Rotavirus
Rotavirus is the most common cause of diarrhea among infants and young children. In fact, nearly every child in the world has been infected with rotavirus at least once by the age of five. Immunity develops with each infection, so subsequent infections are less severe; adults are rarely affected. There are five species of this virus, referred to as A, B, C, D, and E.
Rotavirus A, the most common species, causes more than 90% of infections in humans. The virus is transmitted by the fecal-oral route. It infects and damages the cells that line the small intestine and causing “stomach flu”. While rotavirus is usually an easily managed disease of childhood, nearly 60,000 children are hospitalized annually. Deaths are rare in the US.
Approximately 30 deaths have occurred each year due to severe and inappropriately recognized dehydration. There are two versions of the rotavirus vaccine: Rotarix and RotaTeq. A third, Rotashield, was taken off the market in 2010 for causing a serious complication called intussusception.
Rotavirus Vaccine (RotaShield®) and Intussusception – Historical information as RotaShield® was taken off U.S. market in 1999, licensed by the Food and Drug Administration (FDA) in August 1998
November 28, 2019 - The rotavirus vaccine development pipeline "However, concerns continue about rare but severe adverse events, such as intussusception, as well as the lower vaccine effectiveness in less developed settings. WHO evaluated the risk-benefit of oral rotavirus vaccines with respect to public health impact and the rare occurrence of serious adverse events, such as intussusception and found that the risk benefit analysis weighed heavily in the favor of rotavirus immunization. Nevertheless, the occurrence of even a small risk remains a public health concern, and has stimulated interest i'n an alternative, parenteral approach to immunization based on the successes of the inactivated poliovirus vaccine."
December 18, 2017 – Potential for a booster dose of rotavirus vaccine to further reduce diarrhea mortality – CDC Foundation, United States – Department of Epidemiology, Emory University, United States – Division of Viral Diseases, US Centers for Disease Control and Prevention, United States “Some post licensure, ‘‘real world” effectiveness evaluations in several low and middle-income settings also indicate there may be waning protection after the first year of life, though they were not sufficiently powered to detect differential vaccine performance by age group. Rotarix VE after 12 months of age was found to be a median of 31% lower in middle income countries, compared to 5% higher in high income countries in a recent systematic literature review.” Comment: So even though 98% of children have experienced – and fully recovered from – rotavirus by age 2, we need to give boosters and more of a worthless vaccine. They will, of course, launch this new schedule in the US first, where the money is.
August 1, 2017 – Rotavirus Infection and Disease in a Multisite Birth Cohort: Results From the MAL-ED Study (full text) “Among factors contributing to rotavirus infection and disease, being infected with other pathogens and living in crowded homes were associated with greater risk demonstrating the critical role of the environment in pathogen exposure. It is difficult to explain why presence of siblings could decrease risk of infection in some Asian sites; this could partly be due to greater exposure among mothers with more children, resulting in higher maternal antibodies protecting the newborn during infancy.
August 2017 – The Residual Vaccine-preventable Burden of Rotavirus Disease (full text) “'Only 24% of rotavirus-positive children ≥15 weeks of age were vaccine failures. Comment: “Only 24%” that is roughly about 214 are vaccine failures? It’s okay for those children who don’t respond? Why aren’t they responding?
August 2017 – Safety and immunogenicity of a parenteral P2-VP8-P[8 subunit rotavirus vaccine in toddlers and infants in South Africa: a randomised, double-blind, placebo-controlled trial] (full text) “Efficacy of live oral rotavirus vaccines is reduced in low-income compared with high-income settings. Parenteral non-replicating rotavirus vaccines might offer benefits over oral vaccines. We assessed the safety and immunogenicity of the P2-VP8-P[8] subunit rotavirus vaccine at different doses in South African toddlers and infants.
July 24, 2017 – Risk of intussusception following rotavirus vaccination: An evidence based meta-analysis of cohort and case-control studies “The cohort data revealed that there was an associated increased risk of intussusception after the first 7 days post first dose of the vaccine(RR:3.71, 95% CI:1.08–12.69) and after receiving all doses of the rotavirus vaccine (RR:3.47, 95% CI:1.23–9.78). Similarly, the case-control data found an increased risk of intussusception following the first dose (OR: 8.45, 95% CI: 4.08–17.50) and following all doses (OR: 1.59, 95% CI: 1.11–2.27).
July 2017 – Rotavirus Vaccine: Current Use and Future Considerations (full text) “Concerns regarding intussusception led to age restrictions on administration of the first (initiate by 15 weeks of age) and last doses (complete by 32 weeks of age) of rotavirus vaccine being recommended by the WHO, with some professional organizations and guidelines recommending even stricter limitations of use. As vaccines cannot be administered before 6 weeks of age according to the manufacturers’ labels, this leaves a relatively narrow window of opportunity to initiate vaccination in an infant. These restrictions excluded a substantial number of children from receiving vaccination especially in LMIC where delays in vaccination are common. Using modeling, it was estimated that in LMIC the additional rotavirus deaths prevented by vaccination without age restrictions far exceeded the excess vaccine-associated intussusception deaths. The WHO continues to recommend that the first dose be given as soon as possible after 6 weeks of age, to ensure protection before natural infection, but infants should be allowed to receive rotavirus vaccine together with Diphteria, Tetanus, Pertussis regardless of the time of vaccination. This would allow immunization programs to reach children who were previously excluded from the benefits of the vaccines. However, vaccination of children beyond 24 months of age is not recommended.”
April 2017 – The Association Between Fecal Biomarkers of Environmental Enteropathy and Rotavirus Vaccine Response in Nicaraguan Infants (full text) “In this preliminary study, we found that 2 of the 4 fecal EE biomarkers examined, MPO and CAL, were associated with failure to seroconvert to the first dose of RV5. For example, only 30% of infants in the highest quartile of MPO concentration seroconverted to the first dose of RV5, as compared with 82% of infants in the lowest quartile of MPO concentration. Further, high combined scores of biomarkers were associated with poor RV5 immunogenicity.”
April 2017 – Safety, Tolerability and Immunogenicity of Pentavalent Rotavirus Vaccine Manufactured by a Modified Process “The RV5mp group and RV5 group had comparable safety profiles with respect to the 'prespecified AEs of interest: diarrhea, vomiting, elevated temperature, irritability and intussusception. A total of 2 subjects discontinued the study as a result of AEs of intussusception, which were considered serious. The 2 cases of intussusception reported were in the RV5mp group, and they occurred more than 30 days postdose 2 at ~5 months of age, the time of peak incidence for naturally occurring intussusception in the absence of rotavirus vaccination.”
March 14, 2017 – Rotavirus immunization: Global coverage and local barriers for implementation “Elevated cost of vaccine (49%) is the main barrier for implementation of RVI. High costs of vaccination (rs = −0.39, p = 0.02) and coverage of expenses by families (rs = 0.5, p = 0.002) significantly correlate with a lower immunization rate. Limited perception of RV illness severity by the families (47%), public-health authorities (37%) or physicians (24%) and the timing of administration (16%) are further major barriers to large- scale RVI programs.”
February 2017 – Lot-to-lot Consistency, Safety, Tolerability and Immunogenicity of an Investigational Hexavalent Vaccine in US Infants “There were 5 SAEs assessed as vaccine-related (all HV group): 1 case of ileocolic intussusception, considered related to third dose of RV5; 3 cases of fever, considered related to all study vaccines; and 1 case of diarrhea, considered related to first dose of RV5. No participants discontinued due to a vaccine-related SAE. During the entire study duration, 5 participants (0.2%) of 2308 participants in the HV group died: obstructive hydrocephalus (1 participant) 1 day postdose 2; death of unknown cause (1 participant) 44 days postdose 1; group A streptococcal sepsis (1 participant) 2 days postdose 1; and sudden infant death syndrome (2 participants) 10 days postdose 2 and 49 days postdose 1, respectively. No death was assessed to be related to the study vaccinations'. None of the participants in the Control group (N = 402) died.
January 18, 2017 – Secretor and Salivary ABO Blood Group Antigen Status Predict Rotavirus Vaccine Take in Infants “Among 181 Pakistani infants in a G1P[8] rotavirus vaccine trial who were seronegative at baseline, anti–rotavirus immunoglobulin A seroconversion rates after 3 vaccine doses differed significantly by salivary HBGA phenotype, with the lowest rate (19%) among infants who were nonsecretors …”among secretors with non–blood group O, and the highest rate (51%) among secretors with O blood group. Differences in HBGA expression may be responsible for some of the discrepancy in the level of protection detected for the current rotavirus vaccines in low-income versus high-income settings.”
January 2017 – Contribution of Maternal Immunity to Decreased Rotavirus Vaccine Performance in Low- and Middle-Income Countries “Breastfeeding withholding has no effect on vaccine responses, but higher levels of transplacental rotavirus-specific IgG antibody contribute to reduced vaccine seroconversion.
December 12, 2016 – The Association Between Fecal Biomarkers of Environmental Enteropathy and Rotavirus Vaccine Response in Nicaraguan Infants. “Results. Of the 43 enrolled infants, 24 (56%) seroconverted following the first dose of RV5. As compared to infants who seroconverted, those who did not seroconvert had higher median concentrations of both myeloperoxidase (3.1 vs.1.1 [micro]g/mL, p=0.002) and calprotectin (199.1 vs. 156.2 [micro]g/mL, p=0.03). Further, those who did not seroconvert had a higher median combined score of the 4 biomarkers as compared to those who seroconverted (6.5 vs. 4.5, p=0.017).”
December 9, 2016 – Shedding of porcine circovirus type 1 DNA and rotavirus RNA by infants vaccinated with Rotarix® “We found that 21% of infants did not shed Rotarix® RVA RNA beyond the day 3 sample, which may suggest lack of vaccine virus replication. Of the infants in whom Rotarix RVA RNA shedding continued, peak copy numbers were reached on days 3–5 for ∼40%, and after day 5 in ∼60%, 'and shedding can be prolonged (≥45 days).”
November 21, 2016 – Rotavirus, vaccine failure or diagnostic error? “The large percentage of false positives, due to an excessive number of tests in vaccinated and out of the RV season, if interpreted as vaccine failures, can cause a loss of confidence in the vaccine and lower the estimates of vaccine effectiveness.”
October 31, 2016 – The infant gut microbiome correlates significantly with rotavirus vaccine response in rural Ghana “78 Ghanaian infants, equalling 39 RVV responder and non-responder pairs, were analysed. The overall microbiome composition was significantly different between RVV-responders and non-responders (FDR=0.12), and Ghanaian responders were more similar to Dutch infants than non-responders (p=0.002). RVV-response correlated with an increased abundance of Streptococcus bovis and a decreased abundance of the Bacteroidetes phylum in comparisons between Ghanaian RVV-responders and non-responders (FDR=0.008, FDR=0.003) as well as between Dutch infants and Ghanaian non-responders (FDR=0.002, FDR=0.009).”
August 17, 2016 – Measuring indirect effects of rotavirus vaccine in low income countries (full text) “Horizontal transmission of RV5 to siblings of vaccinated infants was described 'in the US and transmission of RV1 occurred in 19% of 100 sets of twins during a randomised controlled trial in the Dominican Republic; approximately a quarter of whom developed anti-rotavirus IgA sero-conversion.” Comment: Will there be cases of Rotavirus vaccine strain cases just as there is for live virus Polio vaccines?
July 12, 2016 – The risk of intussusception following monovalent rotavirus vaccination in England: A self-controlled case-series evaluation (full text) “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.”
June 14, 2016 – Rotavirus Strain Trends during the Post-Licensure Vaccine Era: United States, 2008-2013 “Vaccine (RotaTeq®, Rotarix®) strains were detected in 0.6-3.4% of genotyped samples each season. Uncommon and unusual strains (e.g., G8P[4], G3P[24], G2P[8], G3P[4], G3P[6], G24P[14], G4P[6], G9P[4]) were detected sporadically over the study period. Year, study site, and race were found to be significant predictors of genotype. Conclusion. Continued active surveillance is needed to monitor RVA genotypes in the U.S. and to detect potential changes since vaccine licensure.
May 23, 2016 – A Randomized Controlled Trial with Delayed Dosing of Oral Rotavirus Vaccine Demonstrates Decreased Risk of Rotavirus Gastroenteritis Associated with Serum Zinc “Serum zinc (OR 0.77, p=0.002) and lack of rotavirus 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.”…”Beyond vaccination, only serum zinc and IgA seroconversion were strongly associated with protection from RVD, and both were independent of vaccination status. This suggests that, regardless of vaccine performance, improvement in these variables would decrease risk and overall burden of RVD. In the final model, only vaccination and serum zinc retained significance.”
May 11, 2016 – Stability of live attenuated rotavirus vaccine with selected preservatives and primary containers “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 that was similar to its profile in standard glass vials. This study demonstrates that there are multiple options for the primary container for rotavirus vaccines intended for oral delivery. Selection of an optimal primary container should take into consideration additional factors, including stability as well as cold chain volume, usability, cost, and manufacturing feasibility.”
May 2016 – Temporal Changes in Pediatric Gastroenteritis Following Rotavirus Vaccination in Quebec. “Conclusions: Norovirus infections were more prevalent than rotavirus' infections among pediatric gastroenteritis cases hospitalized or seeking emergency care. Rotavirus cases were, on average, more clinically severe than norovirus cases among participants of the same age.”
March 14, 2016 – Evaluation of the Intussusception Risk after Pentavalent Rotavirus Vaccination in Finnish Infants “52 IS cases were reported during the 7 years prior to the vaccines were available (January 1999-December 2005), and 37 cases during the 3 years and 8 months while the vaccine was available in the market but not in the national programme (2006- August 2009). The corresponding cumulative incidences at 1 year of age during the three periods were 7.4 cases per year prior, 10.1 cases per year while vaccine was sold and 13.8 annual cases during the universal vaccination programme.”…”Thus, the benefits of rotavirus immunisation programme clearly outweigh possible small risks of intussusception.” Comment: The benefits outweigh the risks? Ask the parents of the children affected if they agree with that statement.
March 14, 2016 – Association of Maternal Immunity with Rotavirus Vaccine Immunogenicity in Zambian Infants (full text) “Low immunogenicity of RV1 vaccine could be explained in part by exposure to high antibody titres in breast milk and early exposure to wild-type rotavirus infections. Potential interference of anti-RV specific IgA in breast milk and pre-vaccination serum RV specific-IgA and IgG titres with RV1 seroconversion and effectiveness requires further research.”
November 27, 2015 – Value of post-licensure data on benefits and risks of vaccination to inform vaccine policy: The example of 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.”…”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.”
November 2015 –G2P[4-RotaTeq Reassortant Rotavirus in Vaccinated Child, United States] “In conclusion, we identified an NSP2 gene RotaTeq reassortant in an RVA with a DS-1 like genotype. Although the child from whom the NSP2 reassortment specimen was obtained had been vaccinated with a complete regimen of 3 doses of RotaTeq in 2007, no other RotaTeq genes could be detected in the fecal sample. “…” RVA /human-wt/USA/2011729115/2011/
October 28, 2015 – Investigational hexavalent vaccine safe, effective when given with RotaTeq, Prevnar 13 “According to Block, six deaths occurred in the investigational group during the study, three of which were attributed to sudden infant death syndrome. These deaths occurred in a time frame beyond any practical association with the vaccine, he said. There was one case of SIDS reported in the control group. “Instead of lots of sticks in backs, bladders, veins and quadriceps, you are going to do fewer sticks,” Block said. “Hexavalent vaccine is your vaccine of the future.”
September 8, 2015 – “Active surveillance for intussusception in a phase III efficacy trial of an oral monovalent rotavirus vaccine in India” “The authors have no leeway for discretion in this matter as it pertains to vaccine safety and the lives of children. They cannot conceal data just because it is goes against the narrative they are attempting to tell. They need to retract their paper otherwise.”
September 3, 2015 – Preferences for Vaccination Does Health Literacy Make a Difference? “Lower educated and lower health literate respondents considered protection duration to be more important and vaccine effectiveness and frequency of severe side effects to be less important compared with higher educated and higher health literate respondents. While all respondents were willing to vaccinate against rotavirus when the vaccine was offered as part of the National Immunization Program, only lower educated and lower health literate parents were willing to vaccinate when the vaccine was offered on the free market.”
June 2015 – Evidence of Herd Immunity and Sustained Impact of Rotavirus Vaccination on the Reduction of Rotavirus-Related Medical Encounters Among Infants from 2006 through 2011 in the United States "A large national health insurance claims database was used to identify infants born from January 2002 through July 2011. From this cohort, infants were divided into three groups: (1) those who received a RVV, (2) those receiving a diphtheria, tetanus, and acellular pertussis (DTaP) vaccine before the introduction of RVV (February 2006), and (3) those receiving DTaP without a concurrent RVV during the period of RVV availability."
May 27, 2015 – Post-marketing monitoring of intussusception after rotavirus vaccination in Japan “All IS cases spontaneously reported post-vaccination (Brighton collaboration levels 1, 2, and 3) were extracted from the GlaxoSmithKline spontaneous report database on the 11th of January 2013. Expected numbers of IS cases were estimated using the number of vaccine doses distributed and the Japanese incidence rate of IS stratified by month of age. The observed versus expected analysis considered the IS cases for each risk period (7 and 30 days post-vaccination) and for each vaccine dose (two doses).”… “A statistically significant excess of IS cases was observed within 7 days post-dose 1, but not post-dose 2. These results are consistent with previous observations in large post-marketing safety studies in other world regions.”
May 21, 2015 – Accuracy of administrative claims data to identify dose specific rotavirus vaccination information: Implications for studies of vaccine safety“Conclusions: Administrative claims contained inaccuracies in dose number or administration date for 13% of RV5 first doses identified.
April 10, 2015 – Risk of Intussusception After Rotavirus Vaccination: Meta-Analysis of Postlicensure Studies.“Conclusions: This meta-analysis showed a similar increased risk of intussusception, during the first 7 days after administration of dose 1 and, to a lesser extent, dose 2, for both currently available rotavirus vaccines.This suggests that intussusception may be a class effect of currently available oral rotavirus vaccines.”
April 8, 2015 – European Society for Paediatric Infectious Diseases Consensus Recommendations for Rotavirus Vaccination in Europe. Update 2014. “It is now strongly recommended that all HIV-infected or HIV-exposed infants be vaccinated with oral rotavirus vaccine. While specific information on many immunodeficiencies is lacking, infants with known severe combined immunodeficiency 'should not receive live rotavirus vaccine.”
April 2015 – Rotavirus vaccines roll-out in resource-deprived regions (full text) “Differential serotype and genotype effectiveness will have to be 'continuously monitored and the search for even better vaccines and strategies must continue. Although, the natural history of rotavirus infection and disease in low-resource regions suggests that oral vaccines that mimic protection conferred by natural infections might have reached their maximum effectiveness, this figure is still substantial and vaccines could potentially prevent nearly 300 000 deaths of infants and children every year.”
March 19, 2015 – Trends in Hospitalizations for Intussusception in California in Relationship to the Introduction of New Rotavirus Vaccines, 1985-2010. “Results: 6241 intussusception hospitalizations were identified; 4696 also had pertinent procedure codes. There was an upward trend in yearly IRs during 2006-2010 (+2 excess cases/100,000 births/year; p=0.023); the change in slopes between 2006-2010 and 2000-2005 was +3.2 excess cases/100,000 births/year (p=0.052) and the IR in 2006-2010 was 10% higher than in 2000-2005 (IRR: 1.10; 95% CIs 1.01-1.19). The IRR in 2006-2010 vs. 2000-2005 for the 6-14 weeks age-subgroup was 1.90 (95% CIs 1.33-2.74). In the restricted cohort, trends were similar, though, not nominally significant. Conclusions: We documented at a population-level a small increased risk in intussusception hospitalizations post-introduction of the new rotavirus vaccines.”
March 2015 – Rotavirus Vaccine Virus Shedding, Viremia and Clearance in Infants with Severe Combined Immune Deficiency “We report for the first time Rotarix vaccine-acquired rotavirus infections with viremia in 2 infants vaccinated before being diagnosed with severe combined immune deficiency.”
March 2015 – Detection of Vaccine-derived Rotavirus Strains in Nonimmunocompromised Children up to 3–6 Months After RotaTeq® Vaccination “The latest detection was at the age of 8 months. We conclude that asymptomatic long-time shedding of RotaTeq viruses is not uncommon, and is particularly associated with genotype G1.”
March 2015 – A ‘cocoon immunization strategy’ among patients with inflammatory bowel disease “Conclusion: The use of nonmandatory vaccines recommended in family members of patients with IBD is insufficient. Further vaccine promotion and education of patients as well as their healthcare providers is required. A particular concern is associated with the pneumococcal, influenza, rotaviruses, and varicella infections. Nonimmunized and varicella-zoster virus-seronegative patients should be vaccinated, and in case of immunosuppression, vaccination of children in the household is required.”
February 18, 2015 – Intussusception risk after RotaTeq vaccination: Evaluation from worldwide spontaneous reporting data using a self-controlled case series approach “The risk of intussusception occurring in either of the 0- to 2-day, 3- to 7-day or 8- to 14-day risk periods, was compared to the risk in the 15- to 30-day period. A total of 502 cases occurring 0–30 days after a vaccine dose were studied, including 188 cases after the first dose, 190 cases after the second dose, and 124 cases after the third dose.The incidence risk ratio relative to the control period was highest for the 3- to 7-day period and equal to 3.45 (95% CI 1.84–6.55), 1.63 (0.86–3.13) and 1.73 (0.86–3.51) after the first, second and third dose, respectively. Rotavirus vaccination with RV5 increases the risk of intussusception 3–7 days following vaccination, mainly after the first dose and marginally after the second and third doses. The risk is small and restricted to a short time window. It does not outweigh the benefit of the vaccination, but parents of vaccinated infants should be informed in order to react appropriately to the first symptoms.”
January 2015 – Rotavirus-specific IgG Antibodies From Mothers’ Serum May Inhibit Infant Immune Responses to the Pentavalent Rotavirus Vaccine “The clinical manifestation and diagnosis of SCID patients might be delayed well into the life period after the recommended vaccination schedule. Therefore, we emphasize the negative effect that rotavirus vaccination might have in these endangered patients and we strongly support efforts of mandatory newborn screening for SCID.”
January 2015 – Conquering rotavirus: From discovery to global vaccine implementation (full text) “Conflict of interest: JEB and CDK are involved in the development of the RV3 rotavirus vaccine candidate based at Murdoch Childrens Research Institute. CDK holds a provisional patent fo the RV3-BB vaccine. CDK is Director of the Australian Rotavirus Surveillance Program, which is supported by research grants from the vaccine manufacturers, Commonwealth Serum Laboratories and GlaxoSmithKline,as well as the Australian Department of Health and Aging.”
December 1, 2014 – Reduced Rotavirus Vaccine Effectiveness Among Children Born During the Rotavirus Season: A Pooled Analysis of 5 Case-control Studies From the Americas “In the first year of life, adjusted VE was 72% for children born in rotavirus season and 84% with children born in other months (P = .01). Seasonal factors may interfere with vaccine performance.”
October 29, 2014 – Parental preferences for rotavirus vaccination in young children: A discrete choice experiment “Potential vaccination coverage ranged between 22.7 and 86.2%, depending on vaccine scenario (i.e., vaccine effectiveness and protection duration) and implementation strategy (i.e., out-of-pocket costs and healthcare facility that administrates vaccination). Comment: Rotavirus vaccine is not mandatory in any state for school entrance. Why would any parent consider a reduction in effectiveness for lower side effects? It just confirms either the Rotavirus vaccine is dangerous, or it just doesn’t work. Highest coverage can be achieved if the vaccine is implemented within the current NIP (The National Vaccine Plan). '
October 2014 – Dietary Rice Bran Protects against Rotavirus Diarrhea and Promotes Th1-Type Immune Responses to Human Rotavirus Vaccine in Gnotobiotic Pigs “RB feeding significantly protected against diarrhea upon virulent HRV challenge and enhanced the protective rate of the vaccine against rotavirus diarrhea. Consistent with protection, RB significantly increased gamma interferon (IFN-γ)-producing CD4+ and CD8+ T cell responses in intestinal and systemic lymphoid tissues.” Comment: So why the need for Rotavirus vaccine?
September 25, 2014 – Detection of Vaccine-Derived Rotavirus Strains in Non-Immunocompromised Children up to 3-6 Months after RotaTeq(R) Vaccination. “We conducted a survey on the presence of RotaTeq(R) vaccine viruses in infants hospitalized with respiratory infection, and detected shedding in 17 % of children (<2 years of age) who had ever received the vaccine. The latest detection was at the age of 8 months. We conclude that asymptomatic long-time shedding of RotaTeq(R) viruses is not uncommon, and is particularly associated with genotype G1.”
September 2014 – Intussusception After Monovalent Human Rotavirus Vaccine in Australia: Severity and Comparison of Using Healthcare Database Records Versus Case Confirmation to Assess Risk (full text) “The incidence of IS in Australia was notably higher in Australia (71–81 cases per 100,000) than that in some other comparable countries (37–57 cases per 100,000 population).Differential levels of misclassification between study settings may account for some differences in incidence reported using such data. Of note, however, recent vaccine-attributable risk estimate of 5–6 additional IS cases for every 100,000 infants vaccinated included adjustment of ICD-coded IS confirmed as Brighton level 1.”
July 1, 2014 – Vaccines: Can Transparency Increase Confidence and Reduce Hesitancy? (pdf) “The authors did report adverse events associated with vaccines, including high-quality evidence that the MMR vaccine is associated with febrile seizures and the varicella vaccine is associated with complications in immune-deficient people. There was moderate-quality evidence for purpura associated with the hepatitis A and MMR vaccines, febrile seizures with the pneumococcal conjugate 13 vaccine, and intussusception with rotavirus vaccines.
June 28, 2014 – Compliance of mothers following recommendations to breastfeed or withhold breast milk during rotavirus vaccination in North India: a randomized clinical trial (pdf) “At least two other studies are underway to assess the importance of withholding breast milk to improve the immunogenicity' 'of oral vaccine. Advising mothers to withhold breast milk around the time of vaccination may be contemplated if there is clear benefit.”
June 21, 2014 – Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial “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; p<0·0001) in the first year of life. Comment: What placebo was used?
June 5, 2014 – Rotaviruses: Is their surveillance needed? “Though the introduction of vaccines (RotaTeq and Rotarix) proved to be very effective in declining rotavirus associated morbidity and mortality, the number of infections remained same. Unusual genotypes' significantly contribute to the rotavirus associated diarrhoeal burden, 'may reduce the efficacy of the vaccines in use' and hence 'vaccinated individuals may not be benefited.”
May 6, 2014 – Perceptions of personal belief vaccine exemption policy: A survey of Arizona vaccine providers “A total of 152 practitioners providing care to a wide geographic and economic population of Arizona responded to the survey. Respondents were generally strong advocates of all immunizations but were more accepting of parents’ desires to refuse hepatitis B and rotavirus vaccines. Almost all providers indicated that they see patients whose parents request to refuse or delay from vaccinations at least occasionally (88% and 97%, respectively). Only 37% of respondents indicated that they would be supportive of a policy requiring them to sign off on a parent’s decision to refuse vaccination.”
May 1, 2014 – Intussusception Risk after Rotavirus Vaccination in U.S. Infants “These data showed an increase in the incidence of intussusception, defined according to the diagnosis code,2 from 31.9 cases per 100,000 visits in 2009 to 74.1 cases per 100,000 visits in 2013 (odds ratio, 2.32; 95% confidence interval, 1.74 to 3.11).”
April 30, 2014 – Rotaviruses: Is their surveillance needed? “This interplay between vaccines and rotavirus strains is yet to be explored, but it certainly enforces the need to continuously monitor these changes in strains prevalence in a particular region. Furthermore, these fluctuations should be considered while administration or 'development of a vaccine', if rotavirus associated mortality is ever to be controlled.”
April 18, 2014 – Intussusception Following Monovalent Human Rotavirus Vaccine in Australia: Severity and Comparison of Using Healthcare Database Records versus Case-Confirmation To Assess Risk “Results: Of 179 unique episodes coded as IS, 110 '(61%) met Brighton level 1 criteria; SCCS analysis found a relative incidence (RI) of IS in days 1-7 following the first dose of RV1 of 11.1 (95% CI: 2.6-48.0). When all coded episodes of IS were included RI was 4.0 (95% CI: 1.3-12.7). The proportion of Brighton 1 'cases requiring surgery was 39% for those within 21 days of vaccine receipt and 34% for others (p=0.67).”
March 12, 2014 – Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial “We recorded six cases of intussusception in the vaccine group and two in the placebo group, all of which happened after the third dose. 25' '(<1%) infants in the 'vaccine group' and 17 (<1%) in the placebo group 'died'; no death was regarded as related to the study product.”…”Vaccine and placebo were given 5—10 min after administration of 2·5 mL of buffer. Other childhood vaccines (combined diphtheria, pertussis, tetanus, Haemophilus influenzae type b and hepatitis b, and oral polio vaccine) were given concurrently. Mothers were not given specific instructions about breastfeeding around the time of vaccination.”
February 7, 2014 – Prenatal vitamin A deficiency impairs adaptive immune responses to pentavalent rotavirus vaccine (RotaTeq®) in a neonatal gnotobiotic pig model “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 conclusion, VAD impaired antibody responses to RotaTeq® and vaccine efficacy. Oral supplementation of 100,000 IU vitamin A concurrent with RV vaccine failed to increase the vaccine efficacy in VAD piglets.”
February 2014 – Safety of second-generation rotavirus vaccines, intussusception “Recent data from passive and active surveillance systems in the United States indicate that RV1 and RV5 vaccines may possibly cause a small increase in the risk of intussusception; an estimated 1–3 US infants out of 100 000 might develop intussusception within 7 days of getting their first dose of rotavirus vaccine.”
January 31, 2014 – Notes from the Field: Rotavirus Vaccine Administration Errors — United States, 2006–2013 “There were 39 reports of administration by injection (33 for RV1 and six for RV5). This included a cluster of six reports involving RV1 by a nurse who did not receive proper training or read the package insert. Nineteen of the 39 reports (49%) documented an adverse event; irritability (seven cases) and injection site redness (five) were the most commonly reported adverse events. Thirty of 39 reports (77%) did not have an explanation for the error; for those that did, reasons included misinterpreting package insert instructions, confusing the RV1 oral applicator syringe with a syringe for injection, confusing the RV1 vial with a vial used for injectable vaccine, inadequate training, and not reading the package insert.”
January 14, 2014 – Rotavirus Vaccines — Balancing Intussusception Risks and Health Benefits “While assessing the huge and immediate impact of these vaccines on children’s health, Australia, Mexico, and Brazil, each of which has high vaccine coverage and well-tuned medical record systems, also detected a 'small but significant' increase in the risk of intussusception, primarily in the 1 to 7 days immediately after administration of the first dose of vaccine'''. In the United States, the first hint that intussusception might occur after immunization was detected by the national Vaccine Adverse Event Reporting System (VAERS), which passively receives reports of any adverse events from physicians or parents.”
2014 – Screening of Viral Pathogens from Pediatric Ileal Tissue Samples after Vaccination (full text) “Contamination of Rotarix with PCV-1 was subsequently confirmed by the vaccine manufacturer. In March 2010, in light of these findings, the US Food and Drug Administration (FDA) recommended temporarily suspending the use of Rotarix. On May 6, 2010, the FDA reported preliminary findings that the RotaTeq vaccine also contained detectable PCV material.
December 9, 2013 – Detection of Rotateq(R) Vaccine-Derived Double Reassortant Rotavirus in a 7-Year-Old Child with Acute Gastroenteritis “We propose that human-bovine double reassortant G1P[8] may be formed in RotaTeq(R)-vaccinated infants and can occasionally cause gastroenteritis symptoms in vaccine recipients who may rarely transmit the virus to close contacts'''. The present case suggests that such viruses can remain stable in the environment longer than one transmission cycle.”
December 2013 – Rotavirus Vaccines, Intussusception, and Risk-Benefit Assessments “According to CDC estimates, 45 to 213 excess cases of intussusception are anticipated in each fully vaccinated US birth cohort by 5 years of age, the majority of which would require hospitalization”
November 2013 – Evidence of Vaccine-related Reassortment of Rotavirus, Brazil, 2008–2010 “Considering the segmented RVA genome and that the Rotarix vaccine is an attenuated RVA human strain, it is expected that reassortants will arise and circulate among humans. The effects of such events are not known. This study described 'strains that originated from reassortment events between the Rotarix vaccine strain and strains detected in vaccinated and unvaccinated children'.”
September 24, 2013 – Comparison of virus shedding after lived attenuated and pentavalent reassortant rotavirus vaccine “Transmission of rotavirus vaccine or vaccine-reassortant strains to unvaccinated contacts has been reported. Therefore, it is essential to evaluate and characterize the nature of vaccine–virus shedding among rotavirus vaccine recipients. Two groups of healthy infants who received a complete course of RotaTeq (RV5) or Rotarix (RV2) were enrolled (between March 2010 and June 2011) to compare fecal shedding for one month after each vaccine dose.”…”Clinical significance of higher shedding viral loads in RV2 should be further observed.”
September 7, 2013 – A New Self-Controlled Case Series Method for Analyzing Spontaneous Reports of Adverse Events After Vaccination “The estimated risk during the 3- to 7-day period after vaccination was approximately 5 times higher after dose 1 of Rotarix than after dose 2, which is similar to published findings on the same topic.”
September 3, 2013 – Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection (full text)”We previously reported thata rice-based vaccine containing the cholera toxin B subunit (MucoRice-CTB) was effective against cholera. Recently, we also introduced RNAi technology in an attempt to suppress internal storage rice protein production in order to enhance accumulation of foreign proteins in rice seed. In this study, we extended this system further to include a rice-based, orally administered product against RV by producing rice expressing an antibody fragment,ARP1 (MucoRice-ARP1). MucoRice-ARP1 rice powder or rice water offer what we believe are novel approaches to the prevention and treatment of RV-induced diarrhea, which may be used to reduce the medical and economic burden in both developed and developing countries, complement current vaccine-based prophylaxis, and in situations where live attenuated vaccines are contraindicated.”
August 19, 2013 – Intussusception risk and disease prevention associated with rotavirus vaccines in Australia’s national immunisation program “Based on 306 confirmed cases of IS, the relative incidence (RI) of intussusception in the 1-7 day period following the first vaccine dose, was 6.8 (95% confidence interval [CI] 2.4 to 19.0, p<0.001) for RV1, and 9.9 (95% CI 3.7 to 26.4, p<0.001) for RV5.”…”We found a similarly increased risk of IS following both vaccines but the balance of benefits and risks at population level was highly favourable, a finding likely to extend to other settings despite varying incidence of IS and potentially higher morbidity and mortality from both gastroenteritis and intussusception.”
August 2013 – Detection of Novel Rotavirus Strain by Vaccine Postlicensure Surveillance “Nevertheless, the rotavirus strain we identified appears to be an unusual reassortant containing equine, human, simian, and bovine rotavirus genes. Further study of this and other unusual reassortant rotaviruses may lead to insight on rotavirus evolution. Continued surveillance is critical for assessing whether unusual genotypes of rotavirus become more prevalent after the implementation of rotavirus vaccination.”
July 22, 2013 – Childhood Intussusception: A Literature Review (full text) “That is, the higher rates of intussusception among infants older than 3–4 months indicates that any vaccine associated risk of intussusception could lead to more cases of intussusception associated with vaccine in settings where delays in vaccination are common. If vaccine is linked to a potential risk of intussusception, age stratified data on intussusception are necessary for interpreting these estimates of vaccine-associated risk and calculating the number of cases that are potentially attributable to vaccine after the implementation of a vaccine program. The age-stratified data in this review will be a valuable resource for conducting benefit risk analyses, should a rotavirus vaccine program be linked to any potential risk of intussusception.
July 22, 2013 – RotaTeq (Rotavirus Vaccine, Live, Oral, Pentavalent) Oral Solution – Detailed View: Safety Labeling Changes Approved By FDA Center for Biologics Evaluation and Research (CBER) – June 2013 “The Mini-Sentinel PRISM study is the largest study of intussusception after rotavirus vaccines to date and identified an increased risk of intussusception in the 21 day time period after the first dose of RotaTeq, with most cases occurring in the first 7 days after vaccination. No increased risk was found after the second or third doses. These findings translate into 1 to 1.5 additional cases of intussusception per 100,000 first doses of RotaTeq.”
May 13, 2013 – Intussusception After Rotavirus Vaccines Reported to US VAERS, 2006–2012 “The Vaccine Adverse Event Reporting System received 584 confirmed intussusception reports after RV5 and 52 after RV1, with clustering 3 to 6 days after both vaccines. The DRR comparing the 3- to 6-day and the 0- to 2-day periods after RV5 dose 1 was 3.75 (95% confidence interval = 1.90 to 7.39).”
April 8, 2013 – Probiotics and colostrum/milk differentially affect neonatal humoral immune responses to oral rotavirus vaccine “In vaccinated pigs without col/milk, probiotic colonization did not affect IgA HRV antibody titers, but serum IgG HRV antibody titers and gut IgG ASC numbers were lower, suggesting that certain probiotics differentially impact HRV vaccine responses. Our findings suggest that col/milk components (soluble mediators) affect initial probiotic colonization, and together, they modulate neonatal antibody responses to oral AttHRV vaccine in complex ways.”
March 21, 2013 – Norovirus and Medically Attended Gastroenteritis in U.S. Children “Since the introduction of rotavirus vaccines, norovirus has become the leading cause of medically attended acute gastroenteritis in U.S. children and is associated with nearly 1 million health care visits annually. (Funded by the Centers for Disease Control and Prevention.) “Comment: This combined vaccine has been already been in the planning stages. Norovirus VLPs and rotavirus VP6 protein as combined vaccine for childhood gastroenteritis.
March 2013 – Effectiveness of an Incomplete RotaTeq (RV5) Vaccination Regimen in Preventing Rotavirus Gastroenteritis in the United States (full text) “The contract grants OptumInsight Epidemiology oversight of the study conduct, reporting and interpretation, as well as final wording of any resulting articles. T.C.M. is an employee of Merck & Co., Inc.”
January 2013 – Potential Intussusception Risk versus Benefits of Rotavirus Vaccination in the United States “For a US birth cohort of 4.3 million infants, vaccine-associated intussusception could cause an excess 0.2 (range: 0.1 – 0.3) deaths, 45 (range: 21 – 86) hospitalizations, and 13 (range: 6 – 25) cases managed in short-stay or emergency department settings. Vaccination would avert 14 (95% CI: 10 – 19) rotavirus-associated deaths, 53,444 (95% CI: 37,622 – 72,882) hospitalizations, and 169,949 (95% CI: 118,161-238,630) emergency department visits. Summary benefit-risk ratios for death and hospitalization are 71:1 and 1,093:1, respectively.”
November 6, 2012 – The cost-effectiveness of pentavalent rotavirus vaccination in England and Wales “Our results indicate that rotavirus vaccination would be beneficial to public health and could be economically sound. Since rotavirus vaccination is not presently on the immunization schedule for England and Wales but is currently under review, this study can inform policymakers of the cost-effectiveness and budget impact of implementing a mass rotavirus vaccine strategy.”
October 2012 – Surveillance of human rotaviruses in 2007–2011, Hungary: Exploring the genetic relatedness between vaccine and field strains “In total, 2380 strains were genotyped. During the 5-year surveillance we observed the dominating prevalence of genotype G1P[8] (44.87%) strains, followed by G4P[8] (23.4%), G2P[4] (14.75%) and G9P[8] (6.81%) genotypes. Uncommon strains were identified in a low percentage of samples (4.12%). Phylogenetic analysis of 318 G1P[8] strains identified 55 strains similar to the Rotarix strain (nt sequence identities; VP7, up to 97.9%; VP4, up to 98.5%) although their vaccine origin was unlikely.
Summer 2012 – Cost effectiveness of infant vaccination for rotavirus in Canada (pdf) “From a societal perspective, a universal vaccination program against rotavirus will be both cost saving and more effective than no vaccination. Because the majority of rotavirus infections do not require emergency department visits or hospital admission, from a health care system perspective, a program would not be considered cost effective.
September 4, 2012 – Rotavirus Vaccine Effectiveness and Case-Control Study on Risk Factors for Breakthrough Infections in Germany, 2010-2011 “Breastfeeding might impair VE, but further research is needed to identify the critical time-window for this interference and to develop appropriate recommendations.”
September 2012 – Vaccine-derived Human-bovine Double Reassortant Rotavirus in Infants With Acute Gastroenteritis “We describe 3 cases of acute gastroenteritis in healthy infants after vaccination with RotaTeq, shedding a G1P[8] human-bovine double reassortant rotavirus in stools. Such a double reassortant virus appears stable in vitro and may explain diarrheal symptoms in a small percentage of RotaTeq recipients, and might also be transmitted to contacts in the environment.”
August 7, 2012 – Symptomatic infection and detection of vaccine and vaccine-reassortant rotavirus strains in 5 children: A case series (full text)”Vaccine or vaccine-reassortant rotavirus strains were detected in fecal specimens from 5 (4.7%) of 106 immunocompetent children who r'equired treatment for rotavirus gastroenteritis at a large pediatric hospital in Texas in 2009-2010.”
July 2012 – Postmarketing Surveillance of Intussusception Following Mass Introduction of the Attenuated Human Rotavirus Vaccine in Mexico (full text) “This study was funded by GlaxoSmithKline Biologicals. The study sponsor was involved in the design and conduct of the trial, and in data collection and analysis'''. All authors had full access to the clinical trial report and reviewed all drafts of the manuscript. The corresponding author had final responsibility for the decision to submit for publication.”…”A temporal increase in the relative risk of intussusception within 7 days post–dose 1 was observed in Mexican infants, corresponding to a risk of approximately 2 additional hospitalizations for intussusception per 100,000 infants vaccinated. In Brazilian infants, no increase in the relative risk of intussusception was seen after the first vaccine dose;however, an increased risk was seen 1–7 days after the second dose, although this was smaller than that seen after the first dose in Mexico. Recent data from the Australian National Immunization Program suggest a possible temporal clustering of intussusception episodes during the 7 days post–dose 1 with both the attenuated human rotavirus vaccine and the pentavalent bovine–human rotavirus vaccine.”
May 21, 2012 – Identification of Strains of Rotavirus Vaccine RotaTeq in Infants with Gastroenteritis Following Routine Vaccination “Thirteen of the 61 samples collected from infants developing gastroenteritis after RotaTeq vaccination contained vaccine-derived rotavirus strains. During replication and excretion of RotaTeq, reassortment of parental strains can occur.'' The benefits of vaccination outweigh any small risk of vaccine-associated gastroenteritis.” Comment: Reassortment is the mixing of the genetic material of two different viruses to create a new viral species. There are five rotavirus strains in the RotaTeq vaccine. They are combining to form new viruses with unknown virulence. Previous research has shown that two benign viruses can combine in mice to create deadly viruses that can be passed on to other mice.'''
May 21, 2012 – Rotavirus vaccine series completion and adherence to vaccination schedules among infants in managed care in the United States ” Two rotavirus vaccines are currently approved in the United States: 3-dose RotaTeq (RV5; Merck & Co) is administered at ages 2, 4, and 6 months; and 2-dose Rotarix (RV1; GlaxoSmithKline) is administered at ages 2 and 4 months. Our objective was to compare rotavirus vaccine series completion and dosing schedule compliance between cohorts of infants who received these vaccines. The proportion of infants that completed the series was greater and compliance with dosing schedules was higher among infants vaccinated with 'RV1 (two doses) than among infants who received RV5 (3 doses).”
April 27, 2012 – Methodology and lessons-learned from the efficacy clinical trial of the pentavalent rotavirus vaccine in Bangladesh (full text) “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.”
March 19, 2012 – Vaccine Derived Human-Bovine Double Reassortant Rotavirus in Infants with Acute Gastroenteritis “We describe three cases of acute gastroenteritis in healthy infants after vaccination with RotaTeq(R), and shedding a G1P[8] human-bovine double reassortant rotavirus in stools.” Comment: So this means that RotaTeq is not only causing diarrhea, it is shedding viruses that could cause rotavirus diarrhea in others who are exposed to the' virus.
February 1, 2012 – The temporal relationship between RotaTeq immunization and intussusception adverse events in the Vaccine Adverse Event Reporting System (VAERS) (full text) “Conclusions: The present study significantly associates RotaTeq vaccination with intussusception AEs”
December 2012 - Completeness of Reporting in Randomized Controlled Trials of 3 Vaccines: A Review of Adherence to the CONSORT Checklist “The reporting of RCTs of vaccines is incomplete, with important methodological details missing from most reports. Journals could play a leading role in implementing changes. Improved reporting would make publications of vaccine trials easier to find, the findings easier to interpret, and aid the incorporation of findings into policy.”
November 8, 2011 – False Statements from David Tayloe and Paul Offit About Dangerous, Withdrawn Vaccine – “Recently, Dr. David Tayloe, past president of the American Academy of Pediatrics, gave false statements about Dr. Paul Offit’s involvement in both the approval and the removal of the first Rotavirus vaccine, RotaShield. The vaccine was taken off the market more than a decade ago because it caused intussusception – a severe gastrointestinal condition that killed eight children. Last year, Paul Offit denied his involvement in RotaShield’s approval, claiming he did not vote to add it to the CDC’s childhood vaccination schedule, when he in fact voted for it three times.”
October 21, 2011 – Addition of history of intussusception as a contraindication for rotavirus vaccination
October 19, 2011 – Rotavirus shedding in premature infants following first immunization “Results: Rotavirus antigen shedding after immunization was detected, with positive rotavirus EIA results in 53.3% of premature infants and in 22.1% of 86 stool samples collected.”
October 6, 2011 – Cost-effectiveness of universal rotavirus vaccination in reducing rotavirus gastroenteritis in Ireland. “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.”
May 31, 2011 – Detection of fecal shedding of rotavirus vaccine in infants following their first dose of pentavalent rotavirus vaccine. “Rotavirus antigen was detected as early as post-vaccination day 3 and as late as day 9, with peak numbers of shedding on post-vaccination days 6 through 8.”
June 11, 2010 – Addition of Severe Combined Immunodeficiency as a Contraindication for Administration of Rotavirus Vaccine
May 20, 2010 – Vaccine Safety Critics Call For RotaTeq Vaccine Recall & Clean-Up
May 17, 2010 – FDA Tells Docs to Resume Rotavirus Vaccinations – Rotarix, RotaTeq Deemed Safe, Despite Presence of DNA from Porcine Virus “The agency said it is working with both GlaxoSmithKline and Merck to update the labeling for the vaccines to include information about the presence of PCV1 in Rotarix and DNA from PCV1 and PCV2 in RotaTeq.”
May 6, 2010 – Porcine Circovirus and Rotavirus Vaccines – “The Vaccines and Related Biological Products Advisory Committee meeting on May 7th will discuss the findings shared with the public on March 22, 2010, that porcine circovirus type 1 (PCV1) DNA was found in GlaxoSmithKline Biologicals’ Rotarix Vaccine. Additional data pertaining to the Rotarix vaccine will also be presented to the committee. FDA recently received information from Merck & Co, Inc. that its preliminary studies have identified fragments of DNA from PCV1 and from a related porcine circovirus type 2 (PCV2) in its RotaTeq vaccine.”
March 29, 2010 – Deep sequencing reveals viral vaccine contaminants “How did a porcine virus contaminate Rotarix, which is produced in Vero cells? The answer is not known, but the authors speculate that the culprit might be porcine trypsin, which is used during the propagation of Vero cells. Over 100,000 porcine circovirus 1 DNA molecules were detected in each vaccine dose, fully 10 times higher than the amount of rotavirus present. However, it’s not known if the porcine circovirus present is infectious.”
March 22, 2010 – Components of Extraneous Virus Detected in Rotarix Vaccine; No Known Safety Risk – FDA Recommends Clinicians Temporarily Suspend Use of Vaccine as Agency Learns More
March 2010 – Update on Rotavirus Vaccine – FDA became aware of the presence PCV1 in Rotarix and DNA from PCV1 and PCV2 in RotaTeq
February 2010 – Sibling transmission of vaccine-derived rotavirus (RotaTeq) associated with rotavirus gastroenteritis. “Conclusions: Reassortment between RotaTeq vaccine strains of genotypes P7[5]G1 and P1A[8]G6 occurred during intestinal replication, and transmission occurred to an unvaccinated, older sibling, which caused symptomatic rotavirus gastroenteritis that required ED medical care.”
March 2008 – RotaTeq vaccine adverse events and policy considerations “Conclusions: These observations, coupled with limited rotavirus disease burden, cost-effectiveness, and potential contact viral transmission concerns, raise serious questions regarding the use of RotaTeq in the US.”
March 16, 2007 – Postmarketing Monitoring of Intussusception After RotaTeq™ Vaccination — United States, February 1, 2006–February 15, 2007
February 13, 2007 – FDA Public Health Notification: Information on RotaTeq and Intussusception “The Food and Drug Administration (FDA) is notifying health care providers and consumers about 28 post-marketing reports of intussusception following administration of Rotavirus, Live, Oral, Pentavalent vaccine (trade name RotaTeq), manufactured by Merck and Co., Inc.”
2007 – Kawasaki Disease After Vaccination “Through October 14, 2007, 107 KD reports were received by VAERS: 26 were categorized as classic cases, 19 atypical, 52 possible, and 10 were noncases. Of the 97 cases, 91% were children <5 years.”
September 1, 2005 – More on RotaShield and Intussusception: The Role of Age at the Time of Vaccination
January 13, 2005 – Infant’s death could be the result of vaccine treatment “‘Doctors only told me the vaccine may bring on a fever as a side-effect. I didn’t know she would die of it,’ the mother said. Doctors at the hospital said that the unlicensed rotavirus vaccine should be safe, despite the fact that it is still undergoing clinical trials.”
January 2005 – Rotavirus vaccines and intussusception risk.
September 3, 2004 – Suspension of Rotavirus Vaccine After Reports of Intussusception —United States, 1999
April 2004 – An analysis of rotavirus vaccine reports to the vaccine adverse event reporting system: more than intussusception alone? “Conclusions. Intussusception and gastroenteritis were the most commonly reported outcomes; however, a substantial number of reports indicate signs and symptoms consistent with either illness, possibly suggestive of a spectrum of gastrointestinal illness(es) related to RRV-TV [rhesus-human rotavirus reassortant-tetravalent vaccine].”
January 12, 2004 – Hyping Vaccines: An Investigation – Chickenpox, Lyme, Rotavirus, And A Highly Revealing Analysis Of Flu Statistics by: Dr. F. Edward Yazbak
December 2003 – Addressing Parents’ Concerns: Do Vaccines Contain Harmful Preservatives, Adjuvants, Additives, or Residuals? (full text) “Some vaccines discussed in this article are manufactured by Merck and Co. Dr. Offit is the co-holder of a patent on a bovine-human reassortant rotavirus vaccine that is being developed by Merck. Dr. Offit’s laboratory support comes from the National Institutes of Health, and he does not receive personal support or honoraria from Merck and does not have a financial interest in the company.”
March 20, 2002 – Rotavirus Vaccine and the News Media, 1987-2001 “In August 1998, the US Food and Drug Administration licensed the first vaccine against rotavirus, the most important cause of severe childhood diarrhea. Fourteen months later, amid intense media activity, the vaccine was withdrawn after an association was found with intussusception.”
February 22, 2001 – Intussusception among infants given an oral rotavirus vaccine. “Conclusions: The strong association between vaccination with RRV-TV and intussusception among otherwise healthy infants supports the existence of a causal relation. Rotavirus vaccines with an improved safety profile are urgently needed.”
August 21, 2000 – Conflicts of Interest in Vaccine Policy Making, Majority Staff Report, Committee on Government Reform, U.S. House of Representatives “*Four out of eight CDC advisory committee members who voted to approve guidelines for the rotavirus vaccine in June 1998 had financial ties to pharmaceutical companies that were developing different versions of the vaccine. *3 out of 5 FDA advisory committee members who voted to approve the rotavirus vaccine in December 1997 had financial ties to pharmaceutical companies that were developing different versions of the vaccine. A more complete discussion of specific conflict of interest problems identified by Government Reform Committee staff can be found in Sections 4 and 5 of this report. To provide focus to the discussion, this report examines the deliberations of the two committees on one specific vaccine — the Rotavirus vaccine. Approved for use by the FDA on August 31, 1998, the Rotavirus vaccine was pulled from the market 13 months later after serious adverse reactions to the vaccine emerged.”
April 6, 2000 – Rotavirus Vaccine Withdrawal Prompts Doctors to Ask for Congressional Investigation of Vaccine Approval Process – CDC and FDA May Have Ignored or Concealed Data About Life Threatening Side Effects to Infants “The Association of American Physicians and Surgeons (AAPS) has asked Rep. Dan Burton to initiate a congressional investigation of the process by which all vaccines are tested, approved, and recommended as mandatory by the CDC. This action was prompted by the recent withdrawal of the rotavirus vaccine after it was revealed that between the vaccine’s approval in August of 1998 and this July, at least 15 infants suffered life threatening intestinal obstructions (intussusception) after receiving the vaccine. But what may be even more alarming is the rate of intussusception in the clinical trials that were the basis for the vaccine’s approval. A search of the records by AAPS reveals that it was thirty times the expected rate. But neither physicians nor parents were warned for watch for symptoms of intussusception. Eight infants have needed surgery, and one lost 7 inches of bowel.”
November 5, 1999 – Withdrawal of Rotavirus Vaccine Recommendation “In July 1999, CDC recommended that health-care providers and parents postpone use of the rhesus rotavirus vaccine-tetravalent (RRV-TV) (RotaShield[Registered]*, Wyeth Laboratories, Inc., Marietta, Pennsylvania), for infants, at least until November 1999. This action was based on reports to the Vaccine Adverse Event Reporting System of intussusception (a type of bowel obstruction that occurs when the bowel folds in on itself) among 15 infants who received rotavirus vaccine. Also at that time, the manufacturer, in consultation with the Food and Drug Administration, voluntarily ceased further distribution of the vaccine. On October 22, 1999, the Advisory Committee on Immunization Practices (ACIP), after a review of scientific data from several sources, concluded that intussusception occurs with significantly increased frequency in the first 1-2 weeks after vaccination with RRV-TV, particularly following the first dose. Therefore, ACIP no longer recommends vaccination of infants in the United States with RRV-TV and withdraws its recommendation that RRV-TV be administered at 2, 4, and 6 months of age.”
September 4, 1999 – Doctors Ask Congress To Probe Vaccine Approval Process
August 31, 1999 – Letter to The Honorable Dan Burton from Jane M. Orient, M.D., Executive Director, Association of American Physicians and Surgeons (AAPS) “The situation with the rotavirus vaccine may be a clue to a far more serious problem with the vaccine approval process. The Surgeon General and CDC claim the vaccine’s withdrawal was prompted by the VAERS reports received through July 1999. But why was the vaccine approved in the first place when the incidence of the serious complication of intussusception was far higher in prelicensure trials than in the VAERS reports? We must ask, what did they know and when they know it? AAPS has been studying the reports and has concluded that the FDA and CDC may have ignored or concealed data that showed the problems from the outset. The tragedy of the rotavirus vaccine might never have happened if the public had access to the data used by the FDA and CDC in recommending the vaccine. The Shelby Amendment, if properly implemented, would ensure that federally financed research about vaccines could not be withheld from the public. Ultimately this rule should be extended to all data on which the government makes vaccine policy decisions, including privately funded research data as well. This would greatly improve the integrity of vaccine policymaking.”
July 16, 1999 – Intussusception Among Recipients of Rotavirus Vaccine — United States, 1998-1999
July 16, 1999 – Vaccine Safety Organization Questions Licensing and Policymaking Standards Applied to Rotavirus Vaccine
August 31, 1998 – FDA Approves RotaShield Vaccine For Use In The Prevention of Rotavirus “As with all vaccines, serious reactions might rarely occur after administration of RotaShield. When compared to placebo, the most common adverse event was fever after the first dose. Administration to infants with persistent diarrhea or vomiting or to those who are known or suspected to be immunocompromised is contraindicated. It is not to be given to infants who are hypersensitive to latex or to any component of the vaccine, including aminoglycoside antibiotics, amphotericin B, or monosodium glutamate.”
November 5, 1999 – Withdrawal of Rotavirus Vaccine Recommendation “In July 1999, CDC recommended that health-care providers and parents postpone use of the rhesus rotavirus vaccine-tetravalent (RRV-TV) (RotaShield[Registered]*, Wyeth Laboratories, Inc., Marietta, Pennsylvania), for infants, at least until November 1999. This action was based on reports to the Vaccine Adverse Event Reporting System of intussusception (a type of bowel obstruction that occurs when the bowel folds in on itself) among 15 infants who received rotavirus vaccine. Also at that time, the manufacturer, in consultation with the Food and Drug Administration, voluntarily ceased further distribution of the vaccine. On October 22, 1999, the Advisory Committee on Immunization Practices (ACIP), after a review of scientific data from several sources, concluded that intussusception occurs with significantly increased frequency in the first 1-2 weeks after vaccination with RRV-TV, particularly following the first dose. Therefore, ACIP no longer recommends vaccination of infants in the United States with RRV-TV and withdraws its recommendation that RRV-TV be administered at 2, 4, and 6 months of age.”
September 4, 1999 – Doctors Ask Congress To Probe Vaccine Approval Process
August 31, 1999 – Letter to The Honorable Dan Burton from Jane M. Orient, M.D., Executive Director, Association of American Physicians and Surgeons (AAPS) “The situation with the rotavirus vaccine may be a clue to a far more serious problem with the vaccine approval process. The Surgeon General and CDC claim the vaccine’s withdrawal was prompted by the VAERS reports received through July 1999. But why was the vaccine approved in the first place when the incidence of the serious complication of intussusception was far higher in prelicensure trials than in the VAERS reports (see enclosed fact sheet for data)? We must ask, what did they know and when they know it? AAPS has been studying the reports and has concluded that the FDA and CDC may have ignored or concealed data that showed the problems from the outset. The tragedy of the rotavirus vaccine might never have happened if the public had access to the data used by the FDA and CDC in recommending the vaccine. The Shelby Amendment, if properly implemented, would ensure that federally financed research about vaccines could not be withheld from the public. Ultimately this rule should be extended to all data on which the government makes vaccine policy decisions, including privately funded research data as well. This would greatly improve the integrity of vaccine policymaking.”
July 16, 1999 – Intussusception Among Recipients of Rotavirus Vaccine — United States, 1998-1999
July 16, 1999 – Vaccine Safety Organization Questions Licensing and Policymaking Standards Applied to Rotavirus Vaccine
August 31, 1998 – FDA Approves RotaShield Vaccine For Use In The Prevention of Rotavirus “As with all vaccines, serious reactions might rarely occur after administration of RotaShield. When compared to placebo, the most common adverse event was fever after the first dose. Administration to infants with persistent diarrhea or vomiting or to those who are known or suspected to be immunocompromised is contraindicated. It is not to be given to infants who are hypersensitive to latex or to any component of the vaccine, including aminoglycoside antibiotics, amphotericin B, or monosodium glutamate.”