-1.44; P = 0.39. There were no significant differences found in the length of hospital stay by age groups studied in each time period. The percent of cases treated with antibiotics was similar in both study periods (29.7% versus 25.2%; P = 0.08. CONCLUSIONS: The introduction of infant rotavirus vaccination was not found to lead to a significant reduction in hospital admission rates for gastroenteritis among children less than 5 years of age. Significant changes in morbidity and in antibiotics use were not found after the introduction of the vaccine.

  6. Sequence analysis of the whole genomes of five African human G9 rotavirus strains.

    Science.gov (United States)

    Nyaga, Martin M; Jere, Khuzwayo C; Peenze, Ina; Mlera, Luwanika; van Dijk, Alberdina A; Seheri, Mapaseka L; Mphahlele, M Jeffrey

    2013-06-01

    The G9 rotaviruses are amongst the most common global rotavirus strains causing severe childhood diarrhoea. However, the whole genomes of only a few G9 rotaviruses have been fully sequenced and characterised of which only one G9P[6] and one G9P[8] are from Africa. We determined the consensus sequence of the whole genomes of five African human group A G9 rotavirus strains, four G9P[8] strains and one G9P[6] strain collected in Cameroon (central Africa), Kenya (eastern Africa), South Africa and Zimbabwe (southern Africa) in 1999, 2009 and 2010. Strain RVA/Human-wt/ZWE/MRC-DPRU1723/2009/G9P[8] from Zimbabwe, RVA/Human-wt/ZAF/MRC-DPRU4677/2010/G9P[8] from South Africa, RVA/Human-wt/CMR/1424/2009/G9P[8] from Cameroon and RVA/Human-wt/KEN/MRC-DPRU2427/2010/G9P[8] from Kenya were on a Wa-like genetic backbone and were genotyped as G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. Strain RVA/Human-wt/ZAF/MRC-DPRU9317/1999/G9P[6] from South Africa was genotyped as G9-P[6]-I2-R2-C2-M2-A2-N1-T2-E2-H2. Rotavirus A strain MRC-DPRU9317 is the second G9 strain to be reported on a DS-1-like genetic backbone, the other being RVA/Human-wt/ZAF/GR10924/1999/G9P[6]. MRC-DPRU9317 was found to be a reassortant between DS-1-like (I2, R2, C2, M2, A2, T2, E2 and H2) and Wa-like (N1) genome segments. All the genome segments of the five strains grouped strictly according to their genotype Wa- or DS-1-like clusters. Within their respective genotypes, the genome segments of the three G9 study strains from southern Africa clustered most closely with rotaviruses from the same geographical origin and with those with the same G and P types. The highest nucleotide identity of genome segments of the study strains from eastern and central Africa regions on a Wa-like backbone was not limited to rotaviruses with G9P[8] genotypes only, they were also closely related to G12P[6], G8P[8], G1P[8] and G11P[25] rotaviruses, indicating a close inter-genotype relationship between the G9 and other rotavirus genotypes

  7. Comparative review of three cost-effectiveness models for rotavirus vaccines in national immunization programs; a generic approach applied to various regions in the world

    NARCIS (Netherlands)

    Postma, Maarten J.; Jit, Mark; Rozenbaum, Mark H.; Standaert, Baudouin; Tu, Hong-Anh; Hutubessy, Raymond C. W.

    2011-01-01

    Background: This study aims to critically review available cost-effectiveness models for rotavirus vaccination, compare their designs using a standardized approach and compare similarities and differences in cost-effectiveness outcomes using a uniform set of input parameters. Methods: We identified

  8. Estimating and comparing the clinical and economic impact of paediatric rotavirus vaccination in Turkey using a simple versus an advanced model

    NARCIS (Netherlands)

    Bakir, Mustafa; Standaert, Baudouin; Turel, Ozden; Bilge, Zeynep Ece; Postma, Maarten

    2013-01-01

    Background: The burden of rotavirus disease is high in Turkey, reflecting the large birth cohort (> 1.2 million) and the risk of disease. Modelling can help to assess the potential economic impact of vaccination. We compared the output of an advanced model with a simple model requiring fewer data

  9. In-season and out-of-season variation of rotavirus genotype distribution and age of infection across 12 European countries before the introduction of routine vaccination, 2007/08 to 2012/13

    DEFF Research Database (Denmark)

    Hungerford, Daniel; Vivancos, Roberto; Read, Jonathan M

    2016-01-01

    distribution and age distribution of rotavirus gastroenteritis (RVGE) cases in and out of peak season in 12 countries which were yet to implement routine rotavirus vaccination. In multinomial multivariate logistic regression, adjusting for year, country and age, the odds of infection caused by genotype...

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

    DEFF Research Database (Denmark)

    Midgley, Sofie; Gram, N.; Hjulsager, Charlotte Kristiane

    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...... 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...... 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...

  11. Antibody response in vaccinated pregnant mares to recent G3BP[12] and G14P[12] equine rotaviruses

    Directory of Open Access Journals (Sweden)

    Nemoto Manabu

    2012-11-01

    Full Text Available Abstract Background Both the G3P[12] and the G14P[12] type of equine group A rotavirus (RVA have recently become predominant in many countries, including Japan. G3 types are classified further into G3A and G3B. The G3A viruses have been circulating in Europe, Australia, and Argentina, and the G3B viruses have been circulating in Japan. However, only an inactivated vaccine containing a single G3BP[12] strain is commercially available in Japan. To assess the efficacy of the current vaccine against recently circulating equine RVA strains, we examined antibody responses in pregnant mares to recent G3BP[12] and G14P[12] strains by virus neutralization test. Findings After vaccination in five pregnant mares, the geometric mean serum titers of virus-neutralizing antibody to recent G3BP[12] strains increased 5.3- to 7.0-fold and were similar to that against homologous vaccine strain. Moreover, antibody titers to recent G14P[12] strains were also increased 3.0- to 3.5-fold. Conclusions These results suggest that inoculation of mares with the current vaccine should provide foals with virus-neutralizing antibodies against not only the G3BP[12] but also the G14P[12] RVA strain via the colostrum.

  12. Changes in Rotavirus Genotypes before and after Vaccine Introduction: a Multicenter, Prospective Observational Study in Three Areas of Japan.

    Science.gov (United States)

    Tanaka, Takaaki; Kamiya, Hajime; Asada, Kazutoyo; Suga, Shigeru; Ido, Masaru; Umemoto, Masakazu; Ouchi, Kazunobu; Ito, Hiroaki; Kuroki, Haruo; Nakano, Takashi; Taniguchi, Koki

    2017-07-24

    In Japan, monovalent and pentavalent rotavirus (RV) vaccines were approved in 2011 and 2012, respectively. To monitor changes in the RV genotypes before and after vaccine introduction, we performed a prospective observational study among children (< 5 years) with gastroenteritis who tested RV-positive on antigen rapid tests. Stool samples were collected from 3 different sites in Japan: Tsu City, Mie Prefecture; Kurashiki City, Okayama Prefecture; and Isumi City, Chiba Prefecture. RV genotypes were determined using reverse transcription-polymerase chain reaction. In Tsu City, G3P[8] was dominant (61.0-77.1%) before vaccine introduction, but decreased after introduction. Meanwhile, in an inverse proportion to the decrease in G3P[8], G1P[8] increased until the 2013/14 season, when a sudden predominance of G2P[4] (100%) occurred. A similar trend was observed in Kurashiki City in terms of the extent of reduction in G3P[8] and the emergence of G2P[4]. In Isumi City, G1P[8] was dominant (70.3%) before vaccine introduction, and G9P[8] became predominant (83.3%) in the 2013/14 season. To determine whether the genotype changes are attributable to vaccines or natural epidemiological changes, ongoing continuous monitoring of the RV genotypes is required.

  13. The epidemiology of rotavirus diarrhea in Latin America: anticipating rotavirus vaccines La epidemiología de la diarrea por rotavirus en América Latina: perspectivas de vacunación frente al rotavirus

    Directory of Open Access Journals (Sweden)

    Erin M. Kane

    2004-12-01

    Full Text Available OBJECTIVE: To assess the disease burden and characterize the epidemiology of rotavirus diarrhea in Latin America. METHODS: We conducted a literature review of studies of children OBJETIVO: Valorar la carga de enfermedad e identificar las características epidemiológicas de la diarrea causada por rotavirus en América Latina. MÉTODOS: Realizamos una revisión de la literatura que abarcaba los estudios de niños menores de 5 años que fueron hospitalizados o atendidos como pacientes ambulatorios a causa de la diarrea, y en los cuales se buscó al rotavirus como agente etiológico de la diarrea. Nuestro trabajo de revisión incluye los estudios publicados desde el año 1998 sobre pacientes ingresados y ambulatorios, que incluyeron a 100 niños o más, y que informaron sobre actividades de vigilancia que se prolongaron durante al menos 12 meses consecutivos. RESULTADOS: Un total de 18 estudios de pacientes ingresados y 10 estudios de pacientes ambulatorios satisficieron los criterios de inclusión de nuestro trabajo de revisión. Se detectó el rotavirus en el 31% (mediano de los pacientes ingresados (intervalo del 16% al 52% y en el 30.5% de los pacientes ambulatorios (intervalo del 4% al 42%. La tasa mediana de detección fue mayor en los estudios que emplearon un ensayo de encimoinmunoanálisis (ELISA (pacientes ingresados: 38%, pacientes ambulatorios: 33% frente a otros métodos de detección menos sensibles. La distribución de la enfermedad rotavírica según la edad difería entre países, aunque la proporción de niños hospitalizados durante el primer año de vida fue del 65% al 85%. En la mayoría de los países se produjeron ingresos hospitalarios por rotavirus durante todo el año, y el rotavirus normalmente mostraba un máximo estacional en el invierno tanto en las zonas de clima tropical como en aquellas de clima templado. CONCLUSIONES: La importante carga de enfermedad que se atribuye al rotavirus en América Latina sugiere que las

  14. Impact of five years of rotavirus vaccination in Finland - And the associated cost savings in secondary healthcare.

    Science.gov (United States)

    Leino, Tuija; Baum, Ulrike; Scott, Peter; Ollgren, Jukka; Salo, Heini

    2017-10-09

    This study aimed to estimate the impact of the national rotavirus (RV) vaccination programme, starting 2009, on the total hospital-treated acute gastroenteritis (AGE) and severe RV disease burden in Finland during the first five years of the programme. This study also evaluated the costs saved in secondary healthcare by the RV vaccination programme. The RV related outcome definitions were based on ICD10 diagnostic codes recorded in the Care Register for Health Care. Incidences of hospitalised and hospital outpatient cases of AGE (A00-A09, R11) and RVGE (A08.0) were compared prior (1999-2005) and after (2010-2014) the start of the programme among children less than five years of age. The reduction in disease burden in 2014, when all children under five years of age have been eligible for RV vaccination, was 92.9% (95%CI: 91.0%-94.5%) in hospitalised RVGE and 68.5% (66.6%-70.3%) in the total hospitalised AGE among children less than five years of age. For the corresponding hospital outpatient cases, there was a reduction of 91.4% (82.4%-96.6%) in the RVGE incidence, but an increase of 6.3% (2.7%-9.9%) in the AGE incidence. The RV vaccination programme prevented 2206 secondary healthcare AGE cases costing €4.5 million annually. As the RV immunisation costs were €2.3 million, the total net savings just in secondary healthcare costs were €2.2 million, i.e. €33 per vaccinated child. The RV vaccination programme clearly controlled the severe, hospital-treated forms of RVGE. The total disease burden is a more valuable end point than mere specifically diagnosed cases as laboratory confirmation practises usually change after vaccine introduction. The RV vaccination programme annually pays for itself at least two times over. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Economic analysis for evidence-based policy-making on a national immunization program: a case of rotavirus vaccine in Thailand.

    Science.gov (United States)

    Muangchana, Charung; Riewpaiboon, Arthorn; Jiamsiri, Suchada; Thamapornpilas, Piyanit; Warinsatian, Porpit

    2012-04-16

    Severe diarrhea caused by rotavirus is a health problem worldwide, including Thailand. The World Health Organization has recommended incorporating rotavirus vaccination into national immunization programs. This policy has been implemented in several countries, but not in Thailand where the mortality rate is not high. This leads to the question of whether it would be cost-effective to implement such a policy. The Thai National Vaccine Committee, through the Immunization Practice Subcommittee, has conducted an economic analysis. Their study aimed to estimate the costs of rotavirus diarrhea and of a rotavirus vaccination program, and the cost-effectiveness of such a program including budget impact analysis. The study was designed as an economic evaluation, employing modeling technique in both provider and societal perspectives. A birth cohort of Thai children in 2009 was used in the analysis, with a 5-year time horizon. Costs were composed of cost of the illness and the vaccination program. Outcomes were measured in the form of lives saved and DALYs averted. Both costs and outcomes were discounted at 3%. The study found the discounted number of deaths to be 7.02 and 20.52 for vaccinated and unvaccinated cohorts, respectively (13.5 deaths averted). Discounted DALYs were 263.33 and 826.57 for vaccinated and unvaccinated cohorts, respectively (563.24 DALYs averted). Costs of rotavirus diarrhea in a societal perspective were US$6.6 million and US$21.0 million for vaccinated and unvaccinated cohorts, respectively. At base case, the costs per additional death averted were US$5.1 million and US$5.7 for 2-dose and 3-dose vaccines, respectively, in a societal perspective. Costs per additional DALYs averted were US$128,063 and US$142,144, respectively. In a societal perspective, with a cost-effectiveness threshold at 1 GDP per capita per DALYs averted, vaccine prices per dose were US$4.98 and US$3.32 for 2-dose and 3-dose vaccines, respectively; in a provider perspective, they

  16. The risk of intussusception following monovalent rotavirus vaccination in England: A self-controlled case-series evaluation.

    Science.gov (United States)

    Stowe, Julia; Andrews, Nick; Ladhani, Shamez; Miller, Elizabeth

    2016-07-12

    To investigate the risk of intussusception after monovalent rotavirus vaccine (RV1) given to infants aged 2 and 3 months in England. Hospital Episode Statistics (HES) were used to identify infants aged 48-183 days admitted between 11/03/2013 and 31/10/2014 with intussusception. Diagnosis was confirmed from medical records and HES procedure codes. Vaccination status was obtained from general practitioners. The risk of admission within 1-7 and 8-21 days of vaccination was analysed using the self-controlled case-series (SCCS) method with age effect adjustment by including historical data before RVI introduction in July 2013. A total of 119 cases were identified during the study period and intussusception confirmed in 95 of whom 39 were vaccinated 1-21 days before onset. An increased relative incidence (RI) in this period was found, 4.53 (95% confidence interval 2.34-8.58) and 2.60 (1.43-4.81) respectively after the 1st and 2nd doses with an attributable risk of 1.91 and 1.49 per 100,000 doses respectively. The peak risk was 1-7 days after the first dose, RI 13.81 (6.44-28.32), with an estimated 93% of the 15 cases being vaccine-attributable. Mean interval between onset and admission, and clinical features were similar between vaccine-associated and background cases. Despite intussusception being a contraindication to rotavirus vaccination, 10 infants received a further dose; none had a recurrence. The RIs in a meta-analysis combing our results with Australia, Mexico, Brazil and Singapore using RV1, a 2, 4 month schedule and SCCS gave pooled RI estimates of 2.35 (1.45-3.8) and 1.77 (1.29-2.43) in the 21 day period after the 1st and 2nd doses, respectively. The earlier age at the 2nd dose in England did not affect the risk. We estimate that the RVI programme causes around 21 intussusception admissions annually in England but, since it prevents around 25,000 gastro-intestinal infection admissions, its benefit/risk profile remains strongly positive. Crown Copyright

  17. Selection and Interpretation of Scientific Evidence in Preparation for Policy Decisions: A Case Study Regarding Introduction of Rotavirus Vaccine Into National Immunization Programs in Sweden, Norway, Finland, and Denmark

    Directory of Open Access Journals (Sweden)

    Gry St-Martin

    2018-05-01

    Full Text Available The World Health Organization recommends inclusion of rotavirus vaccines in national immunization programs (NIPs worldwide. Nordic countries are usually considered comparable in terms of demographics and health-care services and have comparable rotavirus disease burden. Nevertheless, the countries have reached different decisions regarding rotavirus vaccine: Norway and Finland have already introduced rotavirus vaccines into their NIPs and Sweden is currently changing its recommendation and vaccines will now be introduced on a national scale while Denmark has decided against it. This study focuses on the selection and interpretation of medical and epidemiological evidence used during the decision-making processes in Sweden, Norway, Finland, and Denmark. The so-called “severity criteria” is identified as one of the main reasons for the different policy decisions reached across the Nordic countries.

  18. Genome characterization of Turkey Rotavirus G strains from the United States identifies potential recombination events with human Rotavirus B strains.

    Science.gov (United States)

    Chen, Fangzhou; Knutson, Todd P; Porter, Robert E; Ciarlet, Max; Mor, Sunil Kumar; Marthaler, Douglas G

    2017-12-01

    Rotavirus G (RVG) strains have been detected in a variety of avian species, but RVG genomes have been published from only a single pigeon and two chicken strains. Two turkey RVG strains were identified and characterized, one in a hatchery with no reported health issues and the other in a hatchery with high embryo/poult mortality. The two turkey RVG strains shared only an 85.3 % nucleotide sequence identity in the VP7 gene while the other genes possessed high nucleotide identity among them (96.3-99.9 %). Low nucleotide percentage identities (31.6-87.3 %) occurred among the pigeon and chicken RVG strains. Interestingly, potential recombination events were detected between our RVG strains and a human RVB strain, in the VP6 and NSP3 segments. The epidemiology of RVG in avian flocks and the pathogenicity of the two different RVG strains should be further investigated to understand the ecology and impact of RVG in commercial poultry flocks.

  19. Severe Rotavirus gastroenteritis in a patient with infant leukemia

    Directory of Open Access Journals (Sweden)

    Hatice Uygun

    2011-03-01

    Full Text Available Rotavirus is the most common cause of severe gastroenteritis in infants and young children. Reports about the clinical relevance of rotavirus in immunocompromised children are rare. We herein presented a case of life-threatening Rotavirus gastroenteritis in an infant with acute myeloblastic leukemia which could be prevented by recently recommended Rotavirus vaccination.

  20. 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

  1. Comparative review of three cost-effectiveness models for rotavirus vaccines in national immunization programs; a generic approach applied to various regions in the world

    Directory of Open Access Journals (Sweden)

    Tu Hong-Anh

    2011-07-01

    Full Text Available Abstract Background This study aims to critically review available cost-effectiveness models for rotavirus vaccination, compare their designs using a standardized approach and compare similarities and differences in cost-effectiveness outcomes using a uniform set of input parameters. Methods We identified various models used to estimate the cost-effectiveness of rotavirus vaccination. From these, results using a standardized dataset for four regions in the world could be obtained for three specific applications. Results Despite differences in the approaches and individual constituting elements including costs, QALYs Quality Adjusted Life Years and deaths, cost-effectiveness results of the models were quite similar. Differences between the models on the individual components of cost-effectiveness could be related to some specific features of the respective models. Sensitivity analysis revealed that cost-effectiveness of rotavirus vaccination is highly sensitive to vaccine prices, rotavirus-associated mortality and discount rates, in particular that for QALYs. Conclusions The comparative approach followed here is helpful in understanding the various models selected and will thus benefit (low-income countries in designing their own cost-effectiveness analyses using new or adapted existing models. Potential users of the models in low and middle income countries need to consider results from existing studies and reviews. There will be a need for contextualization including the use of country specific data inputs. However, given that the underlying biological and epidemiological mechanisms do not change between countries, users are likely to be able to adapt existing model designs rather than developing completely new approaches. Also, the communication established between the individual researchers involved in the three models is helpful in the further development of these individual models. Therefore, we recommend that this kind of comparative study

  2. Veterinary and human vaccine evaluation methods

    Science.gov (United States)

    Knight-Jones, T. J. D.; Edmond, K.; Gubbins, S.; Paton, D. J.

    2014-01-01

    Despite the universal importance of vaccines, approaches to human and veterinary vaccine evaluation differ markedly. For human vaccines, vaccine efficacy is the proportion of vaccinated individuals protected by the vaccine against a defined outcome under ideal conditions, whereas for veterinary vaccines the term is used for a range of measures of vaccine protection. The evaluation of vaccine effectiveness, vaccine protection assessed under routine programme conditions, is largely limited to human vaccines. Challenge studies under controlled conditions and sero-conversion studies are widely used when evaluating veterinary vaccines, whereas human vaccines are generally evaluated in terms of protection against natural challenge assessed in trials or post-marketing observational studies. Although challenge studies provide a standardized platform on which to compare different vaccines, they do not capture the variation that occurs under field conditions. Field studies of vaccine effectiveness are needed to assess the performance of a vaccination programme. However, if vaccination is performed without central co-ordination, as is often the case for veterinary vaccines, evaluation will be limited. This paper reviews approaches to veterinary vaccine evaluation in comparison to evaluation methods used for human vaccines. Foot-and-mouth disease has been used to illustrate the veterinary approach. Recommendations are made for standardization of terminology and for rigorous evaluation of veterinary vaccines. PMID:24741009

  3. [Nosocomial rotavirus gastroenteritis].

    Science.gov (United States)

    Marinosci, A; Doit, C; Koehl, B; Belhacel, K; Mariani Kurkdjian, P; Melki, I; Renaud, A; Lemaitre, C; Ammar Khodja, N; Blachier, A; Bonacorsi, S; Faye, A; Lorrot, M

    2016-11-01

    Rotavirus is the most common cause of gastroenteritis in children requiring hospitalization. It is a very resistant and contagious virus causing nosocomial gastroenteritis. In France, the vaccine against rotavirus has been available since 2006, but the vaccine is not recommended for infant vaccination. The aim of this retrospective study was to describe nosocomial rotavirus gastroenteritis (NRGE) and to assess its impact on children hospitalized in the General Pediatrics Department of Robert-Debré Hospital (Paris) between 1 January 2009 and 31 December 2013. We analyzed the demographic characteristics of children (age, term birth, underlying diseases) and the severity of the NRGE (oral or intravenous hydration), and assessed whether these children could benefit from vaccination against rotavirus. One hundred thirty-six children presented nosocomial rotavirus infection, with an incidence of 2.5 NRGE per 1000 days of hospitalization. The incidence of NRGE was stable between 2009 and 2013 despite the introduction of specific hygiene measures. The average age of the children was 7 months (range: 0.5-111 months). Most often NRGE occurred in children hospitalized for respiratory diseases (65% of cases) and requiring prolonged hospitalization (median: 18 days). One-third of children were born premature (25%). Hydration was oral in 80 patients (59%), by intravenous infusion in 18 patients (13%), and intraosseous in one patient. Half of the patients were aged less than 5 months and could benefit from the protection afforded by vaccination. NRGE are common. Rotavirus mass vaccination should have a positive impact on the incidence of NRGE by reducing the number of children hospitalized for gastroenteritis, therefore indirectly reducing the number of hospital cross-infections of hospitalized children who are too young to be vaccinated. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Effect of human milk prostaglandins and lactoferrin on respiratory syncytial virus and rotavirus.

    Science.gov (United States)

    Grover, M; Giouzeppos, O; Schnagl, R D; May, J T

    1997-03-01

    The effect of lactoferrin and prostaglandins E and F2 alpha on the growth of rotavirus and respiratory syncytial virus in cell culture was investigated. Lactoferrin inhibited the growth of respiratory syncytial virus at a concentration tenfold lower than that normally present in human milk. The prostaglandins had no effect on either virus growth, even at a concentration of 100-fold more than that found in human milk. Lactoferrin may have some antiviral properties in human milk in addition to its known antibacterial functions.

  5. Exploring the potential impact of rotavirus vaccination on work absenteeism among female administrative personnel of the City of Antwerp through a retrospective database analysis.

    Science.gov (United States)

    Standaert, Baudouin; Van de Mieroop, Els; Nelen, Vera

    2015-06-30

    Rotavirus vaccination has been reimbursed in Belgium since November 2006 with a high uptake (>85%). Economic analyses of the vaccine have been reported, including estimates of indirect cost gain related to the reduction in work absenteeism. The objective of this study was to evaluate the latter parameter using real-life data. A simple model estimated the reduction in absent workdays per working mother with a firstborn baby after the introduction of the rotavirus vaccine. Next, data on work absences were retrospectively analysed (from 2003 to 2012) using a database of administrative employees (n=11,600 working women per year) in the City of Antwerp. Observed reductions in absenteeism after the introduction of the vaccine were compared with the results from the model. These reductions would most likely be observed during the epidemic periods of rotavirus (from January to the end of May) for short-duration absences of ≤ 5 days. We compared data from outside epidemic periods (from June to December), expecting no changes over time prevaccine and postvaccine introduction, as well as with a control group of women aged 30-35 years with no first child. Model estimates were 0.73 working days gained per working mother. In the database of the City of Antwerp, we identified a gain of 0.88 working days during the epidemic period, and an accumulated gain of 2.24 days over a 3-year follow-up period. In the control group, no decrease in absenteeism was measured. Giving vaccine access to working mothers resulted in an estimated accumulated net cost gain of €187 per mother. Reduction in absenteeism among working mothers was observed during periods of the epidemic after the introduction of the rotavirus vaccine in Belgium. This reduction is in line with estimates of indirect cost gains used in economic evaluations of the rotavirus vaccine. HO-12-12768. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  6. The "Performance of Rotavirus and Oral Polio Vaccines in Developing Countries" (PROVIDE) study: description of methods of an interventional study designed to explore complex biologic problems.

    Science.gov (United States)

    Kirkpatrick, Beth D; Colgate, E Ross; Mychaleckyj, Josyf C; Haque, Rashidul; Dickson, Dorothy M; Carmolli, Marya P; Nayak, Uma; Taniuchi, Mami; Naylor, Caitlin; Qadri, Firdausi; Ma, Jennie Z; Alam, Masud; Walsh, Mary Claire; Diehl, Sean A; Petri, William A

    2015-04-01

    Oral vaccines appear less effective in children in the developing world. Proposed biologic reasons include concurrent enteric infections, malnutrition, breast milk interference, and environmental enteropathy (EE). Rigorous study design and careful data management are essential to begin to understand this complex problem while assuring research subject safety. Herein, we describe the methodology and lessons learned in the PROVIDE study (Dhaka, Bangladesh). A randomized clinical trial platform evaluated the efficacy of delayed-dose oral rotavirus vaccine as well as the benefit of an injectable polio vaccine replacing one dose of oral polio vaccine. This rigorous infrastructure supported the additional examination of hypotheses of vaccine underperformance. Primary and secondary efficacy and immunogenicity measures for rotavirus and polio vaccines were measured, as well as the impact of EE and additional exploratory variables. Methods for the enrollment and 2-year follow-up of a 700 child birth cohort are described, including core laboratory, safety, regulatory, and data management practices. Intense efforts to standardize clinical, laboratory, and data management procedures in a developing world setting provide clinical trials rigor to all outcomes. Although this study infrastructure requires extensive time and effort, it allows optimized safety and confidence in the validity of data gathered in complex, developing country settings. © The American Society of Tropical Medicine and Hygiene.

  7. Cost-effectiveness analysis of routine rotavirus vaccination in Brazil Análisis de la relación costo-efectividad de la vacunación programada contra rotavirus en Brasil

    Directory of Open Access Journals (Sweden)

    Patrícia Coelho de Soárez

    2008-04-01

    Full Text Available OBJECTIVE: The objective of this study was to conduct a cost-effectiveness analysis of a universal rotavirus vaccination program among children OBJETIVO: Analizar la relación costo-efectividad de un programa universal de vacunación contra rotavirus en niños de hasta 5 años en Brasil. MÉTODOS: Se consideró una cohorte hipotética anual de aproximadamente 3 300 000 recién nacidos con un seguimiento de 5 años. Mediante un modelo de árbol de decisión se analizaron los posibles efectos clínicos y económicos de la infección por rotavirus con la vacunación programada de niños y sin ella. Las probabilidades y los costos unitarios se tomaron de investigaciones publicadas y de los datos oficiales nacionales. Para evaluar el impacto de diferentes estimados de los parámetros clave se realizó un análisis de sensibilidad. El análisis se efectuó tanto desde la perspectiva del sistema sanitario como de la sociedad. RESULTADOS: Se estimó que el programa de vacunación evitaría aproximadamente 1 735 351 (54% de los 3 210 361 casos de gastroenteritis por rotavirus y 703 (75% de las 933 muertes asociadas con la infección por rotavirus en un período de 5 años. A un precio de la vacuna de 18,6 reales brasileños (R$ por dosis, este programa costaría R$ 121 673 966 y ahorraría R$ 38 536 514 en costos directos al sistema de salud pública y R$ 71 778 377 en costos directos e indirectos a la sociedad. El costo estimado del programa por año de vida salvado sería de R$ 1 028 y R$ 1 713, desde el punto de vista de la sociedad y del sistema de salud, respectivamente. CONCLUSIONES: La estrategia de vacunación universal contra rotavirus presentó una buena relación costo-efectividad según ambas perspectivas. Sin embargo, estos resultados son muy sensibles a cambios en la incidencia de diarreas, la proporción de casos graves, la cobertura de vacunación y el precio de la vacuna.

  8. Identification of human rotavirus serotype by hybridization to polymerase chain reaction-generated probes derived from a hyperdivergent region of the gene encoding outer capsid protein VP7

    International Nuclear Information System (INIS)

    Flores, J.; Sears, J.; Schael, I.P.; White, L.; Garcia, D.; Lanata, C.; Kapikian, A.Z.

    1990-01-01

    We have synthesized 32 P-labeled hybridization probes from a hyperdivergent region (nucleotides 51 to 392) of the rotavirus gene encoding the VP7 glycoprotein by using the polymerase chain reaction method. Both RNA (after an initial reverse transcription step) and cloned cDNA from human rotavirus serotypes 1 through 4 could be used as templates to amplify this region. High-stringency hybridization of each of the four probes to rotavirus RNAs dotted on nylon membranes allowed the specific detection of corresponding sequences and thus permitted identification of the serotype of the strains dotted. The procedure was useful when applied to rotaviruses isolated from field studies

  9. Identification of human rotavirus serotype by hybridization to polymerase chain reaction-generated probes derived from a hyperdivergent region of the gene encoding outer capsid protein VP7

    Energy Technology Data Exchange (ETDEWEB)

    Flores, J.; Sears, J.; Schael, I.P.; White, L.; Garcia, D.; Lanata, C.; Kapikian, A.Z. (National Institutes of Health, Bethesda, MD (USA))

    1990-08-01

    We have synthesized {sup 32}P-labeled hybridization probes from a hyperdivergent region (nucleotides 51 to 392) of the rotavirus gene encoding the VP7 glycoprotein by using the polymerase chain reaction method. Both RNA (after an initial reverse transcription step) and cloned cDNA from human rotavirus serotypes 1 through 4 could be used as templates to amplify this region. High-stringency hybridization of each of the four probes to rotavirus RNAs dotted on nylon membranes allowed the specific detection of corresponding sequences and thus permitted identification of the serotype of the strains dotted. The procedure was useful when applied to rotaviruses isolated from field studies.

  10. 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 ...

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  13. Characterisation of a rare, reassortant human G10P[14] rotavirus strain detected in Honduras.

    Science.gov (United States)

    Quaye, Osbourne; Roy, Sunando; Rungsrisuriyachai, Kunchala; Esona, Mathew D; Xu, Ziqian; Tam, Ka Ian; Banegas, Dina J Castro; Rey-Benito, Gloria; Bowen, Michael D

    2018-01-01

    Although first detected in animals, the rare rotavirus strain G10P[14] has been sporadically detected in humans in Slovenia, Thailand, United Kingdom and Australia among other countries. Earlier studies suggest that the strains found in humans resulted from interspecies transmission and reassortment between human and bovine rotavirus strains. In this study, a G10P[14] rotavirus genotype detected in a human stool sample in Honduras during the 2010-2011 rotavirus season, from an unvaccinated 30-month old boy who reported at the hospital with severe diarrhea and vomiting, was characterised to determine the possible evolutionary origin of the rare strain. For the sample detected as G10P[14], 10% suspension was prepared and used for RNA extraction and sequence independent amplification. The amplicons were sequenced by next-generation sequencing using the Illumina MiSeq 150 paired end method. The sequence reads were analysed using CLC Genomics Workbench 6.0 and phylogenetic trees were constructed using PhyML version 3.0. The next generation sequencing and phylogenetic analyses of the 11-segmented genome of the G10P[14] strain allowed classification as G10-P[14]-I2-R2-C2-M2-A3-N2-T6-E2-H3. Six of the genes (VP1, VP2, VP3, VP6, NSP2 and NSP4) were DS-1-like. NSP1 and NSP5 were AU-1-like and NSP3 was T6, which suggests that multiple reassortment events occurred in the evolution of the strain. The phylogenetic analyses and genetic distance calculations showed that the VP7, VP4, VP6, VP1, VP3, NSP1, NSP3 and NSP4 genes clustered predominantly with bovine strains. NSP2 and VP2 genes were most closely related to simian and human strains, respectively, and NSP5 was most closely related to a rhesus strain. The genetic characterisation of the G10P[14] strain from Honduras suggests that its genome resulted from multiple reassortment events which were possibly mediated through interspecies transmissions.

  14. Human papillomavirus vaccine policy and delivery in Latin America and the Caribbean.

    Science.gov (United States)

    Andrus, Jon Kim; Lewis, Merle J; Goldie, Sue J; García, Patricia J; Winkler, Jennifer L; Ruiz-Matus, Cuauhtémoc; de Quadros, Ciro A

    2008-08-19

    Cervical cancer caused by human papillomavirus (HPV) is a major preventable public health problem. Two vaccines are now available for primary prevention of HPV infection and their introduction offers new opportunities to enhance comprehensive cervical cancer prevention and control. Currently, HPV vaccine price is a significant barrier to rapid vaccine introduction and access. Therefore, making evidence-based decisions about whether and how to introduce HPV vaccine into the immunization schedule in the countries of Latin America and the Caribbean (LAC) requires a rigorous analysis of several factors. These include: estimates of disease burden, cost-effectiveness, operational feasibility of reaching a population of adolescent females and other key analyses that have been used in recent years to support the introduction of other vaccines, such as rotavirus and pneumococcal conjugate vaccines. Given the large number of public health priorities that are competing for limited public resources, developing and using a sound evidence base is of particular importance for vaccines, like HPV, which are currently available only at prices higher than other vaccines now in use. HPV vaccination provides the opportunity to dramatically improve women's health and partnerships must also be broad-based and effectively coordinated. This can be achieved by developing programs based on the lessons learned from vaccination strategies used to eliminate rubella and neonatal tetanus and for scaling up influenza vaccination in countries of LAC.

  15. Novel vaccines to human rabies.

    Directory of Open Access Journals (Sweden)

    Hildegund C J Ertl

    Full Text Available Rabies, the most fatal of all infectious diseases, remains a major public health problem in developing countries, claiming the lives of an estimated 55,000 people each year. Most fatal rabies cases, with more than half of them in children, result from dog bites and occur among low-income families in Southeast Asia and Africa. Safe and efficacious vaccines are available to prevent rabies. However, they have to be given repeatedly, three times for pre-exposure vaccination and four to five times for post-exposure prophylaxis (PEP. In cases of severe exposure, a regimen of vaccine combined with a rabies immunoglobulin (RIG preparation is required. The high incidence of fatal rabies is linked to a lack of knowledge on the appropriate treatment of bite wounds, lack of access to costly PEP, and failure to follow up with repeat immunizations. New, more immunogenic but less costly rabies virus vaccines are needed to reduce the toll of rabies on human lives. A preventative vaccine used for the immunization of children, especially those in high incidence countries, would be expected to lower fatality rates. Such a vaccine would have to be inexpensive, safe, and provide sustained protection, preferably after a single dose. Novel regimens are also needed for PEP to reduce the need for the already scarce and costly RIG and to reduce the number of vaccine doses to one or two. In this review, the pipeline of new rabies vaccines that are in pre-clinical testing is provided and an opinion on those that might be best suited as potential replacements for the currently used vaccines is offered.

  16. Distributional cost-effectiveness analysis in low- and middle-income countries: illustrative example of rotavirus vaccination in Ethiopia.

    Science.gov (United States)

    Dawkins, Bryony R; Mirelman, Andrew J; Asaria, Miqdad; Johansson, Kjell Arne; Cookson, Richard A

    2018-04-01

    Reducing health inequality is a major policy concern for low- and middle-income countries (LMICs) on the path to universal health coverage. However, health inequality impacts are rarely quantified in cost-effectiveness analyses of health programmes. Distributional cost-effectiveness analysis (DCEA) is a method developed to analyse the expected social distributions of costs and health benefits, and the potential trade-offs that may exist between maximising total health and reducing health inequality. This is the first paper to show how DCEA can be applied in LMICs. Using the introduction of rotavirus vaccination in Ethiopia as an illustrative example, we analyse a hypothetical re-designed vaccination programme, which invests additional resources into vaccine delivery in rural areas, and compare this with the standard programme currently implemented in Ethiopia. We show that the re-designed programme has an incremental cost-effectiveness ratio of US$69 per health-adjusted life year (HALY) compared with the standard programme. This is potentially cost-ineffective when compared with current estimates of health opportunity cost in Ethiopia. However, rural populations are typically less wealthy than urban populations and experience poorer lifetime health. Prioritising such populations can thus be seen as being equitable. We analyse the trade-off between cost-effectiveness and equity using the Atkinson inequality aversion parameter, ε, representing the decision maker's strength of concern for reducing health inequality. We find that the more equitable programme would be considered worthwhile by a decision maker whose inequality concern is greater than ε = 5.66, which at current levels of health inequality in Ethiopia implies that health gains are weighted at least 3.86 times more highly in the poorest compared with the richest wealth quintile group. We explore the sensitivity of this conclusion to a range of assumptions and cost-per-HALY threshold values, to

  17. 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.

  18. [Vaccine against human papilloma virus].

    Science.gov (United States)

    Juárez-Albarrán, Alfredo César; Juárez-Gámez, Carlos Alberto

    2008-01-01

    Genital human papilloma virus infection (HPV) is the most common sexually transmitted infection worldwide, it is the cause of genital warts, and it is related with cervical cancer, the second most common cause of death from cancer in women in America, and the first in underdeveloped countries, and it is related with penis and prostate cancer in males also, and with anal cancer in both genders. This review examines the most important actual facts about HPV infection, and the new prophylactic vaccines. Two versions of the vaccine had been developed, both target HPV 16 and HPV 18, which involve approximately 70% of cervical cancer. One of them also targets HPV 6 and HPV 11, which account for approximately 90% of external genital warts. Both vaccines have an excellent safety profile, are highly immunogenic, and have atributed complete type specific protection against persistent infection and associated lesions in fully vaccinated girls and young women. The role of men as carriers of HPV as well as vectors for transmission is well documented. Several clinical trials are currently under way to determine the efficacy of vaccinating men. Reducing the cost of vaccination would be a priority for the developing world in order to get a broad target in poor countries.

  19. Adolescent Male Human Papillomavirus Vaccination

    Directory of Open Access Journals (Sweden)

    Vivian C. Nanagas MD, MSc

    2016-04-01

    Full Text Available Objective. To determine male vaccination rates with quadrivalent human papillomavirus vaccine (HPV4 before and after the October 2011 national recommendation to routinely immunize adolescent males. Methods. We reviewed HPV4 dose 1 (HPV4-1 uptake in 292 adolescent males in our urban clinic prior to national recommendations and followed-up for HPV4 series completion rates. After national recommendation, 248 urban clinic and 247 suburban clinic males were reviewed for HPV4-1 uptake. Factors associated with HPV4-1 refusal were determined with multiple logistic regression. Results. Of the initial 292 males, 78% received HPV4-1 and 38% received the 3-dose series. After recommendation, HPV4-1 uptake was 59% and 7% in urban and suburban clinics, respectively. Variables associated with HPV4-1 uptake/refusal included time period, race, type of insurance, and receipt of concurrent vaccines. Conclusions. HPV4-1 vaccination rates in our urban clinic were high before and after routine HPV vaccine recommendations for adolescent males. Our vaccination rates were much higher than in a suburban practice.

  20. Introduktion. Om rotavirus. Teknologi

    DEFF Research Database (Denmark)

    Wejse, Christian

    2012-01-01

    vil skyldes rotavirus. Typisk vil børnene få feber, opkastninger og/eller diarré. Sygdommen går sædvanligvis over af sig selv i løbet af 3 til 7 dage. Nogle børn får dog væske- og saltmangel i en sådan grad, at de må indlægges på hospital til behandling med drop og væske direkte ind i årerne. 85 – 90...... % 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...

  1. Rotavirus Infections

    Science.gov (United States)

    Rotavirus is a virus that causes gastroenteritis. Symptoms include severe diarrhea, vomiting, fever, and dehydration. Almost all ... the U.S. are likely to be infected with rotavirus before their 5th birthday. Infections happen most often ...

  2. Morphological response of human rotavirus to ultra-violet radiation, heat and disinfectants

    International Nuclear Information System (INIS)

    Rodgers, F.G.; Hufton, P.; Kurzawska, E.; Molloy, C.; Morgan, S.

    1985-01-01

    The morphological damage induced in human rotavirus particles by exposure to UV radiation (254 nm) increased progressively with length of treatment. Exposure of the virus in suspension to 9000 ergs/cm 2 /s removed the smooth capsid layer from 50% of particles after 1 min and from all the virions within 10 min. By this time, the number of stain-penetrated or empty particles increased markedly, along with the appearance of virus-derived debris in the form of disrupted and isolated capsomeres. After treatment for 120 min no intact virus particles were observed. The action of wet (100 0 C) or dry (60 0 C) heat resulted in changes similar to those effected by UV radiation. Sodium hypochlorite, cetrimide and 70% ethanol induced a rapid loss of the outer capsid layer, but, compared with UV radiation or heat, a slower increase in the number of stain-penetrated particles was noted. Chlorhexidine and phenol had effects on virus structure only after extended periods of exposure, whilst glutaraldehyde treatment had little influence on virus morphology. Glutaraldehyde 2% v/v would appear to be most suitable for the disinfection of rotavirus-containing electron microscope grids before their examination. (author)

  3. 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

  4. Rotavirus infection

    Science.gov (United States)

    Crawford, Sue E.; Ramani, Sasirekha; Tate, Jacqueline E.; Parashar, Umesh D.; Svensson, Lennart; Hagbom, Marie; Franco, Manuel A.; Greenberg, Harry B.; O’Ryan, Miguel; Kang, Gagandeep; Desselberger, Ulrich; Estes, Mary K.

    2017-01-01

    Rotavirus infections are a leading cause of severe, dehydrating gastroenteritis in children rotavirus over a decade ago, rotavirus infections still result in >200,000 deaths annually, mostly in low-income countries. Rotavirus primarily infects enterocytes and induces diarrhoea through the destruction of absorptive enterocytes (leading to malabsorption), intestinal secretion stimulated by rotavirus non-structural protein 4 and activation of the enteric nervous system. In addition, rotavirus infections can lead to antigenaemia (which is associated with more severe manifestations of acute gastroenteritis) and viraemia, and rotavirus can replicate in systemic sites, although this is limited. Reinfections with rotavirus are common throughout life, although the disease severity is reduced with repeat infections. The immune correlates of protection against rotavirus reinfection and recovery from infection are poorly understood, although rotavirus-specific immunoglobulin A has a role in both aspects. The management of rotavirus infection focuses on the prevention and treatment of dehydration, although the use of antiviral and anti-emetic drugs can be indicated in some cases. PMID:29119972

  5. Effectiveness of the live attenuated rotavirus vaccine produced by a domestic manufacturer in China studied using a population-based case-control design.

    Science.gov (United States)

    Zhen, Shan-Shan; Li, Yue; Wang, Song-Mei; Zhang, Xin-Jiang; Hao, Zhi-Yong; Chen, Ying; Wang, Dan; Zhang, Yan-Hong; Zhang, Zhi-Yong; Ma, Jing-Chen; Zhou, Peng; Zhang, Zhen; Jiang, Zhi-Wei; Zhao, Yu-Liang; Wang, Xuan-Yi

    2015-10-01

    A universal rotavirus (RV) immunization program is a potentially cost-effective measure for preventing RV infection in China. However, the efficacy of the only licensed RV vaccine (Lanzhou lamb rotavirus vaccine, LLR), which is made by a domestic manufacturer, has not been proven by a properly designed clinical trial. In October 2011 to March 2012, to measure the potential protection provided by LLR, a case-control study nested in a population-based active diarrhea surveillance study of children control study comparing non-RV viral diarrheal cases with non-diarrheal controls in the same population found that the RV vaccine offered no protection against non-RV diarrhea. Even under a less ideal immunization schedule, the oral LLR conferred a certain level of protection against RV gastroenteritis. However, further studies are needed to understand the full characteristics of the LLR, including its efficacy when administered following the optimal regimen, the potential risk of inducing intussusception, and the direct and indirect protective effects of LLR.

  6. 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

  7. Recombinant Human Papillomavirus (HPV) Bivalent Vaccine

    Science.gov (United States)

    This page contains brief information about recombinant human papillomavirus (HPV) bivalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.

  8. Recombinant Human Papillomavirus (HPV) Nonavalent Vaccine

    Science.gov (United States)

    This page contains brief information about recombinant human papillomavirus (HPV) nonavalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.

  9. Recombinant Human Papillomavirus (HPV) Quadrivalent Vaccine

    Science.gov (United States)

    This page contains brief information about recombinant human papillomavirus (HPV) quadrivalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.

  10. Chicken Egg Yolk Antibodies (IgY) for Prophylaxis and Treatment of Rotavirus Diarrhea in Human and Animal Neonates: A Concise Review

    Science.gov (United States)

    Thu, Hlaing Myat; Myat, Theingi Win; Win, Mo Mo; Thant, Kyaw Zin; Rahman, Shofiqur; Umeda, Kouji; Nguyen, Sa Van; Icatlo, Faustino C.; Higo-Moriguchi, Kyoko; Taniguchi, Koki; Tsuji, Takao; Oguma, Keiji; Kim, Sang Jong; Bae, Hyun Suk

    2017-01-01

    The rotavirus-induced diarrhea of human and animal neonates is a major public health concern worldwide. Until recently, no effective therapy is available to specifically inactivate the rotavirion particles within the gut. Passive immunotherapy by oral administration of chicken egg yolk antibody (IgY) has emerged of late as a fresh alternative strategy to control infectious diseases of the alimentary tract and has been applied in the treatment of diarrhea due to rotavirus infection. The purpose of this concise review is to evaluate evidence on the properties and performance of anti-rotavirus immunoglobulin Y (IgY) for prevention and treatment of rotavirus diarrhea in human and animal neonates. A survey of relevant anti-rotavirus IgY basic studies and clinical trials among neonatal animals (since 1994-2015) and humans (since 1982-2015) have been reviewed and briefly summarized. Our analysis of a number of rotavirus investigations involving animal and human clinical trials revealed that anti-rotavirus IgY significantly reduced the severity of clinical manifestation of diarrhea among IgY-treated subjects relative to a corresponding control or placebo group. The accumulated information as a whole depicts oral IgY to be a safe and efficacious option for treatment of rotavirus diarrhea in neonates. There is however a clear need for more randomized, placebo controlled and double-blind trials with bigger sample size to further solidify and confirm claims of efficacy and safety in controlling diarrhea caused by rotavirus infection especially among human infants with health issues such as low birth weights or compromised immunity in whom it is most needed. PMID:28316465

  11. Global challenges of implementing human papillomavirus vaccines

    Directory of Open Access Journals (Sweden)

    Mishra Amrita

    2011-06-01

    Full Text Available Abstract Human Papillomavirus vaccines are widely hailed as a sweeping pharmaceutical innovation for the universal benefit of all women. The implementation of the vaccines, however, is far from universal or equitable. Socio-economically marginalized women in emerging and developing, and many advanced economies alike, suffer a disproportionately large burden of cervical cancer. Despite the marketing of Human Papillomavirus vaccines as the solution to cervical cancer, the market authorization (licensing of the vaccines has not translated into universal equitable access. Vaccine implementation for vulnerable girls and women faces multiple barriers that include high vaccine costs, inadequate delivery infrastructure, and lack of community engagement to generate awareness about cervical cancer and early screening tools. For Human Papillomavirus vaccines to work as a public health solution, the quality-assured delivery of cheaper vaccines must be integrated with strengthened capacity for community-based health education and screening.

  12. 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 ... abcs of mmr & dtp thimerosal vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus ...

  13. Comparison of electron microscopy, enzyme-linked immunosorbent assay, solid-phase radioimmunoassay, and indirect immunofluorescence for detection of human rotavirus antigen in faeces

    Energy Technology Data Exchange (ETDEWEB)

    Birch, C J; Lehmann, N I; Hawker, A J; Marshall, J A; Gust, I D [Fairfield Hospital for Communicable Diseases, Victoria (Australia). Virology Dept.

    1979-07-01

    Four techniques were compared for their practicability, speed, and sensitivity for the detection of human rotavirus. Radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) were found to be the most sensitive means of identifying rotavirus and, once processed, up to 40 specimens could be examined daily. Electron microscopy, although less sensitive than these techniques, had the advantage of being able to detect other viral agents present in faecal extracts. Indirect immunofluorescence failed to detect rotavirus as often as the other three methods. In laboratories where routine examination of faecal specimens from patients with gastroenteritis is required, ELISA and RIA are useful alternatives to electron microscopy.

  14. Comparison of electron microscopy, enzyme-linked immunosorbent assay, solid-phase radioimmunoassay, and indirect immunofluorescence for detection of human rotavirus antigen in faeces

    International Nuclear Information System (INIS)

    Birch, C.J.; Lehmann, N.I.; Hawker, A.J.; Marshall, J.A.; Gust, I.D.

    1979-01-01

    Four techniques were compared for their practicability, speed, and sensitivity for the detection of human rotavirus. Radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) were found to be the most sensitive means of identifying rotavirus and, once processed, up to 40 specimens could be examined daily. Electron microscopy, although less sensitive than these techniques, had the advantage of being able to detect other viral agents present in faecal extracts. Indirect immunofluorescence failed to detect rotavirus as often as the other three methods. In laboratories where routine examination of faecal specimens from patients with gastroenteritis is required, ELISA and RIA are useful alternatives to electron microscopy. (author)

  15. Safety of human papillomavirus vaccines: a review

    OpenAIRE

    Stillo, Michela; Carrillo Santisteve, Paloma; Lopalco, Pier Luigi

    2015-01-01

    Introduction: Between 2006 and 2009, two different human papillomavirus virus (HPV) vaccines were licensed for use: a quadrivalent (qHPVv) and a bivalent (bHPVv) vaccine. Since 2008, HPV vaccination programmes have been implemented in the majority of the industrialized countries. Since 2013, HPV vaccination has been part of the national programs of 66 countries including almost all countries in North America and Western Europe. Despite all the efforts made by individual countries, coverage ra...

  16. 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.

  17. 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.

  18. Analysis of Host Range Restriction Determinants in the Rabbit Model: Comparison of Homologous and Heterologous Rotavirus Infections

    Science.gov (United States)

    Ciarlet, Max; Estes, Mary K.; Barone, Christopher; Ramig, Robert F.; Conner, Margaret E.

    1998-01-01

    The main limitation of both the rabbit and mouse models of rotavirus infection is that human rotavirus (HRV) strains do not replicate efficiently in either animal. The identification of individual genes necessary for conferring replication competence in a heterologous host is important to an understanding of the host range restriction of rotavirus infections. We recently reported the identification of the P type of the spike protein VP4 of four lapine rotavirus strains as being P[14]. To determine whether VP4 is involved in host range restriction in rabbits, we evaluated infection in rotavirus antibody-free rabbits inoculated orally with two P[14] HRVs, PA169 (G6) and HAL1166 (G8), and with several other HRV strains and animal rotavirus strains of different P and G types. We also evaluated whether the parental rhesus rotavirus (RRV) (P5B[3], G3) and the derived RRV-HRV reassortant candidate vaccine strains RRV × D (G1), RRV × DS-1 (G2), and RRV × ST3 (G4) would productively infect rabbits. Based on virus shedding, limited replication was observed with the P[14] HRV strains and with the SA11 Cl3 (P[2], G3) and SA11 4F (P6[1], G3) animal rotavirus strains, compared to the homologous ALA strain (P[14], G3). However, even limited infection provided complete protection from rotavirus infection when rabbits were challenged orally 28 days postinoculation (DPI) with 103 50% infective doses of ALA rabbit rotavirus. Other HRVs did not productively infect rabbits and provided no significant protection from challenge, in spite of occasional seroconversion. Simian RRV replicated as efficiently as lapine ALA rotavirus in rabbits and provided complete protection from ALA challenge. Live attenuated RRV reassortant vaccine strains resulted in no, limited, or productive infection of rabbits, but all rabbits were completely protected from heterotypic ALA challenge. The altered replication efficiency of the reassortants in rabbits suggests a role for VP7 in host range restriction

  19. Analyses of health outcomes from the 5 sites participating in the Africa and Asia clinical efficacy trials of the oral pentavalent rotavirus vaccine.

    Science.gov (United States)

    Breiman, Robert F; Zaman, K; Armah, George; Sow, Samba O; Anh, Dang Duc; Victor, John C; Hille, Darcy; Ciarlet, Max; Neuzil, Kathleen M

    2012-04-27

    Efficacy of the pentavalent rotavirus vaccine (PRV), RotaTeq(®), against severe rotavirus gastroenteritis (RVGE) was evaluated in two double-blind, placebo-controlled, multicenter Phase III clinical trials conducted in GAVI-eligible countries in Africa (Ghana, Kenya, and Mali) and in Asia (Bangladesh and Vietnam) from March 2007 through March 2009. The findings from each continent have been analyzed and presented separately, according to a single identical protocol. Ad hoc analyses combining data from the five sites were performed to further assess the impact of PRV. 6674 infants (4705 infants from Africa and 1969 infants from Asia), randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6-, 10-, and 14-weeks of age according to each country's EPI schedule, were included in the per protocol efficacy analysis. Breastfeeding and concomitant administration of EPI vaccines, including OPV, were allowed. Episodes of gastroenteritis (GE) in infants who presented to study facilities were captured and scored using the 20-point Vesikari scale. Stool samples were analyzed by rotavirus-specific EIA to detect presence of rotavirus antigen and RT-PCR to determine the G/P genotypes. We assessed efficacy to prevent all-cause GE and RVGE at a variety of cut-off points (score≥11, severe; score≥15, very severe). Vaccine efficacy (VE) against RVGE, regardless of serotype, through the entire follow-up period for any severity, severe (score≥11), and very severe (score≥15) was 33.9%, 95% CI (22.7, 43.5), 42.5%, 95% CI (27.4, 54.6), and 51.2%, 95% CI (26.3, 68.2), respectively. Through the first year of life, VE against severe RVGE was 58.9%, 95% CI (40.0, 72.3) and against all-cause severe GE was 23.0%, 95% CI (5.4, 37.3). VE against severe RVGE caused by non-vaccine G serotypes, G8 and G9, through the entire follow-up period was 87.5%, 95% CI (6.8, 99.7) and 48.0%, 95% CI (-5.5, 75.6), respectively. All G8 strains were associated with P2A[6] (a P-type not contained

  20. Monitoring the circulation of rotavirus among children after the introduction of the RotarixTM vaccine in Goiânia, Brazil

    Directory of Open Access Journals (Sweden)

    Ana Maria Tavares Borges

    2011-06-01

    Full Text Available The epidemiological features of rotavirus A (RVA infection differ between children from developing and developed countries which could result in differences in vaccine efficacy around the world. To evaluate the impact of RotarixTM on RVA prevalence, we monitored RVA genotypes circulating in Goiânia by monitoring virus in faecal samples from children that had or had not been previously vaccinated. From February-November of 2008, 220 faecal samples were collected from children in seven day-care centres. RVA detection was performed by two methodologies and the results were confirmed by polyacrylamide gel electrophoresis. From the 220 samples, eight were RVA-positive (3.6% and five were from children that had received either one or two doses of the vaccine. All positive samples were collected from children with diarrhoea during August and September. Genotyping of the RVA characterised five of the viral samples as genotype G2P[4] and one as G8P[4], suggesting that G2P[4] was the predominant circulating genotype in Goiânia during the study. The fact that vaccinated children were also infected by RVA suggests that the vaccine does not fully protect against infection by the G2[P4] RVA genotype.

  1. Chicken Egg Yolk Antibodies (IgY) for Prophylaxis and Treatment of Rotavirus Diarrhea in Human and Animal Neonates: A Concise Review

    OpenAIRE

    Thu, Hlaing Myat; Myat, Theingi Win; Win, Mo Mo; Thant, Kyaw Zin; Rahman, Shofiqur; Umeda, Kouji; Nguyen, Sa Van; Icatlo, Faustino C.; Higo-Moriguchi, Kyoko; Taniguchi, Koki; Tsuji, Takao; Oguma, Keiji; Kim, Sang Jong; Bae, Hyun Suk; Choi, Hyuk Joon

    2017-01-01

    The rotavirus-induced diarrhea of human and animal neonates is a major public health concern worldwide. Until recently, no effective therapy is available to specifically inactivate the rotavirion particles within the gut. Passive immunotherapy by oral administration of chicken egg yolk antibody (IgY) has emerged of late as a fresh alternative strategy to control infectious diseases of the alimentary tract and has been applied in the treatment of diarrhea due to rotavirus infection. The purpos...

  2. SHIFT IN HUMAN ROTAVIRUS DISTRIBUTION IN BELO HORIZONTE, BRAZIL DETECTED BY RIBONUCLEIC ACID ELECTROPHORESIS

    Directory of Open Access Journals (Sweden)

    Millan Scarabeli Alves Coelho da Silva

    2013-04-01

    Full Text Available Rotavirus has been considered the main agent of infectious diarrhea especially among younger children. We addressed the prevalence of rotavirus-associated diarrhea and the diversity of circulating electropherotypes by immunochromatography and RNA electrophoresis. Stool samples were taken from 391 children (267 with diarrhea from the lower socioeconomic stratum who sought treatment in the Hospital Infantil João Paulo II/Belo Horizonte, during 2005 and 2006. Rotavirus was detected in 79/20.2% of subjects, 64/24.0% with diarrhea and 15/12.1% with no diarrhea. The virus was strongly associated with diarrhea (p = 0.003. A total of 76/19.4% and 69/17.6% rotavirus-positive children were identified by immunochromatography and electrophoresis, respectively. Rotavirus-associated diarrhea was more frequently detected in dry months (p < 0.001 and almost exclusively in children aged up to three years. Long profile strains prevailed (54/78.3% but a shift toward short electropherotype was identified. Despite the decrease seen in 2006, rotavirus infection is still very common in our area. Although viral RNA electrophoresis is useful as a typing method, it should not be used exclusively in the diagnosis of rotavirus infection. We confirmed a shift from long to short profile strains, as already described for other South American countries.

  3. Capturing Budget Impact Considerations Within Economic Evaluations: A Systematic Review of Economic Evaluations of Rotavirus Vaccine in Low- and Middle-Income Countries and a Proposed Assessment Framework.

    Science.gov (United States)

    Carvalho, Natalie; Jit, Mark; Cox, Sarah; Yoong, Joanne; Hutubessy, Raymond C W

    2018-01-01

    In low- and middle-income countries, budget impact is an important criterion for funding new interventions, particularly for large public health investments such as new vaccines. However, budget impact analyses remain less frequently conducted and less well researched than cost-effectiveness analyses. The objective of this study was to fill the gap in research on budget impact analyses by assessing (1) the quality of stand-alone budget impact analyses, and (2) the feasibility of extending cost-effectiveness analyses to capture budget impact. We developed a budget impact analysis checklist and scoring system for budget impact analyses, which we then adapted for cost-effectiveness analyses, based on current International Society for Pharmacoeconomics and Outcomes Research Task Force recommendations. We applied both budget impact analysis and cost-effectiveness analysis checklists and scoring systems to examine the extent to which existing economic evaluations provide sufficient evidence about budget impact to enable decision making. We used rotavirus vaccination as an illustrative case in which low- and middle-income countries uptake has been limited despite demonstrated cost effectiveness. A systematic literature review was conducted to identify economic evaluations of rotavirus vaccine in low- and middle-income countries published between January 2000 and February 2017. We critically appraised the quality of budget impact analyses, and assessed the extension of cost-effectiveness analyses to provide useful budget impact information. Six budget impact analyses and 60 cost-effectiveness analyses were identified. Budget impact analyses adhered to most International Society for Pharmacoeconomics and Outcomes Research recommendations, with key exceptions being provision of undiscounted financial streams for each budget period and model validation. Most cost-effectiveness analyses could not be extended to provide useful budget impact information; cost

  4. Accounting for equity considerations in cost-effectiveness analysis: a systematic review of rotavirus vaccine in low- and middle-income countries.

    Science.gov (United States)

    Boujaoude, Marie-Anne; Mirelman, Andrew J; Dalziel, Kim; Carvalho, Natalie

    2018-01-01

    Cost-effectiveness analysis (CEA) is frequently used as an input for guiding priority setting in health. However, CEA seldom incorporates information about trade-offs between total health gains and equity impacts of interventions. This study investigates to what extent equity considerations have been taken into account in CEA in low- and middle-income countries (LMICs), using rotavirus vaccination as a case study. Specific equity-related indicators for vaccination were first mapped to the Guidance on Priority Setting in Health Care (GPS-Health) checklist criteria. Economic evaluations of rotavirus vaccine in LMICs identified via a systematic review of the literature were assessed to explore the extent to which equity was considered in the research objectives and analysis, and whether it was reflected in the evaluation results. The mapping process resulted in 18 unique indicators. Under the 'disease and intervention' criteria, severity of illness was incorporated in 75% of the articles, age distribution of the disease in 70%, and presence of comorbidities in 5%. For the 'social groups' criteria, relative coverage reflecting wealth-based coverage inequality was taken into account in 30% of the articles, geographic location in 27%, household income level in 8%, and sex at birth in 5%. For the criteria of 'protection against the financial and social effects of ill health', age weighting was incorporated in 43% of the articles, societal perspective in 58%, caregiver's loss of productivity in 45%, and financial risk protection in 5%. Overall, some articles incorporated the indicators in their model inputs (20%) while the majority (80%) presented results (costs, health outcomes, or incremental cost-effectiveness ratios) differentiated according to the indicators. Critically, less than a fifth (17%) of articles incorporating indicators did so due to an explicit study objective related to capturing equity considerations. Most indicators were increasingly incorporated over

  5. Expression and characterization of human group C rotavirus virus-like particles in insect cells

    International Nuclear Information System (INIS)

    Clark, Kristina B.; Lin, S.-C.; Humphrey, Charles; Foytich, Kimberly; Esona, Mathew; Wang Yuhuan; Liu, Merry; Jiang Baoming

    2009-01-01

    Group C rotavirus (GpC RV) is a causative agent of acute gastroenteritis in children and adults. We expressed the three major capsid proteins VP2, VP6 and VP7 of human GpC RV in baculovirus and demonstrated the self-assembly of VP2/6/7 or VP6/7 virus-like particles (VLPs) in insect cells. We examined a number of parameters, including the kinetics of protein synthesis in different cell lines and media, to optimize the most favorable conditions for the synthesis of recombinant viral proteins and the production of VLPs in Sf9 cells. Hyperimmune serum to VP2/6/7 and VP6/7 VLPs recognized individual recombinant proteins of human GpC RV by Western blot analysis. This serum also showed specific reactivities with the corresponding GpC VLPs but not GpA RV by using immune electron microscopy (IEM) and enzyme immunoassay (EIA). The ability to produce an unlimited amount of GpC RV antigen and the availability of high quality antibody will allow us to develop sensitive and specific diagnostic assays to better determine the epidemiology and disease burden of GpC RV in humans.

  6. Clinical and Molecular Characteristics of Human Rotavirus G8P[8] Outbreak Strain, Japan, 2014.

    Science.gov (United States)

    Kondo, Kenji; Tsugawa, Takeshi; Ono, Mayumi; Ohara, Toshio; Fujibayashi, Shinsuke; Tahara, Yasuo; Kubo, Noriaki; Nakata, Shuji; Higashidate, Yoshihito; Fujii, Yoshiki; Katayama, Kazuhiko; Yoto, Yuko; Tsutsumi, Hiroyuki

    2017-06-01

    During March-July 2014, rotavirus G8P[8] emerged as the predominant cause of rotavirus gastroenteritis among children in Hokkaido Prefecture, Japan. Clinical characteristics were similar for infections caused by G8 and non-G8 strains. Sequence and phylogenetic analyses suggest the strains were generated by multiple reassortment events between DS-1-like P[8] strains and bovine strains from Asia.

  7. Nosocomial outbreak of neonatal gastroenteritis caused by a new serotype 4, subtype 4B human rotavirus.

    Science.gov (United States)

    Gerna, G; Forster, J; Parea, M; Sarasini, A; Di Matteo, A; Baldanti, F; Langosch, B; Schmidt, S; Battaglia, M

    1990-07-01

    A nosocomial outbreak of rotavirus gastroenteritis involving 52 newborns occurred between June and September 1988 at the University Children's Hospital of Freiburg, Federal Republic of Germany. Stools from 27 representative patients were examined for rotavirus serotypes, using a monoclonal antibody-based enzyme-linked immunosorbent assay. The electropherotype was also examined by polyacrylamide gel electrophoresis of genomic RNA. As many as 18 patients were found to be infected by serotype 4, subtype 4B strain, and in all of them the same electropherotype was detected. Although rotavirus from the remaining nine patients could not be typed, the electropherotype in four was identical to that of the serotype 4, subtype 4B strain. Thus, most of the patients in the outbreak were infected by the same rotavirus strain. Retrospective epidemiological studies showed that the 4B strain began to circulate at the hospital in January 1988, whereas only rotavirus serotypes 1, 3, and 4A were detected in 1985-1987. The primary case of the outbreak was presumably a newborn with acute gastroenteritis, admitted to the hospital from a small maternity unit in the same urban area. During the outbreak, 12 of 44 healthy newborns in the nurseries of the Children's Hospital and other maternity hospitals were found to be asymptomatic rotavirus carriers, and in three of the newborns the same 4B strain was detected. This is the first reported outbreak caused by a serotype 4, subtype 4B strain.

  8. Comparison of viral RNA electrophoresis and indirect ELISA methods in the diagnosis of human rotavirus infection

    Energy Technology Data Exchange (ETDEWEB)

    Avendano, L F; Dubinovsky, S; James, Jr, H D

    1984-01-01

    A total of 177 stool samples from Chilean diarrhea patients under two years of age were tested for rotavirus by two methods - the indirect enzyme-linked immunosorbent assay (indirect ELISA) and viral RNA electrophoresis in agarose gels (v RNA EPH). Fifty of the specimens came from patients with acute diarrhea and 127 came from patients with protracted diarrhea. The indirect ELISA testing was performed at the National Institutes of Health in the United States: the electrophoretic testing was carried out in Santiago, Chile by the authors. The electrophoretic method detected rotavirus in 36% of the acute samples and 25% of the samples from protracted cases, while the indirect ELISA method detected rotavirus in higher percentages of samples - 46% and 38%, respectively. These results support the conclusion that v RNA EPH is a less sensitive method for detecting rotavirus than the indirect ELISA. Nevertheless, the former method's high specificity, ease of application, and low cost make it a worthwhile alternative to indirect ELISA. Thus, considering the important role played by rotavirus in infant diarrhea and the need for a diagnostic technique that can be incorporated into the routines of medical center laboratories in developing countries, there is good reason to conclude that v RNA EPH is a useful tool for studying rotavirus diarrhea. 18 refs, 3 tabs. Also published in the Bol. Oficina Sanit. Panam. (1984) v. 97(1), p. 1-7 (In Spanish).

  9. Comparison of viral RNA electrophoresis and indirect ELISA methods in the diagnosis of human rotavirus infection

    International Nuclear Information System (INIS)

    Avendano, L.F.; Dubinovsky, S.

    1984-01-01

    A total of 177 stool samples from Chilean diarrhea patients under two years of age were tested for rotavirus by two methods - the indirect enzyme-linked immunosorbent assay (indirect ELISA) and viral RNA electrophoresis in agarose gels (v RNA EPH). Fifty of the specimens came from patients with acute diarrhea and 127 came from patients with protracted diarrhea. The indirect ELISA testing was performed at the National Institutes of Health in the United States: the electrophoretic testing was carried out in Santiago, Chile by the authors. The electrophoretic method detected rotavirus in 36% of the acute samples and 25% of the samples from protracted cases, while the indirect ELISA method detected rotavirus in higher percentages of samples - 46% and 38%, respectively. These results support the conclusion that v RNA EPH is a less sensitive method for detecting rotavirus than the indirect ELISA. Nevertheless, the former method's high specificity, ease of application, and low cost make it a worthwhile alternative to indirect ELISA. Thus, considering the important role played by rotavirus in infant diarrhea and the need for a diagnostic technique that can be incorporated into the routines of medical center laboratories in developing countries, there is good reason to conclude that v RNA EPH is a useful tool for studying rotavirus diarrhea. (author)

  10. Misconception: human papillomavirus vaccine and infertility.

    Science.gov (United States)

    Schuler, Christine L; Hanley, Chassidy J; Coyne-Beasley, Tamera

    2014-02-01

    This study sought to determine if parents of males express concerns about vaccine-associated infertility (VAI) with the human papillomavirus (HPV) vaccine and to understand the impact of those concerns. Parents of sons were surveyed to determine VAI concerns. Logistic regression was used to find if parents worried about VAI had lower knowledge of HPV disease, more concern for side effects, lacked information about vaccination, or had lower intention to vaccinate. In all, 39% of parents were worried about VAI. Parents worried about VAI had similar knowledge of HPV compared with other parents. Parents worried about VAI had twice the odds of agreeing the vaccine may cause side effects and agreeing they did not have enough information compared to their counterparts. Parents worried about VAI less often intended to vaccinate sons than other parents. These findings suggest many parents worry about VAI in sons with HPV vaccine.

  11. One-step multiplex real-time RT-PCR assay for detecting and genotyping wild-type group A rotavirus strains and vaccine strains (Rotarix® and RotaTeq®) in stool samples

    Science.gov (United States)

    Mijatovic-Rustempasic, Slavica; Esona, Mathew D.; Tam, Ka Ian; Quaye, Osbourne; Bowen, Michael D.

    2016-01-01

    Background. Group A rotavirus (RVA) infection is the major cause of acute gastroenteritis (AGE) in young children worldwide. Introduction of two live-attenuated rotavirus vaccines, RotaTeq® and Rotarix®, has dramatically reduced RVA associated AGE and mortality in developed as well as in many developing countries. High-throughput methods are needed to genotype rotavirus wild-type strains and to identify vaccine strains in stool samples. Quantitative RT-PCR assays (qRT-PCR) offer several advantages including increased sensitivity, higher throughput, and faster turnaround time. Methods. In this study, a one-step multiplex qRT-PCR assay was developed to detect and genotype wild-type strains and vaccine (Rotarix® and RotaTeq®) rotavirus strains along with an internal processing control (Xeno or MS2 RNA). Real-time RT-PCR assays were designed for VP7 (G1, G2, G3, G4, G9, G12) and VP4 (P[4], P[6] and P[8]) genotypes. The multiplex qRT-PCR assay also included previously published NSP3 qRT-PCR for rotavirus detection and Rotarix® NSP2 and RotaTeq® VP6 qRT-PCRs for detection of Rotarix® and RotaTeq® vaccine strains respectively. The multiplex qRT-PCR assay was validated using 853 sequence confirmed stool samples and 24 lab cultured strains of different rotavirus genotypes. By using thermostable rTth polymerase enzyme, dsRNA denaturation, reverse transcription (RT) and amplification (PCR) steps were performed in single tube by uninterrupted thermocycling profile to reduce chances of sample cross contamination and for rapid generation of results. For quantification, standard curves were generated using dsRNA transcripts derived from RVA gene segments. Results. The VP7 qRT-PCRs exhibited 98.8–100% sensitivity, 99.7–100% specificity, 85–95% efficiency and a limit of detection of 4–60 copies per singleplex reaction. The VP7 qRT-PCRs exhibited 81–92% efficiency and limit of detection of 150–600 copies in multiplex reactions. The VP4 qRT-PCRs exhibited 98.8

  12. The future of human DNA vaccines.

    Science.gov (United States)

    Li, Lei; Saade, Fadi; Petrovsky, Nikolai

    2012-12-31

    DNA vaccines have evolved greatly over the last 20 years since their invention, but have yet to become a competitive alternative to conventional protein or carbohydrate based human vaccines. Whilst safety concerns were an initial barrier, the Achilles heel of DNA vaccines remains their poor immunogenicity when compared to protein vaccines. A wide variety of strategies have been developed to optimize DNA vaccine immunogenicity, including codon optimization, genetic adjuvants, electroporation and sophisticated prime-boost regimens, with each of these methods having its advantages and limitations. Whilst each of these methods has contributed to incremental improvements in DNA vaccine efficacy, more is still needed if human DNA vaccines are to succeed commercially. This review foresees a final breakthrough in human DNA vaccines will come from application of the latest cutting-edge technologies, including "epigenetics" and "omics" approaches, alongside traditional techniques to improve immunogenicity such as adjuvants and electroporation, thereby overcoming the current limitations of DNA vaccines in humans. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. The incidence and clinical presentation of infantile rotavirus ...

    African Journals Online (AJOL)

    Objectives. An effective vaccine is needed to protect against severe rotavirus disease, an important cause of gastroenteritis. Since there are no data on the incidence and antigenic diversity of rotavirus infection in Sierra Leone, we studied its epidemiology to enable an effective vaccine strategy to be designed. Methods.

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

    NARCIS (Netherlands)

    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

  15. 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 totalinghuman 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.

  16. 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

  17. Unexpected detection of porcine rotavirus C strains carrying human origin VP6 gene.

    Science.gov (United States)

    Kattoor, Jobin Jose; Saurabh, Sharad; Malik, Yashpal Singh; Sircar, Shubhankar; Dhama, Kuldeep; Ghosh, Souvik; Bányai, Krisztián; Kobayashi, Nobumichi; Singh, Raj Kumar

    2017-12-01

    Rotavirus C (RVC), a known etiological agent of diarrheal outbreaks, mainly inflicts swine population globally with sporadic incidence in human, cattle, ferret, mink and dog. To demonstrate the presence of RVC in Indian swine population and characterization of its selected structural (VP6) and non-structural (NSP4 and NSP5) genes. A total of 108 diarrheic samples from different regions of India were used. Isolated RNA was loaded onto polyacrylamide gel to screen for the presence of RVs through the identification of specific electrophoretic genomic migration pattern. To characterize the RVC strains, VP6 gene and NSP4 and NSP5 genes were amplified, sequenced and analyzed. Based on VP6 gene specific diagnostic RT-PCR, the presence of RVC was confirmed in 12.0% (13/108) piglet fecal specimens. The nucleotide sequence analysis of VP6 gene, encoding inner capsid protein, from selected porcine RVC (PoRVC) strains revealed more than 93% homologies to human RVC strains (HuRVC) of Eurasian origin. These strains were distant from hitherto reported PoRVCs and clustered with HuRVCs, owning I2 genotype. However, the two non-structural genes, i.e. NSP4 and NSP5, of these strains were found to be of swine type, signifying a re-assortment event that has occurred in the Indian swine population. The findings indicate the presence of human-like RVC in Indian pigs and division of RVC clade with I2 genotype into further sub-clades. To the best of our knowledge, this appears to be the first report of RVC in Indian swine population. Incidence of human-like RVC VP6 gene in swine supports its subsequent zoonotic prospective.

  18. 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 < .001). Healthy control participants of Hispanic ethnicity were significantly less likely to be nonsecretors (13%) compared with healthy children who were not of Hispanic ethnicity (25%) (P < .001). After controlling for vaccination and other factors, children with the nonsecretor FUT2 polymorphism appeared statistically protected (98% [95% CI, 84%–100%]) against severe rotavirus gastroenteritis. CONCLUSIONS AND RELEVANCE Severe rotavirus gastroenteritis was virtually absent among US children who had a genetic

  19. Safety of human papillomavirus vaccines: a review.

    Science.gov (United States)

    Stillo, Michela; Carrillo Santisteve, Paloma; Lopalco, Pier Luigi

    2015-05-01

    Between 2006 and 2009, two different human papillomavirus virus (HPV) vaccines were licensed for use: a quadrivalent (qHPVv) and a bivalent (bHPVv) vaccine. Since 2008, HPV vaccination programmes have been implemented in the majority of the industrialized countries. Since 2013, HPV vaccination has been part of the national programs of 66 countries including almost all countries in North America and Western Europe. Despite all the efforts made by individual countries, coverage rates are lower than expected. Vaccine safety represents one of the main concerns associated with the lack of acceptance of HPV vaccination both in the European Union/European Economic Area and elsewhere. Safety data published on bivalent and quadrivalent HPV vaccines, both in pre-licensure and post-licensure phase, are reviewed. Based on the latest scientific evidence, both HPV vaccines seem to be safe. Nevertheless, public concern and rumors about adverse events (AE) represent an important barrier to overcome in order to increase vaccine coverage. Passive surveillance of AEs is an important tool for detecting safety signals, but it should be complemented by activities aimed at assessing the real cause of all suspect AEs. Improved vaccine safety surveillance is the first step for effective communication based on scientific evidence.

  20. Caracterização de genótipos de rotavírus em creches: era pré- e pós-vacinação contra o rotavírus Characterization of rotavirus strains from day care centers: pre- and post-rotavirus vaccine era

    Directory of Open Access Journals (Sweden)

    Simone G. Morillo

    2010-04-01

    Full Text Available OBJETIVOS: Em 2006, a vacina contra rotavírus foi incluída no Programa Nacional de Imunização. Este estudo teve como objetivo analisar os resultados da vigilância de genótipos de rotavírus em crianças OBJECTIVES: In 2006 the rotavirus vaccine was included in the Brazilian Immunization Program. The aim of this study was to report the results of a 5-year surveillance study of rotavirus strains in children < 5 years with acute gastroenteritis from day care centers in the state of São Paulo, Brazil. METHODS: This retrospective study was conducted with 30 day care centers from 2004 to 2008 with convenient surveillance fecal specimens, investigated by ELISA, SDS-PAGE, RT-PCR and gene sequencing to genotype characterization. RESULTS: Rotavirus infection was detected in 28.3% of samples (38/134. The most frequent genotypes detected were G9P[8] and G1P[8] in 2004; G1P[8] in 2005; GNTP[NT] in 2006; G2P[4] in 2007; and there were no cases in 2008. Mixed infections were not observed. Detection rate declined from 65.7% (23/35 in 2004 to 50% (9/18 in 2007. CONCLUSIONS: Genotype distribution varied according to collection year, accompanied by a reduction in detection rate. Use of rotavirus vaccine requires implementation of post-marketing surveillance to monitor rotavirus strain diversity and its efficacy against possible new emerging genotypes.

  1. 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 ...

  2. Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of the VP8* carbohydrate-binding protein of the human rotavirus strain Wa

    International Nuclear Information System (INIS)

    Kraschnefski, Mark J.; Scott, Stacy A.; Holloway, Gavan; Coulson, Barbara S.; Itzstein, Mark von; Blanchard, Helen

    2005-01-01

    The carbohydrate-binding component (VP8* 64–223 ) of the human Wa rotavirus spike protein has been overexpressed in E. coli, purified and crystallized in two different crystal forms. X-ray diffraction data have been collected that have enabled determination of the Wa VP8* 64–223 structure by molecular replacement. Rotaviruses exhibit host-specificity and the first crystallographic information on a rotavirus strain that infects humans is reported here. Recognition and attachment to host cells, leading to invasion and infection, is critically linked to the function of the outer capsid spike protein of the rotavirus particle. In some strains the VP8* component of the spike protein is implicated in recognition and binding of sialic-acid-containing cell-surface carbohydrates, thereby enabling infection by the virus. The cloning, expression, purification, crystallization and initial X-ray diffraction analysis of the VP8* core from human Wa rotavirus is reported. Two crystal forms (trigonal P3 2 21 and monoclinic P2 1 ) have been obtained and X-ray diffraction data have been collected, enabling determination of the VP8* 64–223 structure by molecular replacement

  3. Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of the VP8* carbohydrate-binding protein of the human rotavirus strain Wa

    Energy Technology Data Exchange (ETDEWEB)

    Kraschnefski, Mark J.; Scott, Stacy A. [Institute for Glycomics, Griffith University (Gold Coast Campus), PMB 50 Gold Coast Mail Centre, Queensland 9726 (Australia); Holloway, Gavan; Coulson, Barbara S.; Itzstein, Mark von [Department of Microbiology and Immunology, The University of Melbourne, Victoria 3010 (Australia); Blanchard, Helen, E-mail: h.blanchard@griffith.edu.au [Institute for Glycomics, Griffith University (Gold Coast Campus), PMB 50 Gold Coast Mail Centre, Queensland 9726 (Australia)

    2005-11-01

    The carbohydrate-binding component (VP8*{sub 64–223}) of the human Wa rotavirus spike protein has been overexpressed in E. coli, purified and crystallized in two different crystal forms. X-ray diffraction data have been collected that have enabled determination of the Wa VP8*{sub 64–223} structure by molecular replacement. Rotaviruses exhibit host-specificity and the first crystallographic information on a rotavirus strain that infects humans is reported here. Recognition and attachment to host cells, leading to invasion and infection, is critically linked to the function of the outer capsid spike protein of the rotavirus particle. In some strains the VP8* component of the spike protein is implicated in recognition and binding of sialic-acid-containing cell-surface carbohydrates, thereby enabling infection by the virus. The cloning, expression, purification, crystallization and initial X-ray diffraction analysis of the VP8* core from human Wa rotavirus is reported. Two crystal forms (trigonal P3{sub 2}21 and monoclinic P2{sub 1}) have been obtained and X-ray diffraction data have been collected, enabling determination of the VP8*{sub 64–223} structure by molecular replacement.

  4. Human papilloma virus vaccine associated uveitis.

    Science.gov (United States)

    Holt, Henry D; Hinkle, David M; Falk, Naomi S; Fraunfelder, Frederick T; Fraunfelder, Frederick W

    2014-03-01

    To report a possible association between human papilloma virus (HPV) vaccination and uveitis. Spontaneous reports from the National Registry of Drug-Induced Ocular Side effects, World Health Organization and Food and Drug Administration were collected on uveitis associated with human papilloma virus vaccination. A MEDLINE search was performed using keywords "uveitis," "iritis," "iridocyclitis," "human papilloma virus," "Cervarix", and "Gardasil." Data garnered from spontaneous reports included the age, gender, adverse drug reaction (ADR), date of administration, concomitant administration of other vaccinations, time until onset of ADR, other systemic reactions, and dechallenge and rechallenge data. A total of 24 case reports of uveitis associated with human papilloma virus vaccination were identified, all cases were female, and the median age was 17. Median time from HPV vaccination to reported ADR was 30 days (range 0-476 days). According to World Health Organization criteria, the relationship between human papilloma virus vaccination and uveitis is "possible." Causality assessments are based on the time relationship of drug administration, uveitis development and re-challenge data. Clinicians should be aware of a possible bilateral uveitis and papillitis following HPV vaccination.

  5. Human papillomavirus vaccination among adolescents in Georgia.

    Science.gov (United States)

    Underwood, Natasha L; Weiss, Paul; Gargano, Lisa M; Seib, Katherine; Rask, Kimberly J; Morfaw, Christopher; Murray, Dennis; DiClemente, Ralph J; Hughes, James M; Sales, Jessica M

    2015-01-01

    Human papillomavirus (HPV) vaccination coverage for adolescent females and males remains low in the United States. We conducted a 3-arm randomized controlled trial (RCT) conducted in middle and high schools in eastern Georgia from 2011-2013 to determine the effect of 2 educational interventions used to increase adolescent vaccination coverage for the 4 recommended adolescent vaccines: Tdap, MCV4, HPV and influenza. As part of this RCT, this article focuses on: 1) describing initiation and completion of HPV vaccine series among a diverse population of male and female adolescents; 2) assessing parental attitudes toward HPV vaccine; and 3) examining correlates of HPV vaccine series initiation and completion. Parental attitude score was the strongest predictor of HPV vaccine initiation among adolescents (adjusted odds ratio (aOR): 2.08; 95% confidence interval (CI): 1.80, 2.39). Other correlates that significantly predicted HPV series initiation were gender, study year, and intervention arm. Parental attitudes remained a significant predictor of receipt of 3 doses of HPV vaccine along with gender, race, school type and insurance type. This study demonstrates that positive parental attitudes are important predictors of HPV vaccination and critical to increasing coverage rates. Our findings suggest that more research is needed to understand how parental attitudes are developed and evolve over time.

  6. Human rotavirus strains bearing VP4 gene P[6] allele recovered from asymptomatic or symptomatic infections share similar, if not identical, VP4 neutralization specificities

    International Nuclear Information System (INIS)

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

    2003-01-01

    A rotavirus VP4 gene P[6] allele has been documented in a number of countries to be characteristically associated with an endemic predominantly asymptomatic infection in neonates in maternity hospital nurseries. The mechanisms underlying the endemicity and asymptomatic nature of such neonatal infections remain unknown. Rotavirus strains sharing this same P genotype, however, have more recently been recovered from an increasing number of symptomatic diarrheal episodes in infants and young children in various parts of the world. Previously, we have shown that an asymptomatic P[6] rotavirus neonatal infection is not associated with a unique VP7 (G) serotype but may occur in conjunction with various G types. Although amino acid sequence comparisons of the VP4 gene between selected 'asymptomatic' and 'symptomatic' P[6] rotavirus strains have been reported and yielded information concerning their VP4 genotypes, serotypic comparisons of the outer capsid spike protein VP4 of such viruses have not been studied systematically by two-way cross-neutralizations. We determined the VP4 neutralization specificities of four asymptomatic and four symptomatic P[6] strains: two each of asymptomatic and symptomatic strains by two-way tests, and two each of additional asymptomatic and symptomatic strains by one-way tests. Both asymptomatic and symptomatic P[6] strains were shown to bear similar, if not identical, VP4 neutralization specificities. Thus, P[6] rotavirus strains causing asymptomatic or symptomatic infections did not appear to belong to unique P (VP4) serotypes. In addition, a close VP4 serotypic relationship between human P[6] rotavirus strains and the porcine P[6] rotavirus Gottfried strain was confirmed

  7. Rotavirus (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Rotavirus KidsHealth / For Parents / Rotavirus What's in this article? ... the Doctor Print en español El rotavirus About Rotavirus Almost all kids have had a rotavirus infection ...

  8. Gene-Specific-Candidate-Driven Study to decipher Genetic Predisposition to Rotavirus Infection

    Directory of Open Access Journals (Sweden)

    Kshitija Rane-Yadav

    2017-10-01

    Full Text Available Recent report of WHO shows 113000 children in India succumb to death due to Rotavirus diarrhea. Lack of knowledge about pathogenesis of virus has led to lack of therapy for severely infected patients. Previous studies have found that, animal rotavirus requires sialyl glycan moieties on cell surface for pathogenesis. Present study states that human rotaviruses also follows same path and this specificity of virus leads to host genetic predisposition for the infection as well as the disease. Two hundred children less than 5 years of age clinically suspected of viral diarrhea were screened for rotavirus infection. EDTA blood was processed for analyzing DNA sequences of various fucosyltransferase genes. Lewis antigens which are secretory form of ABO Histo Blood Group Antigens were correlated with the genotype of patient. Genetics of HBGA secretion, particularly, basis of Leb expression manifested by fucosyltransferase-2 enzyme was studied in healthy individuals and was compared in cases of rotavirus positive and negative diarrhea. Positive clinical isolates with various genotypes were purified from stool samples and gene for VP4 - surface spike protein was sequenced. Using Bioinformatics interphase, three dimensional protein structures were modeled and their functional domains were analyzed. All these modeled proteins were docked with Leb HBGA (Lewis-b Histo Blood Group Antigens using molecular docking software. In present study, to investigate possible association of the rotavirus with host genome, we screened highly suspected genes involved in expression of glycoproteins on enterocytes. This study performed for prevalent Indian strains of rotaviruses provides possible evidence that, VP8 domain of VP4 spike protein utilizes Leb surface antigen for attachment and entry to enterocytes in the intestine. The FUT2 and FUT3 gene has been found to show significant association with the rotavirus infection hence can serve as a biomarker for genetic

  9. [Human papillomavirus vaccine. Efficacy and safety].

    Science.gov (United States)

    Bruni, Laia; Serrano, Beatriz; Bosch, Xavier; Castellsagué, Xavier

    2015-05-01

    Human papillomavirus (HPV) related disease remains a major cause of morbidity and mortality worldwide. Prophylactic vaccines have been recognized as the most effective intervention to control for HPV-related diseases. This article reviews the major phaseii/iii trials of the bivalent (HPVs16/18), quadrivalent (HPVs6/11/16/18), and the recently approved 9-valent vaccine (HPVs6/11/16/18/31/33/45/52/58). Large trials have been conducted showing the safety, immunogenicity and high efficacy of the bivalent and quadrivalent vaccines in the prevention of pre-invasive lesions and infection, especially when administered at young ages before exposure to HPV. Trials of the 9-valent vaccine have also demonstrated the safety, immunogenicity and efficacy of the vaccine in the prevention of infection and disease associated with the vaccine types, and its potential to substantially increase the overall prevention of HPV-related diseases. Post-licensure country reports have shown the recent and early impact of these vaccines at population level after the implementation of established HPV vaccination programs, including decreases in the prevalence of vaccine HPV types, the incidence of genital warts, and the incidence of high-grade cervical abnormalities. If widely implemented, current HPV vaccines may drastically reduce the incidence of cervical cancer and other HPV-related cancers and diseases. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  10. Health economics of rotavirus immunization in Vietnam : Potentials for favorable cost-effectiveness in developing countries

    NARCIS (Netherlands)

    Tu, Hong-Anh T.; Rozenbaum, Mark H.; Coyte, Peter C.; Li, Shu Chuen; Woerdenbag, Herman J.; Postma, Maarten J.

    2012-01-01

    Introduction: Rotavirus is the most common cause of severe diarrhoea worldwide. Vietnam is situated in the region of high rotavirus infection incidence and eligible for financial support to introduce rotavirus vaccines into the Expanded Program of Immunization (EPI) from the GAVI. This study was

  11. Variables associated with human papillomavirus (HPV) vaccine acceptance by men.

    Science.gov (United States)

    Ferris, Daron G; Waller, Jennifer L; Miller, Jeremiah; Patel, Pratik; Price, George A; Jackson, Lanier; Wilson, Courtesia

    2009-01-01

    To determine correlates of human papillomavirus (HPV) vaccine acceptance for men. A convenience sample of men aged 18 to 45 years read a one-page information sheet about HPV and the HPV vaccine, then completed a 29-item questionnaire. chi(2) tests were used to determine whether differences in demographic, sexual, and vaccine-related variables existed between levels of wanting the HPV vaccine. Positive correlates of HPV vaccine acceptance included higher education (P acceptance of the HPV vaccine by men.

  12. Screening of Viral Pathogens from Pediatric Ileal Tissue Samples after Vaccination

    Directory of Open Access Journals (Sweden)

    Laura Hewitson

    2014-01-01

    Full Text Available In 2010, researchers reported that the two US-licensed rotavirus vaccines contained DNA or DNA fragments from porcine circovirus (PCV. Although PCV, a common virus among pigs, is not thought to cause illness in humans, these findings raised several safety concerns. In this study, we sought to determine whether viruses, including PCV, could be detected in ileal tissue samples of children vaccinated with one of the two rotavirus vaccines. A broad spectrum, novel DNA detection technology, the Lawrence Livermore Microbial Detection Array (LLMDA, was utilized, and confirmation of viral pathogens using the polymerase chain reaction (PCR was conducted. The LLMDA technology was recently used to identify PCV from one rotavirus vaccine. Ileal tissue samples were analyzed from 21 subjects, aged 15–62 months. PCV was not detected in any ileal tissue samples by the LLMDA or PCR. LLMDA identified a human rotavirus A from one of the vaccinated subjects, which is likely due to a recent infection from a wild type rotavirus. LLMDA also identified human parechovirus, a common gastroenteritis viral infection, from two subjects. Additionally, LLMDA detected common gastrointestinal bacterial organisms from the Enterobacteriaceae, Bacteroidaceae, and Streptococcaceae families from several subjects. This study provides a survey of viral and bacterial pathogens from pediatric ileal samples, and may shed light on future studies to identify pathogen associations with pediatric vaccinations.

  13. Epidemiology of rotavirus-associated hospital admissions in the province of Ferrara, Italy.

    Science.gov (United States)

    Marsella, Maria; Raimondi, Licia; Bergamini, Mauro; Sprocati, Monica; Bigi, Ettore; De Sanctis, Vincenzo; Borgna-Pignatti, Caterina; Gabutti, Giovanni

    2009-12-01

    Hospital discharge forms with specific codes for rotavirus gastroenteritis in children 0 to 14 years of age were reviewed in the period 2003-2005 in the province of Ferrara. A total of 4,238 children were admitted to the pediatric departments; 151 patients were diagnosed with rotavirus gastroenteritis. The average annual rate of hospitalization for rotavirus gastroenteritis was 1.54/1,000 children Italy and underline the potential impact of rotavirus vaccination in our province.

  14. An evaluation of the Australian Rotavirus Surveillance Program.

    Science.gov (United States)

    Roberts-Witteveen, April R; Patel, Mahomed S; Roche, Paul W

    2008-09-01

    The Australian Rotavirus Serotyping Program (ARSP) serotypes rotavirus isolates obtained from stool samples sent from Australian laboratories. In collaboration with ARSP the Australian Government Department of Health and Ageing evaluated the program for its utility and capacity to monitor effectiveness of the rotavirus vaccines recently introduced into the Australian National Immunisation Pro