KMバイオロジクス：クアトロバック皮下注シリンジインタビューフォーム（2020年11月（第12版））.
第一三共：スクエアキッズ皮下注シリンジインタビューフォーム（2019年4月（第8版））.
Linjie Zhang, Sílvio O M Prietsch, Inge Axelsson, Scott A Halperin
Acellular vaccines for preventing whooping cough in children.
Cochrane Database Syst Rev. 2014 Sep 17;(9):CD001478. doi: 10.1002/14651858.CD001478.pub6. Epub 2014 Sep 17.
Abstract/Text
BACKGROUND: Routine use of whole-cell pertussis (wP) vaccines was suspended in some countries in the 1970s and 1980s because of concerns about adverse effects. Following this action, there was a resurgence of whooping cough. Acellular pertussis (aP) vaccines, containing purified or recombinant Bordetella pertussis (B. pertussis) antigens, were developed in the hope that they would be as effective, but less reactogenic than the whole-cell vaccines. This is an update of a Cochrane review first published in 1999, and previously updated in 2012. In this update, we included no new studies.
OBJECTIVES: To assess the efficacy and safety of acellular pertussis vaccines in children and to compare them with the whole-cell vaccines.
SEARCH METHODS: We searched CENTRAL (2013, Issue 12), MEDLINE (1950 to January week 2, 2014), EMBASE (1974 to January 2014), Biosis Previews (2009 to January 2014) and CINAHL (2009 to January 2014).
SELECTION CRITERIA: We selected double-blind randomised efficacy and safety trials of aP vaccines in children up to six years old, with active follow-up of participants and laboratory verification of pertussis cases.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias in the studies. Differences in trial design precluded a meta-analysis of the efficacy data. We pooled the safety data from individual trials using a random-effects meta-analysis model.
MAIN RESULTS: We included six efficacy trials with a total of 46,283 participants and 52 safety trials with a total of 136,541 participants. Most of the safety trials did not report the methods for random sequence generation, allocation concealment and blinding, which made it difficult to assess the risk of bias in the studies. The efficacy of multi-component (≥ three) vaccines varied from 84% to 85% in preventing typical whooping cough (characterised by 21 or more consecutive days of paroxysmal cough with confirmation of B. pertussis infection by culture, appropriate serology or contact with a household member who has culture-confirmed pertussis), and from 71% to 78% in preventing mild pertussis disease (characterised by seven or more consecutive days of cough with confirmation of B. pertussis infection by culture or appropriate serology). In contrast, the efficacy of one- and two-component vaccines varied from 59% to 78% against typical whooping cough and from 41% to 58% against mild pertussis disease. Multi-component acellular vaccines are more effective than low-efficacy whole-cell vaccines, but may be less effective than the highest-efficacy whole-cell vaccines. Most systemic and local adverse events were significantly less common with aP vaccines than with wP vaccines for the primary series as well as for the booster dose.
AUTHORS' CONCLUSIONS: Multi-component (≥ three) aP vaccines are effective in preventing whooping cough in children. Multi-component aP vaccines have higher efficacy than low-efficacy wP vaccines, but they may be less efficacious than the highest-efficacy wP vaccines. Acellular vaccines have fewer adverse effects than whole-cell vaccines for the primary series as well as for booster doses.
T Roice Fulton, Varun K Phadke, Walter A Orenstein, Alan R Hinman, Wayne D Johnson, Saad B Omer
Protective Effect of Contemporary Pertussis Vaccines: A Systematic Review and Meta-analysis.
Clin Infect Dis. 2016 May 1;62(9):1100-1110. doi: 10.1093/cid/ciw051. Epub 2016 Feb 7.
Abstract/Text
BACKGROUND: Acellular pertussis (aP) and whole-cell (wP) pertussis vaccines are presumed to have similar short-term (<3 years after completion of the primary series) efficacy. However, vaccine effect varies between individual pertussis vaccine formulations, and many originally studied formulations are now unavailable. An updated analysis of the short-term protective effect of pertussis vaccines limited to formulations currently on the market in developed countries is needed.
METHODS: We conducted a systematic review and meta-analysis of published studies that evaluated pertussis vaccine efficacy or effectiveness within 3 years after completion (>3 doses) of a primary series of a currently available aP or wP vaccine formulation. The primary outcome was based on the World Health Organization (WHO) clinical case definitions for pertussis. Study quality was assessed using the approach developed by the Child Health Epidemiology Research Group. We determined overall effect sizes using random-effects meta-analyses, stratified by vaccine (aP or wP) and study (efficacy or effectiveness) type.
RESULTS: Meta-analysis of 2 aP vaccine efficacy studies (assessing the 3-component GlaxoSmithKline and 5-component Sanofi-Pasteur formulations) yielded an overall aP vaccine efficacy of 84% (95% confidence interval [CI], 81%-87%). Meta-analysis of 3 wP vaccine effectiveness studies (assessing the Behringwerke, Pasteur/Mérieux, and SmithKline Beecham formulations) yielded an overall wP vaccine effectiveness of 94% (95% CI, 88%-97%) (bothI(2)= 0%).
CONCLUSIONS: Although all contemporary aP and wP formulations protect against pertussis disease, in this meta-analysis the point estimate for short-term protective effect against WHO-defined pertussis in young children was lower for currently available aP vaccines than wP vaccines.
© 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.
衛藤義勝（監）. ネルソン小児科学. エルゼビアジャパン株式会社, 東京.
American College of Obstetricians and Gynecologists（ACOG）：[https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/09/update-on-immunization-and-pregnancy-tetanus-diphtheria-and-pertussis-vaccination Update on Immunization and Preg.
D Lavanchy
Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures.
J Viral Hepat. 2004 Mar;11(2):97-107.
Abstract/Text
Hepatitis B virus (HBV) infection is a serious global health problem, with 2 billion people infected worldwide, and 350 million suffering from chronic HBV infection. The 10th leading cause of death worldwide, HBV infections result in 500 000 to 1.2 million deaths per year caused by chronic hepatitis, cirrhosis, and hepatocellular carcinoma; the last accounts for 320 000 deaths per year. In Western countries, the disease is relatively rare and acquired primarily in adulthood, whereas in Asia and most of Africa, chronic HBV infection is common and usually acquired perinatally or in childhood. More efficacious treatments, mass immunization programs, and safe injection techniques are essential for eliminating HBV infection and reducing global HBV-related morbidity and mortality. Safe and effective vaccines against HBV infection have been available since 1982. The implementation of mass immunization programs, which have been recommended by the World Health Organization since 1991, have dramatically decreased the incidence of HBV infection among infants, children, and adolescents in many countries. However, not all countries have adopted these recommendations and there remains a large number of persons that were infected with HBV prior to the implementation of immunization programs. Antiviral treatment is the only way to reduce morbidity and mortality from chronic HBV infection. Conventional interferon alfa and lamivudine have been the primary treatments to date. Conventional interferon alfa produces a durable response in a moderate proportion of patients but has undesirable side-effects and must be administered subcutaneously three times per week. Lamivudine also produces a response in a modest proportion of patients and causes few side-effects. However, prolonged treatment is often necessary to prevent relapse on cessation of therapy, and continuous treatment can lead to the development of lamivudine resistance. Promising emerging new treatments include adefovir, entecavir and peginterferon alfa-2a (40 kDa).
C Lee, Y Gong, J Brok, E H Boxall, C Gluud
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers.
Cochrane Database Syst Rev. 2006 Apr 19;(2):CD004790. doi: 10.1002/14651858.CD004790.pub2. Epub 2006 Apr 19.
Abstract/Text
BACKGROUND: Hepatitis B vaccine and hepatitis B immunoglobulin are considered for newborn infants of HBsAg-positive mothers to prevent hepatitis B infection.
OBJECTIVES: To assess the beneficial and harmful effects of hepatitis B vaccines and hepatitis B immunoglobulin in newborn infants of HBsAg-positive mothers.
SEARCH STRATEGY: Trials were identified through The Cochrane Neonatal Group Controlled Trials Register, The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, and EMBASE (until February 2004), authors of trials, and pharmaceutical companies.
SELECTION CRITERIA: Randomised clinical trials comparing: plasma-derived vaccine (PDV) or recombinant vaccine (RV) versus no intervention, placebo, or other active vaccines; hepatitis B immunoglobulin versus no intervention, placebo, or other control immunoglobulin; as well as PDV or RV plus hepatitis B immunoglobulin versus no intervention, placebo, or other control vaccines or immunoglobulin.
DATA COLLECTION AND ANALYSIS: Outcomes are assessed at maximal follow-up. The primary outcome measure was hepatitis B occurrence, based on a blood specimen positive for HBsAg, HBeAg, or antibody to hepatitis B core antigen (anti-HBc). Binary outcomes are reported as relative risks (RR) with 95% confidence interval (CI). Subgroup analyses were performed with regard to methodological quality of the trial, mother's HBe-Ag status, and time of immunisation after birth.
MAIN RESULTS: We identified 29 randomised clinical trials, five of which were considered high quality. Only three trials reported inclusion of hepatitis B e-antigen negative mothers. Compared with placebo/no intervention, vaccine reduced hepatitis B occurrence (RR 0.28, 95% confidence interval (CI) 0.20 to 0.40, 4 trials). No significant differences of hepatitis B occurrence were found comparing recombinant vaccine (RV) versus plasma-derived vaccine (PDV) (RR 1.00, 95% CI 0.71 to 1.42, 4 trials) and high-dose versus low-dose vaccine (PDV: RR 0.97, 95% CI 0.55 to 1.68, 3 trials; RV: RR 0.78, 95% CI 0.31 to 1.94, 1 trial). Compared with placebo/no intervention, hepatitis B immunoglobulin or the combination of vaccine plus hepatitis B immunoglobulin reduced hepatitis B occurrence (hepatitis B immunoglobulin: RR 0.50, 95% CI 0.41 to 0.60, 1 trial; PDV plus hepatitis B immunoglobulin: RR 0.08, 95% CI 0.03 to 0.17, 3 trials). Compared with vaccine, vaccine plus hepatitis B immunoglobulin reduced hepatitis B occurrence (RR 0.54, 95% CI 0.41 to 0.73, 10 trials). Hepatitis B vaccine and hepatitis B immunoglobulin seem safe, but few trials reported on adverse events.
AUTHORS' CONCLUSIONS: Vaccine, hepatitis B immunoglobulin, and vaccine plus hepatitis B immunoglobulin prevent hepatitis B occurrence in newborn infants of HBsAg positive mothers.
Eric E Mast, Harold S Margolis, Anthony E Fiore, Edward W Brink, Susan T Goldstein, Susan A Wang, Linda A Moyer, Beth P Bell, Miriam J Alter, Advisory Committee on Immunization Practices (ACIP)
A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents.
MMWR Recomm Rep. 2005 Dec 23;54(RR-16):1-31.
Abstract/Text
This report is the first of a two-part statement from the Advisory Committee on Immunization Practices (ACIP) that updates the strategy to eliminate hepatitis B virus (HBV) transmission in the United States. The report provides updated recommendations to improve prevention of perinatal and early childhood HBV transmission, including implementation of universal infant vaccination beginning at birth, and to increase vaccine coverage among previously unvaccinated children and adolescents. Strategies to enhance implementation of the recommendations include 1) establishing standing orders for administration of hepatitis B vaccination beginning at birth; 2) instituting delivery hospital policies and procedures and case management programs to improve identification of and administration of immunoprophylaxis to infants born to mothers who are hepatitis B surface antigen (HBsAg) positive and to mothers with unknown HBsAg status at the time of delivery; and 3) implementing vaccination record reviews for all children aged 11-12 years and children and adolescents aged <19 years who were born in countries with intermediate and high levels of HBV endemicity, adopting hepatitis B vaccine requirements for school entry, and integrating hepatitis B vaccination services into settings that serve adolescents. The second part of the ACIP statement, which will include updated recommendations and strategies to increase hepatitis B vaccination of adults, will be published separately.
Chunfeng Qu, Taoyang Chen, Chunsun Fan, Qimin Zhan, Yuting Wang, Jianhua Lu, Ling-ling Lu, Zhengping Ni, Fei Huang, Hongyu Yao, Jian Zhu, Jian Fan, Yuanrong Zhu, Zhiyuan Wu, Guoting Liu, Wenhong Gao, Mengya Zang, Dongmei Wang, Min Dai, Chu Chieh Hsia, Yawei Zhang, Zongtang Sun
Efficacy of neonatal HBV vaccination on liver cancer and other liver diseases over 30-year follow-up of the Qidong hepatitis B intervention study: a cluster randomized controlled trial.
PLoS Med. 2014 Dec;11(12):e1001774. doi: 10.1371/journal.pmed.1001774. Epub 2014 Dec 30.
Abstract/Text
BACKGROUND: Neonatal hepatitis B vaccination has been implemented worldwide to prevent hepatitis B virus (HBV) infections. Its long-term protective efficacy on primary liver cancer (PLC) and other liver diseases has not been fully examined.
METHODS AND FINDINGS: The Qidong Hepatitis B Intervention Study, a population-based, cluster randomized, controlled trial between 1985 and 1990 in Qidong, China, included 39,292 newborns who were randomly assigned to the vaccination group in which 38,366 participants completed the HBV vaccination series and 34,441 newborns who were randomly assigned to the control group in which the participants received neither a vaccine nor a placebo. However, 23,368 (67.8%) participants in the control group received catch-up vaccination at age 10-14 years. By December 2013, a total of 3,895 (10.2%) in the vaccination group and 3,898 (11.3%) in the control group were lost to follow-up. Information on PLC incidence and liver disease mortality were collected through linkage of all remaining cohort members to a well-established population-based tumor registry until December 31, 2013. Two cross-sectional surveys on HBV surface antigen (HBsAg) seroprevalence were conducted in 1996-2000 and 2008-2012. The participation rates of the two surveys were 57.5% (21,770) and 50.7% (17,204) in the vaccination group and 36.3% (12,184) and 58.6% (17,395) in the control group, respectively. Using intention-to-treat analysis, we found that the incidence rate of PLC and the mortality rates of severe end-stage liver diseases and infant fulminant hepatitis were significantly lower in the vaccination group than the control group with efficacies of 84% (95% CI 23%-97%), 70% (95% CI 15%-89%), and 69% (95% CI 34%-85%), respectively. The estimated efficacy of catch-up vaccination on HBsAg seroprevalence in early adulthood was 21% (95% CI 10%-30%), substantially weaker than that of the neonatal vaccination (72%, 95% CI 68%-75%). Receiving a booster at age 10-14 years decreased HBsAg seroprevalence if participants were born to HBsAg-positive mothers (hazard ratio [HR] = 0.68, 95% CI 0.47-0.97). Limitations to consider in interpreting the study results include the small number of individuals with PLC, participants lost to follow-up, and the large proportion of participants who did not provide serum samples at follow-up.
CONCLUSIONS: Neonatal HBV vaccination was found to significantly decrease HBsAg seroprevalence in childhood through young adulthood and subsequently reduce the risk of PLC and other liver diseases in young adults in rural China. The findings underscore the importance of neonatal HBV vaccination. Our results also suggest that an adolescence booster should be considered in individuals born to HBsAg-positive mothers and who have completed the HBV neonatal vaccination series. Please see later in the article for the Editors' Summary.
Tom Jefferson, Alessandro Rivetti, Carlo Di Pietrantonj, Vittorio Demicheli
Vaccines for preventing influenza in healthy children.
Cochrane Database Syst Rev. 2018 Feb 1;2:CD004879. doi: 10.1002/14651858.CD004879.pub5. Epub 2018 Feb 1.
Abstract/Text
BACKGROUND: The consequences of influenza in children and adults are mainly absenteeism from school and work. However, the risk of complications is greatest in children and people over 65 years of age. This is an update of a review published in 2011. Future updates of this review will be made only when new trials or vaccines become available. Observational data included in previous versions of the review have been retained for historical reasons but have not been updated because of their lack of influence on the review conclusions.
OBJECTIVES: To assess the effects (efficacy, effectiveness, and harm) of vaccines against influenza in healthy children.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 12), which includes the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE (1966 to 31 December 2016), Embase (1974 to 31 December 2016), WHO International Clinical Trials Registry Platform (ICTRP; 1 July 2017), and ClinicalTrials.gov (1 July 2017).
SELECTION CRITERIA: Randomised controlled trials comparing influenza vaccines with placebo or no intervention in naturally occurring influenza in healthy children under 16 years. Previous versions of this review included 19 cohort and 11 case-control studies. We are no longer updating the searches for these study designs but have retained the observational studies for historical purposes.
DATA COLLECTION AND ANALYSIS: Review authors independently assessed risk of bias and extracted data. We used GRADE to rate the certainty of evidence for the key outcomes of influenza, influenza-like illness (ILI), complications (hospitalisation, ear infection), and adverse events. Due to variation in control group risks for influenza and ILI, absolute effects are reported as the median control group risk, and numbers needed to vaccinate (NNVs) are reported accordingly. For other outcomes aggregate control group risks are used.
MAIN RESULTS: We included 41 clinical trials (> 200,000 children). Most of the studies were conducted in children over the age of two and compared live attenuated or inactivated vaccines with placebo or no vaccine. Studies were conducted over single influenza seasons in the USA, Western Europe, Russia, and Bangladesh between 1984 and 2013. Restricting analyses to studies at low risk of bias showed that influenza and otitis media were the only outcomes where the impact of bias was negligible. Variability in study design and reporting impeded meta-analysis of harms outcomes.Live attenuated vaccinesCompared with placebo or do nothing, live attenuated influenza vaccines probably reduce the risk of influenza infection in children aged 3 to 16 years from 18% to 4% (risk ratio (RR) 0.22, 95% confidence interval (CI) 0.11 to 0.41; 7718 children; moderate-certainty evidence), and they may reduce ILI by a smaller degree, from 17% to 12% (RR 0.69, 95% CI 0.60 to 0.80; 124,606 children; low-certainty evidence). Seven children would need to be vaccinated to prevent one case of influenza, and 20 children would need to be vaccinated to prevent one child experiencing an ILI. Acute otitis media is probably similar following vaccine or placebo during seasonal influenza, but this result comes from a single study with particularly high rates of acute otitis media (RR 0.98, 95% CI 0.95 to 1.01; moderate-certainty evidence). There was insufficient information available to determine the effect of vaccines on school absenteeism due to very low-certainty evidence from one study. Vaccinating children may lead to fewer parents taking time off work, although the CI includes no effect (RR 0.69, 95% CI 0.46 to 1.03; low-certainty evidence). Data on the most serious consequences of influenza complications leading to hospitalisation were not available. Data from four studies measuring fever following vaccination varied considerably, from 0.16% to 15% in children who had live vaccines, while in the placebo groups the proportions ranged from 0.71% to 22% (very low-certainty evidence). Data on nausea were not reported.Inactivated vaccinesCompared with placebo or no vaccination, inactivated vaccines reduce the risk of influenza in children aged 2 to 16 years from 30% to 11% (RR 0.36, 95% CI 0.28 to 0.48; 1628 children; high-certainty evidence), and they probably reduce ILI from 28% to 20% (RR 0.72, 95% CI 0.65 to 0.79; 19,044 children; moderate-certainty evidence). Five children would need to be vaccinated to prevent one case of influenza, and 12 children would need to be vaccinated to avoid one case of ILI. The risk of otitis media is probably similar between vaccinated children and unvaccinated children (31% versus 27%), although the CI does not exclude a meaningful increase in otitis media following vaccination (RR 1.15, 95% CI 0.95 to 1.40; 884 participants; moderate-certainty evidence). There was insufficient information available to determine the effect of vaccines on school absenteeism due to very low-certainty evidence from one study. We identified no data on parental working time lost, hospitalisation, fever, or nausea.We found limited evidence on secondary cases, requirement for treatment of lower respiratory tract disease, and drug prescriptions. One brand of monovalent pandemic vaccine was associated with a sudden loss of muscle tone triggered by the experience of an intense emotion (cataplexy) and a sleep disorder (narcolepsy) in children. Evidence of serious harms (such as febrile fits) was sparse.
AUTHORS' CONCLUSIONS: In children aged between 3 and 16 years, live influenza vaccines probably reduce influenza (moderate-certainty evidence) and may reduce ILI (low-certainty evidence) over a single influenza season. In this population inactivated vaccines also reduce influenza (high-certainty evidence) and may reduce ILI (low-certainty evidence). For both vaccine types, the absolute reduction in influenza and ILI varied considerably across the study populations, making it difficult to predict how these findings translate to different settings. We found very few randomised controlled trials in children under two years of age. Adverse event data were not well described in the available studies. Standardised approaches to the definition, ascertainment, and reporting of adverse events are needed. Identification of all global cases of potential harms is beyond the scope of this review.
Mei-Hwei Chang, San-Lin You, Chien-Jen Chen, Chun-Jen Liu, Chuan-Mo Lee, Shi-Ming Lin, Heng-Cheng Chu, Tzee-Chung Wu, Sheng-Shun Yang, Hsu-Sung Kuo, Ding-Shinn Chen, Taiwan Hepatoma Study Group
Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: a 20-year follow-up study.
J Natl Cancer Inst. 2009 Oct 7;101(19):1348-55. doi: 10.1093/jnci/djp288. Epub 2009 Sep 16.
Abstract/Text
BACKGROUND: Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma. This population-based study aimed to investigate whether prevention of hepatocellular carcinoma by the universal Taiwanese HBV vaccine program, launched in July 1984, has extended beyond childhood and to identify the predictors of hepatocellular carcinoma for vaccinated birth cohorts.
METHODS: Data on 1958 patients with hepatocellular carcinoma who were aged 6-29 years at diagnosis in Taiwan between 1983 and 2004 were collected from two national hepatocellular carcinoma registries. Age- and sex-specific incidence among vaccinated and unvaccinated birth cohorts were analyzed by using Poisson regression models. All statistical tests were two-sided. Records of 64 hepatocellular carcinoma patients and 5 524 435 HBV vaccinees who were born after the initiation of the vaccination program were compared for HBV immunization characteristics during infancy and prenatal maternal hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) serostatus.
RESULTS: Hepatocellular carcinoma incidence was statistically significantly lower among children aged 6-19 years in vaccinated compared with unvaccinated birth cohorts (64 hepatocellular cancers among vaccinees in 37 709 304 person-years vs 444 cancers in unvaccinated subjects in 78 496 406 person-years, showing an age- and sex-adjusted relative risk of 0.31, P < .001, for persons vaccinated at birth). The risk of developing hepatocellular carcinoma for vaccinated cohorts was statistically significantly associated with incomplete HBV vaccination (for those who received fewer than three doses of HBV vaccine, odds ratio [OR] = 4.32, 95% confidence interval [CI] = 2.34 to 7.91); with prenatal maternal HBsAg seropositivity (OR = 29.50, 95% CI = 13.98 to 62.60); with prenatal maternal HBeAg seropositivity (with administration of hepatitis B immunoglobulin at birth, OR = 5.13, 95% CI = 2.24 to 11.71; and without it, OR = 9.43, 95% CI = 3.54 to 25.11).
CONCLUSION: The prevention of hepatocellular carcinoma by this HBV vaccine extends from childhood to early adulthood. Failure to prevent hepatocellular carcinoma results mostly from unsuccessful control of HBV infection by highly infectious mothers.
Chun-Ju Chiang, Ya-Wen Yang, San-Lin You, Mei-Shu Lai, Chien-Jen Chen
Thirty-year outcomes of the national hepatitis B immunization program in Taiwan.
JAMA. 2013 Sep 4;310(9):974-6. doi: 10.1001/jama.2013.276701.
Abstract/Text
Katharina Schönberger, Christina Riedel, Simon Rückinger, Ulrich Mansmann, Wolfgang Jilg, Rüdiger V Kries
Determinants of Long-term protection after hepatitis B vaccination in infancy: a meta-analysis.
Pediatr Infect Dis J. 2013 Apr;32(4):307-13. doi: 10.1097/INF.0b013e31827bd1b0.
Abstract/Text
BACKGROUND: The duration of protection after hepatitis B vaccination in early infancy is unclear and may be related to vaccination schedule, dosage, vaccine type and population characteristics. Factors potentially influencing waning immunity were assessed.
METHODS: A systematic review was performed. The main outcomes were prevalence of anti-hepatits B antibodies ≥ 10 mIU/mL after primary or booster vaccination. Factors potentially influencing protection were assessed in an adjusted random-effects meta-analysis model by age for both outcomes. Results of both meta-analyses were combined in a prognostic model.
RESULTS: Forty-six studies reporting on the anti-hepatits B antibodies ≥ 10 mIU/mL 5 to 20 years after primary immunization and 29 on booster response were identified. The adjusted meta-analyses identified maternal carrier status (odds ratio [OR]: 2.37 [1.11; 5.08]), lower vaccine dosage than presently recommended (OR: 0.14 [0.06; 0.30]) and gap time between last and preceding dose of the primary vaccine series (OR: 0.44 [0.22; 0.86]) as determinants for persistence of anti-hepatits B antibodies ≥ 10. A lower vaccine dosage was also associated with failure to respond to booster (OR: 0.20 [0.10; 0.38]). The prognostic model predicted long-term protection of 90% [77%; 100%] at the age of 17 years for offspring of noncarrier mothers vaccinated with a presently recommended dose and vaccination schedule.
CONCLUSIONS: Based on meta-analyses, predictors of waning immunity after hepatitis B vaccination in infancy could be identified. A prognostic model for long-term protection after hepatitis B vaccination in infancy was developed.
E Tauber, H Kollaritsch, M Korinek, P Rendi-Wagner, B Jilma, C Firbas, S Schranz, E Jong, A Klingler, S Dewasthaly, C S Klade
Safety and immunogenicity of a Vero-cell-derived, inactivated Japanese encephalitis vaccine: a non-inferiority, phase III, randomised controlled trial.
Lancet. 2007 Dec 1;370(9602):1847-53. doi: 10.1016/S0140-6736(07)61780-2.
Abstract/Text
BACKGROUND: Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis in southeast Asia. Although no treatment is currently available, vaccination effectively prevents the disease. In a non-inferiority study, we aimed to compare the safety and immunogenicity of a novel, second-generation, inactivated candidate vaccine for JEV with a licensed, mouse-brain-derived vaccine.
METHODS: We included 867 adults in a multicentre, multinational, observer-blinded, randomised controlled phase III trial. Study sites were located in the USA, Germany, and Austria. Volunteers received either the JEV test vaccine intramuscularly on a two-dose schedule (on days 0 and 28; n=430) or the licensed vaccine subcutaneously according to its recommended three-dose schedule (on days 0, 7, and 28; n=437). The primary endpoint was immunogenicity, with respect to neutralising JEV-specific antibodies assessed by a plaque-reduction neutralisation test, which was assessable in 725 patients in the per-protocol population. This trial is registered as a clinical trial, EudraCT number 2004-002474-36.
FINDINGS: The safety profile of the test vaccine was good, and its local tolerability profile was more favourable than that of the licensed vaccine. Frequency of adverse events was similar between treatment groups, and vaccine-related adverse events were generally mild. The seroconversion rate of the test vaccine was 98% compared with 95% for the licensed vaccine on day 56 (95% CI for the difference -1.33 to 3.43). Geometric mean titre for recipients of the test vaccine was 244 (range 5-19 783), compared with 102 (5-1864) for the licensed vaccine (ratio 2.3 [95% CI 1.967-2.75]).
INTERPRETATION: The test JEV vaccine has a promising immunogenicity and safety profile.
C H Hoke, A Nisalak, N Sangawhipa, S Jatanasen, T Laorakapongse, B L Innis, S Kotchasenee, J B Gingrich, J Latendresse, K Fukai
Protection against Japanese encephalitis by inactivated vaccines.
N Engl J Med. 1988 Sep 8;319(10):608-14. doi: 10.1056/NEJM198809083191004.
Abstract/Text
Encephalitis caused by Japanese encephalitis virus occurs in annual epidemics throughout Asia, making it the principal cause of epidemic viral encephalitis in the world. No currently available vaccine has demonstrated efficacy in preventing this disease in a controlled trial. We performed a placebo-controlled, blinded, randomized trial in a northern Thai province, with two doses of monovalent (Nakayama strain) or bivalent (Nakayama plus Beijing strains) inactivated, purified Japanese encephalitis vaccine made from whole virus derived from mouse brain. We examined the effect of these vaccines on the incidence and severity of Japanese encephalitis and dengue hemorrhagic fever, a disease caused by a closely related flavivirus. Between November 1984 and March 1985, 65,224 children received two doses of monovalent Japanese encephalitis vaccine (n = 21,628), bivalent Japanese encephalitis vaccine (n = 22,080), or tetanus toxoid placebo (n = 21,516), with only minor side effects. The cumulative attack rate for encephalitis due to Japanese encephalitis virus was 51 per 100,000 in the placebo group and 5 per 100,000 in each vaccine group. The efficacy in both vaccine groups combined was 91 percent (95 percent confidence interval, 70 to 97 percent). Attack rates for dengue hemorrhagic fever declined, but not significantly. The severity of cases of dengue was also reduced. We conclude that two doses of inactivated Japanese encephalitis vaccine, either monovalent or bivalent, protect against encephalitis due to Japanese encephalitis virus and may have a limited beneficial effect on the severity of dengue hemorrhagic fever.
Peter Goon, Chris Sonnex, Piyush Jani, Margaret Stanley, Holger Sudhoff
Recurrent respiratory papillomatosis: an overview of current thinking and treatment.
Eur Arch Otorhinolaryngol. 2008 Feb;265(2):147-51. doi: 10.1007/s00405-007-0546-z. Epub 2007 Nov 29.
Abstract/Text
Human papillomaviruses (HPV) infection in benign laryngeal papillomas is well established. The vast majority of recurrent respiratory papillomatosis lesions are due to HPV types 6 and 11. Human papillomaviruses are small non-enveloped viruses (>8 kb), that replicate within the nuclei of infected host cells. Infected host basal cell keratinocytes and papillomas arise from the disordered proliferation of these differentiating keratinocytes. Surgical debulking of papillomas is currently the treatment of choice; newer surgical approaches utilizing microdebriders are replacing laser ablation. Surgery aims to secure an adequate airway and improve and maintain an acceptable quality of voice. Adjuvant treatments currently used include cidofovir, indole-3-carbinol, ribavirin, mumps vaccine, and photodynamic therapy. The recent licensing of prophylactic HPV vaccines is a most interesting development. The low incidence of RRP does pose significant problems in recruitment of sufficient numbers to show statistical significance. Large multi-centre collaborative clinical trials are therefore required. Even so, sufficient clinical follow-up data would take several years.
若年性喉頭乳頭腫の1例 小児感染免疫 2014.25:303-307.
Nubia Muñoz, Ricardo Manalastas, Punee Pitisuttithum, Damrong Tresukosol, Joseph Monsonego, Kevin Ault, Christine Clavel, Joaquin Luna, Evan Myers, Sara Hood, Oliver Bautista, Janine Bryan, Frank J Taddeo, Mark T Esser, Scott Vuocolo, Richard M Haupt, Eliav Barr, Alfred Saah
Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24-45 years: a randomised, double-blind trial.
Lancet. 2009 Jun 6;373(9679):1949-57. doi: 10.1016/S0140-6736(09)60691-7. Epub 2009 Jun 1.
Abstract/Text
BACKGROUND: Although the peak incidence of human papillomavirus (HPV) infection occurs in most populations within 5-10 years of first sexual experience, all women remain at risk for acquisition of HPV infections. We tested the safety, immunogenicity, and efficacy of the quadrivalent HPV (types 6, 11, 16, 18) L1 virus-like-particle vaccine in women aged 24-45 years.
METHODS: Women aged 24-45 years with no history of genital warts or cervical disease were enrolled from community health centres, academic health centres, and primary health-care providers into an ongoing multicentre, parallel, randomised, placebo-controlled, double-blind study. Participants were allocated by computer-generated schedule to receive quadrivalent HPV vaccine (n=1911) or placebo (n=1908) at day 1, and months 2 and 6. All study site investigators and personnel, study participants, monitors, and central laboratory personnel were blinded to treatment allocation. Coprimary efficacy endpoints were 6 months' or more duration of infection and cervical and external genital disease due to HPV 6, 11, 16, 18; and due to HPV 16 and 18 alone. Primary efficacy analyses were done in a per-protocol population, but intention-to-treat analyses were also undertaken. This study is registered with ClinicalTrials.gov, number NCT00090220.
FINDINGS: 1910 women received at least one dose of vaccine and 1907 at least one dose of placebo. In the per-protocol population, efficacy against the first coprimary endpoint (disease or infection related to HPV 6, 11, 16, and 18) was 90.5% (95% CI 73.7-97.5, four of 1615 cases in the vaccine group vs 41/1607 in the placebo group) and 83.1% (50.6-95.8, four of 1601 cases vs 23/1579 cases) against the second coprimary endpoint (disease or infection related to HPV 16 and 18 alone). In the intention-to-treat population, efficacy against the first coprimary endpoint was 30.9% (95% CI 11.1-46.5, 108/1886 cases vs 154/1883 cases) and against the second coprimary endpoint was 22.6% (-2.9 to 41.9, 90/1886 cases vs 115/1883 cases), since infection and disease were present at baseline. We recorded no vaccine-related serious adverse events.
INTERPRETATION: The quadrivalent HPV vaccine is efficacious in women aged 24-45 years not infected with the relevant HPV types at enrolment.
FUNDING: Merck (USA).
Beibei Lu, Ambuj Kumar, Xavier Castellsagué, Anna R Giuliano
Efficacy and safety of prophylactic vaccines against cervical HPV infection and diseases among women: a systematic review & meta-analysis.
BMC Infect Dis. 2011 Jan 12;11:13. doi: 10.1186/1471-2334-11-13. Epub 2011 Jan 12.
Abstract/Text
BACKGROUND: We conducted a systematic review and meta-analysis to assess efficacy and safety of prophylactic HPV vaccines against cervical cancer precursor events in women.
METHODS: Randomized-controlled trials of HPV vaccines were identified from MEDLINE, Cochrane Central Register of Controlled Trials, conference abstracts and references of identified studies, and assessed by two independent reviewers. Efficacy data were synthesized using fixed-effect models, and evaluated for heterogeneity using I2 statistic.
RESULTS: Seven unique trials enrolling 44,142 females were included. The fixed-effect Relative Risk (RR) and 95% confidence intervals were 0.04 (0.01-0.11) and 0.10 (0.03-0.38) for HPV-16 and HPV 18-related CIN2+ in the per-protocol populations (PPP). The corresponding RR was 0.47 (0.36-0.61) and 0.16 (0.08-0.34) in the intention-to-treat populations (ITT). Efficacy against CIN1+ was similar in scale in favor of vaccine. Overall vaccines were highly efficacious against 6-month persistent infection with HPV 16 and 18, both in the PPP cohort (RR: 0.06 [0.04-0.09] and 0.05 [0.03-0.09], respectively), and the ITT cohorts (RR: 0.15 [0.10-0.23] and 0.24 [0.14-0.42], respectively). There was limited prophylactic effect against CIN2+ and 6-month persistent infections associated with non-vaccine oncogenic HPV types. The risk of serious adverse events (RR: 1.00, 0.91-1.09) or vaccine-related serious adverse events (RR: 1.82; 0.79-4.20) did not differ significantly between vaccine and control groups. Data on abnormal pregnancy outcomes were underreported.
CONCLUSIONS: Prophylactic HPV vaccines are safe, well tolerated, and highly efficacious in preventing persistent infections and cervical diseases associated with vaccine-HPV types among young females. However, long-term efficacy and safety needs to be addressed in future trials.
Mélanie Drolet, Élodie Bénard, Marie-Claude Boily, Hammad Ali, Louise Baandrup, Heidi Bauer, Simon Beddows, Jacques Brisson, Julia M L Brotherton, Teresa Cummings, Basil Donovan, Christopher K Fairley, Elaine W Flagg, Anne M Johnson, Jessica A Kahn, Kimberley Kavanagh, Susanne K Kjaer, Erich V Kliewer, Philippe Lemieux-Mellouki, Lauri Markowitz, Aminata Mboup, David Mesher, Linda Niccolai, Jeannie Oliphant, Kevin G Pollock, Kate Soldan, Pam Sonnenberg, Sepehr N Tabrizi, Clare Tanton, Marc Brisson
Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis.
Lancet Infect Dis. 2015 May;15(5):565-80. doi: 10.1016/S1473-3099(14)71073-4. Epub 2015 Mar 3.
Abstract/Text
BACKGROUND: Human papillomavirus (HPV) vaccination programmes were first implemented in several countries worldwide in 2007. We did a systematic review and meta-analysis to assess the population-level consequences and herd effects after female HPV vaccination programmes, to verify whether or not the high efficacy reported in randomised controlled clinical trials are materialising in real-world situations.
METHODS: We searched the Medline and Embase databases (between Jan 1, 2007 and Feb 28, 2014) and conference abstracts for time-trend studies that analysed changes, between the pre-vaccination and post-vaccination periods, in the incidence or prevalence of at least one HPV-related endpoint: HPV infection, anogenital warts, and high-grade cervical lesions. We used random-effects models to derive pooled relative risk (RR) estimates. We stratified all analyses by age and sex. We did subgroup analyses by comparing studies according to vaccine type, vaccination coverage, and years since implementation of the vaccination programme. We assessed heterogeneity across studies using I(2) and χ(2) statistics and we did trends analysis to examine the dose-response association between HPV vaccination coverage and each study effect measure.
FINDINGS: We identified 20 eligible studies, which were all undertaken in nine high-income countries and represent more than 140 million person-years of follow-up. In countries with female vaccination coverage of at least 50%, HPV type 16 and 18 infections decreased significantly between the pre-vaccination and post-vaccination periods by 68% (RR 0·32, 95% CI 0·19-0·52) and anogenital warts decreased significantly by 61% (0·39, 0·22-0·71) in girls 13-19 years of age. Significant reductions were also recorded in HPV types 31, 33, and 45 in this age group of girls (RR 0·72, 95% CI 0·54-0·96), which suggests cross-protection. Additionally, significant reductions in anogenital warts were also reported in boys younger than 20 years of age (0·66 [95% CI 0·47-0·91]) and in women 20-39 years of age (0·68 [95% CI 0·51-0·89]), which suggests herd effects. In countries with female vaccination coverage lower than 50%, significant reductions in HPV types 16 and 18 infection (RR 0·50, 95% CI 0·34-0·74]) and in anogenital warts (0·86 [95% CI 0·79-0·94]) occurred in girls younger than 20 years of age, with no indication of cross-protection or herd effects.
INTERPRETATION: Our results are promising for the long-term population-level effects of HPV vaccination programmes. However, continued monitoring is essential to identify any signals of potential waning efficacy or type-replacement.
FUNDING: The Canadian Institutes of Health Research.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Marc Arbyn, Lan Xu, Cindy Simoens, Pierre Pl Martin-Hirsch
Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors.
Cochrane Database Syst Rev. 2018 May 9;5:CD009069. doi: 10.1002/14651858.CD009069.pub3. Epub 2018 May 9.
Abstract/Text
BACKGROUND: Persistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical precancer and cancer. HPV types 16 and 18 cause approximately 70% of cervical cancers worldwide.
OBJECTIVES: To evaluate the harms and protection of prophylactic human papillomaviruses (HPV) vaccines against cervical precancer and HPV16/18 infection in adolescent girls and women.
SEARCH METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase (June 2017) for reports on effects from trials. We searched trial registries and company results' registers to identify unpublished data for mortality and serious adverse events.
SELECTION CRITERIA: Randomised controlled trials comparing efficacy and safety in females offered HPV vaccines with placebo (vaccine adjuvants or another control vaccine).
DATA COLLECTION AND ANALYSIS: We used Cochrane methodology and GRADE to rate the certainty of evidence for protection against cervical precancer (cervical intraepithelial neoplasia grade 2 and above [CIN2+], CIN grade 3 and above [CIN3+], and adenocarcinoma-in-situ [AIS]), and for harms. We distinguished between the effects of vaccines by participants' baseline HPV DNA status. The outcomes were precancer associated with vaccine HPV types and precancer irrespective of HPV type. Results are presented as risks in control and vaccination groups and risk ratios (RR) with 95% confidence intervals in brackets.
MAIN RESULTS: We included 26 trials (73,428 participants). Ten trials, with follow-up of 1.3 to 8 years, addressed protection against CIN/AIS. Vaccine safety was evaluated over a period of 6 months to 7 years in 23 studies. Studies were not large enough or of sufficient duration to evaluate cervical cancer outcomes. All but one of the trials was funded by the vaccine manufacturers. We judged most included trials to be at low risk of bias. Studies involved monovalent (N = 1), bivalent (N = 18), and quadrivalent vaccines (N = 7). Most women were under 26 years of age. Three trials recruited women aged 25 and over. We summarize the effects of vaccines in participants who had at least one immunisation.Efficacy endpoints by initial HPV DNA statushrHPV negativeHPV vaccines reduce CIN2+, CIN3+, AIS associated with HPV16/18 compared with placebo in adolescent girls and women aged 15 to 26. There is high-certainty evidence that vaccines lower CIN2+ from 164 to 2/10,000 (RR 0.01 (0 to 0.05)) and CIN3+ from 70 to 0/10,000 (RR 0.01 (0.00 to 0.10). There is moderate-certainty evidence that vaccines reduce the risk of AIS from 9 to 0/10,000 (RR 0.10 (0.01 to 0.82).HPV vaccines reduce the risk of any CIN2+ from 287 to 106/10,000 (RR 0.37 (0.25 to 0.55), high certainty) and probably reduce any AIS lesions from 10 to 0/10,000 (RR 0.1 (0.01 to 0.76), moderate certainty). The size of reduction in CIN3+ with vaccines differed between bivalent and quadrivalent vaccines (bivalent: RR 0.08 (0.03 to 0.23), high certainty; quadrivalent: RR 0.54 (0.36 to 0.82), moderate certainty). Data in older women were not available for this comparison.HPV16/18 negativeIn those aged 15 to 26 years, vaccines reduce CIN2+ associated with HPV16/18 from 113 to 6 /10,000 (RR 0.05 (0.03 to 0.10). In women 24 years or older the absolute and relative reduction in the risk of these lesions is smaller (from 45 to 14/10,000, (RR 0.30 (0.11 to 0.81), moderate certainty). HPV vaccines reduce the risk of CIN3+ and AIS associated with HPV16/18 in younger women (RR 0.05 (0.02 to 0.14), high certainty and RR 0.09 (0.01 to 0.72), moderate certainty, respectively). No trials in older women have measured these outcomes.Vaccines reduce any CIN2+ from 231 to 95/10,000, (RR 0.41 (0.32 to 0.52)) in younger women. No data are reported for more severe lesions.Regardless of HPV DNA statusIn younger women HPV vaccines reduce the risk of CIN2+ associated with HPV16/18 from 341 to 157/10,000 (RR 0.46 (0.37 to 0.57), high certainty). Similar reductions in risk were observed for CIN3+ associated with HPV16/18 (high certainty). The number of women with AIS associated with HPV16/18 is reduced from 14 to 5/10,000 with HPV vaccines (high certainty).HPV vaccines reduce any CIN2+ from 559 to 391/10,000 (RR 0.70 (0.58 to 0.85, high certainty) and any AIS from 17 to 5/10,000 (RR 0.32 (0.15 to 0.67), high certainty). The reduction in any CIN3+ differed by vaccine type (bivalent vaccine: RR 0.55 (0.43 to 0.71) and quadrivalent vaccine: RR 0.81 (0.69 to 0.96)).In women vaccinated at 24 to 45 years of age, there is moderate-certainty evidence that the risks of CIN2+ associated with HPV16/18 and any CIN2+ are similar between vaccinated and unvaccinated women (RR 0.74 (0.52 to 1.05) and RR 1.04 (0.83 to 1.30) respectively). No data are reported in this age group for CIN3+ or AIS.Adverse effectsThe risk of serious adverse events is similar between control and HPV vaccines in women of all ages (669 versus 656/10,000, RR 0.98 (0.92 to 1.05), high certainty). Mortality was 11/10,000 in control groups compared with 14/10,000 (9 to 22) with HPV vaccine (RR 1.29 [0.85 to 1.98]; low certainty). The number of deaths was low overall but there is a higher number of deaths in older women. No pattern in the cause or timing of death has been established.Pregnancy outcomesAmong those who became pregnant during the studies, we did not find an increased risk of miscarriage (1618 versus 1424/10,000, RR 0.88 (0.68 to 1.14), high certainty) or termination (931 versus 838/10,000 RR 0.90 (0.80 to 1.02), high certainty). The effects on congenital abnormalities and stillbirths are uncertain (RR 1.22 (0.88 to 1.69), moderate certainty and (RR 1.12 (0.68 to 1.83), moderate certainty, respectively).
AUTHORS' CONCLUSIONS: There is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and young women aged 15 to 26. The effect is higher for lesions associated with HPV16/18 than for lesions irrespective of HPV type. The effect is greater in those who are negative for hrHPV or HPV16/18 DNA at enrolment than those unselected for HPV DNA status. There is moderate-certainty evidence that HPV vaccines reduce CIN2+ in older women who are HPV16/18 negative, but not when they are unselected by HPV DNA status.We did not find an increased risk of serious adverse effects. Although the number of deaths is low overall, there were more deaths among women older than 25 years who received the vaccine. The deaths reported in the studies have been judged not to be related to the vaccine. Increased risk of adverse pregnancy outcomes after HPV vaccination cannot be excluded, although the risk of miscarriage and termination are similar between trial arms. Long-term of follow-up is needed to monitor the impact on cervical cancer, occurrence of rare harms and pregnancy outcomes.
Jiayao Lei, Alexander Ploner, K Miriam Elfström, Jiangrong Wang, Adam Roth, Fang Fang, Karin Sundström, Joakim Dillner, Pär Sparén
HPV Vaccination and the Risk of Invasive Cervical Cancer.
N Engl J Med. 2020 Oct 1;383(14):1340-1348. doi: 10.1056/NEJMoa1917338.
Abstract/Text
BACKGROUND: The efficacy and effectiveness of the quadrivalent human papillomavirus (HPV) vaccine in preventing high-grade cervical lesions have been shown. However, data to inform the relationship between quadrivalent HPV vaccination and the subsequent risk of invasive cervical cancer are lacking.
METHODS: We used nationwide Swedish demographic and health registers to follow an open population of 1,672,983 girls and women who were 10 to 30 years of age from 2006 through 2017. We assessed the association between HPV vaccination and the risk of invasive cervical cancer, controlling for age at follow-up, calendar year, county of residence, and parental characteristics, including education, household income, mother's country of birth, and maternal disease history.
RESULTS: During the study period, we evaluated girls and women for cervical cancer until their 31st birthday. Cervical cancer was diagnosed in 19 women who had received the quadrivalent HPV vaccine and in 538 women who had not received the vaccine. The cumulative incidence of cervical cancer was 47 cases per 100,000 persons among women who had been vaccinated and 94 cases per 100,000 persons among those who had not been vaccinated. After adjustment for age at follow-up, the incidence rate ratio for the comparison of the vaccinated population with the unvaccinated population was 0.51 (95% confidence interval [CI], 0.32 to 0.82). After additional adjustment for other covariates, the incidence rate ratio was 0.37 (95% CI, 0.21 to 0.57). After adjustment for all covariates, the incidence rate ratio was 0.12 (95% CI, 0.00 to 0.34) among women who had been vaccinated before the age of 17 years and 0.47 (95% CI, 0.27 to 0.75) among women who had been vaccinated at the age of 17 to 30 years.
CONCLUSIONS: Among Swedish girls and women 10 to 30 years old, quadrivalent HPV vaccination was associated with a substantially reduced risk of invasive cervical cancer at the population level. (Funded by the Swedish Foundation for Strategic Research and others.).
Copyright © 2020 Massachusetts Medical Society.
HPV Information Centre：[Human Papillomavirus and Related. Diseases in the World. Summary Report 17 June 2019 https://hpvcentre.net/statistics/reports/JPN.pdf].
Sadao Suzuki, Akihiro Hosono
No association between HPV vaccine and reported post-vaccination symptoms in Japanese young women: Results of the Nagoya study.
Papillomavirus Res. 2018 Jun;5:96-103. doi: 10.1016/j.pvr.2018.02.002. Epub 2018 Feb 23.
Abstract/Text
Nagoya City introduced free HPV vaccination in 2010 and in April 2013 the Ministry of Health, Labour and Welfare included the HPV vaccine in the National Immunization Program. However, in June 2013, the Ministry suspended proactive recommendation of the vaccine after unconfirmed reports of adverse events. To investigate any potential association between the vaccine and reported symptoms, Nagoya City conducted a questionnaire-based survey. Participants were 71,177 female residents of Nagoya City born between April 2, 1994 and April 1, 2001. The anonymous postal questionnaire investigated the onset of 24 symptoms (primary outcome), associated hospital visits, frequency, and influence on school attendance. Totally, 29,846 residents responded. No significant increase in occurrence of any of the 24 reported post-HPV vaccination symptoms was found. The vaccine was associated with increased age-adjusted odds of hospital visits for "abnormal amount of menstrual bleeding" (OR: 1.43, 95% CI: 1.13-1.82), "irregular menstruation" (OR: 1.29, 95% CI: 1.12-1.49), "severe headaches" (OR: 1.19, 95% CI: 1.02-1.39), and chronic, persisting "abnormal amount of menstrual bleeding" (OR 1.41, 95% CI: 1.11-1.79). No symptoms significantly influenced school attendance and no accumulation of symptoms was observed. The results suggest no causal association between the HPV vaccines and reported symptoms.
Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
Dongwon Yoon, Ji-Ho Lee, Hyesung Lee, Ju-Young Shin
Association between human papillomavirus vaccination and serious adverse events in South Korean adolescent girls: nationwide cohort study.
BMJ. 2021 Jan 29;372:m4931. doi: 10.1136/bmj.m4931. Epub 2021 Jan 29.
Abstract/Text
OBJECTIVE: To evaluate the association between human papillomavirus (HPV) vaccination and serious adverse events in adolescent girls in South Korea.
DESIGN: Cohort study.
SETTING: A large linked database created by linking the Korea Immunization Registry Information System and the National Health Information Database, between January 2017 and December 2019.
PARTICIPANTS: 441 399 girls aged 11-14 years who had been vaccinated in 2017: 382 020 had been vaccinated against HPV and 59 379 had not been vaccinated against HPV.
MAIN OUTCOME MEASURES: Outcomes were 33 serious adverse events, including endocrine, gastrointestinal, cardiovascular, musculoskeletal, haematological, dermatological, and neurological diseases. A cohort design was used for the primary analysis and a self-controlled risk interval design for the secondary analysis; both analyses used a risk period of one year after HPV vaccination for each outcome. Incidence rate and adjusted rate ratios were estimated using Poisson regression in the primary analysis, comparing the HPV vaccinated group with the HPV unvaccinated group, and adjusted relative risks were estimated using conditional logistic regression in the secondary analysis.
RESULTS: Among the 33 predefined serious adverse events, no associations were found with HPV vaccination in the cohort analysis, including Hashimoto's thyroiditis (incidence rate per 100 000 person years: 52.7 v 36.3 for the vaccinated and unvaccinated groups; adjusted rate ratio 1.24, 95% confidence interval 0.78 to 1.94) and rheumatoid arthritis (incidence rate per 100 000 person years: 168.1 v 145.4 for the vaccinated and unvaccinated groups; 0.99, 0.79 to 1.25), with the exception of an increased risk observed for migraine (incidence rate per 100 000 person years: 1235.0 v 920.9 for the vaccinated and unvaccinated groups; 1.11, 1.02 to 1.22). Secondary analysis using self-controlled risk intervals confirmed no associations between HPV vaccination and serious adverse events, including migraine (adjusted relative risk 0.67, 95% confidence interval 0.58 to 0.78). Results were robust to varying follow-up periods and for vaccine subtypes.
CONCLUSIONS: In this nationwide cohort study, with more than 500 000 doses of HPV vaccines, no evidence was found to support an association between HPV vaccination and serious adverse events using both cohort analysis and self-controlled risk interval analysis. Inconsistent findings for migraine should be interpreted with caution considering its pathophysiology and the population of interest.
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Masayoshi Shinjoh, Norio Sugaya, Yoshio Yamaguchi, Yuka Tomidokoro, Shinichiro Sekiguchi, Keiko Mitamura, Motoko Fujino, Hiroyuki Shiro, Osamu Komiyama, Nobuhiko Taguchi, Yuji Nakata, Naoko Yoshida, Atsushi Narabayashi, Michiko Myokai, Masanori Sato, Munehiro Furuichi, Hiroaki Baba, Hisayo Fujita, Akihiro Sato, Ichiro Ookawara, Kenichiro Tsunematsu, Makoto Yoshida, Mio Kono, Fumie Tanaka, Chiharu Kawakami, Takahisa Kimiya, Takao Takahashi, Satoshi Iwata, Keio Pediatric Influenza Research Group
Effectiveness of Trivalent Inactivated Influenza Vaccine in Children Estimated by a Test-Negative Case-Control Design Study Based on Influenza Rapid Diagnostic Test Results.
PLoS One. 2015;10(8):e0136539. doi: 10.1371/journal.pone.0136539. Epub 2015 Aug 28.
Abstract/Text
We assessed vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza in children 6 months to 15 years of age in 22 hospitals in Japan during the 2013-14 season. Our study was conducted according to a test-negative case-control design based on influenza rapid diagnostic test (IRDT) results. Outpatients who came to our clinics with a fever of 38 °C or over and had undergone an IRDT were enrolled in this study. Patients with positive IRDT results were recorded as cases, and patients with negative results were recorded as controls. Between November 2013 and March 2014, a total of 4727 pediatric patients (6 months to 15 years of age) were enrolled: 876 were positive for influenza A, 66 for A(H1N1)pdm09 and in the other 810 the subtype was unknown; 1405 were positive for influenza B; and 2445 were negative for influenza. Overall VE was 46% (95% confidence interval [CI], 39-52). Adjusted VE against influenza A, influenza A(H1N1)pdm09, and influenza B was 63% (95% CI, 56-69), 77% (95% CI, 59-87), and 26% (95% CI, 14-36), respectively. Influenza vaccine was not effective against either influenza A or influenza B in infants 6 to 11 months of age. Two doses of influenza vaccine provided better protection against influenza A infection than a single dose did. VE against hospitalization influenza A infection was 76%. Influenza vaccine was effective against influenza A, especially against influenza A(H1N1)pdm09, but was much less effective against influenza B.
Melissa A Rolfes, Brendan Flannery, Jessie R Chung, Alissa O'Halloran, Shikha Garg, Edward A Belongia, Manjusha Gaglani, Richard K Zimmerman, Michael L Jackson, Arnold S Monto, Nisha B Alden, Evan Anderson, Nancy M Bennett, Laurie Billing, Seth Eckel, Pam Daily Kirley, Ruth Lynfield, Maya L Monroe, Melanie Spencer, Nancy Spina, H Keipp Talbot, Ann Thomas, Salina M Torres, Kimberly Yousey-Hindes, James A Singleton, Manish Patel, Carrie Reed, Alicia M Fry, US Influenza Vaccine Effectiveness (Flu VE) Network, the Influenza Hospitalization Surveillance Network, and the Assessment Branch, Immunization Services Division, Centers for Disease Control and Prevention
Effects of Influenza Vaccination in the United States During the 2017-2018 Influenza Season.
Clin Infect Dis. 2019 Nov 13;69(11):1845-1853. doi: 10.1093/cid/ciz075.
Abstract/Text
BACKGROUND: The severity of the 2017-2018 influenza season in the United States was high, with influenza A(H3N2) viruses predominating. Here, we report influenza vaccine effectiveness (VE) and estimate the number of vaccine-prevented influenza-associated illnesses, medical visits, hospitalizations, and deaths for the 2017-2018 influenza season.
METHODS: We used national age-specific estimates of 2017-2018 influenza vaccine coverage and disease burden. We estimated VE against medically attended reverse-transcription polymerase chain reaction-confirmed influenza virus infection in the ambulatory setting using a test-negative design. We used a compartmental model to estimate numbers of influenza-associated outcomes prevented by vaccination.
RESULTS: The VE against outpatient, medically attended, laboratory-confirmed influenza was 38% (95% confidence interval [CI], 31%-43%), including 22% (95% CI, 12%-31%) against influenza A(H3N2), 62% (95% CI, 50%-71%) against influenza A(H1N1)pdm09, and 50% (95% CI, 41%-57%) against influenza B. We estimated that influenza vaccination prevented 7.1 million (95% CrI, 5.4 million-9.3 million) illnesses, 3.7 million (95% CrI, 2.8 million-4.9 million) medical visits, 109 000 (95% CrI, 39 000-231 000) hospitalizations, and 8000 (95% credible interval [CrI], 1100-21 000) deaths. Vaccination prevented 10% of expected hospitalizations overall and 41% among young children (6 months-4 years).
CONCLUSIONS: Despite 38% VE, influenza vaccination reduced a substantial burden of influenza-associated illness, medical visits, hospitalizations, and deaths in the United States during the 2017-2018 season. Our results demonstrate the benefit of current influenza vaccination and the need for improved vaccines.
Published by Oxford University Press for the Infectious Diseases Society of America 2019.
T F Brewer
Preventing tuberculosis with bacillus Calmette-Guérin vaccine: a meta-analysis of the literature.
Clin Infect Dis. 2000 Sep;31 Suppl 3:S64-7. doi: 10.1086/314072.
Abstract/Text
This article reviews a previously published meta-analysis of 1264 titles or abstracts and 70 selected studies for evaluation of the efficacy of bacillus Calmette-Guérin (BCG) vaccine in preventing tuberculosis. Following review, data from 26 studies were included in the analysis. These 26 studies reveal that vaccination with BCG significantly reduces the risk of tuberculosis by an average of 50%. This level of protection persists across a number of subgroups defined by age at vaccination and study design. Vaccination with BCG was significantly associated with a reduction in the incidence of pulmonary tuberculosis and extrapulmonary disease. In general, the results of this meta-analysis lend weight and confidence to arguments favoring the use of BCG vaccine.
I Abubakar, L Pimpin, C Ariti, R Beynon, P Mangtani, J A C Sterne, P E M Fine, P G Smith, M Lipman, D Elliman, J M Watson, L N Drumright, P F Whiting, E Vynnycky, L C Rodrigues
Systematic review and meta-analysis of the current evidence on the duration of protection by bacillus Calmette-Guérin vaccination against tuberculosis.
Health Technol Assess. 2013 Sep;17(37):1-372, v-vi. doi: 10.3310/hta17370.
Abstract/Text
BACKGROUND: Recent evidence suggests that the duration of protection by bacillus Calmette-Guérin (BCG) may exceed previous estimates with potential implications for estimating clinical and cost-efficacy.
OBJECTIVES: To estimate the protection and duration of protection provided by BCG vaccination against tuberculosis, explore how this protection changes with time since vaccination, and examine the reasons behind the variation in protection and the rate of waning of protection.
DATA SOURCES: Electronic databases including MEDLINE, Excerpta Medica Database (EMBASE), Cochrane Databases, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE), Web of Knowledge, Biosciences Information Service (BIOSIS), Latin American and Caribbean Health Sciences Literature (LILACs), MEDCARIB Database, Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched from inception to May 2009. Index to Theses, System for Information on Grey Literature in Europe (SIGLE), Centre for Agricultural Bioscience International (CABI) Abstracts, Scopus, Article First, Academic Complete, Africa-Wide Information, Google Scholar, Global Health, British National Bibliography for Report Literature, and clinical trial registration websites were searched from inception to October 2009.
REVIEW METHODS: Electronic databases searches, screening of identified studies, data extraction and analysis were undertaken. Meta-analysis was used to present numerical and graphical summaries of clinical efficacy and efficacy by time since vaccination. Evidence of heterogeneity was assessed using the tau-squared statistic. Meta-regression allowed the investigation of observed heterogeneity. Factors investigated included BCG strain, latitude, stringency of pre-BCG vaccination tuberculin testing, age at vaccination, site of disease, study design and vulnerability to biases. Rate of waning of protection was estimated using the ratio of the measure of efficacy after 10 years compared with the efficacy in the first 10 years of a study.
RESULTS: Study selection. A total of 21,030 references were identified, providing data on 132 studies after abstract and full-text review. Efficacy. Protection against pulmonary tuberculosis in adults is variable, ranging from substantial protection in the UK MRC trial {rate ratio 0.22 [95% confidence interval (CI) 0.16 to 0.31]}, to absence of clinically important benefit, as in the large Chingleput trial [rate ratio 1.05 (95% CI 0.88 to 1.25)] and greater in latitudes further away from the equator. BCG vaccination efficacy was usually high, and varied little by form of disease (with higher protection against meningeal and miliary tuberculosis) or study design when BCG vaccination was given only to infants or to children after strict screening for tuberculin sensitivity. High levels of protection against death were observed from both trials and observational studies. The observed protective effect of BCG vaccination did not differ by the strain of BCG vaccine used in trials.
DURATION: Reviewed studies showed that BCG vaccination protects against pulmonary and extrapulmonary tuberculosis for up to 10 years. Most studies either did not follow up participants for long enough or had very few cases after 15 years. This should not be taken to indicate an absence of effect: five studies (one trial and four observational studies) provided evidence of measurable protection at least 15 years after vaccination. Efficacy declined with time. The rate of decline was variable, with faster decline in latitudes further from the equator and in situations where BCG vaccination was given to tuberculin-sensitive participants after stringent tuberculin testing.
LIMITATIONS: The main limitation of this review relates to quality of included trials, most of which were conducted before current standards for reporting were formulated. In addition, data were lacking in some areas and the review had to rely on evidence from observational studies.
CONCLUSIONS: BCG vaccination protection against tuberculosis varies between populations, to an extent that cannot be attributed to chance alone. Failure to exclude those already sensitised to mycobacteria and study latitude closer to the equator were associated with lower efficacy. These factors explained most of the observed variation. There is good evidence that BCG vaccination protection declines with time and that protection can last for up to 10 years. Data on protection beyond 15 years are limited; however, a small number of trials and observational studies suggest that BCG vaccination may protect for longer. Further studies are required to investigate the duration of protection by BCG vaccination.
FUNDING: The National Institute for Health Research Health Technology Assessment programme.
日本小児感染症学会（監）. 小児の臓器移植および免疫不全状態における予防接種ガイドライン 2014. 協和企画, 東京 ,2014.
Karla Soares-Weiser, Hanna Bergman, Nicholas Henschke, Femi Pitan, Nigel Cunliffe
Vaccines for preventing rotavirus diarrhoea: vaccines in use.
Cochrane Database Syst Rev. 2019 Mar 25;3:CD008521. doi: 10.1002/14651858.CD008521.pub4. Epub 2019 Mar 25.
Abstract/Text
BACKGROUND: Rotavirus results in more diarrhoea-related deaths in children under five years than any other single agent in countries with high childhood mortality. It is also a common cause of diarrhoea-related hospital admissions in countries with low childhood mortality. Rotavirus vaccines that have been prequalified by the World Health Organization (WHO) include a monovalent vaccine (RV1; Rotarix, GlaxoSmithKline), a pentavalent vaccine (RV5; RotaTeq, Merck), and, more recently, another monovalent vaccine (Rotavac, Bharat Biotech).
OBJECTIVES: To evaluate rotavirus vaccines prequalified by the WHO (RV1, RV5, and Rotavac) for their efficacy and safety in children.
SEARCH METHODS: On 4 April 2018 we searched MEDLINE (via PubMed), the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (published in the Cochrane Library), Embase, LILACS, and BIOSIS. We also searched the WHO ICTRP, ClinicalTrials.gov, clinical trial reports from manufacturers' websites, and reference lists of included studies and relevant systematic reviews.
SELECTION CRITERIA: We selected randomized controlled trials (RCTs) in children comparing rotavirus vaccines prequalified for use by the WHO versus placebo or no intervention.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and assessed risks of bias. One review author extracted data and a second author cross-checked them. We combined dichotomous data using the risk ratio (RR) and 95% confidence interval (CI). We stratified the analysis by country mortality rate and used GRADE to evaluate evidence certainty.
MAIN RESULTS: Fifty-five trials met the inclusion criteria and enrolled a total of 216,480 participants. Thirty-six trials (119,114 participants) assessed RV1, 15 trials (88,934 participants) RV5, and four trials (8432 participants) Rotavac.RV1 Children vaccinated and followed up the first year of life In low-mortality countries, RV1 prevents 84% of severe rotavirus diarrhoea cases (RR 0.16, 95% CI 0.09 to 0.26; 43,779 participants, 7 trials; high-certainty evidence), and probably prevents 41% of cases of severe all-cause diarrhoea (RR 0.59, 95% CI 0.47 to 0.74; 28,051 participants, 3 trials; moderate-certainty evidence). In high-mortality countries, RV1 prevents 63% of severe rotavirus diarrhoea cases (RR 0.37, 95% CI 0.23 to 0.60; 6114 participants, 3 trials; high-certainty evidence), and 27% of severe all-cause diarrhoea cases (RR 0.73, 95% CI 0.56 to 0.95; 5639 participants, 2 trials; high-certainty evidence).Children vaccinated and followed up for two yearsIn low-mortality countries, RV1 prevents 82% of severe rotavirus diarrhoea cases (RR 0.18, 95% CI 0.14 to 0.23; 36,002 participants, 9 trials; high-certainty evidence), and probably prevents 37% of severe all-cause diarrhoea episodes (rate ratio 0.63, 95% CI 0.56 to 0.71; 39,091 participants, 2 trials; moderate-certainty evidence). In high-mortality countries RV1 probably prevents 35% of severe rotavirus diarrhoea cases (RR 0.65, 95% CI 0.51 to 0.83; 13,768 participants, 2 trials; high-certainty evidence), and 17% of severe all-cause diarrhoea cases (RR 0.83, 95% CI 0.72 to 0.96; 2764 participants, 1 trial; moderate-certainty evidence).No increased risk of serious adverse events (SAE) was detected (RR 0.88 95% CI 0.83 to 0.93; high-certainty evidence). There were 30 cases of intussusception reported in 53,032 children after RV1 vaccination and 28 cases in 44,214 children after placebo or no intervention (RR 0.70, 95% CI 0.46 to 1.05; low-certainty evidence).RV5 Children vaccinated and followed up the first year of life In low-mortality countries, RV5 probably prevents 92% of severe rotavirus diarrhoea cases (RR 0.08, 95% CI 0.03 to 0.22; 4132 participants, 5 trials; moderate-certainty evidence). We did not identify studies reporting on severe all-cause diarrhoea in low-mortality countries. In high-mortality countries, RV5 prevents 57% of severe rotavirus diarrhoea (RR 0.43, 95% CI 0.29 to 0.62; 5916 participants, 2 trials; high-certainty evidence), but there is probably little or no difference between vaccine and placebo for severe all-cause diarrhoea (RR 0.80, 95% CI 0.58 to 1.11; 1 trial, 4085 participants; moderate-certainty evidence).Children vaccinated and followed up for two yearsIn low-mortality countries, RV5 prevents 82% of severe rotavirus diarrhoea cases (RR 0.18, 95% CI 0.08 to 0.39; 7318 participants, 4 trials; moderate-certainty evidence). We did not identify studies reporting on severe all-cause diarrhoea in low-mortality countries. In high-mortality countries, RV5 prevents 41% of severe rotavirus diarrhoea cases (RR 0.59, 95% CI 0.43 to 0.82; 5885 participants, 2 trials; high-certainty evidence), and 15% of severe all-cause diarrhoea cases (RR 0.85, 95% CI 0.75 to 0.98; 5977 participants, 2 trials; high-certainty evidence).No increased risk of serious adverse events (SAE) was detected (RR 0.93 95% CI 0.86 to 1.01; moderate to high-certainty evidence). There were 16 cases of intussusception in 43,629 children after RV5 vaccination and 20 cases in 41,866 children after placebo (RR 0.77, 95% CI 0.41 to 1.45; low-certainty evidence).Rotavac Children vaccinated and followed up the first year of life Rotavac has not been assessed in any RCT in countries with low child mortality. In India, a high-mortality country, Rotavac probably prevents 57% of severe rotavirus diarrhoea cases (RR 0.43, 95% CI 0.30 to 0.60; 6799 participants, moderate-certainty evidence); the trial did not report on severe all-cause diarrhoea at one-year follow-up.Children vaccinated and followed up for two yearsRotavac probably prevents 54% of severe rotavirus diarrhoea cases in India (RR 0.46, 95% CI 0.35 to 0.60; 6541 participants, 1 trial; moderate-certainty evidence), and 16% of severe all-cause diarrhoea cases (RR 0.84, 95% CI 0.71 to 0.98; 6799 participants, 1 trial; moderate-certainty evidence).No increased risk of serious adverse events (SAE) was detected (RR 0.93 95% CI 0.85 to 1.02; moderate-certainty evidence). There were eight cases of intussusception in 5764 children after Rotavac vaccination and three cases in 2818 children after placebo (RR 1.33, 95% CI 0.35 to 5.02; very low-certainty evidence).There was insufficient evidence of an effect on mortality from any rotavirus vaccine (198,381 participants, 44 trials; low- to very low-certainty evidence), as the trials were not powered to detect an effect at this endpoint.
AUTHORS' CONCLUSIONS: RV1, RV5, and Rotavac prevent episodes of rotavirus diarrhoea. Whilst the relative effect estimate is smaller in high-mortality than in low-mortality countries, there is a greater number of episodes prevented in these settings as the baseline risk is much higher. We found no increased risk of serious adverse events.
Eric S Weintraub, James Baggs, Jonathan Duffy, Claudia Vellozzi, Edward A Belongia, Stephanie Irving, Nicola P Klein, Jason M Glanz, Steven J Jacobsen, Allison Naleway, Lisa A Jackson, Frank DeStefano
Risk of intussusception after monovalent rotavirus vaccination.
N Engl J Med. 2014 Feb 6;370(6):513-9. doi: 10.1056/NEJMoa1311738. Epub 2014 Jan 14.
Abstract/Text
BACKGROUND: Although current rotavirus vaccines were not associated with an increased risk of intussusception in large trials before licensure, recent postlicensure data from international settings suggest the possibility of a small increase in risk of intussusception after monovalent rotavirus vaccination. We examined this risk in a population in the United States.
METHODS: Participants were infants between the ages of 4 and 34 weeks who were enrolled in six integrated health care organizations in the Vaccine Safety Datalink (VSD) project. We reviewed medical records and visits for intussusception within 7 days after monovalent rotavirus vaccination from April 2008 through March 2013. Using sequential analyses, we then compared the risk of intussusception among children receiving monovalent rotavirus vaccine with historical background rates. We further compared the risk after monovalent rotavirus vaccination with the risk in a concurrent cohort of infants who received the pentavalent rotavirus vaccine.
RESULTS: During the study period, 207,955 doses of monovalent rotavirus vaccine (including 115,908 first doses and 92,047 second doses) were administered in the VSD population. We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine. For the two doses combined, the expected number of intussusception cases was 0.72, resulting in a significant relative risk of 8.4. For the pentavalent rotavirus vaccine, 1,301,810 doses were administered during the study period, with 8 observed intussusception cases (7.11 expected), for a nonsignificant relative risk of 1.1. The relative risk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination, as compared with the risk after pentavalent rotavirus vaccination, was 9.4 (95% confidence interval, 1.4 to 103.8). The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 5.3 per 100,000 infants vaccinated.
CONCLUSIONS: In this prospective postlicensure study of more than 200,000 doses of monovalent rotavirus vaccine, we observed a significant increase in the rate of intussusception after vaccination, a risk that must be weighed against the benefits of preventing rotavirus-associated illness. (Funded by the Centers for Disease Control and Prevention.).
Guillermo M Ruiz-Palacios, Irene Pérez-Schael, F Raúl Velázquez, Hector Abate, Thomas Breuer, SueAnn Costa Clemens, Brigitte Cheuvart, Felix Espinoza, Paul Gillard, Bruce L Innis, Yolanda Cervantes, Alexandre C Linhares, Pío López, Mercedes Macías-Parra, Eduardo Ortega-Barría, Vesta Richardson, Doris Maribel Rivera-Medina, Luis Rivera, Belén Salinas, Noris Pavía-Ruz, Jorge Salmerón, Ricardo Rüttimann, Juan Carlos Tinoco, Pilar Rubio, Ernesto Nuñez, M Lourdes Guerrero, Juan Pablo Yarzábal, Silvia Damaso, Nadia Tornieporth, Xavier Sáez-Llorens, Rodrigo F Vergara, Timo Vesikari, Alain Bouckenooghe, Ralf Clemens, Béatrice De Vos, Miguel O'Ryan, Human Rotavirus Vaccine Study Group
Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis.
N Engl J Med. 2006 Jan 5;354(1):11-22. doi: 10.1056/NEJMoa052434.
Abstract/Text
BACKGROUND: The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial.
METHODS: We studied 63,225 healthy infants from 11 Latin American countries and Finland who received two oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age. Severe gastroenteritis episodes were identified by active surveillance. The severity of disease was graded with the use of the 20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients).
RESULTS: The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percent; P<0.001). During the 31-day window after each dose, six vaccine recipients and seven placebo recipients had definite intussusception (difference in risk, -0.32 per 10,000 infants; 95 percent confidence interval, -2.91 to 2.18; P=0.78).
CONCLUSIONS: Two oral doses of the live attenuated G1P[8] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception. (ClinicalTrials.gov numbers, NCT00139347 and NCT00263666.)
Copyright 2006 Massachusetts Medical Society.
Dominique Rosillon, Hubert Buyse, Leonard R Friedland, Su-Peing Ng, F Raúl Velázquez, Thomas Breuer
Risk of Intussusception After Rotavirus Vaccination: Meta-analysis of Postlicensure Studies.
Pediatr Infect Dis J. 2015 Jul;34(7):763-8. doi: 10.1097/INF.0000000000000715.
Abstract/Text
BACKGROUND: Postlicensure surveillance studies suggest a small temporal increase in the risk for intussusception with both currently available rotavirus vaccines (RV1; Rotarix, GSK and RV5; RotaTeq, Merck & Co., Inc.). This meta-analysis was undertaken to provide a single overall estimate of the relative risk of intussusception during the 7-day period after administration of RV1 and RV5.
METHODS: Meta-analysis based on estimates of relative risk and corresponding 95% confidence intervals from 5 postlicensure studies providing an estimate of risk of intussusception during the 7-day period after administration of dose 1 and/or dose 2 of RV1 and/or RV5, based on active and/or passive surveillance, for confirmed intussusception cases (Brighton or other method of case confirmation). For each vaccine, the relative risk of intussusception was estimated postdose 1 and postdose 2. Results were pooled using the inverse variance method using both fixed-effect and random-effect models.
RESULTS: The overall estimate of relative risk of intussusception during the 7 days postdose 1 was 5.4 (95% confidence interval: 3.9-7.4, 3 studies) for RV1 and 5.5 (3.3-9.3, 3 studies) for RV5. The overall estimate of relative risk of intussusception during the 7 days postdose 2 was 1.8 (1.3-2.5, 4 studies) for RV1 and 1.7 (1.1-2.6, 3 studies) for RV5.
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.
Dominique Rosillon, Hubert Buyse, Leonard R Friedland, Su-Peing Ng, F Raúl Velázquez, Thomas Breuer
Risk of Intussusception After Rotavirus Vaccination: Meta-analysis of Postlicensure Studies.
Pediatr Infect Dis J. 2015 Jul;34(7):763-8. doi: 10.1097/INF.0000000000000715.
Abstract/Text
BACKGROUND: Postlicensure surveillance studies suggest a small temporal increase in the risk for intussusception with both currently available rotavirus vaccines (RV1; Rotarix, GSK and RV5; RotaTeq, Merck & Co., Inc.). This meta-analysis was undertaken to provide a single overall estimate of the relative risk of intussusception during the 7-day period after administration of RV1 and RV5.
METHODS: Meta-analysis based on estimates of relative risk and corresponding 95% confidence intervals from 5 postlicensure studies providing an estimate of risk of intussusception during the 7-day period after administration of dose 1 and/or dose 2 of RV1 and/or RV5, based on active and/or passive surveillance, for confirmed intussusception cases (Brighton or other method of case confirmation). For each vaccine, the relative risk of intussusception was estimated postdose 1 and postdose 2. Results were pooled using the inverse variance method using both fixed-effect and random-effect models.
RESULTS: The overall estimate of relative risk of intussusception during the 7 days postdose 1 was 5.4 (95% confidence interval: 3.9-7.4, 3 studies) for RV1 and 5.5 (3.3-9.3, 3 studies) for RV5. The overall estimate of relative risk of intussusception during the 7 days postdose 2 was 1.8 (1.3-2.5, 4 studies) for RV1 and 1.7 (1.1-2.6, 3 studies) for RV5.
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.
T Varis, T Vesikari
Efficacy of high-titer live attenuated varicella vaccine in healthy young children.
J Infect Dis. 1996 Nov;174 Suppl 3:S330-4.
Abstract/Text
The efficacy of a high-titer, reformulated varicella vaccine was studied in 513 10- to 30-month-old children. Vaccinees were randomly allocated to 5 groups to receive one of two lots of an original high-titer vaccine, one of two lots of a partially heat-inactivated vaccine, or placebo. Both vaccines were well tolerated. Seroconversion was detected in 100% and 99% of children immunized with the high- and low-titer vaccines, respectively. Sixty-five cases of serologically confirmed varicella-like disease were discovered during follow-up (mean, 29.3 months): 5 in the high-titer vaccine group, 19 in the low-titer vaccine group, and 41 in the placebo group (P < or = .005 for each difference). Thus, the protective efficacy of live attenuated varicella vaccine is dependent on vaccine titer. High-titer varicella vaccine induces excellent protection in healthy young children.
T Varis, T Vesikari
Efficacy of high-titer live attenuated varicella vaccine in healthy young children.
J Infect Dis. 1996 Nov;174 Suppl 3:S330-4.
Abstract/Text
The efficacy of a high-titer, reformulated varicella vaccine was studied in 513 10- to 30-month-old children. Vaccinees were randomly allocated to 5 groups to receive one of two lots of an original high-titer vaccine, one of two lots of a partially heat-inactivated vaccine, or placebo. Both vaccines were well tolerated. Seroconversion was detected in 100% and 99% of children immunized with the high- and low-titer vaccines, respectively. Sixty-five cases of serologically confirmed varicella-like disease were discovered during follow-up (mean, 29.3 months): 5 in the high-titer vaccine group, 19 in the low-titer vaccine group, and 41 in the placebo group (P < or = .005 for each difference). Thus, the protective efficacy of live attenuated varicella vaccine is dependent on vaccine titer. High-titer varicella vaccine induces excellent protection in healthy young children.
Barbara Kuter, Holly Matthews, Henry Shinefield, Steve Black, Penelope Dennehy, Barbara Watson, Keith Reisinger, Lee Lian Kim, Lisa Lupinacci, Jonathan Hartzel, Ivan Chan, Study Group for Varivax
Ten year follow-up of healthy children who received one or two injections of varicella vaccine.
Pediatr Infect Dis J. 2004 Feb;23(2):132-7. doi: 10.1097/01.inf.0000109287.97518.67.
Abstract/Text
BACKGROUND: The rate of varicella and persistence of varicella antibody after a one dose vs. a two dose regimen of varicella virus vaccine live Oka/Merck (VARIVAX; Merck & Co., Inc., West Point, PA) in approximately 2000 children were compared during a 9- to 10-year follow-up period.
METHODS: Children 12 months to 12 years of age with a negative history of varicella were randomized in late 1991 to early 1993 to receive either one or two injections of varicella vaccine given 3 months apart. Subjects were actively followed for varicella, any varicella-like illness or zoster and any exposures to varicella or zoster on a yearly basis for 10 years after vaccination. Persistence of varicella antibody was measured yearly for 9 years.
RESULTS: Most cases of varicella reported in recipients of one or two injections of vaccine were mild. The risk of developing varicella >42 days postvaccination during the 10-year observation period was 3.3-fold lower (P < 0.001) in children who received two injections than in those who received one injection (2.2% vs. 7.3%, respectively). The estimated vaccine efficacy for the 10-year observation period was 94.4% for one injection and 98.3% for two injections (P < 0.001). Measurable serum antibody persisted for 9 years in all subjects.
CONCLUSIONS: Administration of either one or two injections of varicella vaccine to healthy children results in long term protection against most varicella disease. The two dose regimen was significantly more effective than a single injection.
Barbara Kuter, Holly Matthews, Henry Shinefield, Steve Black, Penelope Dennehy, Barbara Watson, Keith Reisinger, Lee Lian Kim, Lisa Lupinacci, Jonathan Hartzel, Ivan Chan, Study Group for Varivax
Ten year follow-up of healthy children who received one or two injections of varicella vaccine.
Pediatr Infect Dis J. 2004 Feb;23(2):132-7. doi: 10.1097/01.inf.0000109287.97518.67.
Abstract/Text
BACKGROUND: The rate of varicella and persistence of varicella antibody after a one dose vs. a two dose regimen of varicella virus vaccine live Oka/Merck (VARIVAX; Merck & Co., Inc., West Point, PA) in approximately 2000 children were compared during a 9- to 10-year follow-up period.
METHODS: Children 12 months to 12 years of age with a negative history of varicella were randomized in late 1991 to early 1993 to receive either one or two injections of varicella vaccine given 3 months apart. Subjects were actively followed for varicella, any varicella-like illness or zoster and any exposures to varicella or zoster on a yearly basis for 10 years after vaccination. Persistence of varicella antibody was measured yearly for 9 years.
RESULTS: Most cases of varicella reported in recipients of one or two injections of vaccine were mild. The risk of developing varicella >42 days postvaccination during the 10-year observation period was 3.3-fold lower (P < 0.001) in children who received two injections than in those who received one injection (2.2% vs. 7.3%, respectively). The estimated vaccine efficacy for the 10-year observation period was 94.4% for one injection and 98.3% for two injections (P < 0.001). Measurable serum antibody persisted for 9 years in all subjects.
CONCLUSIONS: Administration of either one or two injections of varicella vaccine to healthy children results in long term protection against most varicella disease. The two dose regimen was significantly more effective than a single injection.
Carlo Di Pietrantonj, Alessandro Rivetti, Pasquale Marchione, Maria Grazia Debalini, Vittorio Demicheli
Vaccines for measles, mumps, rubella, and varicella in children.
Cochrane Database Syst Rev. 2020 Apr 20;4:CD004407. doi: 10.1002/14651858.CD004407.pub4. Epub 2020 Apr 20.
Abstract/Text
BACKGROUND: Measles, mumps, rubella, and varicella (chickenpox) are serious diseases that can lead to serious complications, disability, and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness. This is an update of a review published in 2005 and updated in 2012.
OBJECTIVES: To assess the effectiveness, safety, and long- and short-term adverse effects associated with the trivalent vaccine, containing measles, rubella, mumps strains (MMR), or concurrent administration of MMR vaccine and varicella vaccine (MMR+V), or tetravalent vaccine containing measles, rubella, mumps, and varicella strains (MMRV), given to children aged up to 15 years.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2019, Issue 5), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to 2 May 2019), Embase (1974 to 2 May 2019), the WHO International Clinical Trials Registry Platform (2 May 2019), and ClinicalTrials.gov (2 May 2019).
SELECTION CRITERIA: We included randomised controlled trials (RCTs), controlled clinical trials (CCTs), prospective and retrospective cohort studies (PCS/RCS), case-control studies (CCS), interrupted time-series (ITS) studies, case cross-over (CCO) studies, case-only ecological method (COEM) studies, self-controlled case series (SCCS) studies, person-time cohort (PTC) studies, and case-coverage design/screening methods (CCD/SM) studies, assessing any combined MMR or MMRV / MMR+V vaccine given in any dose, preparation or time schedule compared with no intervention or placebo, on healthy children up to 15 years of age.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the methodological quality of the included studies. We grouped studies for quantitative analysis according to study design, vaccine type (MMR, MMRV, MMR+V), virus strain, and study settings. Outcomes of interest were cases of measles, mumps, rubella, and varicella, and harms. Certainty of evidence of was rated using GRADE.
MAIN RESULTS: We included 138 studies (23,480,668 participants). Fifty-one studies (10,248,159 children) assessed vaccine effectiveness and 87 studies (13,232,509 children) assessed the association between vaccines and a variety of harms. We included 74 new studies to this 2019 version of the review. Effectiveness Vaccine effectiveness in preventing measles was 95% after one dose (relative risk (RR) 0.05, 95% CI 0.02 to 0.13; 7 cohort studies; 12,039 children; moderate certainty evidence) and 96% after two doses (RR 0.04, 95% CI 0.01 to 0.28; 5 cohort studies; 21,604 children; moderate certainty evidence). The effectiveness in preventing cases among household contacts or preventing transmission to others the children were in contact with after one dose was 81% (RR 0.19, 95% CI 0.04 to 0.89; 3 cohort studies; 151 children; low certainty evidence), after two doses 85% (RR 0.15, 95% CI 0.03 to 0.75; 3 cohort studies; 378 children; low certainty evidence), and after three doses was 96% (RR 0.04, 95% CI 0.01 to 0.23; 2 cohort studies; 151 children; low certainty evidence). The effectiveness (at least one dose) in preventing measles after exposure (post-exposure prophylaxis) was 74% (RR 0.26, 95% CI 0.14 to 0.50; 2 cohort studies; 283 children; low certainty evidence). The effectiveness of Jeryl Lynn containing MMR vaccine in preventing mumps was 72% after one dose (RR 0.24, 95% CI 0.08 to 0.76; 6 cohort studies; 9915 children; moderate certainty evidence), 86% after two doses (RR 0.12, 95% CI 0.04 to 0.35; 5 cohort studies; 7792 children; moderate certainty evidence). Effectiveness in preventing cases among household contacts was 74% (RR 0.26, 95% CI 0.13 to 0.49; 3 cohort studies; 1036 children; moderate certainty evidence). Vaccine effectiveness against rubella is 89% (RR 0.11, 95% CI 0.03 to 0.42; 1 cohort study; 1621 children; moderate certainty evidence). Vaccine effectiveness against varicella (any severity) after two doses in children aged 11 to 22 months is 95% in a 10 years follow-up (rate ratio (rr) 0.05, 95% CI 0.03 to 0.08; 1 RCT; 2279 children; high certainty evidence). Safety There is evidence supporting an association between aseptic meningitis and MMR vaccines containing Urabe and Leningrad-Zagreb mumps strains, but no evidence supporting this association for MMR vaccines containing Jeryl Lynn mumps strains (rr 1.30, 95% CI 0.66 to 2.56; low certainty evidence). The analyses provide evidence supporting an association between MMR/MMR+V/MMRV vaccines (Jeryl Lynn strain) and febrile seizures. Febrile seizures normally occur in 2% to 4% of healthy children at least once before the age of 5. The attributable risk febrile seizures vaccine-induced is estimated to be from 1 per 1700 to 1 per 1150 administered doses. The analyses provide evidence supporting an association between MMR vaccination and idiopathic thrombocytopaenic purpura (ITP). However, the risk of ITP after vaccination is smaller than after natural infection with these viruses. Natural infection of ITP occur in 5 cases per 100,000 (1 case per 20,000) per year. The attributable risk is estimated about 1 case of ITP per 40,000 administered MMR doses. There is no evidence of an association between MMR immunisation and encephalitis or encephalopathy (rate ratio 0.90, 95% CI 0.50 to 1.61; 2 observational studies; 1,071,088 children; low certainty evidence), and autistic spectrum disorders (rate ratio 0.93, 95% CI 0.85 to 1.01; 2 observational studies; 1,194,764 children; moderate certainty). There is insufficient evidence to determine the association between MMR immunisation and inflammatory bowel disease (odds ratio 1.42, 95% CI 0.93 to 2.16; 3 observational studies; 409 cases and 1416 controls; moderate certainty evidence). Additionally, there is no evidence supporting an association between MMR immunisation and cognitive delay, type 1 diabetes, asthma, dermatitis/eczema, hay fever, leukaemia, multiple sclerosis, gait disturbance, and bacterial or viral infections.
AUTHORS' CONCLUSIONS: Existing evidence on the safety and effectiveness of MMR/MMRV vaccines support their use for mass immunisation. Campaigns aimed at global eradication should assess epidemiological and socioeconomic situations of the countries as well as the capacity to achieve high vaccination coverage. More evidence is needed to assess whether the protective effect of MMR/MMRV could wane with time since immunisation.
Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Carlo Di Pietrantonj, Alessandro Rivetti, Pasquale Marchione, Maria Grazia Debalini, Vittorio Demicheli
Vaccines for measles, mumps, rubella, and varicella in children.
Cochrane Database Syst Rev. 2020 Apr 20;4:CD004407. doi: 10.1002/14651858.CD004407.pub4. Epub 2020 Apr 20.
Abstract/Text
BACKGROUND: Measles, mumps, rubella, and varicella (chickenpox) are serious diseases that can lead to serious complications, disability, and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness. This is an update of a review published in 2005 and updated in 2012.
OBJECTIVES: To assess the effectiveness, safety, and long- and short-term adverse effects associated with the trivalent vaccine, containing measles, rubella, mumps strains (MMR), or concurrent administration of MMR vaccine and varicella vaccine (MMR+V), or tetravalent vaccine containing measles, rubella, mumps, and varicella strains (MMRV), given to children aged up to 15 years.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2019, Issue 5), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to 2 May 2019), Embase (1974 to 2 May 2019), the WHO International Clinical Trials Registry Platform (2 May 2019), and ClinicalTrials.gov (2 May 2019).
SELECTION CRITERIA: We included randomised controlled trials (RCTs), controlled clinical trials (CCTs), prospective and retrospective cohort studies (PCS/RCS), case-control studies (CCS), interrupted time-series (ITS) studies, case cross-over (CCO) studies, case-only ecological method (COEM) studies, self-controlled case series (SCCS) studies, person-time cohort (PTC) studies, and case-coverage design/screening methods (CCD/SM) studies, assessing any combined MMR or MMRV / MMR+V vaccine given in any dose, preparation or time schedule compared with no intervention or placebo, on healthy children up to 15 years of age.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the methodological quality of the included studies. We grouped studies for quantitative analysis according to study design, vaccine type (MMR, MMRV, MMR+V), virus strain, and study settings. Outcomes of interest were cases of measles, mumps, rubella, and varicella, and harms. Certainty of evidence of was rated using GRADE.
MAIN RESULTS: We included 138 studies (23,480,668 participants). Fifty-one studies (10,248,159 children) assessed vaccine effectiveness and 87 studies (13,232,509 children) assessed the association between vaccines and a variety of harms. We included 74 new studies to this 2019 version of the review. Effectiveness Vaccine effectiveness in preventing measles was 95% after one dose (relative risk (RR) 0.05, 95% CI 0.02 to 0.13; 7 cohort studies; 12,039 children; moderate certainty evidence) and 96% after two doses (RR 0.04, 95% CI 0.01 to 0.28; 5 cohort studies; 21,604 children; moderate certainty evidence). The effectiveness in preventing cases among household contacts or preventing transmission to others the children were in contact with after one dose was 81% (RR 0.19, 95% CI 0.04 to 0.89; 3 cohort studies; 151 children; low certainty evidence), after two doses 85% (RR 0.15, 95% CI 0.03 to 0.75; 3 cohort studies; 378 children; low certainty evidence), and after three doses was 96% (RR 0.04, 95% CI 0.01 to 0.23; 2 cohort studies; 151 children; low certainty evidence). The effectiveness (at least one dose) in preventing measles after exposure (post-exposure prophylaxis) was 74% (RR 0.26, 95% CI 0.14 to 0.50; 2 cohort studies; 283 children; low certainty evidence). The effectiveness of Jeryl Lynn containing MMR vaccine in preventing mumps was 72% after one dose (RR 0.24, 95% CI 0.08 to 0.76; 6 cohort studies; 9915 children; moderate certainty evidence), 86% after two doses (RR 0.12, 95% CI 0.04 to 0.35; 5 cohort studies; 7792 children; moderate certainty evidence). Effectiveness in preventing cases among household contacts was 74% (RR 0.26, 95% CI 0.13 to 0.49; 3 cohort studies; 1036 children; moderate certainty evidence). Vaccine effectiveness against rubella is 89% (RR 0.11, 95% CI 0.03 to 0.42; 1 cohort study; 1621 children; moderate certainty evidence). Vaccine effectiveness against varicella (any severity) after two doses in children aged 11 to 22 months is 95% in a 10 years follow-up (rate ratio (rr) 0.05, 95% CI 0.03 to 0.08; 1 RCT; 2279 children; high certainty evidence). Safety There is evidence supporting an association between aseptic meningitis and MMR vaccines containing Urabe and Leningrad-Zagreb mumps strains, but no evidence supporting this association for MMR vaccines containing Jeryl Lynn mumps strains (rr 1.30, 95% CI 0.66 to 2.56; low certainty evidence). The analyses provide evidence supporting an association between MMR/MMR+V/MMRV vaccines (Jeryl Lynn strain) and febrile seizures. Febrile seizures normally occur in 2% to 4% of healthy children at least once before the age of 5. The attributable risk febrile seizures vaccine-induced is estimated to be from 1 per 1700 to 1 per 1150 administered doses. The analyses provide evidence supporting an association between MMR vaccination and idiopathic thrombocytopaenic purpura (ITP). However, the risk of ITP after vaccination is smaller than after natural infection with these viruses. Natural infection of ITP occur in 5 cases per 100,000 (1 case per 20,000) per year. The attributable risk is estimated about 1 case of ITP per 40,000 administered MMR doses. There is no evidence of an association between MMR immunisation and encephalitis or encephalopathy (rate ratio 0.90, 95% CI 0.50 to 1.61; 2 observational studies; 1,071,088 children; low certainty evidence), and autistic spectrum disorders (rate ratio 0.93, 95% CI 0.85 to 1.01; 2 observational studies; 1,194,764 children; moderate certainty). There is insufficient evidence to determine the association between MMR immunisation and inflammatory bowel disease (odds ratio 1.42, 95% CI 0.93 to 2.16; 3 observational studies; 409 cases and 1416 controls; moderate certainty evidence). Additionally, there is no evidence supporting an association between MMR immunisation and cognitive delay, type 1 diabetes, asthma, dermatitis/eczema, hay fever, leukaemia, multiple sclerosis, gait disturbance, and bacterial or viral infections.
AUTHORS' CONCLUSIONS: Existing evidence on the safety and effectiveness of MMR/MMRV vaccines support their use for mass immunisation. Campaigns aimed at global eradication should assess epidemiological and socioeconomic situations of the countries as well as the capacity to achieve high vaccination coverage. More evidence is needed to assess whether the protective effect of MMR/MMRV could wane with time since immunisation.
Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Kristine Macartney, Peter McIntyre
Vaccines for post-exposure prophylaxis against varicella (chickenpox) in children and adults.
Cochrane Database Syst Rev. 2008 Jul 16;(3):CD001833. doi: 10.1002/14651858.CD001833.pub2. Epub 2008 Jul 16.
Abstract/Text
BACKGROUND: Live attenuated varicella vaccines for the prevention of varicella (chickenpox) has been demonstrated both in randomised controlled trials (RCTs) and in population-based immunisation programmes in countries such as the United States. However, many countries do not routinely immunise children against varicella, and exposures continue to occur. Although the disease is often mild, complications such as secondary bacterial infection, pneumonitis and encephalitis occur in about 1% of cases, usually leading to hospitalisation. The use of varicella vaccine in persons who have recently been exposed to the varicella zoster virus has been studied as a form of post-exposure prophylaxis (PEP).
OBJECTIVES: To assess the efficacy and safety of vaccines for use as PEP for the prevention of varicella in children and adults.
SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2008, Issue 1); MEDLINE (1966 to February 2008); and EMBASE (January 1990 to February 2008).
SELECTION CRITERIA: RCTs and quasi-RCTs of varicella vaccine for PEP compared with placebo or no intervention. The outcome measures were efficacy in prevention of clinical cases and/or laboratory-confirmed clinical cases and adverse effects following vaccination.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and analysed data using Review Manager software.
MAIN RESULTS: Three studies involving 110 healthy children who were siblings of household contacts were identified as suitable for inclusion. The studies varied in quality, study design, vaccine used, and outcomes measured and, as such, were not suitable for meta-analysis. Overall, 13 out of 56 vaccine recipients (18%) developed varicella compared with 42 out of 54 placebo (or no vaccine) recipients (78%). Of the vaccine recipients who developed varicella, the majority only had mild disease (with less than 50 skin lesions). In the three studies, most subjects received PEP within three days following exposure; too few subjects were vaccinated four to five days post exposure to ascertain the efficacy of vaccine given more than three days after exposure. No included studies reported on adverse events following immunisation.
AUTHORS' CONCLUSIONS: These small trials suggest varicella vaccine administered within three days to children following household contact with a varicella case reduces infection rates and severity of cases. No RCTs for adolescents or adults were identified. However safety was not adequately addressed.
Kristine Macartney, Peter McIntyre
Vaccines for post-exposure prophylaxis against varicella (chickenpox) in children and adults.
Cochrane Database Syst Rev. 2008 Jul 16;(3):CD001833. doi: 10.1002/14651858.CD001833.pub2. Epub 2008 Jul 16.
Abstract/Text
BACKGROUND: Live attenuated varicella vaccines for the prevention of varicella (chickenpox) has been demonstrated both in randomised controlled trials (RCTs) and in population-based immunisation programmes in countries such as the United States. However, many countries do not routinely immunise children against varicella, and exposures continue to occur. Although the disease is often mild, complications such as secondary bacterial infection, pneumonitis and encephalitis occur in about 1% of cases, usually leading to hospitalisation. The use of varicella vaccine in persons who have recently been exposed to the varicella zoster virus has been studied as a form of post-exposure prophylaxis (PEP).
OBJECTIVES: To assess the efficacy and safety of vaccines for use as PEP for the prevention of varicella in children and adults.
SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2008, Issue 1); MEDLINE (1966 to February 2008); and EMBASE (January 1990 to February 2008).
SELECTION CRITERIA: RCTs and quasi-RCTs of varicella vaccine for PEP compared with placebo or no intervention. The outcome measures were efficacy in prevention of clinical cases and/or laboratory-confirmed clinical cases and adverse effects following vaccination.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and analysed data using Review Manager software.
MAIN RESULTS: Three studies involving 110 healthy children who were siblings of household contacts were identified as suitable for inclusion. The studies varied in quality, study design, vaccine used, and outcomes measured and, as such, were not suitable for meta-analysis. Overall, 13 out of 56 vaccine recipients (18%) developed varicella compared with 42 out of 54 placebo (or no vaccine) recipients (78%). Of the vaccine recipients who developed varicella, the majority only had mild disease (with less than 50 skin lesions). In the three studies, most subjects received PEP within three days following exposure; too few subjects were vaccinated four to five days post exposure to ascertain the efficacy of vaccine given more than three days after exposure. No included studies reported on adverse events following immunisation.
AUTHORS' CONCLUSIONS: These small trials suggest varicella vaccine administered within three days to children following household contact with a varicella case reduces infection rates and severity of cases. No RCTs for adolescents or adults were identified. However safety was not adequately addressed.
Vittorio Demicheli, Alessandro Rivetti, Maria Grazia Debalini, Carlo Di Pietrantonj
Vaccines for measles, mumps and rubella in children.
Cochrane Database Syst Rev. 2012 Feb 15;2:CD004407. doi: 10.1002/14651858.CD004407.pub3. Epub 2012 Feb 15.
Abstract/Text
BACKGROUND: Mumps, measles and rubella (MMR) are serious diseases that can lead to potentially fatal illness, disability and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness.
OBJECTIVES: To assess the effectiveness and adverse effects associated with the MMR vaccine in children up to 15 years of age.
SEARCH METHODS: For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, PubMed (July 2004 to May week 2, 2011) and Embase.com (July 2004 to May 2011).
SELECTION CRITERIA: We used comparative prospective or retrospective trials assessing the effects of the MMR vaccine compared to placebo, do nothing or a combination of measles, mumps and rubella antigens on healthy individuals up to 15 years of age.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed methodological quality of the included studies. One review author arbitrated in case of disagreement.
MAIN RESULTS: We included five randomised controlled trials (RCTs), one controlled clinical trial (CCT), 27 cohort studies, 17 case-control studies, five time-series trials, one case cross-over trial, two ecological studies, six self controlled case series studies involving in all about 14,700,000 children and assessing effectiveness and safety of MMR vaccine. Based on the available evidence, one MMR vaccine dose is at least 95% effective in preventing clinical measles and 92% effective in preventing secondary cases among household contacts.Effectiveness of at least one dose of MMR in preventing clinical mumps in children is estimated to be between 69% and 81% for the vaccine prepared with Jeryl Lynn mumps strain and between 70% and 75% for the vaccine containing the Urabe strain. Vaccination with MMR containing the Urabe strain has demonstrated to be 73% effective in preventing secondary mumps cases. Effectiveness of Jeryl Lynn containing MMR in preventing laboratory-confirmed mumps cases in children and adolescents was estimated to be between 64% to 66% for one dose and 83% to 88% for two vaccine doses. We did not identify any studies assessing the effectiveness of MMR in preventing rubella.The highest risk of association with aseptic meningitis was observed within the third week after immunisation with Urabe-containing MMR (risk ratio (RR) 14.28; 95% confidence interval (CI) from 7.93 to 25.71) and within the third (RR 22.5; 95% CI 11.8 to 42.9) or fifth (RR 15.6; 95% CI 10.3 to 24.2) weeks after immunisation with the vaccine prepared with the Leningrad-Zagreb strain. A significant risk of association with febrile seizures and MMR exposure during the two previous weeks (RR 1.10; 95% CI 1.05 to 1.15) was assessed in one large person-time cohort study involving 537,171 children aged between three months and five year of age. Increased risk of febrile seizure has also been observed in children aged between 12 to 23 months (relative incidence (RI) 4.09; 95% CI 3.1 to 5.33) and children aged 12 to 35 months (RI 5.68; 95% CI 2.31 to 13.97) within six to 11 days after exposure to MMR vaccine. An increased risk of thrombocytopenic purpura within six weeks after MMR immunisation in children aged 12 to 23 months was assessed in one case-control study (RR 6.3; 95% CI 1.3 to 30.1) and in one small self controlled case series (incidence rate ratio (IRR) 5.38; 95% CI 2.72 to 10.62). Increased risk of thrombocytopenic purpura within six weeks after MMR exposure was also assessed in one other case-control study involving 2311 children and adolescents between one month and 18 years (odds ratio (OR) 2.4; 95% CI 1.2 to 4.7). Exposure to the MMR vaccine was unlikely to be associated with autism, asthma, leukaemia, hay fever, type 1 diabetes, gait disturbance, Crohn's disease, demyelinating diseases, bacterial or viral infections.
AUTHORS' CONCLUSIONS: The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate. The evidence of adverse events following immunisation with the MMR vaccine cannot be separated from its role in preventing the target diseases.
Vittorio Demicheli, Alessandro Rivetti, Maria Grazia Debalini, Carlo Di Pietrantonj
Vaccines for measles, mumps and rubella in children.
Cochrane Database Syst Rev. 2012 Feb 15;2:CD004407. doi: 10.1002/14651858.CD004407.pub3. Epub 2012 Feb 15.
Abstract/Text
BACKGROUND: Mumps, measles and rubella (MMR) are serious diseases that can lead to potentially fatal illness, disability and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness.
OBJECTIVES: To assess the effectiveness and adverse effects associated with the MMR vaccine in children up to 15 years of age.
SEARCH METHODS: For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, PubMed (July 2004 to May week 2, 2011) and Embase.com (July 2004 to May 2011).
SELECTION CRITERIA: We used comparative prospective or retrospective trials assessing the effects of the MMR vaccine compared to placebo, do nothing or a combination of measles, mumps and rubella antigens on healthy individuals up to 15 years of age.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed methodological quality of the included studies. One review author arbitrated in case of disagreement.
MAIN RESULTS: We included five randomised controlled trials (RCTs), one controlled clinical trial (CCT), 27 cohort studies, 17 case-control studies, five time-series trials, one case cross-over trial, two ecological studies, six self controlled case series studies involving in all about 14,700,000 children and assessing effectiveness and safety of MMR vaccine. Based on the available evidence, one MMR vaccine dose is at least 95% effective in preventing clinical measles and 92% effective in preventing secondary cases among household contacts.Effectiveness of at least one dose of MMR in preventing clinical mumps in children is estimated to be between 69% and 81% for the vaccine prepared with Jeryl Lynn mumps strain and between 70% and 75% for the vaccine containing the Urabe strain. Vaccination with MMR containing the Urabe strain has demonstrated to be 73% effective in preventing secondary mumps cases. Effectiveness of Jeryl Lynn containing MMR in preventing laboratory-confirmed mumps cases in children and adolescents was estimated to be between 64% to 66% for one dose and 83% to 88% for two vaccine doses. We did not identify any studies assessing the effectiveness of MMR in preventing rubella.The highest risk of association with aseptic meningitis was observed within the third week after immunisation with Urabe-containing MMR (risk ratio (RR) 14.28; 95% confidence interval (CI) from 7.93 to 25.71) and within the third (RR 22.5; 95% CI 11.8 to 42.9) or fifth (RR 15.6; 95% CI 10.3 to 24.2) weeks after immunisation with the vaccine prepared with the Leningrad-Zagreb strain. A significant risk of association with febrile seizures and MMR exposure during the two previous weeks (RR 1.10; 95% CI 1.05 to 1.15) was assessed in one large person-time cohort study involving 537,171 children aged between three months and five year of age. Increased risk of febrile seizure has also been observed in children aged between 12 to 23 months (relative incidence (RI) 4.09; 95% CI 3.1 to 5.33) and children aged 12 to 35 months (RI 5.68; 95% CI 2.31 to 13.97) within six to 11 days after exposure to MMR vaccine. An increased risk of thrombocytopenic purpura within six weeks after MMR immunisation in children aged 12 to 23 months was assessed in one case-control study (RR 6.3; 95% CI 1.3 to 30.1) and in one small self controlled case series (incidence rate ratio (IRR) 5.38; 95% CI 2.72 to 10.62). Increased risk of thrombocytopenic purpura within six weeks after MMR exposure was also assessed in one other case-control study involving 2311 children and adolescents between one month and 18 years (odds ratio (OR) 2.4; 95% CI 1.2 to 4.7). Exposure to the MMR vaccine was unlikely to be associated with autism, asthma, leukaemia, hay fever, type 1 diabetes, gait disturbance, Crohn's disease, demyelinating diseases, bacterial or viral infections.
AUTHORS' CONCLUSIONS: The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate. The evidence of adverse events following immunisation with the MMR vaccine cannot be separated from its role in preventing the target diseases.
H Campbell, N Andrews, K E Brown, E Miller
Review of the effect of measles vaccination on the epidemiology of SSPE.
Int J Epidemiol. 2007 Dec;36(6):1334-48. doi: 10.1093/ije/dym207. Epub 2007 Nov 23.
Abstract/Text
BACKGROUND: When measles vaccines were widely introduced in the 1970s, there were concerns that they might cause subacute sclerosing panencephalitis (SSPE): a very rare, late-onset, neurological complication of natural measles infection. Therefore, SSPE registries and routine measles immunization were established in many countries concurrently. We conducted a comprehensive review of the impact of measles immunization on the epidemiology of SSPE and examined epidemiological evidence on whether there was any vaccine-associated risk.
METHODS: Published epidemiological data on SSPE, national SSPE incidence, measles incidence and vaccine coverage, reports of SSPE in pregnancy or shortly post partum were reviewed. Potential adverse relationships between measles vaccines and SSPE were examined using available data.
RESULTS: Epidemiological data showed that successful measles immunization programmes protect against SSPE and, consistent with virological data, that measles vaccine virus does not cause SSPE. Measles vaccine does not: accelerate the course of SSPE; trigger SSPE or cause SSPE in those with an established benign persistent wild measles infection. Evidence points to wild virus causing SSPE in cases which have been immunized and have had no known natural measles infection. Perinatal measles infection may result in SSPE with a short onset latency and fulminant course. Such cases are very rare. SSPE during pregnancy appears to be fulminant. Infants born to mothers with SSPE have not been subsequently diagnosed with SSPE themselves.
CONCLUSIONS: Successful measles vaccination programmes directly and indirectly protect the population against SSPE and have the potential to eliminate SSPE through the elimination of measles. Epidemiological and virological data suggest that measles vaccine does not cause SSPE.
H Campbell, N Andrews, K E Brown, E Miller
Review of the effect of measles vaccination on the epidemiology of SSPE.
Int J Epidemiol. 2007 Dec;36(6):1334-48. doi: 10.1093/ije/dym207. Epub 2007 Nov 23.
Abstract/Text
BACKGROUND: When measles vaccines were widely introduced in the 1970s, there were concerns that they might cause subacute sclerosing panencephalitis (SSPE): a very rare, late-onset, neurological complication of natural measles infection. Therefore, SSPE registries and routine measles immunization were established in many countries concurrently. We conducted a comprehensive review of the impact of measles immunization on the epidemiology of SSPE and examined epidemiological evidence on whether there was any vaccine-associated risk.
METHODS: Published epidemiological data on SSPE, national SSPE incidence, measles incidence and vaccine coverage, reports of SSPE in pregnancy or shortly post partum were reviewed. Potential adverse relationships between measles vaccines and SSPE were examined using available data.
RESULTS: Epidemiological data showed that successful measles immunization programmes protect against SSPE and, consistent with virological data, that measles vaccine virus does not cause SSPE. Measles vaccine does not: accelerate the course of SSPE; trigger SSPE or cause SSPE in those with an established benign persistent wild measles infection. Evidence points to wild virus causing SSPE in cases which have been immunized and have had no known natural measles infection. Perinatal measles infection may result in SSPE with a short onset latency and fulminant course. Such cases are very rare. SSPE during pregnancy appears to be fulminant. Infants born to mothers with SSPE have not been subsequently diagnosed with SSPE themselves.
CONCLUSIONS: Successful measles vaccination programmes directly and indirectly protect the population against SSPE and have the potential to eliminate SSPE through the elimination of measles. Epidemiological and virological data suggest that measles vaccine does not cause SSPE.
American Academy of Pediatrics. Rubella. In: Red Book: 2018 Report of the Committee on Infectious Diseases, 31st ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Itasca, IL 2018. p.705.
American Academy of Pediatrics. Rubella. In: Red Book: 2018 Report of the Committee on Infectious Diseases, 31st ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Itasca, IL 2018. p.705.
Norma Mongua-Rodriguez, José Luis Díaz-Ortega, Lourdes García-García, Maricela Piña-Pozas, Elizabeth Ferreira-Guerrero, Guadalupe Delgado-Sánchez, Leticia Ferreyra-Reyes, Luis Pablo Cruz-Hervert, Renata Baez-Saldaña, Rogelio Campos-Montero
A systematic review of rubella vaccination strategies implemented in the Americas: impact on the incidence and seroprevalence rates of rubella and congenital rubella syndrome.
Vaccine. 2013 Apr 19;31(17):2145-51. doi: 10.1016/j.vaccine.2013.02.047. Epub 2013 Mar 5.
Abstract/Text
OBJECTIVE: To evaluate the impact of rubella vaccination strategies on the rates of acquired rubella and congenital rubella syndrome in the Americas.
METHODS: We conducted a systematic review of the literature (MEDLINE, PubMed, EMBASE, Cochrane Library, Artemisa Database, LILACS Database, Evidence Portal, VHL-PAHO Portal, Scielo, and Grey-Literature sources) that was published from 1969-2010. We included studies on rubella incidence and seroprevalence rates that were associated with rubella vaccination. The quality of the studies was evaluated according to international guidelines.
RESULTS: A total of 14 studies were identified: 2 clinical trials, 2 cohort studies, 3 transversal studies, 5 ecological studies, and 2 mathematical models. Childhood vaccination reduced the incidence of rubella by 23.6% to 99.6%, increased the occurrence of epidemic cycles in Argentina and in the United States, and shifted the illness to susceptible adults. Vaccination strategies that focused on women and children in Brazil were associated with a 5.5-fold greater incidence of rubella in men leading to new outbreaks and CRS. A combined vaccination strategy with a universal approach that included routine vaccination for boys, girls, women, and men in Mexico and in Costa Rica reduced the incidence of rubella by more than 98% and led to absence of CRS since 2008. A medium and a low risk of bias were found in 3 and 4 articles, respectively.
CONCLUSION: The results of this review demonstrate that the combined vaccination strategy with a universal approach was the most effective strategy as evidenced by a drastic reduction in the number of cases and the interruption of endemic transmission of rubella in the Americas.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Norma Mongua-Rodriguez, José Luis Díaz-Ortega, Lourdes García-García, Maricela Piña-Pozas, Elizabeth Ferreira-Guerrero, Guadalupe Delgado-Sánchez, Leticia Ferreyra-Reyes, Luis Pablo Cruz-Hervert, Renata Baez-Saldaña, Rogelio Campos-Montero
A systematic review of rubella vaccination strategies implemented in the Americas: impact on the incidence and seroprevalence rates of rubella and congenital rubella syndrome.
Vaccine. 2013 Apr 19;31(17):2145-51. doi: 10.1016/j.vaccine.2013.02.047. Epub 2013 Mar 5.
Abstract/Text
OBJECTIVE: To evaluate the impact of rubella vaccination strategies on the rates of acquired rubella and congenital rubella syndrome in the Americas.
METHODS: We conducted a systematic review of the literature (MEDLINE, PubMed, EMBASE, Cochrane Library, Artemisa Database, LILACS Database, Evidence Portal, VHL-PAHO Portal, Scielo, and Grey-Literature sources) that was published from 1969-2010. We included studies on rubella incidence and seroprevalence rates that were associated with rubella vaccination. The quality of the studies was evaluated according to international guidelines.
RESULTS: A total of 14 studies were identified: 2 clinical trials, 2 cohort studies, 3 transversal studies, 5 ecological studies, and 2 mathematical models. Childhood vaccination reduced the incidence of rubella by 23.6% to 99.6%, increased the occurrence of epidemic cycles in Argentina and in the United States, and shifted the illness to susceptible adults. Vaccination strategies that focused on women and children in Brazil were associated with a 5.5-fold greater incidence of rubella in men leading to new outbreaks and CRS. A combined vaccination strategy with a universal approach that included routine vaccination for boys, girls, women, and men in Mexico and in Costa Rica reduced the incidence of rubella by more than 98% and led to absence of CRS since 2008. A medium and a low risk of bias were found in 3 and 4 articles, respectively.
CONCLUSION: The results of this review demonstrate that the combined vaccination strategy with a universal approach was the most effective strategy as evidenced by a drastic reduction in the number of cases and the interruption of endemic transmission of rubella in the Americas.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Hiromi Hashimoto, Masashi Fujioka, Hiroshi Kinumaki, Kinki Ambulatory Pediatrics Study Group
An office-based prospective study of deafness in mumps.
Pediatr Infect Dis J. 2009 Mar;28(3):173-5. doi: 10.1097/INF.0b013e31818a8ca8.
Abstract/Text
BACKGROUND: Deafness is a rare but important complication of mumps virus infection. Its incidence has been estimated at 0.5 to 5.0 per 100,000 cases of mumps, but recent reports from Japan, where mumps is endemic, suggest that the incidence might be higher.
OBJECTIVE: Prospective office-based study to determine the incidence of hearing loss in children with mumps.
METHODS: Forty pediatric practices participated in this survey. The study population consisted of patients < or =20 years old with mumps seen between January 2004 and December 2006. Clinical diagnosis of mumps was made by experienced pediatricians. Among those from whom written consent was obtained, parents were asked to conduct hearing screening tests by rubbing fingers near the ears twice daily for 2 weeks. Patients suspected with hearing loss were further examined by an otolaryngologist.
RESULTS: Among 7400 children who underwent hearing ability assessment after clinical onset of mumps, 7 had confirmed hearing loss; none had been previously vaccinated against mumps. In all cases, hearing loss was unilateral but severe and did not improve over time.
CONCLUSIONS: The incidence of hearing loss in children due to mumps was 7/7400 (approximately 1/1000 cases), which is higher than previously suggested. Prevention of deafness is another important reason for assuring universal immunization against mumps.
Hiromi Hashimoto, Masashi Fujioka, Hiroshi Kinumaki, Kinki Ambulatory Pediatrics Study Group
An office-based prospective study of deafness in mumps.
Pediatr Infect Dis J. 2009 Mar;28(3):173-5. doi: 10.1097/INF.0b013e31818a8ca8.
Abstract/Text
BACKGROUND: Deafness is a rare but important complication of mumps virus infection. Its incidence has been estimated at 0.5 to 5.0 per 100,000 cases of mumps, but recent reports from Japan, where mumps is endemic, suggest that the incidence might be higher.
OBJECTIVE: Prospective office-based study to determine the incidence of hearing loss in children with mumps.
METHODS: Forty pediatric practices participated in this survey. The study population consisted of patients < or =20 years old with mumps seen between January 2004 and December 2006. Clinical diagnosis of mumps was made by experienced pediatricians. Among those from whom written consent was obtained, parents were asked to conduct hearing screening tests by rubbing fingers near the ears twice daily for 2 weeks. Patients suspected with hearing loss were further examined by an otolaryngologist.
RESULTS: Among 7400 children who underwent hearing ability assessment after clinical onset of mumps, 7 had confirmed hearing loss; none had been previously vaccinated against mumps. In all cases, hearing loss was unilateral but severe and did not improve over time.
CONCLUSIONS: The incidence of hearing loss in children due to mumps was 7/7400 (approximately 1/1000 cases), which is higher than previously suggested. Prevention of deafness is another important reason for assuring universal immunization against mumps.
Yoko Inou, Tetsuo Nakayama, Naoko Yoshida, Hajime Uejima, Kenji Yuri, Makoto Kamada, Takuji Kumagai, Hiroshi Sakiyama, Akiko Miyata, Hitoshi Ochiai, Toshiaki Ihara, Teruo Okafuji, Takao Okafuji, Takao Nagai, Eitaro Suzuki, Kunihisa Shimomura, Yuhei Ito, Chiaki Miyazaki
Molecular epidemiology of mumps virus in Japan and proposal of two new genotypes.
J Med Virol. 2004 May;73(1):97-104. doi: 10.1002/jmv.20065.
Abstract/Text
We isolated 872 strains of mumps virus from naso-pharyngeal secretions in seven different districts of Japan from January 2000 to July 2001. Among them, 57 strains were geno-typed by nucleotide sequencing in part of the hemagglutinin-neuraminidase (HN) and small hydrophobic (SH) protein regions. Four different genotypes (B, G, K, and L) of mumps virus were co-circulating in Japan and the distribution of genotypes varied in geographically different districts. Two new clusters designated as genotypes K and L had more than 7% nucleotide variation in the SH gene. Among the 57 strains, 11 were classified as B, 35 as G, three as K, and eight as L, which was mainly isolated in Tokyo. We also examined 104 stains isolated in a clinic in Mie prefecture from 1993 to 2003. Genotype B was the indigenous strain and genotype K was introduced in 1994. Genotypes B and K co-circulated in the 1990s and were replaced by genotype G in 2000. There was no significant change in neutralizing test antibody titers against genotypes B, G, K, and L using seven post-vaccination sera with Hoshino strain (genotype B) and these four genotypes had a different antigenicity from genotype A. We should continue to watch on mumps virus molecular epidemiology.
Copyright 2004 Wiley-Liss, Inc.
Yoko Inou, Tetsuo Nakayama, Naoko Yoshida, Hajime Uejima, Kenji Yuri, Makoto Kamada, Takuji Kumagai, Hiroshi Sakiyama, Akiko Miyata, Hitoshi Ochiai, Toshiaki Ihara, Teruo Okafuji, Takao Okafuji, Takao Nagai, Eitaro Suzuki, Kunihisa Shimomura, Yuhei Ito, Chiaki Miyazaki
Molecular epidemiology of mumps virus in Japan and proposal of two new genotypes.
J Med Virol. 2004 May;73(1):97-104. doi: 10.1002/jmv.20065.
Abstract/Text
We isolated 872 strains of mumps virus from naso-pharyngeal secretions in seven different districts of Japan from January 2000 to July 2001. Among them, 57 strains were geno-typed by nucleotide sequencing in part of the hemagglutinin-neuraminidase (HN) and small hydrophobic (SH) protein regions. Four different genotypes (B, G, K, and L) of mumps virus were co-circulating in Japan and the distribution of genotypes varied in geographically different districts. Two new clusters designated as genotypes K and L had more than 7% nucleotide variation in the SH gene. Among the 57 strains, 11 were classified as B, 35 as G, three as K, and eight as L, which was mainly isolated in Tokyo. We also examined 104 stains isolated in a clinic in Mie prefecture from 1993 to 2003. Genotype B was the indigenous strain and genotype K was introduced in 1994. Genotypes B and K co-circulated in the 1990s and were replaced by genotype G in 2000. There was no significant change in neutralizing test antibody titers against genotypes B, G, K, and L using seven post-vaccination sera with Hoshino strain (genotype B) and these four genotypes had a different antigenicity from genotype A. We should continue to watch on mumps virus molecular epidemiology.
Copyright 2004 Wiley-Liss, Inc.
S Makino, K Sasaki, T Nakayama, S Oka, T Urano, M Kimura, R Kawana, A M Yamamura
A new combined trivalent live measles (AIK-C strain), mumps (Hoshino strain), and rubella (Takahashi strain) vaccine. Findings in clinical and laboratory studies.
Am J Dis Child. 1990 Aug;144(8):905-10.
Abstract/Text
Trivalent virus vaccine, containing measles AIK-C strain, mumps Hoshino strain, and rubella Takahashi strain, was administered to a total of 1369 healthy children, 8 months to 18 years of age. For comparative study, monovalent vaccines of AIK-C strain and Hoshino strain were administered to 147 and 122 initially seronegative children, respectively. The clinical and serological responses following vaccination were analyzed. Among the recipients of the trivalent vaccine, 893 were initially seronegative to all three viruses. Inoculation induced sufficient serological responses: 99.7% for measles and rubella viruses and 96.3% for mumps virus. The incidence of febrile reaction (greater than or equal to 37.5 degrees C axillary temperature) was low, 15.9%, and a temperature of 39.0 degrees C or higher occurred in only 1.3% of the subjects. The seroconversion rate, magnitude of antibody titers, and incidence of clinical reactions following the trivalent vaccination were similar to those occurring after the monovalent measles vaccination.
S Makino, K Sasaki, T Nakayama, S Oka, T Urano, M Kimura, R Kawana, A M Yamamura
A new combined trivalent live measles (AIK-C strain), mumps (Hoshino strain), and rubella (Takahashi strain) vaccine. Findings in clinical and laboratory studies.
Am J Dis Child. 1990 Aug;144(8):905-10.
Abstract/Text
Trivalent virus vaccine, containing measles AIK-C strain, mumps Hoshino strain, and rubella Takahashi strain, was administered to a total of 1369 healthy children, 8 months to 18 years of age. For comparative study, monovalent vaccines of AIK-C strain and Hoshino strain were administered to 147 and 122 initially seronegative children, respectively. The clinical and serological responses following vaccination were analyzed. Among the recipients of the trivalent vaccine, 893 were initially seronegative to all three viruses. Inoculation induced sufficient serological responses: 99.7% for measles and rubella viruses and 96.3% for mumps virus. The incidence of febrile reaction (greater than or equal to 37.5 degrees C axillary temperature) was low, 15.9%, and a temperature of 39.0 degrees C or higher occurred in only 1.3% of the subjects. The seroconversion rate, magnitude of antibody titers, and incidence of clinical reactions following the trivalent vaccination were similar to those occurring after the monovalent measles vaccination.
Mona Marin, Mariel Marlow, Kelly L Moore, Manisha Patel
Recommendation of the Advisory Committee on Immunization Practices for Use of a Third Dose of Mumps Virus-Containing Vaccine in Persons at Increased Risk for Mumps During an Outbreak.
MMWR Morb Mortal Wkly Rep. 2018 Jan 12;67(1):33-38. doi: 10.15585/mmwr.mm6701a7. Epub 2018 Jan 12.
Abstract/Text
A substantial increase in the number of mumps outbreaks and outbreak-associated cases has occurred in the United States since late 2015 (1,2). To address this public health problem, the Advisory Committee on Immunization Practices (ACIP) reviewed the available evidence and determined that a third dose of measles, mumps, rubella (MMR) vaccine is safe and effective at preventing mumps. During its October 2017 meeting, ACIP recommended a third dose of a mumps virus-containing vaccine* for persons previously vaccinated with 2 doses who are identified by public health authorities as being part of a group or population at increased risk for acquiring mumps because of an outbreak. The purpose of the recommendation is to improve protection of persons in outbreak settings against mumps disease and mumps-related complications. This recommendation supplements the existing ACIP recommendations for mumps vaccination (3).
Mona Marin, Mariel Marlow, Kelly L Moore, Manisha Patel
Recommendation of the Advisory Committee on Immunization Practices for Use of a Third Dose of Mumps Virus-Containing Vaccine in Persons at Increased Risk for Mumps During an Outbreak.
MMWR Morb Mortal Wkly Rep. 2018 Jan 12;67(1):33-38. doi: 10.15585/mmwr.mm6701a7. Epub 2018 Jan 12.
Abstract/Text
A substantial increase in the number of mumps outbreaks and outbreak-associated cases has occurred in the United States since late 2015 (1,2). To address this public health problem, the Advisory Committee on Immunization Practices (ACIP) reviewed the available evidence and determined that a third dose of measles, mumps, rubella (MMR) vaccine is safe and effective at preventing mumps. During its October 2017 meeting, ACIP recommended a third dose of a mumps virus-containing vaccine* for persons previously vaccinated with 2 doses who are identified by public health authorities as being part of a group or population at increased risk for acquiring mumps because of an outbreak. The purpose of the recommendation is to improve protection of persons in outbreak settings against mumps disease and mumps-related complications. This recommendation supplements the existing ACIP recommendations for mumps vaccination (3).
B Fritzell, S Plotkin
Efficacy and safety of a Haemophilus influenzae type b capsular polysaccharide-tetanus protein conjugate vaccine.
J Pediatr. 1992 Sep;121(3):355-62. doi: 10.1016/s0022-3476(05)81786-x.
Abstract/Text
A polyribosylribitol phosphate (polysaccharide)-tetanus protein conjugate vaccine (PRP-T) against Haemophilus influenzae type b (Hib) was evaluated for safety and efficacy after vaccination of more than 100,000 infants. No major side effects were attributed to the vaccine. Immunogenicity studies showed an antibody response in 70% to 100% of infants after two doses, and in 98% to 100% of infants after three doses, within the first 6 months of life. Antibodies persisted in 90% of recipients, in whom significant anamnestic responses developed after a booster dose at 18 months of age. In comparison with other available Hib vaccines, PRP-T induces equal or higher mean titers after three doses. Although licensure of other vaccines interrupted controlled efficacy trials, up to that point five cases of Hib disease in those trials had occurred in placebo recipients, and no Hib disease has been reported in the more than 100,000 vaccinated infants who have received more than one dose of PRP-T. Thus PRP-T combined immunogenicity early in life with induction of immunologic memory.
S B Black, H R Shinefield, B Fireman, R Hiatt, M Polen, E Vittinghoff
Efficacy in infancy of oligosaccharide conjugate Haemophilus influenzae type b (HbOC) vaccine in a United States population of 61,080 children. The Northern California Kaiser Permanente Vaccine Study Center Pediatrics Group.
Pediatr Infect Dis J. 1991 Feb;10(2):97-104. doi: 10.1097/00006454-199102000-00004.
Abstract/Text
The efficacy of the HbOC conjugate Haemophilus influenzae type b vaccine was evaluated in a study population of 61,080 infants in the Northern California Kaiser Permanente Medical Care Program. Between February, 1988, and June, 1990, the HbOC vaccine was given as part of a three-dose series at 2, 4, and 6 months of age to 20,800 infants. The study population included children with a well-care visit at a study center during the first 6 months of life. There were 25 cases of Haemophilus influenzae type b disease in the study population: 22 in unvaccinated children and 3 in children who received only one dose of HbOC vaccine. The efficacy of the full three-dose series was evaluated by several methods: a primary analysis comparing fully vaccinated children with unvaccinated children from 7 to 18 months of age; a stratified exact analysis adjusted for age and seasonality; and a case-control analysis which further adjusted for known risk factors. The efficacy of three doses of vaccine was 100% with the lower bound of the 95% confidence interval for the three analyses at 68, 71, and 64%, respectively. There were no cases of disease resulting from two doses of HbOC vaccine yielding an estimate of 100% efficacy (95% confidence interval, 47 to 100) for two doses of HbOC vaccine. However, for children who had received only one dose of HbOC vaccine, vaccine efficacy was estimated to be 26% and the possibility that one dose of HbOC vaccine had no efficacy could not be excluded.(ABSTRACT TRUNCATED AT 250 WORDS)
C O Obonyo, J Lau
Efficacy of Haemophilus influenzae type b vaccination of children: a meta-analysis.
Eur J Clin Microbiol Infect Dis. 2006 Feb;25(2):90-7. doi: 10.1007/s10096-006-0092-4.
Abstract/Text
Haemophilus influenzae type b (Hib) infection is a leading cause of meningitis and pneumonia in infants and children in developing countries, and yet the implementation of routine Hib vaccination is very slow. The aim of the present study was to quantify the protective efficacy of H. influenzae type b vaccination of young children. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials Register were searched. References of selected articles were also reviewed and experts contacted. Eight randomized trials were found that compared the efficacy of H. influenzae type b conjugate vaccine to placebo or no vaccine. Information on study design, patients enrolled, age, vaccine type, cases of invasive H. influenzae type b disease, adverse events, and items to assess potential for bias was recorded. The incidence of invasive H. influenzae type b infection formed the primary outcome. The odds ratio (OR) of developing Hib infection was combined using a random effects model to provide a measure of vaccine efficacy. The protective effect, defined as the relative risk reduction, was estimated as (1-OR). From eight trials, the protective efficacy of the Hib conjugate vaccine was 84% (OR 0.16; 95%CI 0.08-0.30) against invasive Hib disease, 75% (OR 0.25; 95%CI 0.08-0.84) against meningitis, and 69% (OR 0.31; 95%CI 0.10-0.97) against pneumonia. Serious adverse events were rare. The results provide firm evidence that Hib conjugate vaccines are safe and effective in reducing the risk of all forms of invasive Hib disease, further establishing that vaccination of children in developing countries can protect them from a potentially fatal yet preventable disease.
George H Swingler, Desiree Michaels, Gregory Gd Hussey
WITHDRAWN: Conjugate vaccines for preventing Haemophilus influenzae type B infections.
Cochrane Database Syst Rev. 2009 Oct 7;(4):CD001729. doi: 10.1002/14651858.CD001729.pub3. Epub 2009 Oct 7.
Abstract/Text
BACKGROUND: Haemophilus influenzae (H. influenzae) is an important cause of meningitis and pneumonia in children. Vaccine cost is a significant barrier to use in low income countries. Determining the size of the effects of the vaccine will enable cost-effectiveness comparisons with competing priorities in low income countries.
OBJECTIVES: 1. To determine the effects of conjugate Hib vaccine in preventing Hib disease or death in children under five years of age. 2. To determine any variation in effect with type of vaccine, number of doses, age at first dose, in children with known HIV infection, or in high and low income countries. 3. To determine any serious adverse outcomes.
SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2006, issue 4) which contains the Acute Respiratory Infections Group's specialized register; MEDLINE (January 1966 to December 2006); EMBASE (1990 to June 2006) and scanned reference lists and contacting of authors of trial reports.
SELECTION CRITERIA: All randomised controlled trials (RCTs) or quasi-RCTs of conjugate H. influenzae type b vaccines compared with placebo or no treatment in children who were followed until at least two years of age.
DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible studies and extracted data.
MAIN RESULTS: Six studies were included in the review, and four in the meta-analyses. The overall quality of the trials was good. The relative risk for invasive Hib disease was 0.20 (95% confidence interval (CI) 0.07 to 0.54; random-effects model), but there was statistically significant unexplained variation (heterogeneity) in the effects of the four trials in the meta-analysis (P = 0.002). The size of the effects did not appear to differ consistently with different vaccine types, the number of vaccine doses, age at first vaccination or use in high income versus low income countries, but the CIs for the effect estimates were wide. Hib-related mortality data showed a non-significant trend towards benefit (relative risk was 0.29; 95% CI 0.07 to 1.20; random-effects model). The relative risk for all cause mortality in the two trials from which data were available were 1.01 (95% CI 0.38 to 2.67, random-effects model) and 0.97. No serious adverse effects were reported in any of the trials.
AUTHORS' CONCLUSIONS: Hib vaccine is safe and effective. In resource-poor settings, decisions to use the vaccine will depend on its cost, the local burden of Hib disease and competing priorities.
Rosalyn E O'Loughlin, Karen Edmond, Punam Mangtani, Adam L Cohen, Sharmila Shetty, Rana Hajjeh, Kim Mulholland
Methodology and measurement of the effectiveness of Haemophilus influenzae type b vaccine: systematic review.
Vaccine. 2010 Aug 31;28(38):6128-36. doi: 10.1016/j.vaccine.2010.06.107. Epub 2010 Jul 23.
Abstract/Text
The use of the highly effective Haemophilus influenzae type b (Hib) conjugate vaccine has increased globally. We review the benefits and limitations of studies measuring Hib vaccine effectiveness (VE). We critically examine the case-control approach by assessing the similarities and differences in methodology and findings and discuss the need for future Hib VE studies. In the absence of good surveillance data, vaccine effectiveness studies can play an important role, particularly with the increasing use of pneumococcal vaccine that has not been well tested under field conditions in less developed countries. However, the effectiveness of Hib vaccine has been well documented so the need for future VE Hib studies is minimal.
(c) 2010 Elsevier Ltd. All rights reserved.
子どもの予防接種: 日本小児科学会予防接種・感染対策委員会編, 診断と治療社. 東京, 2020.
Kristina A Bryant, Stan L Block, Sherryl A Baker, William C Gruber, Daniel A Scott, PCV13 Infant Study Group
Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine.
Pediatrics. 2010 May;125(5):866-75. doi: 10.1542/peds.2009-1405.
Abstract/Text
OBJECTIVE: Invasive pneumococcal disease rates have declined since immunization with 7-valent pneumococcal conjugate vaccine (PCV7) (Prevenar/Prevnar [Wyeth Pharmaceuticals, Philadelphia, PA]) became routine. Certain nonvaccine Streptococcus pneumoniae serotypes (1, 3, 5, 6A, 7F, and 19A) still cause significant morbidity and mortality. The safety and immunogenicity of PCV7 were compared with those of 13-valent PCV (PCV13), which contains saccharides from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F conjugated to CRM(197).
PATIENTS AND METHODS: Infants were randomly assigned to receive PCV13 or PCV7 at ages 2, 4, and 6 months with other vaccines. Post-third-dose antibodies to each pneumococcal polysaccharide were measured by immunoglobulin G enzyme-linked immunosorbent assay. Antibacterial functional antibodies were measured by opsonophagocytic assay (OPA).
RESULTS: Subjects received PCV13 (n = 122) or PCV7 (n = 127). All PCV13 serotypes were immunogenic, with 88% to 98% of infants achieving antibody concentrations of > or =0.35 microg/mL to shared PCV7 serotypes. For the 6 additional serotypes, 97% to 100% of PCV13-vaccinated infants achieved antibody concentrations of > or =0.35 microg/mL. Geometric mean antibody concentration for PCV13 recipients ranged from 1.32 microg/mL (serotype 23F) to 4.26 microg/mL (serotype 14). The ratio of OPA geometric mean titers for the 7 shared serotypes (PCV13:PCV7) ranged from 0.6 to 1.4, suggesting no clinically meaningful differences. For PCV13-only serotypes, OPA geometric mean titers were significantly higher in the PCV13 group than in the PCV7 group. Local reactions and systemic events were similar between groups.
CONCLUSIONS: PCV13 was well tolerated and immunogenic, with most infants developing antipolysaccharide antibody concentrations of > or =0.35 microg/mL, as well as OPA responses, to each of the 13 serotypes.
Marilla G Lucero, Vernoni E Dulalia, Leilani T Nillos, Gail Williams, Rhea Angela N Parreño, Hanna Nohynek, Ian D Riley, Helena Makela
Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal disease and X-ray defined pneumonia in children less than two years of age.
Cochrane Database Syst Rev. 2009 Oct 7;(4):CD004977. doi: 10.1002/14651858.CD004977.pub2. Epub 2009 Oct 7.
Abstract/Text
BACKGROUND: Pneumonia, caused by Streptococcus pneumoniae, is a major cause of morbidity and mortality among children in low-income countries. The effectiveness of pneumococcal conjugate vaccines (PCVs) against invasive pneumococcal disease (IPD), pneumonia, and mortality needs to be evaluated.
OBJECTIVES: To update the 2004 review on the efficacy of PCVs in preventing vaccine-serotypes IPD (VT-IPD) , X-ray defined pneumonia among HIV-1 negative children, and other new outcomes.
SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 1), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (1990 to Week 4 February 2009); and EMBASE (1974 to March 2009).
SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing PCV with placebo, or another vaccine, in children under two with IPD and clinical / radiographic pneumonia as outcomes.
DATA COLLECTION AND ANALYSIS: Two review authors independently identified studies, extracted data, and evaluated their corresponding risks of bias. Differences were resolved by discussion. Meta-analysis used the inverse variance method.
MAIN RESULTS: We identified 11 publications from six RCTs conducted in Africa, US, Philippines and Finland where 57,015 children received PCV; while 56,029 received placebo or another vaccine. Seven publications provided high quality evidence on PCV efficacy against IPD and four provided moderate quality evidence against pneumonia. None of the five trials with all-cause mortality data were powered to investigate this outcome. Only two trials have data on all-cause admissions.The main analysis for this review involved HIV-1 negative children and used the pooled results of random-effects model, intent-to-treat analysis (ITT).Pooled vaccine efficacy (VE) for VT-IPD was 80% (95% confidence interval (CI) 58% to 90%, P < 0.0001); all serotypes-IPD, 58% (95% CI 29% to 75%, P = 0.001); World Health Organization X-ray defined pneumonia was 27% (95% CI 15% to 36%, P < 0.0001); clinical pneumonia, 6% (95% CI 2% to 9%, P = 0.0006); and all-cause mortality, 11% (95% CI -1% to 21%, P = 0.08). Analysis involving HIV-1 positive children had similar findings.
AUTHORS' CONCLUSIONS: PCV is effective in preventing IPD, X-ray defined pneumonia, and clinical pneumonia among HIV-1 negative and HIV-1 positive children under two years. The impact was greater for VT-IPD than for all serotypes-IPD, and for X-ray defined pneumonia than for clinical pneumonia. An 11% reduction with a 95% CI of -1% to 21% and a P = 0.08 is compatible with reduction in all-cause mortality.
Alexandre C Fortanier, Roderick P Venekamp, Chantal W B Boonacker, Eelko Hak, Anne G M Schilder, Elisabeth A M Sanders, Roger A M J Damoiseaux
Pneumococcal conjugate vaccines for preventing otitis media.
Cochrane Database Syst Rev. 2014 Apr 2;(4):CD001480. doi: 10.1002/14651858.CD001480.pub4. Epub 2014 Apr 2.
Abstract/Text
BACKGROUND: Acute otitis media (AOM) is a very common respiratory infection in early infancy and childhood. The marginal benefits of antibiotics for AOM in low-risk populations in general, the increasing problem of bacterial resistance to antibiotics and the huge estimated direct and indirect annual costs associated with otitis media (OM) have prompted a search for effective vaccines to prevent AOM.
OBJECTIVES: To assess the effect of pneumococcal conjugate vaccines (PCVs) in preventing AOM in children up to 12 years of age.
SEARCH METHODS: We searched CENTRAL (2013, Issue 11), MEDLINE (1995 to November week 3, 2013), EMBASE (1995 to December 2013), CINAHL (2007 to December 2013), LILACS (2007 to December 2013) and Web of Science (2007 to December 2013).
SELECTION CRITERIA: Randomised controlled trials (RCTs) of PCVs to prevent AOM in children aged 12 years or younger, with a follow-up of at least six months after vaccination.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data.
MAIN RESULTS: We included 11 publications of nine RCTs (n = 48,426 children, range 74 to 37,868 per study) of 7- to 11-valent PCV (with different carrier proteins). Five trials (n = 47,108) included infants, while four trials (n = 1318) included children aged one to seven years that were either healthy (one study, n = 264) or had a previous history of upper respiratory tract infection (URTI), including AOM. We judged the methodological quality of the included studies to be moderate to high. There was considerable clinical diversity between studies in terms of study population, type of conjugate vaccine and outcome measures. We therefore refrained from pooling the results.In three studies, the 7-valent PCV with CRM197 as carrier protein (CRM197-PCV7) administered during early infancy was associated with a relative risk reduction (RRR) of all-cause AOM ranging from -5% in high-risk children (95% confidence interval (CI) -25% to 12%) to 7% in low-risk children (95% CI 4% to 9%). Another 7-valent PCV with the outer membrane protein complex of Neisseria meningitidis (N. meningitidis) serogroup B as carrier protein, administered in infancy, did not reduce overall AOM episodes, while a precursor 11-valent PCV with Haemophilus influenzae (H. influenzae) protein D as carrier protein was associated with a RRR of all-cause AOM episodes of 34% (95% CI 21% to 44%).A 9-valent PCV (with CRM197 carrier protein) administered in healthy toddlers was associated with a RRR of (parent-reported) OM episodes of 17% (95% CI -2% to 33%). CRM197-PCV7 followed by 23-valent pneumococcal polysaccharide vaccination administered after infancy in older children with a history of AOM showed no beneficial effect on first occurrence and later AOM episodes. In a study in older children with a previously diagnosed respiratory tract infection, performed during the influenza season, a trivalent influenza vaccine combined with placebo (TIV/placebo) led to fewer all-cause AOM episodes than vaccination with TIV and PCV7 (TIV/PCV7) when compared to hepatitis B vaccination and placebo (HBV/placebo) (RRR 71%, 95% CI 30% to 88% versus RRR 57%, 95% CI 6% to 80%, respectively) indicating that CRM197-PCV7 after infancy may even have negative effects on AOM.
AUTHORS' CONCLUSIONS: Based on current evidence of the effects of PCVs for preventing AOM, the licensed 7-valent CRM197-PCV7 has modest beneficial effects in healthy infants with a low baseline risk of AOM. Administering PCV7 in high-risk infants, after early infancy and in older children with a history of AOM, appears to have no benefit in preventing further episodes. Currently, several RCTs with different (newly licensed, multivalent) PCVs administered during early infancy are ongoing to establish their effects on AOM. Results of these studies may provide a better understanding of the role of the newly licensed, multivalent PCVs in preventing AOM. Also the impact on AOM of the carrier protein D, as used in certain pneumococcal vaccines, needs to be further established.
Allison Thompson, Alejandra Gurtman, Scott Patterson, Christine Juergens, France Laudat, Emilio A Emini, William C Gruber, Daniel A Scott
Safety of 13-valent pneumococcal conjugate vaccine in infants and children: meta-analysis of 13 clinical trials in 9 countries.
Vaccine. 2013 Oct 25;31(45):5289-95. doi: 10.1016/j.vaccine.2013.08.025. Epub 2013 Aug 20.
Abstract/Text
BACKGROUND: Meta-analyses enable summarization and interpretation of data across clinical trials. When applied to safety data they allow for detection of rare events. Recently, a 13-valent pneumococcal conjugate vaccine (PCV13) was approved in multiple countries worldwide for routine immunization of infants and young children. This meta-analysis was conducted to identify potentially clinically important rare safety events associated with PCV13.
OBJECTIVE: To summarize the safety of PCV13 compared with 7-valent pneumococcal conjugate vaccine (PCV7) administered to infants and toddlers.
METHODS: A meta-analysis was performed of integrated safety data from 13 infant studies (PCV13 n=4729 and PCV7 n=2760) conducted in 9 North American, European, and Asian countries. Local reactions at the vaccine injection site and systemic events were collected for 4-7 days after each dose into electronic diaries. Adverse events (AEs) were collected after each vaccination.
RESULTS: Overall, rates of local reactions after any dose of the infant series were similar between PCV13 and PCV7 groups: tenderness (46.7% vs 44.8%, respectively); swelling (28.5% vs 26.9%); and redness (36.4% vs 33.9%). After the toddler dose, tenderness was significantly higher among PCV7 subjects than PCV13 subjects (54.4% vs 48.8%; P=0.005). Frequencies of fever (≥38°C) were similar in both groups and mostly mild (≤39°C); incidence of moderate fever (>39°C to ≤40°C) with PCV13 was ≤2.8% after any infant dose and 5.0% after the toddler dose, compared with ≤2.6% and 7.3%, respectively, with PCV7. Fever >40°C was uncommon in both groups. Frequencies of decreased appetite, irritability, and sleep disturbances were similar in both groups. AEs were the types of conditions and symptoms expected in infants and children, and clinically significant differences between vaccine groups were not observed.
CONCLUSION: PCV13 has a favorable safety profile similar to that of PCV7, a vaccine for which there is >10 years clinical experience.
Copyright © 2013 Elsevier Ltd. All rights reserved.
予防接種ガイドライン等検討委員会：予防接種ガイドライン2016年度版. 予防接種リサーチセンター, 東京, 2016.
小児の臓器移植および免疫不全状態における予防接種ガイドライン2014作成委員会：小児の臓器移植および免疫不全状態における予防接種ガイドライン2014. 協和企画, 東京, 2014.
日本造血細胞移植学会ガイドライン委員会：造血細胞移植ガイドライン 予防接種 第2版.2014.
エビデンスに基づくネフローゼ症候群診療ガイドライン2014作成分科会：エビデンスに基づくネフローゼ症候群診療ガイドライン2014. 東京医学社, 2014.
Susan L Furth, Ronald J Hogg, Joyce Tarver, Lawrence H Moulton, Christina Chan, Barbara A Fivush, Southwest Pediatric Nephrology Study Group
Varicella vaccination in children with chronic renal failure. A report of the Southwest Pediatric Nephrology Study Group.
Pediatr Nephrol. 2003 Jan;18(1):33-8. doi: 10.1007/s00467-002-1006-z. Epub 2002 Nov 22.
Abstract/Text
Children with kidney disease are at risk for serious varicella-related complications. To evaluate the safety and immunogenicity of a two-dose regimen of varicella vaccine in children (aged 1-19 years) with chronic renal insufficiency and on dialysis, the Southwest Pediatric Nephrology Study Group (SPNSG) undertook an open-label, multi-center, prospective 3-year clinical trial. Ninety-six patients without history of varicella were enrolled. Fifty (mean age 4.2 years) had no detectable varicella zoster virus (VZV) antibody; 98% seroconverted after the two-dose regimen. At 1, 2, and 3 years' follow-up, all patients studied maintained VZV antibody, including 16 who received a transplant. No significant vaccine-associated adverse events were seen. One subject developed mild varicella (10-50 maculopapular lesions) 16 months post transplant. In multivariate regression analysis, patients vaccinated after age 6 years had VZV antibody levels 73% (95% confidence interval 33%-89%) lower than patients vaccinated before age 6 years after controlling for gender, estimated glomerular filtration rate, and dialysis treatment. Adjusted analysis also showed that VZV antibody levels were lower after kidney transplantation, but this appeared to be a transient phenomenon. In this study, varicella vaccination with a two-dose regimen of varicella vaccine was generally well tolerated and highly immunogenic in children with chronic kidney disease.
Susan L Furth, Gerald S Arbus, Ronald Hogg, Joyce Tarver, Christina Chan, Barbara A Fivush, Southwest Pediatric Nephrology Study Group
Varicella vaccination in children with nephrotic syndrome: a report of the Southwest Pediatric Nephrology Study Group.
J Pediatr. 2003 Feb;142(2):145-8.
Abstract/Text
OBJECTIVE: To evaluate the safety and immunogenicity of varicella vaccine in children with nephrotic syndrome, including those taking low-dose, alternate-day prednisone.
STUDY DESIGN: Prospective, open-label, multicenter clinical trial of varicella vaccine in a 2-dose regimen in US and Canadian children (12 months to <18 years) with nephrotic syndrome. Varicella Zoster Virus (VZV) antibody levels were measured after the first and second vaccine dose and yearly for 2 years. Patients were monitored for adverse reactions to vaccine, exposure to varicella, dermatomal zoster, and chickenpox.
RESULTS: Twenty-nine children, mean age 4.9 (SD 1.9) years, 45% receiving every-other-day steroids, received 2 vaccine doses. All patients seroconverted and had VZV antibody levels considered protective against breakthrough varicella (>or=5 gpELISA units) after 2 doses. At 2-year follow-up, all patients retained detectable antibody, and 91% (21 of 23) had levels >or=5 gpELISA units. There were no adverse events associated with vaccination.
CONCLUSIONS: Varicella vaccine was generally well tolerated and highly immunogenic in children with nephrotic syndrome, including those on low-dose, alternate-day prednisone.
乳児重症ミオクロニーてんかん（SMEI）症例のワクチン接種状況調査. 脳と発達. 2004;36:318-323.
Anne M McIntosh, Jacinta McMahon, Leanne M Dibbens, Xenia Iona, John C Mulley, Ingrid E Scheffer, Samuel F Berkovic
Effects of vaccination on onset and outcome of Dravet syndrome: a retrospective study.
Lancet Neurol. 2010 Jun;9(6):592-8. doi: 10.1016/S1474-4422(10)70107-1. Epub 2010 May 4.
Abstract/Text
BACKGROUND: Pertussis vaccination has been alleged to cause an encephalopathy that involves seizures and subsequent intellectual disability. In a previous retrospective study, 11 of 14 patients with so-called vaccine encephalopathy had Dravet syndrome that was associated with de-novo mutations of the sodium channel gene SCN1A. In this study, we aimed to establish whether the apparent association of Dravet syndrome with vaccination was caused by recall bias and, if not, whether vaccination affected the onset or outcome of the disorder.
METHODS: We retrospectively studied patients with Dravet syndrome who had mutations in SCN1A, whose first seizure was a convulsion, and for whom validated source data were available. We analysed medical and vaccination records to investigate whether there was an association between vaccination and onset of seizures in these patients. Patients were separated into two groups according to whether seizure onset occurred shortly after vaccination (vaccination-proximate group) or not (vaccination-distant group). We compared clinical features, intellectual outcome, and type of SCN1A mutation between the groups.
FINDINGS: Dates of vaccination and seizure onset were available from source records for 40 patients. We identified a peak in the number of patients who had seizure onset within 2 days after vaccination. Thus, patients who had seizure onset on the day of or the day after vaccination (n=12) were included in the vaccination-proximate group and those who had seizure onset 2 days or more after vaccination (n=25) or before vaccination (n=3) were included in the vaccination-distant group. Mean age at seizure onset was 18.4 weeks (SD 5.9) in the vaccination-proximate group and 26.2 weeks (8.1) in the vaccination-distant group (difference 7.8 weeks, 95% CI 2.6-13.1; p=0.004). There were no differences in intellectual outcome, subsequent seizure type, or mutation type between the two groups (all p values >0.3). Furthermore, in a post-hoc analysis, intellectual outcome did not differ between patients who received vaccinations after seizure onset and those who did not.
INTERPRETATION: Vaccination might trigger earlier onset of Dravet syndrome in children who, because of an SCN1A mutation, are destined to develop the disease. However, vaccination should not be withheld from children with SCN1A mutations because we found no evidence that vaccinations before or after disease onset affect outcome.
Copyright 2010 Elsevier Ltd. All rights reserved.
Nelia Zamponi, Claudia Passamonti, Cristina Petrelli, Pierangelo Veggiotti, Chiara Baldassari, Alberto Verrotti, Giovanni Capovilla, Maurizio Viri, Giangennaro Coppola, Aglaia Vignoli
Vaccination and occurrence of seizures in SCN1A mutation-positive patients: a multicenter Italian study.
Pediatr Neurol. 2014 Mar;50(3):228-32. doi: 10.1016/j.pediatrneurol.2013.09.016. Epub 2013 Oct 5.
Abstract/Text
BACKGROUND: The relation between epileptic seizures and vaccinations is sometimes debated. In the present work, the impact of vaccination on seizure onset and clinical outcome of SCN1A mutation-positive patients is addressed.
METHODS: Seventy-two patients diagnosed with Dravet syndrome or generalized epilepsy with febrile seizure plus, carrying SCN1A mutations or not, were included. Details on vaccination type, temporal relationship between vaccination and seizure occurrence, seizure type at onset and during development, cognitive functioning, and vaccination completion was obtained by reviewing clinical records. Patients were divided into two groups based on the temporal window between vaccination and seizure onset (proximate group: <48 hours; distant group: >48 hours).
RESULTS: Vaccination-related seizures occurred in 25% of patients with SCN1A mutation and 18% of patients without the mutation (no significant difference). The proximate group showed an earlier age at seizure onset and a higher frequency of status epilepticus during development than did the distant group. No other significant differences were found. Subsequent vaccinations did not significantly alter the evolution of the disease.
CONCLUSIONS: Results from this relatively small series provide evidence that vaccinations do not significantly affect clinical and cognitive evolution of Dravet syndrome and generalized epilepsy with febrile seizure plus patients even if they carry SCN1A mutations.
Copyright © 2014 Elsevier Inc. All rights reserved.
基礎疾患をもつ小児に対する予防接種ガイドブック. 診断と治療社, 東京, 2015.
Red book 2015 Report of the committee on infectious diseases 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015.
