厚生労働省：第45回厚生科学審議会予防接種・ワクチン分科会副反応検討部会、令和元年度第13回薬事・食品衛生審議会薬事分科会医薬品等 安全対策部会安全対策調査会（合同開催） 資料, 資料17 ワクチンに関する添付文書の改訂について, 2020.
Rolfes MA, Flannery B, Chung JR, O'Halloran A, Garg S, Belongia EA, Gaglani M, Zimmerman RK, Jackson ML, Monto AS, Alden NB, Anderson E, Bennett NM, Billing L, Eckel S, Kirley PD, Lynfield R, Monroe ML, Spencer M, Spina N, Talbot HK, Thomas A, Torres SM, Yousey-Hindes K, Singleton JA, Patel M, Reed C, Fry AM; 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.
Esposito S, Franco E, Gavazzi G, de Miguel AG, Hardt R, Kassianos G, Bertrand I, Levant MC, Soubeyrand B, López Trigo JA.
The public health value of vaccination for seniors in Europe.
Vaccine. 2018 May 3;36(19):2523-2528. doi: 10.1016/j.vaccine.2018.03.053. Epub 2018 Apr 1.
Abstract/Text
Longer life expectancy and decreasing fertility rates mean that the proportion of older people is continually increasing worldwide, and particularly in Europe. Ageing is associated with an increase in the risk and severity of infectious diseases. These diseases are also more difficult to diagnose and manage in seniors who often have at least one comorbid condition (60% of seniors have two or more conditions). Infectious diseases increase the risk of hospitalization, loss of autonomy and death in seniors. Effective vaccines are available in Europe for infectious diseases such as influenza, pneumococcal diseases, herpes zoster, diphtheria, tetanus and pertussis. Their effectiveness has been demonstrated in terms of reducing the rates of hospitalization, disability, dependency and death. The prevention of diseases in seniors also results in savings in healthcare and societal costs each year in Europe. Despite the availability of vaccines, vaccine-preventable diseases affect millions of European citizens annually, with the greatest burden of disease occurring in seniors, and the medical and economic benefits associated with are not being achieved. Vaccination coverage rates must be improved to achieve the full benefits of vaccination of seniors in Europe.
Copyright © 2018 Elsevier Ltd. All rights reserved.
Iuliano AD, Roguski KM, Chang HH, Muscatello DJ, Palekar R, Tempia S, Cohen C, Gran JM, Schanzer D, Cowling BJ, Wu P, Kyncl J, Ang LW, Park M, Redlberger-Fritz M, Yu H, Espenhain L, Krishnan A, Emukule G, van Asten L, Pereira da Silva S, Aungkulanon S, Buchholz U, Widdowson MA, Bresee JS; Global Seasonal Influenza-associated Mortality Collaborator Network.
Estimates of global seasonal influenza-associated respiratory mortality: a modelling study.
Lancet. 2018 Mar 31;391(10127):1285-1300. doi: 10.1016/S0140-6736(17)33293-2. Epub 2017 Dec 14.
Abstract/Text
BACKGROUND: Estimates of influenza-associated mortality are important for national and international decision making on public health priorities. Previous estimates of 250 000-500 000 annual influenza deaths are outdated. We updated the estimated number of global annual influenza-associated respiratory deaths using country-specific influenza-associated excess respiratory mortality estimates from 1999-2015.
METHODS: We estimated country-specific influenza-associated respiratory excess mortality rates (EMR) for 33 countries using time series log-linear regression models with vital death records and influenza surveillance data. To extrapolate estimates to countries without data, we divided countries into three analytic divisions for three age groups (<65 years, 65-74 years, and ≥75 years) using WHO Global Health Estimate (GHE) respiratory infection mortality rates. We calculated mortality rate ratios (MRR) to account for differences in risk of influenza death across countries by comparing GHE respiratory infection mortality rates from countries without EMR estimates with those with estimates. To calculate death estimates for individual countries within each age-specific analytic division, we multiplied randomly selected mean annual EMRs by the country's MRR and population. Global 95% credible interval (CrI) estimates were obtained from the posterior distribution of the sum of country-specific estimates to represent the range of possible influenza-associated deaths in a season or year. We calculated influenza-associated deaths for children younger than 5 years for 92 countries with high rates of mortality due to respiratory infection using the same methods.
FINDINGS: EMR-contributing countries represented 57% of the global population. The estimated mean annual influenza-associated respiratory EMR ranged from 0·1 to 6·4 per 100 000 individuals for people younger than 65 years, 2·9 to 44·0 per 100 000 individuals for people aged between 65 and 74 years, and 17·9 to 223·5 per 100 000 for people older than 75 years. We estimated that 291 243-645 832 seasonal influenza-associated respiratory deaths (4·0-8·8 per 100 000 individuals) occur annually. The highest mortality rates were estimated in sub-Saharan Africa (2·8-16·5 per 100 000 individuals), southeast Asia (3·5-9·2 per 100 000 individuals), and among people aged 75 years or older (51·3-99·4 per 100 000 individuals). For 92 countries, we estimated that among children younger than 5 years, 9243-105 690 influenza-associated respiratory deaths occur annually.
INTERPRETATION: These global influenza-associated respiratory mortality estimates are higher than previously reported, suggesting that previous estimates might have underestimated disease burden. The contribution of non-respiratory causes of death to global influenza-associated mortality should be investigated.
FUNDING: None.
Copyright © 2018 Elsevier Ltd. All rights reserved.
Reichert TA, Sugaya N, Fedson DS, Glezen WP, Simonsen L, Tashiro M.
The Japanese experience with vaccinating schoolchildren against influenza.
N Engl J Med. 2001 Mar 22;344(12):889-96. doi: 10.1056/NEJM200103223441204.
Abstract/Text
BACKGROUND: Influenza epidemics lead to increased mortality, principally among elderly persons and others at high risk, and in most developed countries, influenza-control efforts focus on the vaccination of this group. Japan, however, once based its policy for the control of influenza on the vaccination of schoolchildren. From 1962 to 1987, most Japanese schoolchildren were vaccinated against influenza. For more than a decade, vaccination was mandatory, but the laws were relaxed in 1987 and repealed in 1994; subsequently, vaccination rates dropped to low levels. When most schoolchildren were vaccinated, it is possible that herd immunity against influenza was achieved in Japan. If this was the case, both the incidence of influenza and mortality attributed to influenza should have been reduced among older persons.
METHODS: We analyzed the monthly rates of death from all causes and death attributed to pneumonia and influenza, as well as census data and statistics on the rates of vaccination for both Japan and the United States from 1949 through 1998. For each winter, we estimated the number of deaths per month in excess of a base-line level, defined as the average death rate in November.
RESULTS: The excess mortality from pneumonia and influenza and that from all causes were highly correlated in each country. In the United States, these rates were nearly constant over time. With the initiation of the vaccination program for schoolchildren in Japan, excess mortality rates dropped from values three to four times those in the United States to values similar to those in the United States. The vaccination of Japanese children prevented about 37,000 to 49,000 deaths per year, or about 1 death for every 420 children vaccinated. As the vaccination of schoolchildren was discontinued, the excess mortality rates in Japan increased.
CONCLUSIONS: The effect of influenza on mortality is much greater in Japan than in the United States and can be measured about equally well in terms of deaths from all causes and deaths attributed to pneumonia or influenza. Vaccinating schoolchildren against influenza provides protection and reduces mortality from influenza among older persons.
Grohskopf LA, Blanton LH, Ferdinands JM, Chung JR, Broder KR, Talbot HK. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2023–24 Influenza Season. MMWR Recomm Rep [Internet]. 2023;72(No.RR-2):1–25. Available from: doi: http://dx.doi.org/10.15585/mmwr.rr7202a1
Song JY, Cheong HJ, Hwang IS, Choi WS, Jo YM, Park DW, Cho GJ, Hwang TG, Kim WJ.
Long-term immunogenicity of influenza vaccine among the elderly: Risk factors for poor immune response and persistence.
Vaccine. 2010 May 21;28(23):3929-35. doi: 10.1016/j.vaccine.2010.03.067. Epub 2010 Apr 13.
Abstract/Text
The elderly have been considered as the priority group for influenza vaccination, but their influenza vaccine-induced antibody was believed to decline more rapidly. Long-term immunogenicity of the influenza vaccine among the elderly was evaluated as compared to young adults. Serum hemagglutinin inhibition (HI) titers were determined at pre- and post-vaccination periods (at 1, 6, and 12 months after vaccination). Of the 1018 subjects, 716 (70.3%) were followed up during a 12-month period. Seroprotection rates at 1 month post-vaccination ranged from 70.1% to 90.3% depending on the age group and influenza vaccine virus strain. At 6 months post-vaccination, seroprotection rates for all three strains had declined significantly in adults >or=65 years (P<0.01), but still met the EMEA criteria. Low pre-vaccination HI titer (<1:40) and advanced age were associated with early decline of HI titers, falling below seroprotective levels around 6 months after vaccination.
Copyright 2010 Elsevier Ltd. All rights reserved.
Kwong JC, Chung H, Jung JK, Buchan SA, Campigotto A, Campitelli MA, Crowcroft NS, Gubbay JB, Karnauchow T, Katz K, McGeer AJ, McNally JD, Richardson DC, Richardson SE, Rosella LC, Schwartz KL, Simor A, Smieja M, Zahariadis G; Canadian Immunization Research Network (CIRN) investigators.
The impact of repeated vaccination using 10-year vaccination history on protection against influenza in older adults: a test-negative design study across the 2010/11 to 2015/16 influenza seasons in Ontario, Canada.
Euro Surveill. 2020 Jan;25(1). doi: 10.2807/1560-7917.ES.2020.25.1.1900245.
Abstract/Text
IntroductionAnnual influenza vaccination is recommended for older adults, but evidence regarding the impact of repeated vaccination has been inconclusive.AimWe investigated vaccine effectiveness (VE) against laboratory-confirmed influenza and the impact of repeated vaccination over 10 previous seasons on current season VE among older adults.MethodsWe conducted an observational test-negative study in community-dwelling adults aged > 65 years in Ontario, Canada for the 2010/11 to 2015/16 seasons by linking laboratory and health administrative data. We estimated VE using multivariable logistic regression. We assessed the impact of repeated vaccination by stratifying by previous vaccination history.ResultsWe included 58,304 testing episodes for respiratory viruses, with 11,496 (20%) testing positive for influenza and 31,004 (53%) vaccinated. Adjusted VE against laboratory-confirmed influenza for the six seasons combined was 21% (95% confidence interval (CI): 18 to 24%). Patients who were vaccinated in the current season, but had received no vaccinations in the previous 10 seasons, had higher current season VE (34%; 95%CI: 9 to 52%) than patients who had received 1-3 (26%; 95%CI: 13 to 37%), 4-6 (24%; 95%CI: 15 to 33%), 7-8 (13%; 95%CI: 2 to 22%), or 9-10 (7%; 95%CI: -4 to 16%) vaccinations (trend test p = 0.001). All estimates were higher after correcting for misclassification of current season vaccination status. For patients who were not vaccinated in the current season, residual protection rose significantly with increasing numbers of vaccinations received previously.ConclusionsAlthough VE appeared to decrease with increasing numbers of previous vaccinations, current season vaccination likely provides some protection against influenza regardless of the number of vaccinations received over the previous 10 influenza seasons.
McLean HQ, Thompson MG, Sundaram ME, Meece JK, McClure DL, Friedrich TC, Belongia EA.
Impact of repeated vaccination on vaccine effectiveness against influenza A(H3N2) and B during 8 seasons.
Clin Infect Dis. 2014 Nov 15;59(10):1375-85. doi: 10.1093/cid/ciu680. Epub 2014 Sep 29.
Abstract/Text
BACKGROUND: Recent studies suggest that influenza vaccination in the previous season may influence the effectiveness of current-season vaccination, but this has not been assessed in a single population over multiple years.
METHODS: Patients presenting with acute respiratory illness were prospectively enrolled during the 2004-2005 through 2012-2013 influenza seasons. Respiratory swabs were tested for influenza and vaccination dates obtained from a validated registry. Vaccination status was determined for the current, previous, and prior 5 seasons. Vaccine effectiveness (VE) was calculated for participants aged ≥9 years using logistic regression models with an interaction term for vaccination history.
RESULTS: There were 7315 enrollments during 8 seasons; 1056 (14%) and 650 (9%) were positive for influenza A(H3N2) and B, respectively. Vaccination during current only, previous only, or both seasons yielded similar protection against H3N2 (adjusted VE range, 31%-36%) and B (52%-66%). In the analysis using 5 years of historical vaccination data, current season VE against H3N2 was significantly higher among vaccinated individuals with no prior vaccination history (65%; 95% confidence interval [CI], 36%-80%) compared with vaccinated individuals with a frequent vaccination history (24%; 95% CI, 3%-41%; P = .01). VE against B was 75% (95% CI, 50%-87%) and 48% (95% CI, 29%-62%), respectively (P = .05). Similar findings were observed when analysis was restricted to adults 18-49 years.
CONCLUSIONS: Current- and previous-season vaccination generated similar levels of protection, and vaccine-induced protection was greatest for individuals not vaccinated during the prior 5 years. Additional studies are needed to understand the long-term effects of annual vaccination.
© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
Demicheli V, Jefferson T, Ferroni E, Rivetti A, Di Pietrantonj C.
Vaccines for preventing influenza in healthy adults.
Cochrane Database Syst Rev. 2018 Feb 1;2(2):CD001269. doi: 10.1002/14651858.CD001269.pub6. Epub 2018 Feb 1.
Abstract/Text
BACKGROUND: The consequences of influenza in adults are mainly time off work. Vaccination of pregnant women is recommended internationally. This is an update of a review published in 2014. 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 due to their lack of influence on the review conclusions.
OBJECTIVES: To assess the effects (efficacy, effectiveness, and harm) of vaccines against influenza in healthy adults, including pregnant women.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 12), MEDLINE (January 1966 to 31 December 2016), Embase (1990 to 31 December 2016), the WHO International Clinical Trials Registry Platform (ICTRP; 1 July 2017), and ClinicalTrials.gov (1 July 2017), as well as checking the bibliographies of retrieved articles.
SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing influenza vaccines with placebo or no intervention in naturally occurring influenza in healthy individuals aged 16 to 65 years. Previous versions of this review included observational comparative studies assessing serious and rare harms cohort and case-control studies. Due to the uncertain quality of observational (i.e. non-randomised) studies and their lack of influence on the review conclusions, we decided to update only randomised evidence. The searches for observational comparative studies are no longer updated.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We rated certainty of evidence for key outcomes (influenza, influenza-like illness (ILI), hospitalisation, and adverse effects) using GRADE.
MAIN RESULTS: We included 52 clinical trials of over 80,000 people assessing the safety and effectiveness of influenza vaccines. We have presented findings from 25 studies comparing inactivated parenteral influenza vaccine against placebo or do-nothing control groups as the most relevant to decision-making. The studies were conducted over single influenza seasons in North America, South America, and Europe between 1969 and 2009. We did not consider studies at high risk of bias to influence the results of our outcomes except for hospitalisation.Inactivated influenza vaccines probably reduce influenza in healthy adults from 2.3% without vaccination to 0.9% (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.36 to 0.47; 71,221 participants; moderate-certainty evidence), and they probably reduce ILI from 21.5% to 18.1% (RR 0.84, 95% CI 0.75 to 0.95; 25,795 participants; moderate-certainty evidence; 71 healthy adults need to be vaccinated to prevent one of them experiencing influenza, and 29 healthy adults need to be vaccinated to prevent one of them experiencing an ILI). The difference between the two number needed to vaccinate (NNV) values depends on the different incidence of ILI and confirmed influenza among the study populations. Vaccination may lead to a small reduction in the risk of hospitalisation in healthy adults, from 14.7% to 14.1%, but the CI is wide and does not rule out a large benefit (RR 0.96, 95% CI 0.85 to 1.08; 11,924 participants; low-certainty evidence). Vaccines may lead to little or no small reduction in days off work (-0.04 days, 95% CI -0.14 days to 0.06; low-certainty evidence). Inactivated vaccines cause an increase in fever from 1.5% to 2.3%.We identified one RCT and one controlled clinical trial assessing the effects of vaccination in pregnant women. The efficacy of inactivated vaccine containing pH1N1 against influenza was 50% (95% CI 14% to 71%) in mothers (NNV 55), and 49% (95% CI 12% to 70%) in infants up to 24 weeks (NNV 56). No data were available on efficacy against seasonal influenza during pregnancy. Evidence from observational studies showed effectiveness of influenza vaccines against ILI in pregnant women to be 24% (95% CI 11% to 36%, NNV 94), and against influenza in newborns from vaccinated women to be 41% (95% CI 6% to 63%, NNV 27).Live aerosol vaccines have an overall effectiveness corresponding to an NNV of 46. The performance of one- or two-dose whole-virion 1968 to 1969 pandemic vaccines was higher (NNV 16) against ILI and (NNV 35) against influenza. There was limited impact on hospitalisations in the 1968 to 1969 pandemic (NNV 94). The administration of both seasonal and 2009 pandemic vaccines during pregnancy had no significant effect on abortion or neonatal death, but this was based on observational data sets.
AUTHORS' CONCLUSIONS: Healthy adults who receive inactivated parenteral influenza vaccine rather than no vaccine probably experience less influenza, from just over 2% to just under 1% (moderate-certainty evidence). They also probably experience less ILI following vaccination, but the degree of benefit when expressed in absolute terms varied across different settings. Variation in protection against ILI may be due in part to inconsistent symptom classification. Certainty of evidence for the small reductions in hospitalisations and time off work is low. Protection against influenza and ILI in mothers and newborns was smaller than the effects seen in other populations considered in this review.Vaccines increase the risk of a number of adverse events, including a small increase in fever, but rates of nausea and vomiting are uncertain. The protective effect of vaccination in pregnant women and newborns is also very modest. We did not find any evidence of an association between influenza vaccination and serious adverse events in the comparative studies considered in this review. Fifteen included RCTs were industry funded (29%).
Demicheli V, Jefferson T, Di Pietrantonj C, Ferroni E, Thorning S, Thomas RE, Rivetti A.
Vaccines for preventing influenza in the elderly.
Cochrane Database Syst Rev. 2018 Feb 1;2(2):CD004876. doi: 10.1002/14651858.CD004876.pub4. Epub 2018 Feb 1.
Abstract/Text
BACKGROUND: The consequences of influenza in the elderly (those age 65 years or older) are complications, hospitalisations, and death. The primary goal of influenza vaccination in the elderly is to reduce the risk of death among people who are most vulnerable. This is an update of a review published in 2010. 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 the elderly.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 11), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (1966 to 31 December 2016); Embase (1974 to 31 December 2016); Web of Science (1974 to 31 December 2016); CINAHL (1981 to 31 December 2016); LILACS (1982 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 (RCTs) and quasi-RCTs assessing efficacy against influenza (laboratory-confirmed cases) or effectiveness against influenza-like illness (ILI) or safety. We considered any influenza vaccine given independently, in any dose, preparation, or time schedule, compared with placebo or with no intervention. Previous versions of this review included 67 cohort and case-control studies. The searches for these trial designs are no longer updated.
DATA COLLECTION AND ANALYSIS: Review authors independently assessed risk of bias and extracted data. We rated the certainty of evidence with GRADE for the key outcomes of influenza, ILI, complications (hospitalisation, pneumonia), and adverse events. We have presented aggregate control group risks to illustrate the effect in absolute terms. We used them as the basis for calculating the number needed to vaccinate to prevent one case of each event for influenza and ILI outcomes.
MAIN RESULTS: We identified eight RCTs (over 5000 participants), of which four assessed harms. The studies were conducted in community and residential care settings in Europe and the USA between 1965 and 2000. Risk of bias reduced our certainty in the findings for influenza and ILI, but not for other outcomes.Older adults receiving the influenza vaccine may experience less influenza over a single season compared with placebo, from 6% to 2.4% (risk ratio (RR) 0.42, 95% confidence interval (CI) 0.27 to 0.66; low-certainty evidence). We rated the evidence as low certainty due to uncertainty over how influenza was diagnosed. Older adults probably experience less ILI compared with those who do not receive a vaccination over the course of a single influenza season (3.5% versus 6%; RR 0.59, 95% CI 0.47 to 0.73; moderate-certainty evidence). These results indicate that 30 people would need to be vaccinated to prevent one person experiencing influenza, and 42 would need to be vaccinated to prevent one person having an ILI.The study providing data for mortality and pneumonia was underpowered to detect differences in these outcomes. There were 3 deaths from 522 participants in the vaccination arm and 1 death from 177 participants in the placebo arm, providing very low-certainty evidence for the effect on mortality (RR 1.02, 95% CI 0.11 to 9.72). No cases of pneumonia occurred in one study that reported this outcome (very low-certainty evidence). No data on hospitalisations were reported. Confidence intervaIs around the effect of vaccines on fever and nausea were wide, and we do not have enough information about these harms in older people (fever: 1.6% with placebo compared with 2.5% after vaccination (RR 1.57, 0.92 to 2.71; moderate-certainty evidence)); nausea (2.4% with placebo compared with 4.2% after vaccination (RR 1.75, 95% CI 0.74 to 4.12; low-certainty evidence)).
AUTHORS' CONCLUSIONS: Older adults receiving the influenza vaccine may have a lower risk of influenza (from 6% to 2.4%), and probably have a lower risk of ILI compared with those who do not receive a vaccination over the course of a single influenza season (from 6% to 3.5%). We are uncertain how big a difference these vaccines will make across different seasons. Very few deaths occurred, and no data on hospitalisation were reported. No cases of pneumonia occurred in one study that reported this outcome. We do not have enough information to assess harms relating to fever and nausea in this population.The evidence for a lower risk of influenza and ILI with vaccination is limited by biases in the design or conduct of the studies. Lack of detail regarding the methods used to confirm the diagnosis of influenza limits the applicability of this result. The available evidence relating to complications is of poor quality, insufficient, or old and provides no clear guidance for public health regarding the safety, efficacy, or effectiveness of influenza vaccines for people aged 65 years or older. Society should invest in research on a new generation of influenza vaccines for the elderly.
Thompson MG, Pierse N, Sue Huang Q, Prasad N, Duque J, Claire Newbern E, Baker MG, Turner N, McArthur C; SHIVERS investigation team.
Influenza vaccine effectiveness in preventing influenza-associated intensive care admissions and attenuating severe disease among adults in New Zealand 2012-2015.
Vaccine. 2018 Sep 18;36(39):5916-5925. doi: 10.1016/j.vaccine.2018.07.028. Epub 2018 Aug 1.
Abstract/Text
BACKGROUND: Little is known about inactivated influenza vaccine effectiveness (IVE) in preventing very severe disease, including influenza-associated intensive care unit (ICU) admissions.
METHODS: The Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance (SHIVERS) project enrolled adults (aged ≥ 18 years) with acute respiratory illness (ARI) in general ward (GW) hospital settings (n = 3034) and ICUs (n = 101) during 2012-2015. IVE was assessed using a test-negative design comparing the odds of influenza vaccination among influenza positives vs. negatives (confirmed by real-time reverse transcription polymerase chain reaction). All models were adjusted for season, weeks from season peak, and a vaccination propensity score.
RESULTS: Influenza virus infection was confirmed in 28% of GW hospital and 41% of ICU patients; influenza vaccination was documented for 56% and 41%, respectively. Across seasons, IVE was 37% (95% confidence intervals [CI] = 23-48%) among GW patients and 82% (95% CI = 45-94%) among ICU patients. IVE point estimates were > 70% against ICU influenza and consistently higher than IVE against GW influenza when stratified by season, by virus (sub)types, and for adults with or without chronic medical conditions and for both adults aged <65 and ≥65 years old. Among hospitalized influenza positives, influenza vaccination was associated with a 59% reduction in the odds of ICU admission (aOR = 0.41, 95% CI = 0.18-0.96) and with shorter ICU lengths of stay (LOS), but not with radiograph-confirmed pneumonia or GW hospital LOS.
CONCLUSION: Inactivated influenza vaccines prevented influenza-associated ICU admissions, may have higher effectiveness in ICU than GW hospital settings, and appeared to reduce the risk of severe disease among those who are infected despite vaccination.
Copyright © 2018 Elsevier Ltd. All rights reserved.
Belongia EA, Simpson MD, King JP, Sundaram ME, Kelley NS, Osterholm MT, McLean HQ.
Variable influenza vaccine effectiveness by subtype: a systematic review and meta-analysis of test-negative design studies.
Lancet Infect Dis. 2016 Aug;16(8):942-51. doi: 10.1016/S1473-3099(16)00129-8. Epub 2016 Apr 6.
Abstract/Text
BACKGROUND: Influenza vaccine effectiveness (VE) can vary by type and subtype. Over the past decade, the test-negative design has emerged as a valid method for estimation of VE. In this design, VE is calculated as 100% × (1 - odds ratio) for vaccine receipt in influenza cases versus test-negative controls. We did a systematic review and meta-analysis to estimate VE by type and subtype.
METHODS: In this systematic review and meta-analysis, we searched PubMed and Embase from Jan 1, 2004, to March 31, 2015. Test-negative design studies of influenza VE were eligible if they enrolled outpatients on the basis of predefined illness criteria, reported subtype-level VE by season, used PCR to confirm influenza, and adjusted for age. We excluded studies restricted to hospitalised patients or special populations, duplicate reports, interim reports superseded by a final report, studies of live-attenuated vaccine, and studies of prepandemic seasonal vaccine against H1N1pdm09. Two reviewers independently assessed titles and abstracts to identify articles for full review. Discrepancies in inclusion and exclusion criteria and VE estimates were adjudicated by consensus. Outcomes were VE against H3N2, H1N1pdm09, H1N1 (pre-2009), and type B. We calculated pooled VE using a random-effects model.
FINDINGS: We identified 3368 unduplicated publications, selected 142 for full review, and included 56 in the meta-analysis. Pooled VE was 33% (95% CI 26-39; I(2)=44·4) for H3N2, 54% (46-61; I(2)=61·3) for type B, 61% (57-65; I(2)=0·0) for H1N1pdm09, and 67% (29-85; I(2)=57·6) for H1N1; VE was 73% (61-81; I(2)=31·4) for monovalent vaccine against H1N1pdm09. VE against H3N2 for antigenically matched viruses was 33% (22-43; I(2)=56·1) and for variant viruses was 23% (2-40; I(2)=55·6). Among older adults (aged >60 years), pooled VE was 24% (-6 to 45; I(2)=17·6) for H3N2, 63% (33-79; I(2)=0·0) for type B, and 62% (36-78; I(2)=0·0) for H1N1pdm09.
INTERPRETATION: Influenza vaccines provided substantial protection against H1N1pdm09, H1N1 (pre-2009), and type B, and reduced protection against H3N2. Vaccine improvements are needed to generate greater protection against H3N2 than with current vaccines.
FUNDING: None.
Copyright © 2016 Elsevier Ltd. All rights reserved.
Rondy M, El Omeiri N, Thompson MG, Levêque A, Moren A, Sullivan SG.
Effectiveness of influenza vaccines in preventing severe influenza illness among adults: A systematic review and meta-analysis of test-negative design case-control studies.
J Infect. 2017 Nov;75(5):381-394. doi: 10.1016/j.jinf.2017.09.010. Epub 2017 Sep 18.
Abstract/Text
OBJECTIVES: Summary evidence of influenza vaccine effectiveness (IVE) against hospitalized influenza is lacking. We conducted a meta-analysis of studies reporting IVE against laboratory-confirmed hospitalized influenza among adults.
METHODS: We searched Pubmed (January 2009 to November 2016) for studies that used test-negative design (TND) to enrol patients hospitalized with influenza-associated conditions. Two independent authors selected relevant articles. We calculated pooled IVE against any and (sub)type specific influenza among all adults, and stratified by age group (18-64 and 65 years and above) using random-effects models.
RESULTS: We identified 3411 publications and 30 met our inclusion criteria. Between 2010-11 and 2014-15, the pooled seasonal IVE was 41% (95%CI:34;48) for any influenza (51% (95%CI:44;58) among people aged 18-64y and 37% (95%CI:30;44) among ≥65 years). IVE was 48% (95%CI:37;59),37% (95%CI:24;50) and 38% (95%CI:23;53) against influenza A(H1N1)pdm09, A(H3N2) and B, respectively. Among persons aged ≥65 year, IVE against A(H3N2) was 43% (95%CI:33;53) in seasons when circulating and vaccine strains were antigenically similar and 14% (95%CI:-3;30) when A(H3N2) variant viruses predominated.
CONCLUSIONS: Influenza vaccines provided moderate protection against influenza-associated hospitalizations among adults. They seemed to provide low protection among elderly in seasons where vaccine and circulating A(H3N2) strains were antigenically variant.
Copyright © 2017 The British Infection Association. All rights reserved.
Osterholm MT, Kelley NS, Sommer A, Belongia EA.
Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis.
Lancet Infect Dis. 2012 Jan;12(1):36-44. doi: 10.1016/S1473-3099(11)70295-X. Epub 2011 Oct 25.
Abstract/Text
BACKGROUND: No published meta-analyses have assessed efficacy and effectiveness of licensed influenza vaccines in the USA with sensitive and highly specific diagnostic tests to confirm influenza.
METHODS: We searched Medline for randomised controlled trials assessing a relative reduction in influenza risk of all circulating influenza viruses during individual seasons after vaccination (efficacy) and observational studies meeting inclusion criteria (effectiveness). Eligible articles were published between Jan 1, 1967, and Feb 15, 2011, and used RT-PCR or culture for confirmation of influenza. We excluded some studies on the basis of study design and vaccine characteristics. We estimated random-effects pooled efficacy for trivalent inactivated vaccine (TIV) and live attenuated influenza vaccine (LAIV) when data were available for statistical analysis (eg, at least three studies that assessed comparable age groups).
FINDINGS: We screened 5707 articles and identified 31 eligible studies (17 randomised controlled trials and 14 observational studies). Efficacy of TIV was shown in eight (67%) of the 12 seasons analysed in ten randomised controlled trials (pooled efficacy 59% [95% CI 51-67] in adults aged 18-65 years). No such trials met inclusion criteria for children aged 2-17 years or adults aged 65 years or older. Efficacy of LAIV was shown in nine (75%) of the 12 seasons analysed in ten randomised controlled trials (pooled efficacy 83% [69-91]) in children aged 6 months to 7 years. No such trials met inclusion criteria for children aged 8-17 years. Vaccine effectiveness was variable for seasonal influenza: six (35%) of 17 analyses in nine studies showed significant protection against medically attended influenza in the outpatient or inpatient setting. Median monovalent pandemic H1N1 vaccine effectiveness in five observational studies was 69% (range 60-93).
INTERPRETATION: Influenza vaccines can provide moderate protection against virologically confirmed influenza, but such protection is greatly reduced or absent in some seasons. Evidence for protection in adults aged 65 years or older is lacking. LAIVs consistently show highest efficacy in young children (aged 6 months to 7 years). New vaccines with improved clinical efficacy and effectiveness are needed to further reduce influenza-related morbidity and mortality.
FUNDING: Alfred P Sloan Foundation.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Darvishian M, van den Heuvel ER, Bissielo A, Castilla J, Cohen C, Englund H, Gefenaite G, Huang WT, la Bastide-van Gemert S, Martinez-Baz I, McAnerney JM, Ntshoe GM, Suzuki M, Turner N, Hak E.
Effectiveness of seasonal influenza vaccination in community-dwelling elderly people: an individual participant data meta-analysis of test-negative design case-control studies.
Lancet Respir Med. 2017 Mar;5(3):200-211. doi: 10.1016/S2213-2600(17)30043-7. Epub 2017 Feb 9.
Abstract/Text
BACKGROUND: Several aggregate data meta-analyses have provided estimates of the effectiveness of influenza vaccination in community-dwelling elderly people. However, these studies ignored the effects of patient-level confounders such as sex, age, and chronic diseases that could bias effectiveness estimates. We aimed to assess the confounder-adjusted effectiveness of influenza vaccines on laboratory-confirmed influenza among elderly people by conducting a global individual participant data meta-analysis.
METHODS: In this individual participant data meta-analysis, we considered studies included in a previously conducted aggregate data meta-analysis that included test-negative design case-control studies published up to July 13, 2014. We contacted all authors of the included studies on Dec 1, 2014, to request individual participant data. Patients were excluded if their unique identifier was missing, their vaccination status was unknown, their outcome status was unknown, or they had had suspected influenza infection more than once in the same influenza season. Cases were patients with influenza-like illness symptoms who tested positive for at least one of A H1N1, A H1N1 pdm09, A H3N2, or B viruses; controls were patients with influenza-like illness symptoms who tested negative for these virus types or subtypes. Influenza vaccine effectiveness against overall and subtype-specific laboratory-confirmed influenza were the primary and secondary outcomes. We used a generalised linear mixed model to calculate adjusted vaccine effectiveness according to vaccine match to the circulating strains of influenza virus and intensity of the virus activity (epidemic or non-epidemic). Vaccine effectiveness was defined as the relative reduction in risk of laboratory-confirmed influenza in vaccinated patients compared with unvaccinated patients. We did subgroup analyses to estimate vaccine effectiveness according to hemisphere, age category, and health status.
FINDINGS: We received 23 of the 53 datasets included in the aggregate data meta-analysis. Furthermore, six additional datasets were provided by data collaborators, which resulted in individual participant data for a total of 5210 participants. A total of 4975 patients had the required data for analysis. Of these, 3146 (63%) were controls and 1829 (37%) were cases. Influenza vaccination was significantly effective during epidemic seasons irrespective of vaccine match status (matched adjusted vaccine effectiveness 44·38%, 95% CI 22·63-60·01; mismatched adjusted vaccine effectiveness 20·00%, 95% CI 3·46-33·68; analyses in the imputed dataset). Seasonal influenza vaccination did not show significant effectiveness during non-epidemic seasons. We found substantial variation in vaccine effectiveness across virus types and subtypes, with the highest estimate for A H1N1 pdm09 (53·19%, 10·25-75·58) and the lowest estimate for B virus types (-1·52%, -39·58 to 26·16). Although we observed no significant differences between subgroups in each category (hemisphere, age, and health status), influenza vaccination showed a protective effect among elderly people with cardiovascular disease, lung disease, or aged 75 years and younger.
INTERPRETATION: Influenza vaccination is moderately effective against laboratory-confirmed influenza in elderly people during epidemic seasons. More research is needed to investigate factors affecting vaccine protection (eg, brand-specific or type-specific vaccine effectiveness and repeated annual vaccination) in elderly people.
FUNDING: University Medical Center Groningen.
Copyright © 2017 Elsevier Ltd. All rights reserved.
DiazGranados CA, Dunning AJ, Kimmel M, Kirby D, Treanor J, Collins A, Pollak R, Christoff J, Earl J, Landolfi V, Martin E, Gurunathan S, Nathan R, Greenberg DP, Tornieporth NG, Decker MD, Talbot HK.
Efficacy of high-dose versus standard-dose influenza vaccine in older adults.
N Engl J Med. 2014 Aug 14;371(7):635-45. doi: 10.1056/NEJMoa1315727.
Abstract/Text
BACKGROUND: As compared with a standard-dose vaccine, a high-dose, trivalent, inactivated influenza vaccine (IIV3-HD) improves antibody responses to influenza among adults 65 years of age or older. This study evaluated whether IIV3-HD also improves protection against laboratory-confirmed influenza illness.
METHODS: We conducted a phase IIIb-IV, multicenter, randomized, double-blind, active-controlled trial to compare IIV3-HD (60 μg of hemagglutinin per strain) with standard-dose trivalent, inactivated influenza vaccine (IIV3-SD [15 μg of hemagglutinin per strain]) in adults 65 years of age or older. Assessments of relative efficacy, effectiveness, safety (serious adverse events), and immunogenicity (hemagglutination-inhibition [HAI] titers) were performed during the 2011-2012 (year 1) and the 2012-2013 (year 2) northern-hemisphere influenza seasons.
RESULTS: A total of 31,989 participants were enrolled from 126 research centers in the United States and Canada (15,991 were randomly assigned to receive IIV3-HD, and 15,998 to receive IIV3-SD). In the intention-to-treat analysis, 228 participants in the IIV3-HD group (1.4%) and 301 participants in the IIV3-SD group (1.9%) had laboratory-confirmed influenza caused by any viral type or subtype associated with a protocol-defined influenza-like illness (relative efficacy, 24.2%; 95% confidence interval [CI], 9.7 to 36.5). At least one serious adverse event during the safety surveillance period was reported by 1323 (8.3%) of the participants in the IIV3-HD group, as compared with 1442 (9.0%) of the participants in the IIV3-SD group (relative risk, 0.92; 95% CI, 0.85 to 0.99). After vaccination, HAI titers and seroprotection rates (the percentage of participants with HAI titers ≥ 1:40) were significantly higher in the IIV3-HD group. Conclusions: Among persons 65 years of age or older, IIV3-HD induced significantly higher antibody responses and provided better protection against laboratory-confirmed influenza illness than did IIV3-SD. (Funded by Sanofi Pasteur; ClinicalTrials.gov number, NCT01427309.).
Wilkinson K, Wei Y, Szwajcer A, Rabbani R, Zarychanski R, Abou-Setta AM, Mahmud SM.
Efficacy and safety of high-dose influenza vaccine in elderly adults: A systematic review and meta-analysis.
Vaccine. 2017 May 15;35(21):2775-2780. doi: 10.1016/j.vaccine.2017.03.092. Epub 2017 Apr 18.
Abstract/Text
INTRODUCTION: Older adults are prioritized for influenza vaccination but also have lowered antibody responses to the vaccine. Higher-doses of influenza antigen may increase immune response and thus be more effective. Our objectives were to compare the efficacy and safety of the high-dose influenza vaccine to the standard-dose influenza vaccine in the elderly (age>65).
METHODS: Data sources: Randomized trials (RCTs) from Medline (Ovid), EMBASE (Ovid), Cochrane Library (Wiley), ClinicalTrials.gov, reference lists of relevant articles, and gray literature.
STUDY SELECTION: Two reviewers independently identified RCTs comparing high-dose influenza vaccine (60μg of hemagglutinin per strain) to standard-dose influenza vaccine (15μg of hemagglutinin per strain) in adults over the age of 65years.
DATA EXTRACTION: Two reviewers independently extracted trial-level data including population characteristics, interventions, outcomes, and funding sources. Risk of bias was assessed using the Cochrane Risk of Bias tool.
RESULTS: We included seven eligible trials; all were categorized as having a low (n=3) or unclear (n=4) risk of bias. Patients receiving the high-dose vaccine had significantly less risk of developing laboratory-confirmed influenza infections (Relative Risk 0.76, 95%CI 0.65 to 0.90; I2 0%, 2 trials, 41,141 patients). Post-vaccination geometric mean titres and seroprotection rates were also higher in high-dose vaccine recipients. There were no protocol-defined serious adverse events in the included trials in either group.
CONCLUSIONS: In elderly adults, the high-dose influenza vaccine was well-tolerated, more immunogenic, and more efficacious in preventing influenza infections than the standard-dose vaccine. Further pragmatic trials are needed to determine if the higher efficacy translates into higher vaccine effectiveness in adults over the age of 65.
Copyright © 2017 Elsevier Ltd. All rights reserved.
Camilloni B, Basileo M, Valente S, Nunzi E, Iorio AM.
Immunogenicity of intramuscular MF59-adjuvanted and intradermal administered influenza enhanced vaccines in subjects aged over 60: A literature review.
Hum Vaccin Immunother. 2015;11(3):553-63. doi: 10.1080/21645515.2015.1011562.
Abstract/Text
Because of the age-related immune system decline, 2 potentiated influenza vaccines were specifically licensed for the elderly: Fluad(®), an MF59-adjuvanted vaccine administered intramuscularly (IM-MF59), and Intanza 15 mcg(®), a non adjuvanted vaccine administered intradermally (ID). The objective of this paper was to conduct a systematic review of studies that evaluated antibody responses in the elderly following immunization with IM-MF59 or ID vaccines. The two potentiated vaccines induced immune responses satisfying, in most instances, the European Medicine Agency immunogenicity criteria, both against vaccine antigens and heterovariant drifted strains. Considering pooled data reported in the articles analyzed and papers directly comparing the 2 vaccines, the antibody responses elicited by IM-MF59 and ID were found to be generally comparable. The use of IM-MF59 and ID vaccines can be proposed as an appropriate strategy for elderly seasonal influenza vaccination although further studies are required for a more complete characterization of the 2 vaccines.
Domnich A, Arata L, Amicizia D, Puig-Barberà J, Gasparini R, Panatto D.
Effectiveness of MF59-adjuvanted seasonal influenza vaccine in the elderly: A systematic review and meta-analysis.
Vaccine. 2017 Jan 23;35(4):513-520. doi: 10.1016/j.vaccine.2016.12.011. Epub 2016 Dec 23.
Abstract/Text
BACKGROUND: In the elderly, traditional influenza inactivated vaccines are often only modestly immunogenic, owing to immunosenescence. Given that adjuvantation is a means of enhancing the immune response, the trivalent inactivated vaccine adjuvanted with MF59 (MF59-TIV) was specifically designed to overcome this problem. Considering that, for ethical reasons, the absolute effectiveness of an influenza vaccine in the elderly cannot be demonstrated in placebo-controlled studies, the present study aimed to assess the effectiveness of MF59-TIV in preventing influenza-related outcomes in the elderly.
METHODS: We conducted a systematic review of observational studies aimed at evaluating the effectiveness of MF59-TIV against influenza-related outcomes. Results of single studies were pooled whenever possible.
RESULTS: Of the 1993 papers screened, 11 (6 case-control, 3 cohort and 2 prospective case-control) studies were identified. Hospitalization due to pneumonia/influenza and laboratory-confirmed influenza were reported in more than one study, while other outcomes (influenza-like illness, cardio- and cerebrovascular accidents) were investigated only by one study each. Pooled analysis of four case-control studies showed an adjusted MF59-TIV effectiveness of 51% (95% CI: 39-61%) against hospitalizations for pneumonia/influenza among community-dwelling seniors. Pooled results of the adjusted vaccine effectiveness against laboratory-confirmed influenza were also high (60.1%), although the 95% CI passed through zero (-1.3 to 84.3%). Other single community-based studies showed very high effectiveness of MF59-TIV in preventing hospitalizations for acute coronary [87% (95% CI: 35-97%)] and cerebrovascular [93% (95% CI: 52-99%)] events. MF59-TIV proved highly effective [94% (95% CI: 47-100%] in reducing influenza-like illness among institutionalized elderly. Furthermore, MF59-TIV displayed greater efficacy than non-adjuvanted vaccines in preventing hospitalizations due to pneumonia/influenza [adjusted risk ratio 0.75 (95% CI: 0.57-0.98)] and laboratory-confirmed influenza [adjusted odds ratio 0.37 (0.14-0.96)].
CONCLUSIONS: Our results suggest that MF59-TIV is effective in reducing several influenza-related outcomes among the elderly, especially hospitalizations due to influenza-related complications.
Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Fukusumi M, Chang B, Tanabe Y, Oshima K, Maruyama T, Watanabe H, Kuronuma K, Kasahara K, Takeda H, Nishi J, Fujita J, Kubota T, Sunagawa T, Matsui T, Oishi K; Adult IPD Study Group.
Invasive pneumococcal disease among adults in Japan, April 2013 to March 2015: disease characteristics and serotype distribution.
BMC Infect Dis. 2017 Jan 3;17(1):2. doi: 10.1186/s12879-016-2113-y. Epub 2017 Jan 3.
Abstract/Text
BACKGROUND: In Japan, the clinical characteristics and recent serotype distribution among adult patients of invasive pneumococcal disease (IPD) have not been fully investigated since the introduction of the pneumococcal conjugate vaccine (PCV) in children. From November 2010, PCV7 was encouraged by an official program, funded by government, subsequently included in the routine schedule in April 2013, and replaced with a PCV13 in November 2013.
METHODS: Between April 2013 and March 2015, patients with IPD older than 15 years were evaluated based on the enhanced national surveillance in ten prefectures of Japan. The serotype distribution of the isolates was analyzed in these patients.
RESULTS: The analysis included 291 patients: 107 patients (37%) were female and the median age was 70 years. Of 281 patients with available data, 202 (72%) had underlying diseases, including 107 patients (38%) with immunocompromised status. The case fatality proportion for all case was 20%. In subgroup analysis, the case fatality proportion (29%) in immunocompromised patients was much higher than that (0-16%) in each age group of nonimmunocompromised patients (15-39 years, 40-64 years, and ≥ 65 years). While the proportion of bacteremia without any focus (27%) was higher than that (8-10%) in nonimmunocompromised patients, the proportions of vaccine types (PCV13, 32%; PPSV23, 51%) of the causative isolates were lower than those in each age group of nonimmunocompromised patients. Among 291 isolates, the most frequent serotypes were 3 (17%), 19A (13%), and 22F (10%). Twelve percent of the isolates were PCV7 serotypes, 46% were PCV13 serotypes, and 66% were PPSV23 serotypes.
CONCLUSIONS: The majority of adult patients of IPD had underlying diseases, including immunocompromised conditions. A low proportion (12%) of PCV7-type IPD was observed in this population where PCV7 for children had been included in the routine immunization schedule.
Huang SS, Johnson KM, Ray GT, Wroe P, Lieu TA, Moore MR, Zell ER, Linder JA, Grijalva CG, Metlay JP, Finkelstein JA.
Healthcare utilization and cost of pneumococcal disease in the United States.
Vaccine. 2011 Apr 18;29(18):3398-412. doi: 10.1016/j.vaccine.2011.02.088. Epub 2011 Mar 11.
Abstract/Text
BACKGROUND: Streptococcus pneumoniae continues to cause a variety of common clinical syndromes, despite vaccination programs for both adults and children. The total U.S. burden of pneumococcal disease is unknown.
METHODS: We constructed a decision tree-based model to estimate U.S. healthcare utilization and costs of pneumococcal disease in 2004. Data were obtained from the 2004-2005 National (Hospital) Ambulatory Medical Care Surveys (outpatient visits, antibiotics) and the National Hospital Discharge Survey (hospitalization rates), and CDC surveillance data. Other assumptions regarding the incidence of each syndrome due to pneumococcus, expected health outcomes, and healthcare utilization were derived from literature and expert opinion. Healthcare and time costs used 2007 dollars.
RESULTS: We estimate that, in 2004, pneumococcal disease caused 4.0 million illness episodes, 22,000 deaths, 445,000 hospitalizations, 774,000 emergency department visits, 5.0 million outpatient visits, and 4.1 million outpatient antibiotic prescriptions. Direct medical costs totaled $3.5 billion. Pneumonia (866,000 cases) accounted for 22% of all cases and 72% of pneumococcal costs. In contrast, acute otitis media and sinusitis (1.5 million cases each) comprised 75% of cases but only 16% of direct medical costs. Patients ≥ 65 years old, accounted for most serious cases and the majority of direct medical costs ($1.8 billion in healthcare costs annually). In this age group, pneumonia caused 242,000 hospitalizations, 1.4 million hospital days, 194,000 emergency department visits, 374,000 outpatient visits, and 16,000 deaths. However, if work loss and productivity are considered, the cost of pneumococcal disease among younger working adults (18-<50) nearly equaled those ≥ 65.
CONCLUSIONS: Pneumococcal disease remains a substantial cause of morbidity and mortality even in the era of routine pediatric and adult vaccination. Continued efforts are warranted to reduce serious pneumococcal disease, especially adult pneumonia.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Vadlamudi NK, Parhar K, Altre Malana KL, Kang A, Marra F.
Immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine compared to 23-valent pneumococcal polysaccharide in immunocompetent adults: A systematic review and meta-analysis.
Vaccine. 2019 Feb 14;37(8):1021-1029. doi: 10.1016/j.vaccine.2019.01.014. Epub 2019 Jan 23.
Abstract/Text
BACKGROUND: Despite the use of 23-valent pneumococcal polysaccharide vaccine (PPV23) in adults there is substantial morbidity and mortality in the elderly due to pneumococcal infections. Since 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) is in use for infant immunization programs to reduce rates of pneumococcal disease, but is not routinely used in adults. Recent literature suggests PCV13 may be used in adult vaccination programs as well.
OBJECTIVE: To determine the immunogenicity and safety of PCV13 compared with the PPV23 in adults.
DESIGN: Systematic review and meta-analysis.
SETTING: Randomized controlled trials evaluating immunogenicity of a single dose of PCV13 and PPV23 in adults by the opsonophagocytic assay (OPA) geometric mean titer (GMT) response at 1-month post-vaccination were considered for inclusion.
RESULTS: Five randomized trials were included with 4561 subjects ranging 50-95.5 years, consisting of 51% females. The pooled OPA GMT ratio (GMTR) in the PCV13 arm was significantly higher for 10 of 13 serotypes (1, 4, 5, 6A, 6B, 9V, 18C, 19A, 19F and 23F) compared with the PPV23 arm. Overall, pooled risk ratios (RR) for local and systemic reactions did not differ between PCV13 and PPV23. Pneumococcal naïve subjects experienced significantly higher local reactions in the PCV13 arm compared with the PPV23 arm (RR: 1.15, 95%CI: 1.05-1.26, p = 0.0025).
CONCLUSION: A single dose of PCV13 elicits a better immune response among adults compared with PPV23, while having a similar safety profile to PPV23.
Copyright © 2019 Elsevier Ltd. All rights reserved.
Haranaka M, Yono M, Kishino H, Igarashi R, Oshima N, Sawata M, Platt HL.
Safety, tolerability, and immunogenicity of a 21-valent pneumococcal conjugate vaccine, V116, in Japanese healthy adults: A Phase I study.
Hum Vaccin Immunother. 2023 Aug 1;19(2):2228162. doi: 10.1080/21645515.2023.2228162.
Abstract/Text
V116 is an investigational 21-valent pneumococcal conjugate vaccine (PCV) to address the burden of residual adult pneumococcal disease after the introduction of pediatric PCVs into national immunization programs (NIPs) and includes serotypes highly prevalent in adult invasive pneumococcal disease (IPD). This Phase I study assessed the safety, tolerability, and immunogenicity of V116 in Japanese adults. Participants ≥20 years of age were randomized to receive a single dose of V116 or 23-valent pneumococcal polysaccharide vaccine (PPSV23) at day 1. Outcomes were solicited injection-site and systemic adverse events (AEs) from day 1 to day 5, vaccine-related serious AEs from day 1 through day 30, and serotype-specific opsonophagocytic antibody (OPA) titers and immunoglobulin G (IgG) concentrations at day 30. Overall, 102 participants were randomized 1:1 to each group. Comparable proportions vaccinated with V116 and PPSV23 experienced ≥1 solicited injection-site AE and ≥1 solicited systemic AE. The most common injection-site AEs were injection-site pain (V116: 54.9%; PPSV23: 66.7%) and swelling (V116 and PPSV23: 13.7%), and the most common systemic AEs were myalgia (V116: 17.6%; PPSV23: 19.6%) and fatigue (V116: 13.7%; PPSV23: 9.8%). Solicited AEs were mostly mild and of ≤3 days duration. No vaccine-related serious AEs or deaths were reported. The OPA and IgG findings showed that the immunogenicity of V116 and PPSV23 were comparable for the 12 common serotypes and V116 was more immunogenic for the nine unique serotypes compared with PPSV23. V116 was well tolerated, with a safety profile similar to PPSV23, and induced functional antibodies against all 21 serotypes.
Maeda H, Gopal Dhoubhadel B, Sando E, Suzuki M, Furumoto A, Asoh N, Yaegashi M, Aoshima M, Ishida M, Hamaguchi S, Otsuka Y, Morimoto K.
Long-term impact of pneumococcal conjugate vaccines for children on adult pneumococcal pneumonia in Japan: Two multicenter observational studies from 2011 to 2020.
Vaccine. 2022 Sep 2;40(37):5504-5512. doi: 10.1016/j.vaccine.2022.07.041. Epub 2022 Aug 10.
Abstract/Text
BACKGROUND: Pediatric pneumococcal conjugate vaccines (PCVs) introduction has directly and indirectly reduced pneumococcal pneumonia and invasive disease caused by PCV-covered serotypes among children and adults globally. In Japan, both PCV7 and PCV13 were introduced into the national immunization program (NIP) for children in 2013. However, the long-term impact of PCV use in children on adult pneumococcal pneumonia in Japan remains unclear.
METHODS: We assessed serotypes isolated from adult pneumococcal pneumonia patients (in- and outpatients) in two multicenter observational studies in Japan: 2011-2014 and 2016-2020. The latter study period was divided into two periods to evaluate changes after PCV introduction in children. The Quellung reaction was used to determine serotypes. We evaluated trends of individual and vaccine-covered serotypes over three periods and assessed the difference in changes by patient group before and after the introduction of pediatric PCVs.
RESULTS: A total of 650 patients were enrolled: 224, 322, and 104 in 2011-2014, 2016-2017, and 2018-2020, respectively. The median age was 73 years; 59.7% (388/650) were male; 86.9% (565/650) had comorbidities; and 10.2% (66/650) were nursing-home residents. The proportion of PCV13 serotypes decreased from 52.7% in 2011-2014 to 30.4% in 2016-2017 (p <0.001) after PCV13 introduction for children. However, PCV13, PCV15, and PCV20 serotypes still accounted for 38.5, 43.3, and 59.6% of total pneumococcal pneumonia in 2018-2020, respectively. Decline of PCV13 serotypes was more marked in patients aged ≥65 (-23.5%; p <0.001) than those aged <65 (-12.3%; p = 0.104) from 2011-2014 to 2016-2020. The proportion of PPSV23 non-PCV13 serotypes didn't change over time.
CONCLUSIONS: The proportion of adult pneumococcal pneumonia caused by PCV13 serotypes in Japan declined after pediatric PCVs introduction into NIP, possibly due to indirect effects of pediatric PCVs. However, use of new PCVs in Japanese adults may potentially prevent additional pneumococcal pneumonia cases. Now, pneumococcal vaccination strategy for older adults requires discussion.
Copyright © 2022. Published by Elsevier Ltd.
Kobayashi M, Pilishvili T, Farrar JL, Leidner AJ, Gierke R, Prasad N, Moro P, Campos-Outcalt D, Morgan RL, Long SS, Poehling KA, Cohen AL.
Pneumococcal Vaccine for Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023.
MMWR Recomm Rep. 2023 Sep 8;72(3):1-39. doi: 10.15585/mmwr.rr7203a1. Epub 2023 Sep 8.
Abstract/Text
THIS REPORT COMPILES AND SUMMARIZES ALL PUBLISHED RECOMMENDATIONS FROM CDC’S ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) FOR USE OF PNEUMOCOCCAL VACCINES IN ADULTS AGED ≥19 YEARS IN THE UNITED STATES. THIS REPORT ALSO INCLUDES UPDATED AND NEW CLINICAL GUIDANCE FOR IMPLEMENTATION FROM CDC:
BEFORE 2021, ACIP RECOMMENDED 23-VALENT PNEUMOCOCCAL POLYSACCHARIDE VACCINE (PPSV23) ALONE (UP TO 2 DOSES), OR BOTH A SINGLE DOSE OF 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE (PCV13) IN COMBINATION WITH 1–3 DOSES OF PPSV23 IN SERIES (PCV13 FOLLOWED BY PPSV23), FOR USE IN U.S. ADULTS DEPENDING ON AGE AND UNDERLYING RISK FOR PNEUMOCOCCAL DISEASE. IN 2021, TWO NEW PNEUMOCOCCAL CONJUGATE VACCINES (PCVS), A 15-VALENT AND A 20-VALENT PCV (PCV15 AND PCV20), WERE LICENSED FOR USE IN U.S. ADULTS AGED ≥18 YEARS BY THE FOOD AND DRUG ADMINISTRATION:
ACIP RECOMMENDATIONS SPECIFY THE USE OF EITHER PCV20 ALONE OR PCV15 IN SERIES WITH PPSV23 FOR ALL ADULTS AGED ≥65 YEARS AND FOR ADULTS AGED 19–64 YEARS WITH CERTAIN UNDERLYING MEDICAL CONDITIONS OR OTHER RISK FACTORS WHO HAVE NOT RECEIVED A PCV OR WHOSE VACCINATION HISTORY IS UNKNOWN. IN ADDITION, ACIP RECOMMENDS USE OF EITHER A SINGLE DOSE OF PCV20 OR ≥1 DOSE OF PPSV23 FOR ADULTS WHO HAVE STARTED THEIR PNEUMOCOCCAL VACCINE SERIES WITH PCV13 BUT HAVE NOT RECEIVED ALL RECOMMENDED PPSV23 DOSES. SHARED CLINICAL DECISION-MAKING IS RECOMMENDED REGARDING USE OF A SUPPLEMENTAL PCV20 DOSE FOR ADULTS AGED ≥65 YEARS WHO HAVE COMPLETED THEIR RECOMMENDED VACCINE SERIES WITH BOTH PCV13 AND PPSV23:
UPDATED AND NEW CLINICAL GUIDANCE FOR IMPLEMENTATION FROM CDC INCLUDES THE RECOMMENDATION FOR USE OF PCV15 OR PCV20 FOR ADULTS WHO HAVE RECEIVED PPSV23 BUT HAVE NOT RECEIVED ANY PCV DOSE. THE REPORT ALSO INCLUDES CLINICAL GUIDANCE FOR ADULTS WHO HAVE RECEIVED 7-VALENT PCV (PCV7) ONLY AND ADULTS WHO ARE HEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS:
O'Brien KL, Hochman M, Goldblatt D.
Combined schedules of pneumococcal conjugate and polysaccharide vaccines: is hyporesponsiveness an issue?
Lancet Infect Dis. 2007 Sep;7(9):597-606. doi: 10.1016/S1473-3099(07)70210-4.
Abstract/Text
Streptococcus pneumoniae is a major cause of morbidity and mortality in children less than 5 years of age. Prevention of pneumococcal disease and death in children in the developing world through vaccination with recently developed, highly efficacious pneumococcal conjugate vaccines (PCVs) is now possible. Schedules combining PCV with 23-valent pneumococcal polysaccharide vaccine (PPV23) have been studied and proposed as a means to expand disease protection against serotypes not included in the PCVs. Studies of group A and C meningococcal polysaccharide vaccine and repeated doses of PPV23 in adults and children have shown that a state of immune tolerance, or hyporesponsiveness, can develop to repeated polysaccharide vaccine antigen exposures. In this Review, we describe the evidence for and against this hyporesponsiveness and explore the possible mechanisms for such an occurrence.
Hammitt LL, Bulkow LR, Singleton RJ, Nuorti JP, Hummel KB, Miernyk KM, Zanis C, Whaley M, Romero-Steiner S, Butler JC, Rudolph K, Hennessy TW.
Repeat revaccination with 23-valent pneumococcal polysaccharide vaccine among adults aged 55-74 years living in Alaska: no evidence of hyporesponsiveness.
Vaccine. 2011 Mar 9;29(12):2287-95. doi: 10.1016/j.vaccine.2011.01.029. Epub 2011 Jan 19.
Abstract/Text
BACKGROUND: Older adults are at highest risk of invasive pneumococcal disease (IPD) and are recommended to receive vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23). Antibody concentrations decline following vaccination. We evaluated the immunogenicity and reactogenicity of revaccination and repeat revaccination.
METHODS: Adults aged 55-74 years were vaccinated with a 1st to 4th dose of PPV23. Participants were eligible for revaccination if a minimum of 6 years had passed since their last dose of PPV23. Blood collected on the day of vaccination and 30 days later was analyzed by ELISA for IgG to five serotypes. Functional antibody activity was measured using an opsonophagocytic killing (OPK) assay. Reactions to vaccination were documented.
RESULTS: Subjects were vaccinated with a 1st dose (n=123), 2nd dose (n=121), or 3rd or 4th dose (n=71) of PPV23. The post-vaccination IgG geometric mean concentrations (GMCs) were similar among first-time vaccinees and re-vaccinees for all serotypes with the exception of a lower GMC for serotype 1 in re-vaccinees. The post-vaccination OPK geometric mean titers (GMTs) were similar among first-time vaccinees and re-vaccinees with the exception of a higher GMT for serotype 6B in re-vaccinees. Compared to first-time vaccinees, re-vaccinees reported more joint pain (p=0.004), fatigue (p=0.019), headache (p=0.014), swelling (p=0.006), and moderate limitation in arm movement (p=0.025).
CONCLUSIONS: Repeat revaccination with PPV23, administered 6 or more years after the prior dose, was immunogenic and generally well tolerated.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Manoff SB, Liss C, Caulfield MJ, Marchese RD, Silber J, Boslego J, Romero-Steiner S, Rajam G, Glass NE, Whitney CG, Carlone GM.
Revaccination with a 23-valent pneumococcal polysaccharide vaccine induces elevated and persistent functional antibody responses in adults aged 65 > or = years.
J Infect Dis. 2010 Feb 15;201(4):525-33. doi: 10.1086/651131.
Abstract/Text
BACKGROUND: Older adults are at high risk of developing invasive pneumococcal disease, but the optimal timing and number of vaccine doses needed to prevent disease among this group are unknown. We compared revaccination with 23-valent pneumococcal polysaccharide vaccine (PN23) with primary vaccination for eliciting initial and persistent functional antibody responses.
METHODS: Subjects aged > or = 65 years were enrolled. Functional (opsonic) and total immunoglobulin (Ig) G antibody levels were measured following either PN23 primary vaccination (n = 60) or revaccination 3-5 years after receiving a first PN23 vaccination (n = 60). Antibody against vaccine serotypes 4, 14, and 23F was measured at prevaccination (day 0), 30 days after vaccination, and 5 years after vaccination.
RESULTS: By day 30, both primary vaccination and revaccination induced significant increases in opsonic and IgG antibody levels. Day 30 levels following revaccination were slightly lower but not significantly different than those after primary vaccination. Year 5 levels were similar in both groups and remained significantly higher than prevaccination levels for primary vaccination subjects. There was good agreement between postvaccination opsonic and IgG antibody levels.
CONCLUSIONS: Revaccination of older adults with PN23 was comparable to primary vaccination for inducing elevated and persistent functional and IgG antibody responses.
Falkenhorst G, Remschmidt C, Harder T, Hummers-Pradier E, Wichmann O, Bogdan C.
Effectiveness of the 23-Valent Pneumococcal Polysaccharide Vaccine (PPV23) against Pneumococcal Disease in the Elderly: Systematic Review and Meta-Analysis.
PLoS One. 2017;12(1):e0169368. doi: 10.1371/journal.pone.0169368. Epub 2017 Jan 6.
Abstract/Text
BACKGROUND: Routine vaccination of elderly people against pneumococcal diseases is recommended in many countries. National guidelines differ, recommending either the 23-valent polysaccharide vaccine (PPV23), the 13-valent conjugate vaccine (PCV13) or both. Considering the ongoing debate on the effectiveness of PPV23, we performed a systematic literature review and meta-analysis of the vaccine efficacy/effectiveness (VE) of PPV23 against invasive pneumococcal disease (IPD) and pneumococcal pneumonia in adults aged ≥60 years living in industrialized countries.
METHODS: We searched for pertinent clinical trials and observational studies in databases MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. We assessed the risk of bias of individual studies using the Cochrane Risk of Bias tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. We rated the overall quality of the evidence by GRADE criteria. We performed meta-analyses of studies grouped by outcome and study design using random-effects models. We applied a sensitivity analysis excluding studies with high risk of bias.
RESULTS: We identified 17 eligible studies. Pooled VE against IPD (by any serotype) was 73% (95%CI: 10-92%) in four clinical trials, 45% (95%CI: 15-65%) in three cohort studies, and 59% (95%CI: 35-74%) in three case-control studies. After excluding studies with high risk of bias, pooled VE against pneumococcal pneumonia (by any serotype) was 64% (95%CI: 35-80%) in two clinical trials and 48% (95%CI: 25-63%) in two cohort studies. Higher VE estimates in trials (follow-up ~2.5 years) than in observational studies (follow-up ~5 years) may indicate waning protection. Unlike previous meta-analyses, we excluded two trials with high risk of bias regarding the outcome pneumococcal pneumonia, because diagnosis was based on serologic methods with insufficient specificity.
CONCLUSIONS: Our meta-analysis revealed significant VE of PPV23 against both IPD and pneumococcal pneumonia by any serotype in the elderly, comparable to the efficacy of PCV13 against vaccine-serotype disease in a recent clinical trial in elderly people. Due to its broader serotype coverage and the decrease of PCV13 serotypes among adults resulting from routine infant immunization with PCV13, PPV23 continues to play an important role for protecting adults against IPD and pneumococcal pneumonia.
Moberley S, Holden J, Tatham DP, Andrews RM.
Vaccines for preventing pneumococcal infection in adults.
Cochrane Database Syst Rev. 2013 Jan 31;2013(1):CD000422. doi: 10.1002/14651858.CD000422.pub3. Epub 2013 Jan 31.
Abstract/Text
BACKGROUND: Diseases caused by Streptococcus pneumoniae (S. pneumoniae) continue to cause substantial morbidity and mortality globally. Whilst pneumococcal polysaccharide vaccines (PPVs) have the potential to prevent disease and death, the degree of protection afforded against various clinical endpoints and within different populations is uncertain.
OBJECTIVES: To assess the efficacy and effectiveness of PPVs in preventing pneumococcal disease or death in adults. We did not assess adverse events.
SEARCH METHODS: We searched CENTRAL 2012, Issue 6, MEDLINE (January 1966 to June Week 2, 2012) and EMBASE (1974 to June 2012).
SELECTION CRITERIA: We considered randomised controlled trials (RCTs) in adults, provided the study outcome met the definition of the outcome considered in the review. We also considered non-RCTs in adults, where the study assessed PPV effectiveness against culture-confirmed invasive pneumococcal disease (IPD), provided the study controlled for important confounding factors.
DATA COLLECTION AND ANALYSIS: Two review authors assessed trial quality of RCTs and three review authors extracted the data. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using a random-effects model. Two review authors assessed study quality and extracted data for non-RCTs. We calculated ORs and 95% CIs using a random-effects model following the conversion of each study outcome to a log OR and standard error (SE).
MAIN RESULTS: Twenty-five studies met our inclusion criteria (18 RCTs involving 64,852 participants and seven non-RCTs involving 62,294 participants). Meta-analysis of the RCTs found strong evidence of PPV efficacy against IPD with no statistical heterogeneity (OR 0.26, 95% CI 0.14 to 0.45; random-effects model, I(2) statistic = 0%). There was efficacy against all-cause pneumonia in low-income (OR 0.54, 95% CI 0.43 to 0.67, I(2) statistic = 19%) but not high-income countries in either the general population (OR 0.71, 95% CI 0.45 to 1.12, I(2) statistic = 93%) or in adults with chronic illness (OR 0.93, 95% CI 0.73 to 1.19, I(2) statistic = 10%). PPV was not associated with substantial reductions in all-cause mortality (OR 0.90, 95% CI 0.74 to 1.09; random-effects model, I(2) statistic = 69%). Vaccine efficacy against primary outcomes appeared poorer in adults with chronic illness. Non-RCTs provided evidence for protection against IPD in populations for whom the vaccine is currently utilised (OR 0.48, 95% CI 0.37 to 0.61; random-effects model, I(2) statistic = 31%). This review did not consider adverse events as it was outside the scope of the review.
AUTHORS' CONCLUSIONS: This meta-analysis provides evidence supporting the recommendation for PPV to prevent IPD in adults. The evidence from RCTs is less clear with respect to adults with chronic illness. This might be because of lack of effect or lack of power in the studies. The meta-analysis does not provide evidence to support the routine use of PPV to prevent all-cause pneumonia or mortality.
Suzuki M, Dhoubhadel BG, Ishifuji T, Yasunami M, Yaegashi M, Asoh N, Ishida M, Hamaguchi S, Aoshima M, Ariyoshi K, Morimoto K; Adult Pneumonia Study Group-Japan (APSG-J).
Serotype-specific effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumococcal pneumonia in adults aged 65 years or older: a multicentre, prospective, test-negative design study.
Lancet Infect Dis. 2017 Mar;17(3):313-321. doi: 10.1016/S1473-3099(17)30049-X. Epub 2017 Jan 24.
Abstract/Text
BACKGROUND: The serotype-specific effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) against pneumococcal pneumonia has not been established in people aged 65 years or older. We assessed the effectiveness of PPV23 in this population.
METHODS: For this multicentre, prospective study, we enrolled all individuals aged 65 years or older with community-onset pneumonia who visited four study hospitals in Japan between Sept 28, 2011, and Aug 23, 2014. Streptococcus pneumoniae was isolated from sputum and blood samples, and serotyped by the capsular Quellung method. Sputum samples were further tested by PCR assay to identify pneumococcal DNA, and positive samples were examined for 50 serotypes by a nanofluidic real-time PCR assay. Urine samples were tested by a urinary antigen test. Serotype-specific vaccine effectiveness was estimated using the test-negative design.
FINDINGS: 2621 eligible patients visited the study hospitals, of whom 585 did not have sputum samples available and were excluded from our analysis. 419 (21%) of 2036 patients were positive for pneumococcal infection (232 by sputum culture, 317 by sputum PCR, 197 by urinary antigen test, and 14 by blood culture). 522 (26%) patients were judged to be vaccinated in the analyses. Effectiveness of PPV23 was 27·4% (95% CI 3·2 to 45·6) against all pneumococcal pneumonia, 33·5% (5·6 to 53·1) against PPV23 serotypes, and 2·0% (-78·9 to 46·3) against non-PPV23 serotypes. Although no significant differences between subgroups were seen, higher protection was noted in people younger than 75 years, women, and individuals with lobar pneumonia or health-care-associated pneumonia.
INTERPRETATION: PPV23 showed low to moderate effectiveness against vaccine serotype pneumococcal pneumonia in people aged 65 years or older. To improve the current pneumococcal vaccination programme, the variability of PPV23 effectiveness in different groups of older people must be further investigated.
FUNDING: Pfizer and Nagasaki University.
Copyright © 2017 Elsevier Ltd. All rights reserved.
Shimbashi R, Suzuki M, Chang B, Watanabe H, Tanabe Y, Kuronuma K, Oshima K, Maruyama T, Takeda H, Kasahara K, Fujita J, Nishi J, Kubota T, Tanaka-Taya K, Matsui T, Sunagawa T, Oishi K; Adult IPD Study Group.
Effectiveness of 23-Valent Pneumococcal Polysaccharide Vaccine against Invasive Pneumococcal Disease in Adults, Japan, 2013-2017.
Emerg Infect Dis. 2020 Oct;26(10):2378-2386. doi: 10.3201/eid2610.191531.
Abstract/Text
The decline in the proportion of pneumococcal conjugate vaccine (PCV)-covered serotypes among adult invasive pneumococcal disease (IPD) patients might change the overall effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) because its effectiveness differs according to serotype. Using the indirect cohort method, we calculated the effectiveness of PPSV23 against IPD among adults in Japan to assess the impact of the national pediatric PCV program. Clinical and epidemiologic information and pneumococcal isolates were collected from IPD patients >20 years of age through enhanced IPD surveillance during April 2013-December 2017. Adjusted effectiveness against PPSV23-serotype IPD was 42.2%. Despite a substantial decline in the proportion of 13-valent PCV serotypes during the study period (45% to 31%), the change in effectiveness for PPSV23-serotype IPD was limited (47.1% to 39.3%) and only marginal in the elderly population (39.9% to 39.4%). The pediatric PCV program had limited impact on PPSV23 effectiveness against IPD in adults.
Yamana H, Ono S, Michihata N, Uemura K, Jo T, Yasunaga H.
Effect of the 23-valent pneumococcal polysaccharide vaccine on the incidence of hospitalization with pneumonia in adults aged ≥65 years: retrospective cohort study using a population-based database in Japan.
Clin Microbiol Infect. 2023 Jul;29(7):904-910. doi: 10.1016/j.cmi.2023.04.006. Epub 2023 Apr 10.
Abstract/Text
OBJECTIVES: The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV23) in preventing pneumonia in older adults remains controversial. Some studies have suggested differences in their effectiveness according to age or sex.
METHODS: We conducted an observational study using a database of vaccine subsidization data and health insurance claims for a city in Japan. Participants were residents from 2014 to 2018 turning 65, 70, 75, 80, 85, 90, or 95 years during a given fiscal year, and PPV23 during the first year of observation were identified. We matched vaccinated and non-vaccinated individuals of the same age using propensity scores for vaccination. The incidence of hospitalization with pneumonia was compared using the Fine-Gray regression model. We summarized the results for each age using random-effects meta-analysis and conducted a subgroup analysis by sex.
RESULTS: A total of 102 136 participants were included, of whom 35% received PPV23. Propensity score matching selected 32 510 pairs of vaccinated and non-vaccinated individuals. Overall, PPV23 administration was associated with a decreased incidence of hospitalization with pneumonia (17.2 vs. 20.4 per 1000 person-years, sub-distribution hazard ratio: 0.84, 95% CI: 0.77 to 0.91). Vaccine effectiveness was the highest among those aged 70 years and decreased with increasing age. No statistically significant effect was observed in those aged 90 or 95 years. Vaccine effectiveness was observed in both males and females.
CONCLUSIONS: PPV23 was associated with an overall decrease in hospitalization with pneumonia in older adults. However, vaccine effectiveness was significant in those aged 65 to 85 years but not in the older population.
Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Bonten MJ, Huijts SM, Bolkenbaas M, Webber C, Patterson S, Gault S, van Werkhoven CH, van Deursen AM, Sanders EA, Verheij TJ, Patton M, McDonough A, Moradoghli-Haftvani A, Smith H, Mellelieu T, Pride MW, Crowther G, Schmoele-Thoma B, Scott DA, Jansen KU, Lobatto R, Oosterman B, Visser N, Caspers E, Smorenburg A, Emini EA, Gruber WC, Grobbee DE.
Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults.
N Engl J Med. 2015 Mar 19;372(12):1114-25. doi: 10.1056/NEJMoa1408544.
Abstract/Text
BACKGROUND: Pneumococcal polysaccharide conjugate vaccines prevent pneumococcal disease in infants, but their efficacy against pneumococcal community-acquired pneumonia in adults 65 years of age or older is unknown.
METHODS: In a randomized, double-blind, placebo-controlled trial involving 84,496 adults 65 years of age or older, we evaluated the efficacy of 13-valent polysaccharide conjugate vaccine (PCV13) in preventing first episodes of vaccine-type strains of pneumococcal community-acquired pneumonia, nonbacteremic and noninvasive pneumococcal community-acquired pneumonia, and invasive pneumococcal disease. Standard laboratory methods and a serotype-specific urinary antigen detection assay were used to identify community-acquired pneumonia and invasive pneumococcal disease.
RESULTS: In the per-protocol analysis of first episodes of infections due to vaccine-type strains, community-acquired pneumonia occurred in 49 persons in the PCV13 group and 90 persons in the placebo group (vaccine efficacy, 45.6%; 95.2% confidence interval [CI], 21.8 to 62.5), nonbacteremic and noninvasive community-acquired pneumonia occurred in 33 persons in the PCV13 group and 60 persons in the placebo group (vaccine efficacy, 45.0%; 95.2% CI, 14.2 to 65.3), and invasive pneumococcal disease occurred in 7 persons in the PCV13 group and 28 persons in the placebo group (vaccine efficacy, 75.0%; 95% CI, 41.4 to 90.8). Efficacy persisted throughout the trial (mean follow-up, 3.97 years). In the modified intention-to-treat analysis, similar efficacy was observed (vaccine efficacy, 37.7%, 41.1%, and 75.8%, respectively), and community-acquired pneumonia occurred in 747 persons in the PCV13 group and 787 persons in placebo group (vaccine efficacy, 5.1%; 95% CI, -5.1 to 14.2). Numbers of serious adverse events and deaths were similar in the two groups, but there were more local reactions in the PCV13 group.
CONCLUSIONS: Among older adults, PCV13 was effective in preventing vaccine-type pneumococcal, bacteremic, and nonbacteremic community-acquired pneumonia and vaccine-type invasive pneumococcal disease but not in preventing community-acquired pneumonia from any cause. (Funded by Pfizer; CAPITA ClinicalTrials.gov number NCT00744263.).
Ewald H, Briel M, Vuichard D, Kreutle V, Zhydkov A, Gloy V.
The Clinical Effectiveness of Pneumococcal Conjugate Vaccines: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Dtsch Arztebl Int. 2016 Mar 4;113(9):139-46. doi: 10.3238/arztebl.2016.0139.
Abstract/Text
BACKGROUND: Streptococcus pneumoniae is responsible for approximately 1.6 million yearly deaths worldwide. An up-to-date evidence base on the effects of pneumococcal conjugate vaccines (PCVs) on infectious diseases and mortality in any population or setting regardless of age or health status is currently lacking.
METHODS: We systematically searched MEDLINE and EMBASE for pertinent randomized controlled trials (RCTs). Two reviewers independently screened 9498 titles/abstracts and 430 full-text papers for eligible trials. The outcomes of our meta-analysis were pooled using relative risks (RRs) with a random effects model or Peto's odds ratios (ORs) if event rates were :lt;1%.
RESULTS: 21 RCTs comprising 361 612 individuals were included. PCVs reduced the risk for invasive pneumococcal disease (odds ratio [OR]: 0.43, 95% confidence interval [CI]: [0.36; 0.51]), all-cause acute otitis media (AOM) (RR: 0.93, 95% CI: [0.86; 1.00]), pneumococcal AOM (RR: 0.57, 95% CI: [0.39; 0.83]), allcause pneumonia (RR: 0.93, 95% CI: [0.89; 0.97]), and pneumococcal pneumonia (RR: 0.78, 95% CI: [0.62; 0.97]). We found no significant effect of PCVs on all-cause mortality (RR: 0.95, 95% CI: [0.88; 1.03]) or recurrent AOM (RR: 0.87, 95% CI: [0.72; 1.05]).
CONCLUSION: PCVs are associated with large risk reductions for pneumococcal infectious diseases, smaller risk reductions for infectious diseases from any cause, and no significant effect on all-cause mortality.
Suga S, Chang B, Asada K, Akeda H, Nishi J, Okada K, Wakiguchi H, Maeda A, Oda M, Ishiwada N, Saitoh A, Oishi T, Hosoya M, Togashi T, Oishi K, Ihara T.
Nationwide population-based surveillance of invasive pneumococcal disease in Japanese children: Effects of the seven-valent pneumococcal conjugate vaccine.
Vaccine. 2015 Nov 9;33(45):6054-60. doi: 10.1016/j.vaccine.2015.07.069. Epub 2015 Jul 31.
Abstract/Text
BACKGROUND: In Japan, the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2010. PCV13 has replaced PCV7 since November 2013.
METHODS: The effectiveness of PCV7 in protecting against invasive pneumococcal disease (IPD) in children aged <5 years was evaluated in a nationwide active population-based surveillance of IPD in 2008-2013 in 10 prefectures in Japan.
RESULTS: 1181 cases were identified; 711 pneumococcal strains were analyzed for serotyping and antimicrobial resistance. Compared with the baseline IPD incidence (25.0 per 100,000), a 98% decline in IPD caused by PCV7 serotypes was found after the introduction of PCV7. This was partially offset by an increased incidence of IPD caused by PCV13 minus PCV7 and non-PCV13 serotypes, resulting in a 57% decline in overall IPD incidence. Absolute increases in the incidence rates of IPD caused by PCV13 minus PCV7 and non-PCV13 serotypes were 2.1 and 2.8 per 100,000 during the study period, respectively. The proportion of meropenem-nonsusceptible strains, especially with serotypes 19A and 15A, increased significantly after PCV7 introduction.
CONCLUSIONS: Our data confirmed a 98% decline in IPD incidence caused by PCV7 serotypes in children aged <5 years and serotype replacement after PCV7 introduction. This shows the importance of continuing surveillance of serotypes responsible for IPD and their antimicrobial resistance in Japan.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Pilishvili T, Lexau C, Farley MM, Hadler J, Harrison LH, Bennett NM, Reingold A, Thomas A, Schaffner W, Craig AS, Smith PJ, Beall BW, Whitney CG, Moore MR; Active Bacterial Core Surveillance/Emerging Infections Program Network.
Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine.
J Infect Dis. 2010 Jan 1;201(1):32-41. doi: 10.1086/648593.
Abstract/Text
BACKGROUND: Changes in invasive pneumococcal disease (IPD) incidence were evaluated after 7 years of 7-valent pneumococcal conjugate vaccine (PCV7) use in US children.
METHODS: Laboratory-confirmed IPD cases were identified during 1998-2007 by 8 active population-based surveillance sites. We compared overall, age group-specific, syndrome-specific, and serotype group-specific IPD incidence in 2007 with that in 1998-1999 (before PCV7) and assessed potential serotype coverage of new conjugate vaccine formulations.
RESULTS: Overall and PCV7-type IPD incidence declined by 45% (from 24.4 to 13.5 cases per 100,000 population) and 94% (from 15.5 to 1.0 cases per 100,000 population), respectively (P< .01 all age groups). The incidence of IPD caused by serotype 19A and other non-PCV7 types increased from 0.8 to 2.7 cases per 100,000 population and from 6.1 to 7.9 cases per 100,000 population, respectively (P< .01 for all age groups). The rates of meningitis and invasive pneumonia caused by non-PCV7 types increased for all age groups (P< .05), whereas the rates of primary bacteremia caused by these serotypes did not change. In 2006-2007, PCV7 types caused 2% of IPD cases, and the 6 additional serotypes included in an investigational 13-valent conjugate vaccine caused 63% of IPD cases among children <5 years-old.
CONCLUSIONS: Dramatic reductions in IPD after PCV7 introduction in the United States remain evident 7 years later. IPD rates caused by serotype 19A and other non-PCV7 types have increased but remain low relative to decreases in PCV7-type IPD.
Muhammad RD, Oza-Frank R, Zell E, Link-Gelles R, Narayan KM, Schaffner W, Thomas A, Lexau C, Bennett NM, Farley MM, Harrison LH, Reingold A, Hadler J, Beall B, Klugman KP, Moore MR.
Epidemiology of invasive pneumococcal disease among high-risk adults since the introduction of pneumococcal conjugate vaccine for children.
Clin Infect Dis. 2013 Mar;56(5):e59-67. doi: 10.1093/cid/cis971. Epub 2012 Nov 15.
Abstract/Text
BACKGROUND: Certain chronic diseases increase risk for invasive pneumococcal disease (IPD) and are indications for receipt of 23-valent pneumococcal polysaccharide vaccine (PPV23). Since the pediatric introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in 2000, incidence of IPD among adults has declined. The relative magnitude of these indirect effects among persons with and without PPV23 indications is unknown.
METHODS: We evaluated IPD incidence among adults with and without PPV23 indications using population- and laboratory-based data collected during 1998-2009 and estimates of the denominator populations with PPV23 indications from the National Health Interview Survey. We compared rates before and after PCV7 use by age, race, PPV23 indication, and serotype.
RESULTS: The proportion of adult IPD cases with PPV23 indications increased from 51% before to 61% after PCV7 introduction (P < .0001). PCV7-serotype IPD declined among all race, age, and PPV23 indication strata, ranging from 82% to 97%. Overall IPD rates declined in most strata, by up to 65%. However, incidence remained highest among adults with PPV23 indications compared with those without (34.9 vs 8.8 cases per 100 000 population, respectively). Apart from age ≥65 years, diabetes is now the most common indication for PPV23 (20% of all cases vs 10% of cases in 1998-1999).
CONCLUSIONS: Although IPD rates have declined among adults, adults with underlying conditions remain at increased risk of IPD and comprise a larger proportion of adult IPD cases in 2009 compared with 2000. A continued increase in the prevalence of diabetes among US adults could lead to increased burden of pneumococcal disease.
Kawai K, Yawn BP, Wollan P, Harpaz R.
Increasing Incidence of Herpes Zoster Over a 60-year Period From a Population-based Study.
Clin Infect Dis. 2016 Jul 15;63(2):221-6. doi: 10.1093/cid/ciw296. Epub 2016 May 8.
Abstract/Text
BACKGROUND: Temporal increases in the incidence of herpes zoster (HZ) have been reported but studies have examined short study periods, and the cause of the increase remains unknown. We examined the long-term trend of HZ.
METHODS: A population-based cohort study was conducted in Olmsted County, Minnesota, using data from 1945-1960 and 1980-2007. Medical records review of possible cases was performed to confirm incident cases of HZ, the patient's immune status, and prescribing of antivirals for HZ. We examined the relative change in the temporal trend in the incidence rates before and after the introduction of the varicella vaccination program.
RESULTS: Of the 8017 patients with HZ, 58.7% were females and 6.6% were immunocompromised. The age- and sex-adjusted incidence rate of HZ increased from 0.76 per 1000 person-years (PY) (95% confidence interval [CI], .63-.89) in 1945-1949 to 3.15 per 1000 PY (95% CI, 3.04-3.26) in 2000-2007. The rate of increase across the time period was 2.5% per year after adjusting for age and sex (adjusted incidence rate ratio, 1.025 [95% CI, 1.023-1.026]; P < .001). The incidence of HZ significantly increased among all age groups and both sexes. We found no change in the rate of increase before vs after the introduction of the varicella vaccination program.
CONCLUSIONS: The incidence of HZ has increased >4-fold over the last 6 decades. This increase is unlikely to be due to the introduction of varicella vaccination, antiviral therapy, or change in the prevalence of immunocompromised individuals.
© 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.
John AR, Canaday DH.
Herpes Zoster in the Older Adult.
Infect Dis Clin North Am. 2017 Dec;31(4):811-826. doi: 10.1016/j.idc.2017.07.016.
Abstract/Text
Herpes zoster (HZ) is the result of reactivation of latent varicella zoster virus (VZV) and occurs most frequently in older adults. Classically, HZ presents as a unilateral, selflimited, dermatomal rash. Postherpetic neuralgia (PHN) is a common sequela, presenting as severe pain that persists after the rash has resolved. In the elderly, PHN can be debilitating and requires a prompt diagnosis, treatment with antivirals, and adequate pain control. A longer-term pain management strategy is required if PHN occurs. A modestly effective vaccine exists and is recommended for older individuals.
Copyright © 2017 Elsevier Inc. All rights reserved.
Tricco AC, Zarin W, Cardoso R, Veroniki AA, Khan PA, Nincic V, Ghassemi M, Warren R, Sharpe JP, Page AV, Straus SE.
Efficacy, effectiveness, and safety of herpes zoster vaccines in adults aged 50 and older: systematic review and network meta-analysis.
BMJ. 2018 Oct 25;363:k4029. doi: 10.1136/bmj.k4029. Epub 2018 Oct 25.
Abstract/Text
OBJECTIVE: To compare the efficacy, effectiveness, and safety of the herpes zoster live attenuated vaccine with the herpes zoster adjuvant recombinant subunit vaccine or placebo for adults aged 50 and older.
DESIGN: Systematic review with bayesian meta-analysis and network meta-analysis.
DATA SOURCES: Medline, Embase, and Cochrane Library (inception to January 2017), grey literature, and reference lists of included studies.
ELIGIBILITY CRITERIA FOR STUDY SELECTION: Experimental, quasi-experimental, and observational studies that compared the live attenuated vaccine with the adjuvant recombinant subunit vaccine, placebo, or no vaccine in adults aged 50 and older. Relevant outcomes were incidence of herpes zoster (primary outcome), herpes zoster ophthalmicus, post-herpetic neuralgia, quality of life, adverse events, and death.
RESULTS: 27 studies (22 randomised controlled trials) including 2 044 504 patients, along with 18 companion reports, were included after screening 2037 titles and abstracts, followed by 175 full text articles. Network meta-analysis of five randomised controlled trials found no statistically significant differences between the live attenuated vaccine and placebo for incidence of laboratory confirmed herpes zoster. The adjuvant recombinant subunit vaccine, however, was statistically superior to both the live attenuated vaccine (vaccine efficacy 85%, 95% credible interval 31% to 98%) and placebo (94%, 79% to 98%). Network meta-analysis of 11 randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more adverse events at injection sites than the live attenuated vaccine (relative risk 1.79, 95% credible interval 1.05 to 2.34; risk difference 30%, 95% credible interval 2% to 51%) and placebo (5.63, 3.57 to 7.29 and 53%, 30% to 73%, respectively). Network meta-analysis of nine randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more systemic adverse events than placebo (2.28, 1.45 to 3.65 and 20%, 6% to 40%, respectively).
CONCLUSIONS: Using the adjuvant recombinant subunit vaccine might prevent more cases of herpes zoster than using the live attenuated vaccine, but the adjuvant recombinant subunit vaccine also carries a greater risk of adverse events at injection sites.
PROTOCOL REGISTRATION: Prospero CRD42017056389.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, Arbeit RD, Simberkoff MS, Gershon AA, Davis LE, Weinberg A, Boardman KD, Williams HM, Zhang JH, Peduzzi PN, Beisel CE, Morrison VA, Guatelli JC, Brooks PA, Kauffman CA, Pachucki CT, Neuzil KM, Betts RF, Wright PF, Griffin MR, Brunell P, Soto NE, Marques AR, Keay SK, Goodman RP, Cotton DJ, Gnann JW Jr, Loutit J, Holodniy M, Keitel WA, Crawford GE, Yeh SS, Lobo Z, Toney JF, Greenberg RN, Keller PM, Harbecke R, Hayward AR, Irwin MR, Kyriakides TC, Chan CY, Chan IS, Wang WW, Annunziato PW, Silber JL; Shingles Prevention Study Group.
A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.
N Engl J Med. 2005 Jun 2;352(22):2271-84. doi: 10.1056/NEJMoa051016.
Abstract/Text
BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults.
METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia.
RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild.
CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.
Copyright 2005 Massachusetts Medical Society.
Gagliardi AM, Andriolo BN, Torloni MR, Soares BG.
Vaccines for preventing herpes zoster in older adults.
Cochrane Database Syst Rev. 2016 Mar 3;3(3):CD008858. doi: 10.1002/14651858.CD008858.pub3. Epub 2016 Mar 3.
Abstract/Text
BACKGROUND: Herpes zoster, also known as 'shingles', is a neurocutaneous disease characterised by the reactivation of the latent varicella zoster virus (VZV), the virus that causes chickenpox when immunity to VZV declines. It is an extremely painful condition that can last many weeks or months and it can significantly compromise the quality of life of affected individuals. The natural process of aging is associated with a reduction in cellular immunity and this predisposes older people to herpes zoster. Vaccination with an attenuated form of VZV activates specific T cell production avoiding viral reactivation. The Food and Drug Administration has approved a herpes zoster vaccine with an attenuated active virus for clinical use among older adults, which has been tested in large populations. A new adjuvanted recombinant VZV subunit zoster vaccine has also been tested. It consists of recombinant VZV glycoprotein E and a liposome-based AS01B adjuvant system. This new vaccine is not yet available for clinical use.
OBJECTIVES: To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults.
SEARCH METHODS: For this 2015 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 9), MEDLINE (1948 to the 3rd week of October 2015), EMBASE (2010 to October 2015), CINAHL (1981 to October 2015) and LILACS (1982 to October 2015).
SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine with placebo or no vaccine, to prevent herpes zoster in older adults (mean age > 60 years).
DATA COLLECTION AND ANALYSIS: Two review authors independently collected and analysed data using a data extraction form. They also performed 'Risk of bias' assessment.
MAIN RESULTS: We identified 13 studies involving 69,916 participants. The largest study included 38,546 participants. All studies were conducted in high-income countries and included only healthy Caucasian individuals ≥ 60 years of age without immunosuppressive comorbidities. Ten studies used live attenuated varicella zoster virus (VZV) vaccines. Three studies tested a new type of vaccine not yet available for clinical use. We judged five of the included studies to be at low risk of bias.The incidence of herpes zoster, at up to three years of follow-up, was lower in participants who received the vaccine than in those who received a placebo: risk ratio (RR) 0.49; 95% confidence interval (CI) 0.43 to 0.56, risk difference (RD) 2%, number needed to treat to benefit (NNTB) 50; GRADE: moderate quality evidence. The vaccinated group had a higher incidence of mild to moderate intensity adverse events. These date came from one large study that included 38,546 people aged 60 years or older.A study including 8122 participants compared the new vaccine (not yet available) to the placebo; the group that received the new vaccine had a lower incidence of herpes zoster at 3.2 years of follow-up: RR 0.04, 95% CI 0.02 to 0.10, RD 3%, NNTB 33; GRADE: moderate quality evidence. The vaccinated group had a higher incidence of adverse events but most them were of mild to moderate intensity.All studies received funding from the pharmaceutical industry.
AUTHORS' CONCLUSIONS: Herpes zoster vaccine is effective in preventing herpes zoster disease and this protection can last three years. In general, zoster vaccine is well tolerated; it produces few systemic adverse events and injection site adverse events of mild to moderate intensity.There are studies of a new vaccine (with a VZV glycoproteic fraction plus adjuvant), which is currently not yet available for clinical use.
Lal H, Cunningham AL, Godeaux O, Chlibek R, Diez-Domingo J, Hwang SJ, Levin MJ, McElhaney JE, Poder A, Puig-Barberà J, Vesikari T, Watanabe D, Weckx L, Zahaf T, Heineman TC; ZOE-50 Study Group.
Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults.
N Engl J Med. 2015 May 28;372(22):2087-96. doi: 10.1056/NEJMoa1501184. Epub 2015 Apr 28.
Abstract/Text
BACKGROUND: In previous phase 1-2 clinical trials involving older adults, a subunit vaccine containing varicella-zoster virus glycoprotein E and the AS01B adjuvant system (called HZ/su) had a clinically acceptable safety profile and elicited a robust immune response.
METHODS: We conducted a randomized, placebo-controlled, phase 3 study in 18 countries to evaluate the efficacy and safety of HZ/su in older adults (≥50 years of age), stratified according to age group (50 to 59, 60 to 69, and ≥70 years). Participants received two intramuscular doses of the vaccine or placebo 2 months apart. The primary objective was to assess the efficacy of the vaccine, as compared with placebo, in reducing the risk of herpes zoster in older adults.
RESULTS: A total of 15,411 participants who could be evaluated received either the vaccine (7698 participants) or placebo (7713 participants). During a mean follow-up of 3.2 years, herpes zoster was confirmed in 6 participants in the vaccine group and in 210 participants in the placebo group (incidence rate, 0.3 vs. 9.1 per 1000 person-years) in the modified vaccinated cohort. Overall vaccine efficacy against herpes zoster was 97.2% (95% confidence interval [CI], 93.7 to 99.0; P<0.001). Vaccine efficacy was between 96.6% and 97.9% for all age groups. Solicited reports of injection-site and systemic reactions within 7 days after vaccination were more frequent in the vaccine group. There were solicited or unsolicited reports of grade 3 symptoms in 17.0% of vaccine recipients and 3.2% of placebo recipients. The proportions of participants who had serious adverse events or potential immune-mediated diseases or who died were similar in the two groups.
CONCLUSIONS: The HZ/su vaccine significantly reduced the risk of herpes zoster in adults who were 50 years of age or older. Vaccine efficacy in adults who were 70 years of age or older was similar to that in the other two age groups. (Funded by GlaxoSmithKline Biologicals; ZOE-50 ClinicalTrials.gov number, NCT01165177.).
Cunningham AL, Lal H, Kovac M, Chlibek R, Hwang SJ, Díez-Domingo J, Godeaux O, Levin MJ, McElhaney JE, Puig-Barberà J, Vanden Abeele C, Vesikari T, Watanabe D, Zahaf T, Ahonen A, Athan E, Barba-Gomez JF, Campora L, de Looze F, Downey HJ, Ghesquiere W, Gorfinkel I, Korhonen T, Leung E, McNeil SA, Oostvogels L, Rombo L, Smetana J, Weckx L, Yeo W, Heineman TC; ZOE-70 Study Group.
Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older.
N Engl J Med. 2016 Sep 15;375(11):1019-32. doi: 10.1056/NEJMoa1603800.
Abstract/Text
BACKGROUND: A trial involving adults 50 years of age or older (ZOE-50) showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01B adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older (ZOE-70).
METHODS: This randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses of HZ/su or placebo (assigned in a 1:1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against herpes zoster and postherpetic neuralgia was assessed in participants from ZOE-70 and in participants pooled from ZOE-70 and ZOE-50.
RESULTS: In ZOE-70, 13,900 participants who could be evaluated (mean age, 75.6 years) received either HZ/su (6950 participants) or placebo (6950 participants). During a mean follow-up period of 3.7 years, herpes zoster occurred in 23 HZ/su recipients and in 223 placebo recipients (0.9 vs. 9.2 per 1000 person-years). Vaccine efficacy against herpes zoster was 89.8% (95% confidence interval [CI], 84.2 to 93.7; P<0.001) and was similar in participants 70 to 79 years of age (90.0%) and participants 80 years of age or older (89.1%). In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001). Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients (79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two study groups.
CONCLUSIONS: In our trial, HZ/su was found to reduce the risks of herpes zoster and postherpetic neuralgia among adults 70 years of age or older. (Funded by GlaxoSmithKline Biologicals; ZOE-50 and ZOE-70 ClinicalTrials.gov numbers, NCT01165177 and NCT01165229 .).
Strezova A, Diez-Domingo J, Al Shawafi K, Tinoco JC, Shi M, Pirrotta P, Mwakingwe-Omari A; Zoster-049 Study Group.
Long-term Protection Against Herpes Zoster by the Adjuvanted Recombinant Zoster Vaccine: Interim Efficacy, Immunogenicity, and Safety Results up to 10 Years After Initial Vaccination.
Open Forum Infect Dis. 2022 Oct;9(10):ofac485. doi: 10.1093/ofid/ofac485. Epub 2022 Oct 23.
Abstract/Text
Approximately 10 years after vaccination with the recombinant zoster vaccine (RZV), an interim analysis of this follow-up study of the ZOE-50/70 trials demonstrated that efficacy against herpes zoster remained high. Moreover, the safety profile remained clinically acceptable, suggesting that the clinical benefit of the RZV in ≥50-year-olds is sustained up to 10 years.
© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
Zerbo O, Bartlett J, Fireman B, Lewis N, Goddard K, Dooling K, Duffy J, Glanz J, Naleway A, Donahue JG, Klein NP.
Effectiveness of Recombinant Zoster Vaccine Against Herpes Zoster in a Real-World Setting.
Ann Intern Med. 2024 Feb;177(2):189-195. doi: 10.7326/M23-2023. Epub 2024 Jan 9.
Abstract/Text
BACKGROUND: A 2-dose series of recombinant zoster vaccine (RZV) was 97% effective against herpes zoster (HZ) in a pivotal clinical trial.
OBJECTIVE: To evaluate real-world effectiveness of RZV against HZ.
DESIGN: Prospective cohort study.
SETTING: Four health care systems in the Vaccine Safety Datalink.
PARTICIPANTS: Persons aged 50 years or older.
MEASUREMENTS: The outcome was incident HZ defined by a diagnosis with an antiviral prescription. Cox regression was used to estimate the hazard of HZ in vaccinated persons compared with unvaccinated persons, with adjustment for covariates. Vaccine effectiveness (VE) was calculated as 1 minus the adjusted hazard ratio and was estimated by time since the last RZV dose and by corticosteroid use.
RESULTS: The study included nearly 2.0 million persons who contributed 7.6 million person-years of follow-up. After adjustment, VE of 1 dose was 64% and VE of 2 doses was 76%. After 1 dose only, VE was 70% during the first year, 45% during the second year, 48% during the third year, and 52% after the third year. After 2 doses, VE was 79% during the first year, 75% during the second year, and 73% during the third and fourth years. Vaccine effectiveness was 65% in persons who received corticosteroids before vaccination and 77% in those who did not.
LIMITATION: Herpes zoster could not be identified as accurately in these observational data as in the previous clinical trials.
CONCLUSION: Two doses of RZV were highly effective, although less effective than in the previous clinical trials. Two-dose effectiveness waned very little during the 4 years of follow-up. However, 1-dose effectiveness waned substantially after 1 year, underscoring the importance of the second dose.
PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.
Kovac M, Lal H, Cunningham AL, Levin MJ, Johnson RW, Campora L, Volpi A, Heineman TC; ZOE-50/70 Study Group.
Complications of herpes zoster in immunocompetent older adults: Incidence in vaccine and placebo groups in two large phase 3 trials.
Vaccine. 2018 Mar 14;36(12):1537-1541. doi: 10.1016/j.vaccine.2018.02.029. Epub 2018 Feb 17.
Abstract/Text
BACKGROUND: An adjuvanted herpes zoster (HZ) subunit vaccine, HZ/su, demonstrated high efficacy against HZ and postherpetic neuralgia (PHN) in two randomized, observer-blind, placebo-controlled trials in adults aged ≥50 and ≥70 years (ZOE-50 and ZOE-70, respectively).
METHODS: Data from ZOE-50 and ZOE-70 trials were analyzed to evaluate the efficacy of HZ/su against mortality, hospitalizations, and non-PHN complications of HZ including HZ-associated vasculitis, stroke, and disseminated, ophthalmic, neurologic, and visceral diseases.
RESULTS: In the pooled ZOE-50/ZOE-70 analysis, 1 of 32 HZ/su recipients (3.1%) and 16 of 477 placebo recipients (3.4%) with a confirmed HZ episode had complications other than PHN. Efficacy against HZ-related complications was 93.7% (95% confidence interval, 59.5-99.9%) in adults aged ≥50 years and 91.6% (43.3-99.8%) in adults ≥70 years. Five HZ-related hospitalizations, all in placebo recipients, and no HZ-related deaths were reported.
CONCLUSIONS: HZ/su reduces the risk of HZ-associated complications in older adults (NCT01165177; NCT01165229).
Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Taquet M, Dercon Q, Todd JA, Harrison PJ.
The recombinant shingles vaccine is associated with lower risk of dementia.
Nat Med. 2024 Jul 25;. doi: 10.1038/s41591-024-03201-5. Epub 2024 Jul 25.
Abstract/Text
There is emerging evidence that the live herpes zoster (shingles) vaccine might protect against dementia. However, the existing data are limited and refer only to the live vaccine, which is now discontinued in the United States and many other countries in favor of a recombinant vaccine. Whether the recombinant shingles vaccine protects against dementia remains unknown. Here we used a natural experiment opportunity created by the rapid transition from the use of live to the use of recombinant vaccines to compare the risk of dementia between vaccine types. We show that the recombinant vaccine is associated with a significantly lower risk of dementia in the 6 years post-vaccination. Specifically, receiving the recombinant vaccine is associated with a 17% increase in diagnosis-free time, translating into 164 additional days lived without a diagnosis of dementia in those subsequently affected. The recombinant shingles vaccine was also associated with lower risks of dementia than were two other vaccines commonly used in older people: influenza and tetanus-diphtheria-pertussis vaccines. The effect was robust across multiple secondary analyses, and was present in both men and women but was greater in women. These findings should stimulate studies investigating the mechanisms underpinning the protection and could facilitate the design of a large-scale randomized control trial to confirm the possible additional benefit of the recombinant shingles vaccine.
© 2024. The Author(s).
Shi T, Denouel A, Tietjen AK, Campbell I, Moran E, Li X, Campbell H, Demont C, Nyawanda BO, Chu HY, Stoszek SK, Krishnan A, Openshaw P, Falsey AR, Nair H; RESCEU Investigators.
Global Disease Burden Estimates of Respiratory Syncytial Virus-Associated Acute Respiratory Infection in Older Adults in 2015: A Systematic Review and Meta-Analysis.
J Infect Dis. 2020 Oct 7;222(Suppl 7):S577-S583. doi: 10.1093/infdis/jiz059.
Abstract/Text
Respiratory syncytial virus-associated acute respiratory infection (RSV-ARI) constitutes a substantial disease burden in older adults aged ≥65 years. We aimed to identify all studies worldwide investigating the disease burden of RSV-ARI in this population. We estimated the community incidence, hospitalization rate, and in-hospital case-fatality ratio (hCFR) of RSV-ARI in older adults, stratified by industrialized and developing regions, using data from a systematic review of studies published between January 1996 and April 2018 and 8 unpublished population-based studies. We applied these rate estimates to population estimates for 2015 to calculate the global and regional burdens in older adults with RSV-ARI in the community and in hospitals for that year. We estimated the number of in-hospital deaths due to RSV-ARI by combining hCFR data with hospital admission estimates from hospital-based studies. In 2015, there were about 1.5 million episodes (95% confidence interval [CI], .3 million-6.9 million) of RSV-ARI in older adults in industrialized countries (data for developing countries were missing), and of these, approximately 14.5% (214 000 episodes; 95% CI, 100 000-459 000) were admitted to hospitals. The global number of hospital admissions for RSV-ARI in older adults was estimated at 336 000 hospitalizations (uncertainty range [UR], 186 000-614 000). We further estimated about 14 000 in-hospital deaths (UR, 5000-50 000) related to RSV-ARI globally. The hospital admission rate and hCFR were higher for those aged ≥65 years than for those aged 50-64 years. The disease burden of RSV-ARI among older adults is substantial, with limited data from developing countries. Appropriate prevention and management strategies are needed to reduce this burden.
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Branche AR, Saiman L, Walsh EE, Falsey AR, Jia H, Barrett A, Alba L, Phillips M, Finelli L.
Change in functional status associated with respiratory syncytial virus infection in hospitalized older adults.
Influenza Other Respir Viruses. 2022 Nov;16(6):1151-1160. doi: 10.1111/irv.13043. Epub 2022 Sep 7.
Abstract/Text
BACKGROUND: Respiratory syncytial virus (RSV) causes severe respiratory illnesses in infants and older adults. Older adults are frequently hospitalized with RSV illness and may experience loss of function. This study evaluated longitudinal changes in function associated with RSV hospitalization in older adults.
METHODS: Adults ≥60 years hospitalized with laboratory-confirmed RSV were enrolled (N = 302). Demographics and comorbidities were collected. Functional status was assessed 2 weeks pre-hospitalization by recall, at enrollment, hospital discharge and 2, 4, and 6 months post-discharge using the Lawton-Brody Instrumental Activities of Daily Living (IADL) (scale 0-8) and Barthel ADL Index (scale 0-100).
RESULTS: RSV-associated hospitalization resulted in acute functional loss. Median IADL (5 vs. 3, p < 0.0001) and ADL (90 vs. 70, p < 0.0001) scores decreased significantly from pre-hospitalization to admission and remained decreased at discharge. There were no statistically significant differences between pre-hospitalization and 2-, 4-, or 6-month scores. However, 33% and 32% of subjects experienced decreased 6-month IADL and ADL scores, respectively. Additionally, 14% required a higher level of care at discharge. When stratified by pre-hospitalization living situation, 6-month IADL scores declined significantly for those admitted from a skilled nursing facility (3 vs. 1, p = 0.001). In multivariate analysis, male sex and diabetes were associated with a 6-month decline in ADL score of ≥10.
CONCLUSIONS: Older adults hospitalized with RSV demonstrate acute functional decline that may become prolonged. Pre-hospitalization living situation may predict patient outcomes. Further study is needed with hospitalized age-matched controls and refined measurement tools to better define the specific impact of RSV on function.
© 2022 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.
Shi T, Vennard S, Jasiewicz F, Brogden R, Nair H; RESCEU Investigators.
Disease Burden Estimates of Respiratory Syncytial Virus related Acute Respiratory Infections in Adults With Comorbidity: A Systematic Review and Meta-Analysis.
J Infect Dis. 2022 Aug 12;226(Suppl 1):S17-S21. doi: 10.1093/infdis/jiab040.
Abstract/Text
BACKGROUND: Respiratory syncytial virus related acute respiratory infection (RSV-ARI) constitutes a substantial disease burden in adults with comorbidities. We aimed to identify all studies investigating the disease burden of RSV-ARI in this group.
METHODS: We estimated the incidence, hospitalization rate, and in-hospital case fatality ratio (hCFR) of RSV-ARI in adults with comorbidities based on a systematic review of studies published between January 1996 and March 2020. We also investigated the association between RSV-ARI and any comorbidity in adults. Meta-analyses based on random effects model were carried out.
RESULTS: Overall, 20 studies were included. The annual incidence rate of RSV-ARI in adults with any comorbidity was 37.6 (95% confidence interval [CI], 20.1-70.3) per 1000 persons per year in industrialized countries and the seasonal incidence rate was 28.4 (11.4-70.9) per 1000 persons per season. The hCFR in industrialized countries was 11.7% (5.8%-23.4%). There were no studies in developing countries. There were insufficient data to generate the meta-estimate of hospitalization rate. The likelihood of experiencing RSV-ARI for those with any comorbidity compared to those without was estimated to be 4.1 (odds ratio [OR], 1.6-10.4) and 1.1 (OR, 0.6-1.8) from studies using univariable and multivariable analysis respectively.
CONCLUSION: The disease burden of RSV-ARI among adults with comorbidity is substantial with limited data available.
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Surie D, Yuengling KA, DeCuir J, Zhu Y, Gaglani M, Ginde AA, Talbot HK, Casey JD, Mohr NM, Ghamande S, Gibbs KW, Files DC, Hager DN, Ali H, Prekker ME, Gong MN, Mohamed A, Johnson NJ, Steingrub JS, Peltan ID, Brown SM, Leis AM, Khan A, Hough CL, Bender WS, Duggal A, Wilson JG, Qadir N, Chang SY, Mallow C, Kwon JH, Exline MC, Lauring AS, Shapiro NI, Columbus C, Vaughn IA, Ramesh M, Safdar B, Halasa N, Chappell JD, Grijalva CG, Baughman A, Rice TW, Womack KN, Han JH, Swan SA, Mukherjee I, Lewis NM, Ellington S, McMorrow ML, Martin ET, Self WH; IVY Network.
Disease Severity of Respiratory Syncytial Virus Compared with COVID-19 and Influenza Among Hospitalized Adults Aged ≥60 Years - IVY Network, 20 U.S. States, February 2022-May 2023.
MMWR Morb Mortal Wkly Rep. 2023 Oct 6;72(40):1083-1088. doi: 10.15585/mmwr.mm7240a2. Epub 2023 Oct 6.
Abstract/Text
On June 21, 2023, CDC's Advisory Committee on Immunization Practices recommended respiratory syncytial virus (RSV) vaccination for adults aged ≥60 years, offered to individual adults using shared clinical decision-making. Informed use of these vaccines requires an understanding of RSV disease severity. To characterize RSV-associated severity, 5,784 adults aged ≥60 years hospitalized with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 U.S. states during February 1, 2022-May 31, 2023. Multivariable logistic regression was used to compare RSV disease severity with COVID-19 and influenza severity on the basis of the following outcomes: 1) standard flow (<30 L/minute) oxygen therapy, 2) high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV), 3) intensive care unit (ICU) admission, and 4) invasive mechanical ventilation (IMV) or death. Overall, 304 (5.3%) enrolled adults were hospitalized with RSV, 4,734 (81.8%) with COVID-19 and 746 (12.9%) with influenza. Patients hospitalized with RSV were more likely to receive standard flow oxygen, HFNC or NIV, and ICU admission than were those hospitalized with COVID-19 or influenza. Patients hospitalized with RSV were more likely to receive IMV or die compared with patients hospitalized with influenza (adjusted odds ratio = 2.08; 95% CI = 1.33-3.26). Among hospitalized older adults, RSV was less common, but was associated with more severe disease than COVID-19 or influenza. High disease severity in older adults hospitalized with RSV is important to consider in shared clinical decision-making regarding RSV vaccination.
Feldman RG, Antonelli-Incalzi R, Steenackers K, Lee DG, Papi A, Ison MG, Fissette L, David MP, Maréchal C, Van der Wielen M, Kostanyan L, Hulstrøm V; AReSVi-006 Study Group.
Respiratory Syncytial Virus Prefusion F Protein Vaccine Is Efficacious in Older Adults With Underlying Medical Conditions.
Clin Infect Dis. 2024 Jan 25;78(1):202-209. doi: 10.1093/cid/ciad471.
Abstract/Text
BACKGROUND: Older adults with chronic cardiorespiratory or endocrine/metabolic conditions are at increased risk of respiratory syncytial virus (RSV)-related acute respiratory illness (RSV-ARI) and severe respiratory disease. In an ongoing, randomized, placebo-controlled, multicountry, phase 3 trial in ≥60-year-old participants, an AS01E-adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD), severe RSV-LRTD, and RSV-ARI. We evaluated efficacy and immunogenicity among participants with coexisting cardiorespiratory or endocrine/metabolic conditions that increase the risk of severe RSV disease ("conditions of interest").
METHODS: Medically stable ≥60-year-old participants received 1 dose of RSVPreF3 OA or placebo. Efficacy against first RSV-LRTD and RSV-ARI episodes was assessed in subgroups with/without coexisting cardiorespiratory or endocrine/metabolic conditions of interest. Immunogenicity was analyzed post hoc in these subgroups.
RESULTS: In total, 12 467 participants received RSVPreF3 OA and 12 499 received placebo. Of these, 39.6% (RSVPreF3 OA) and 38.9% (placebo) had ≥1 coexisting condition of interest. The median efficacy follow-up was 6.7 months. Efficacy against RSV-LRTD was high in participants with ≥1 condition of interest (94.6%), ≥1 cardiorespiratory (92.1%), ≥1 endocrine/metabolic (100%), and ≥2 conditions of interest (92.0%). Efficacy against RSV-ARI was 81.0% in participants with ≥1 condition of interest (88.1% for cardiorespiratory, 79.4% for endocrine/metabolic conditions) and 88.0% in participants with ≥2 conditions of interest. Postvaccination neutralizing titers were at least as high in participants with ≥1 condition of interest as in those without.
CONCLUSIONS: RSVPreF3 OA was efficacious against RSV-LRTD and RSV-ARI in older adults with coexisting medical conditions associated with an increased risk of severe RSV disease.
CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov: NCT04886596.
© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
Wilson E, Goswami J, Baqui AH, Doreski PA, Perez-Marc G, Zaman K, Monroy J, Duncan CJA, Ujiie M, Rämet M, Pérez-Breva L, Falsey AR, Walsh EE, Dhar R, Wilson L, Du J, Ghaswalla P, Kapoor A, Lan L, Mehta S, Mithani R, Panozzo CA, Simorellis AK, Kuter BJ, Schödel F, Huang W, Reuter C, Slobod K, Stoszek SK, Shaw CA, Miller JM, Das R, Chen GL; ConquerRSV Study Group.
Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults.
N Engl J Med. 2023 Dec 14;389(24):2233-2244. doi: 10.1056/NEJMoa2307079.
Abstract/Text
BACKGROUND: Respiratory syncytial virus (RSV) can cause substantial morbidity and mortality among older adults. An mRNA-based RSV vaccine, mRNA-1345, encoding the stabilized RSV prefusion F glycoprotein, is under clinical investigation.
METHODS: In this ongoing, randomized, double-blind, placebo-controlled, phase 2-3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive one dose of mRNA-1345 (50 μg) or placebo. The two primary efficacy end points were the prevention of RSV-associated lower respiratory tract disease with at least two signs or symptoms and with at least three signs or symptoms. A key secondary efficacy end point was the prevention of RSV-associated acute respiratory disease. Safety was also assessed.
RESULTS: Overall, 35,541 participants were assigned to receive the mRNA-1345 vaccine (17,793 participants) or placebo (17,748). The median follow-up was 112 days (range, 1 to 379). The primary analyses were conducted when at least 50% of the anticipated cases of RSV-associated lower respiratory tract disease had occurred. Vaccine efficacy was 83.7% (95.88% confidence interval [CI], 66.0 to 92.2) against RSV-associated lower respiratory tract disease with at least two signs or symptoms and 82.4% (96.36% CI, 34.8 to 95.3) against the disease with at least three signs or symptoms. Vaccine efficacy was 68.4% (95% CI, 50.9 to 79.7) against RSV-associated acute respiratory disease. Protection was observed against both RSV subtypes (A and B) and was generally consistent across subgroups defined according to age and coexisting conditions. Participants in the mRNA-1345 group had a higher incidence than those in the placebo group of solicited local adverse reactions (58.7% vs. 16.2%) and of systemic adverse reactions (47.7% vs. 32.9%); most reactions were mild to moderate in severity and were transient. Serious adverse events occurred in 2.8% of the participants in each trial group.
CONCLUSIONS: A single dose of the mRNA-1345 vaccine resulted in no evident safety concerns and led to a lower incidence of RSV-associated lower respiratory tract disease and of RSV-associated acute respiratory disease than placebo among adults 60 years of age or older. (Funded by Moderna; ConquerRSV ClinicalTrials.gov number, NCT05127434.).
Copyright © 2023 Massachusetts Medical Society.
Phijffer EW, de Bruin O, Ahmadizar F, Bont LJ, Van der Maas NA, Sturkenboom MC, Wildenbeest JG, Bloemenkamp KW.
Respiratory syncytial virus vaccination during pregnancy for improving infant outcomes.
Cochrane Database Syst Rev. 2024 May 2;5(5):CD015134. doi: 10.1002/14651858.CD015134.pub2. Epub 2024 May 2.
Abstract/Text
BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections (LRTIs) in infants. Maternal RSV vaccination is a preventive strategy of great interest, as it could have a substantial impact on infant RSV disease burden. In recent years, the clinical development of maternal RSV vaccines has advanced rapidly.
OBJECTIVES: To assess the efficacy and safety of maternal respiratory syncytial virus (RSV) vaccination for preventing RSV disease in infants.
SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register and two other trials registries on 21 October 2022. We updated the search on 27 July 2023, when we searched MEDLINE, Embase, CENTRAL, CINAHL, and two trials registries. Additionally, we searched the reference lists of retrieved studies and conference proceedings. There were no language restrictions on our searches.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing maternal RSV vaccination with placebo or no intervention in pregnant women of any age. The primary outcomes were hospitalisation with clinically confirmed or laboratory-confirmed RSV disease in infants. The secondary outcomes covered adverse pregnancy outcomes (intrauterine growth restriction, stillbirth, and maternal death) and adverse infant outcomes (preterm birth, congenital abnormalities, and infant death).
DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods and assessed the certainty of evidence using the GRADE approach.
MAIN RESULTS: We included six RCTs (25 study reports) involving 17,991 pregnant women. The intervention was an RSV pre-F protein vaccine in four studies, and an RSV F protein nanoparticle vaccine in two studies. In all studies, the comparator was a placebo (saline, formulation buffer, or sterile water). We judged four studies at overall low risk of bias and two studies at overall high risk (mainly due to selection bias). All studies were funded by pharmaceutical companies. Maternal RSV vaccination compared with placebo reduces infant hospitalisation with laboratory-confirmed RSV disease (risk ratio (RR) 0.50, 95% confidence interval (CI) 0.31 to 0.82; 4 RCTs, 12,216 infants; high-certainty evidence). Based on an absolute risk with placebo of 22 hospitalisations per 1000 infants, our results represent 11 fewer hospitalisations per 1000 infants from vaccinated pregnant women (15 fewer to 4 fewer). No studies reported infant hospitalisation with clinically confirmed RSV disease. Maternal RSV vaccination compared with placebo has little or no effect on the risk of congenital abnormalities (RR 0.96, 95% CI 0.88 to 1.04; 140 per 1000 with placebo, 5 fewer per 1000 with RSV vaccination (17 fewer to 6 more); 4 RCTs, 12,304 infants; high-certainty evidence). Maternal RSV vaccination likely has little or no effect on the risk of intrauterine growth restriction (RR 1.32, 95% CI 0.75 to 2.33; 3 per 1000 with placebo, 1 more per 1000 with RSV vaccination (1 fewer to 4 more); 4 RCTs, 12,545 pregnant women; moderate-certainty evidence). Maternal RSV vaccination may have little or no effect on the risk of stillbirth (RR 0.81, 95% CI 0.38 to 1.72; 3 per 1000 with placebo, no difference with RSV vaccination (2 fewer to 3 more); 5 RCTs, 12,652 pregnant women). There may be a safety signal warranting further investigation related to preterm birth. This outcome may be more likely with maternal RSV vaccination, although the 95% CI includes no effect, and the evidence is very uncertain (RR 1.16, 95% CI 0.99 to 1.36; 6 RCTs, 17,560 infants; very low-certainty evidence). Based on an absolute risk of 51 preterm births per 1000 infants from pregnant women who received placebo, there may be 8 more per 1000 infants from pregnant women with RSV vaccination (1 fewer to 18 more). There was one maternal death in the RSV vaccination group and none in the placebo group. Our meta-analysis suggests that RSV vaccination compared with placebo may have little or no effect on the risk of maternal death (RR 3.00, 95% CI 0.12 to 73.50; 3 RCTs, 7977 pregnant women; low-certainty evidence). The effect of maternal RSV vaccination on the risk of infant death is very uncertain (RR 0.81, 95% CI 0.36 to 1.81; 6 RCTs, 17,589 infants; very low-certainty evidence).
AUTHORS' CONCLUSIONS: The findings of this review suggest that maternal RSV vaccination reduces laboratory-confirmed RSV hospitalisations in infants. There are no safety concerns about intrauterine growth restriction and congenital abnormalities. We must be careful in drawing conclusions about other safety outcomes owing to the low and very low certainty of the evidence. The evidence available to date suggests RSV vaccination may have little or no effect on stillbirth, maternal death, and infant death (although the evidence for infant death is very uncertain). However, there may be a safety signal warranting further investigation related to preterm birth. This is driven by data from one trial, which is not fully published yet. The evidence base would be much improved by more RCTs with substantial sample sizes and well-designed observational studies with long-term follow-up for assessment of safety outcomes. Future studies should aim to use standard outcome measures, collect data on concomitant vaccines, and stratify data by timing of vaccination, gestational age at birth, race, and geographical setting.
Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Warfel JM, Zimmerman LI, Merkel TJ.
Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model.
Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):787-92. doi: 10.1073/pnas.1314688110. Epub 2013 Nov 25.
Abstract/Text
Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have been rising and reached a 50-y high of 42,000 cases in 2012. Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis (aP) vaccines fail to prevent colonization and transmission. To test our hypothesis, infant baboons were vaccinated at 2, 4, and 6 mo of age with aP or whole-cell pertussis (wP) vaccines and challenged with B. pertussis at 7 mo. Infection was followed by quantifying colonization in nasopharyngeal washes and monitoring leukocytosis and symptoms. Baboons vaccinated with aP were protected from severe pertussis-associated symptoms but not from colonization, did not clear the infection faster than naïve animals, and readily transmitted B. pertussis to unvaccinated contacts. Vaccination with wP induced a more rapid clearance compared with naïve and aP-vaccinated animals. By comparison, previously infected animals were not colonized upon secondary infection. Although all vaccinated and previously infected animals had robust serum antibody responses, we found key differences in T-cell immunity. Previously infected animals and wP-vaccinated animals possess strong B. pertussis-specific T helper 17 (Th17) memory and Th1 memory, whereas aP vaccination induced a Th1/Th2 response instead. The observation that aP, which induces an immune response mismatched to that induced by natural infection, fails to prevent colonization or transmission provides a plausible explanation for the resurgence of pertussis and suggests that optimal control of pertussis will require the development of improved vaccines.
Skoff TH, Baumbach J, Cieslak PR.
Tracking Pertussis and Evaluating Control Measures through Enhanced Pertussis Surveillance, Emerging Infections Program, United States.
Emerg Infect Dis. 2015 Sep;21(9):1568-73. doi: 10.3201/eid2109.150023.
Abstract/Text
Despite high coverage with pertussis-containing vaccines, pertussis remains endemic to the United States. There have been increases in reported cases in recent years, punctuated by striking epidemics and shifting epidemiology, both of which raise questions about current policies regarding its prevention and control. Limited data on pertussis reported through the National Notifiable Disease Surveillance System have proved insufficient to answer these questions. To address shortcomings of national pertussis data, the Emerging Infections Program at the US Centers for Disease Control and Prevention launched Enhanced Pertussis Surveillance (EPS), which is characterized by systematic case ascertainment, augmented data collection, and collection of Bordetella pertussis isolates. Data collected through EPS have been instrumental in understanding the rapidly evolving epidemiology and molecular epidemiology of pertussis and have contributed essential information regarding pertussis vaccines. EPS also serves as a platform for conducting critical and timely evaluations of pertussis prevention and control strategies, including targeting of vaccinations and antimicrobial prophylaxis.
Tan T, Dalby T, Forsyth K, Halperin SA, Heininger U, Hozbor D, Plotkin S, Ulloa-Gutierrez R, Wirsing von König CH.
Pertussis Across the Globe: Recent Epidemiologic Trends From 2000 to 2013.
Pediatr Infect Dis J. 2015 Sep;34(9):e222-32. doi: 10.1097/INF.0000000000000795.
Abstract/Text
Pertussis has reemerged as a problem across the world. To better understand the nature of the resurgence, we reviewed recent epidemiologic data and we report disease trends from across the world. Published epidemiologic data from January 2000 to July 2013 were obtained via PubMed searches and open-access websites. Data on vaccine coverage and reported pertussis cases from 2000 through 2012 from the 6 World Health Organization regions were also reviewed. Findings are confounded not only by the lack of systematic and comparable observations in many areas of the world but also by the cyclic nature of pertussis with peaks occurring every 3-5 years. It appears that pertussis incidence has increased in school-age children in North America and western Europe, where acellular pertussis vaccines are used, but an increase has also occurred in some countries that use whole-cell vaccines. Worldwide, pertussis remains a serious health concern, especially for infants, who bear the greatest disease burden. Factors that may contribute to the resurgence include lack of booster immunizations, low vaccine coverage, improved diagnostic methods, and genetic changes in the organism. To better understand the epidemiology of pertussis and optimize disease control, it is important to improve surveillance worldwide, irrespective of pertussis vaccine types and schedules used in each country.
Liko J, Robison SG, Cieslak PR.
Priming with whole-cell versus acellular pertussis vaccine.
N Engl J Med. 2013 Feb 7;368(6):581-2. doi: 10.1056/NEJMc1212006.
Abstract/Text
Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, Kang I; Infectious Diseases Society of America.
2013 IDSA clinical practice guideline for vaccination of the immunocompromised host.
Clin Infect Dis. 2014 Feb;58(3):e44-100. doi: 10.1093/cid/cit684. Epub 2013 Dec 4.
Abstract/Text
An international panel of experts prepared an evidenced-based guideline for vaccination of immunocompromised adults and children. These guidelines are intended for use by primary care and subspecialty providers who care for immunocompromised patients. Evidence was often limited. Areas that warrant future investigation are highlighted.
McNamara LA, Topaz N, Wang X, Hariri S, Fox L, MacNeil JR.
High Risk for Invasive Meningococcal Disease Among Patients Receiving Eculizumab (Soliris) Despite Receipt of Meningococcal Vaccine.
MMWR Morb Mortal Wkly Rep. 2017 Jul 14;66(27):734-737. doi: 10.15585/mmwr.mm6627e1. Epub 2017 Jul 14.
Abstract/Text
Use of eculizumab (Soliris, Alexion Pharmaceuticals), a terminal complement inhibitor, is associated with a 1,000-fold to 2,000-fold increased incidence of meningococcal disease (1). Administration of meningococcal vaccines is recommended for patients receiving eculizumab before beginning treatment (2,3). Sixteen cases of meningococcal disease were identified in eculizumab recipients in the United States during 2008-2016; among these, 11 were caused by nongroupable Neisseria meningitidis. Fourteen patients had documentation of receipt of at least 1 dose of meningococcal vaccine before disease onset. Because eculizumab recipients remain at risk for meningococcal disease even after receipt of meningococcal vaccines, some health care providers in the United States as well as public health agencies in other countries recommend antimicrobial prophylaxis for the duration of eculizumab treatment; a lifelong course of treatment is expected for many patients. Heightened awareness, early care seeking, and rapid treatment of any symptoms consistent with meningococcal disease are essential for all patients receiving eculizumab treatment, regardless of meningococcal vaccination or antimicrobial prophylaxis status.
Furer V, Rondaan C, Heijstek MW, Agmon-Levin N, van Assen S, Bijl M, Breedveld FC, D'Amelio R, Dougados M, Kapetanovic MC, van Laar JM, de Thurah A, Landewé RB, Molto A, Müller-Ladner U, Schreiber K, Smolar L, Walker J, Warnatz K, Wulffraat NM, Elkayam O.
2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases.
Ann Rheum Dis. 2020 Jan;79(1):39-52. doi: 10.1136/annrheumdis-2019-215882. Epub 2019 Aug 14.
Abstract/Text
To update the European League Against Rheumatism (EULAR) recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) published in 2011. Four systematic literature reviews were performed regarding the incidence/prevalence of vaccine-preventable infections among patients with AIIRD; efficacy, immunogenicity and safety of vaccines; effect of anti-rheumatic drugs on the response to vaccines; effect of vaccination of household of AIIRDs patients. Subsequently, recommendations were formulated based on the evidence and expert opinion. The updated recommendations comprise six overarching principles and nine recommendations. The former address the need for an annual vaccination status assessment, shared decision-making and timing of vaccination, favouring vaccination during quiescent disease, preferably prior to the initiation of immunosuppression. Non-live vaccines can be safely provided to AIIRD patients regardless of underlying therapy, whereas live-attenuated vaccines may be considered with caution. Influenza and pneumococcal vaccination should be strongly considered for the majority of patients with AIIRD. Tetanus toxoid and human papilloma virus vaccination should be provided to AIIRD patients as recommended for the general population. Hepatitis A, hepatitis B and herpes zoster vaccination should be administered to AIIRD patients at risk. Immunocompetent household members of patients with AIIRD should receive vaccines according to national guidelines, except for the oral poliomyelitis vaccine. Live-attenuated vaccines should be avoided during the first 6 months of life in newborns of mothers treated with biologics during the second half of pregnancy. These 2019 EULAR recommendations provide an up-to-date guidance on the management of vaccinations in patients with AIIRD.
© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
Danziger-Isakov L, Kumar D; AST ID Community of Practice.
Vaccination of solid organ transplant candidates and recipients: Guidelines from the American society of transplantation infectious diseases community of practice.
Clin Transplant. 2019 Sep;33(9):e13563. doi: 10.1111/ctr.13563. Epub 2019 Jun 5.
Abstract/Text
These updated guidelines of the AST IDCOP review vaccination of solid organ transplant candidates and recipients. General principles of vaccination as well as the use of specific vaccines in this population are discussed. Vaccination should be reviewed in the pre-transplant setting and appropriate vaccines updated. Both inactivated and live vaccines can be given pre-transplant. The timing of vaccination post-transplant should be taken into account. In the post-transplant setting, inactivated vaccines can be administered starting at 3 months post-transplant with the exception of influenza which can be given as early as one month. Inactivated vaccines can be safely administered post-transplant. There is accumulating data that live-attenuated vaccines can also be given to select post-transplant patients. Close contacts of transplant patients can receive most routine live vaccines. Specific vaccines including pneumococcal, influenza, hepatitis B, HPV, and meningococcal vaccines are discussed. Newer vaccines for seasonal influenza vaccine and herpes zoster are highlighted. Live-attenuated vaccines such as measles, mumps, rubella, and varicella are also discussed. Emerging data on live-attenuated vaccines post-transplant are highlighted.
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Ljungman P, Cordonnier C, Einsele H, Englund J, Machado CM, Storek J, Small T; Center for International Blood and Marrow Transplant Research; National Marrow Donor Program; European Blood and Marrow Transplant Group; American Society of Blood and Marrow Transplantation; Canadian Blood and Marrow Transplant Group; Infectious Disease Society of America; Society for Healthcare Epidemiology of America; Association of Medical Microbiology and Infectious Diseases Canada; Centers for Disease Control and Prevention.
Vaccination of hematopoietic cell transplant recipients.
Bone Marrow Transplant. 2009 Oct;44(8):521-6. doi: 10.1038/bmt.2009.263.
Abstract/Text
Ljungman P, de la Camara R, Robin C, Crocchiolo R, Einsele H, Hill JA, Hubacek P, Navarro D, Cordonnier C, Ward KN; 2017 European Conference on Infections in Leukaemia group.
Guidelines for the management of cytomegalovirus infection in patients with haematological malignancies and after stem cell transplantation from the 2017 European Conference on Infections in Leukaemia (ECIL 7).
Lancet Infect Dis. 2019 Aug;19(8):e260-e272. doi: 10.1016/S1473-3099(19)30107-0. Epub 2019 May 29.
Abstract/Text
Cytomegalovirus is one of the most important infections to occur after allogeneic haematopoietic stem cell transplantation (HSCT), and an increasing number of reports indicate that cytomegalovirus is also a potentially important pathogen in patients treated with recently introduced drugs for hematological malignancies. Expert recommendations have been produced by the 2017 European Conference on Infections in Leukaemia (ECIL 7) after a review of the literature on the diagnosis and management of cytomegalovirus in patients after HSCT and in patients receiving other types of therapy for haematological malignancies. These recommendations cover diagnosis, preventive strategies such as prophylaxis and pre-emptive therapy, and management of cytomegalovirus disease. Antiviral drugs including maribavir and letermovir are in development and prospective clinical trials have recently been completed. However, management of patients with resistant or refractory cytomegalovirus infection or cytomegalovirus disease is a challenge. In this Review we summarise the reviewed literature and the recommendations of the ECIL 7 for management of cytomegalovirus in patients with haematological malignancies.
Copyright © 2019 Elsevier Ltd. All rights reserved.
Miller P, Patel SR, Skinner R, Dignan F, Richter A, Jeffery K, Khan A, Heath PT, Clark A, Orchard K, Snowden JA, de Silva TI.
Joint consensus statement on the vaccination of adult and paediatric haematopoietic stem cell transplant recipients: Prepared on behalf of the British society of blood and marrow transplantation and cellular therapy (BSBMTCT), the Children's cancer and Leukaemia Group (CCLG), and British Infection Association (BIA).
J Infect. 2023 Jan;86(1):1-8. doi: 10.1016/j.jinf.2022.11.005. Epub 2022 Nov 15.
Abstract/Text
Haematopoietic stem cell transplant (HSCT) recipients have deficiencies in their adaptive immunity against vaccine preventable diseases. National and International guidance recommends that HSCT recipients are considered 'never vaccinated' and offered a comprehensive course of revaccination. This position statement aims to draw upon the current evidence base and existing guidelines, and align this with national vaccine availability and licensing considerations in order to recommend a pragmatic and standardised re-vaccination schedule for adult and paediatric HSCT recipients in the UK.
Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Mikulska M, Cesaro S, de Lavallade H, Di Blasi R, Einarsdottir S, Gallo G, Rieger C, Engelhard D, Lehrnbecher T, Ljungman P, Cordonnier C; European Conference on Infections in Leukaemia group.
Vaccination of patients with haematological malignancies who did not have transplantations: guidelines from the 2017 European Conference on Infections in Leukaemia (ECIL 7).
Lancet Infect Dis. 2019 Jun;19(6):e188-e199. doi: 10.1016/S1473-3099(18)30601-7. Epub 2019 Feb 8.
Abstract/Text
Patients with haematological malignancies are at high risk of infection because of various mechanisms of humoral and cell-mediated immune deficiencies, which mainly depend on underlying disease and specific therapies. Some of these infections are vaccine preventable. However, these malignancies are different from each other, and the treatment approaches are diverse and rapidly evolving, so it is difficult to have a common programme for vaccination in a haematology ward. Additionally, because of insufficient training about the topic, vaccination is an area often neglected by haematologists, and influenced by cultural differences, even among health-care workers, in compliance to vaccines. Several issues are encountered when addressing vaccination in haematology: the small size of the cohorts that makes it difficult to show the clinical benefits of vaccination, the subsequent need to rely on biological parameters, their clinical pertinence not being established in immunocompromised patients, scarcity of clarity on the optimal timing of vaccination in complex treatment schedules, and the scarcity of data on long-term protection in patients receiving treatments. Moreover, the risk of vaccine-induced disease with live-attenuated vaccines strongly limits their use. Here we summarise guidelines for patients without transplantations, and address the issue by the haematological group-myeloid and lymphoid-of diseases, with a special consideration for children with acute leukaemia.
Copyright © 2019 Elsevier Ltd. All rights reserved.
Martire B, Azzari C, Badolato R, Canessa C, Cirillo E, Gallo V, Graziani S, Lorenzini T, Milito C, Panza R, Moschese V; with Italian Network for Primary Immunodeficiencies (IPINET).
Vaccination in immunocompromised host: Recommendations of Italian Primary Immunodeficiency Network Centers (IPINET).
Vaccine. 2018 Jun 7;36(24):3541-3554. doi: 10.1016/j.vaccine.2018.01.061. Epub 2018 Feb 6.
Abstract/Text
Infectious complications are a major cause of morbidity and mortality in patients with primary or secondary immunodeficiency. Prevention of infectious diseases by vaccines is among the most effective healthcare measures mainly for these subjects. However immunocompromised people vary in their degree of immunosuppression and susceptibility to infection and, therefore, represent a heterogeneous population with regard to immunization. To date there is no well- established evidence for use of vaccines in immunodeficient patients, and indications are not clearly defined even in high-quality reviews and in most of the guidelines prepared to provide recommendations for the active vaccination of immunocompromised hosts. The aim of this document is to issue recommendations based on published literature and the collective experience of the Italian primary immunodeficiency centers, about how and when vaccines can be used in immunocompromised patients, in order to facilitate physician decisions and to ensure the best immune protection with the lowest risk to the health of the patient.
Copyright © 2018 Elsevier Ltd. All rights reserved.
Medical Advisory Committee of the Immune Deficiency Foundation; Shearer WT, Fleisher TA, Buckley RH, Ballas Z, Ballow M, Blaese RM, Bonilla FA, Conley ME, Cunningham-Rundles C, Filipovich AH, Fuleihan R, Gelfand EW, Hernandez-Trujillo V, Holland SM, Hong R, Lederman HM, Malech HL, Miles S, Notarangelo LD, Ochs HD, Orange JS, Puck JM, Routes JM, Stiehm ER, Sullivan K, Torgerson T, Winkelstein J.
Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts.
J Allergy Clin Immunol. 2014 Apr;133(4):961-6. doi: 10.1016/j.jaci.2013.11.043. Epub 2014 Feb 28.
Abstract/Text
The present uncertainty of which live viral or bacterial vaccines can be given to immunodeficient patients and the growing neglect of societal adherence to routine immunizations has prompted the Medical Advisory Committee of the Immune Deficiency Foundation to issue recommendations based on published literature and the collective experience of the committee members. These recommendations address the concern for immunodeficient patients acquiring infections from healthy subjects who have not been immunized or who are shedding live vaccine-derived viral or bacterial organisms. Such transmission of infectious agents can occur within the hospital, clinic, or home or at any public gathering. Collectively, we define this type of transmission as close-contact spread of infectious disease that is particularly relevant in patients with impaired immunity who might have an infection when exposed to subjects carrying vaccine-preventable infectious diseases or who have recently received a live vaccine. Immunodeficient patients who have received therapeutic hematopoietic stem transplantation are also at risk during the time when immune reconstitution is incomplete or while they are receiving immunosuppressive agents to prevent or treat graft-versus-host disease. This review recommends the general education of what is known about vaccine-preventable or vaccine-derived diseases being spread to immunodeficient patients at risk for close-contact spread of infection and describes the relative risks for a child with severe immunodeficiency. The review also recommends a balance between the need to protect vulnerable subjects and their social needs to integrate into society, attend school, and benefit from peer education.
Published by Mosby, Inc.
Ishige T, Shimizu T, Watanabe K, Arai K, Kamei K, Kudo T, Kunisaki R, Tokuhara D, Naganuma M, Mizuochi T, Murashima A, Inoki Y, Iwata N, Iwama I, Koinuma S, Shimizu H, Jimbo K, Takaki Y, Takahashi S, Cho Y, Nambu R, Nishida D, Hagiwara SI, Hikita N, Fujikawa H, Hosoi K, Hosomi S, Mikami Y, Miyoshi J, Yagi R, Yokoyama Y, Hisamatsu T.
Expert consensus on vaccination in patients with inflammatory bowel disease in Japan.
J Gastroenterol. 2023 Feb;58(2):135-157. doi: 10.1007/s00535-022-01953-w. Epub 2023 Jan 11.
Abstract/Text
Immunosuppressive therapies can affect the immune response to or safety of vaccination in patients with inflammatory bowel disease (IBD). The appropriateness of vaccination should be assessed prior to the initiation of IBD treatment because patients with IBD frequently undergo continuous treatment with immunosuppressive drugs. This consensus was developed to support the decision-making process regarding appropriate vaccination for pediatric and adult patients with IBD and physicians by providing critical information according to the published literature and expert consensus about vaccine-preventable diseases (VPDs) [excluding cervical cancer and coronavirus disease 2019 (COVID-19)] in Japan. This consensus includes 19 important clinical questions (CQs) on the following 4 topics: VPDs (6 CQs), live attenuated vaccines (2 CQs), inactivated vaccines (6 CQs), and vaccination for pregnancy, childbirth, and breastfeeding (5 CQs). These topics and CQs were selected under unified consensus by the members of a committee on intractable diseases with support by a Health and Labour Sciences Research Grant. Physicians should provide necessary information on VPDs to their patients with IBD and carefully manage these patients' IBD if various risk factors for the development or worsening of VPDs are present. This consensus will facilitate informed and shared decision-making in daily IBD clinical practice.
© 2023. Japanese Society of Gastroenterology.
Chat VS, Ellebrecht CT, Kingston P, Gondo G, Bell S, Cordoro KM, Desai SR, Duffin KC, Feldman SR, Garg A, Gelfand JM, Gladman D, Green LJ, Gudjonsson J, Han G, Hawkes JE, Kircik L, Koo J, Langley R, Lebwohl M, Michael Lewitt G, Liao W, Martin G, Orbai AM, Reddy SM, Richardson V, Ritchlin CT, Schwartzman S, Siegel EL, Van Voorhees AS, Wallace EB, Weinberg JM, Winthrop KL, Yamauchi P, Armstrong AW.
Vaccination recommendations for adults receiving biologics and oral therapies for psoriasis and psoriatic arthritis: Delphi consensus from the medical board of the National Psoriasis Foundation.
J Am Acad Dermatol. 2024 Jun;90(6):1170-1181. doi: 10.1016/j.jaad.2023.12.070. Epub 2024 Feb 7.
Abstract/Text
BACKGROUND: For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis.
OBJECTIVE: To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines.
METHODS: Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts.
RESULTS: Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination.
LIMITATIONS: Studies regarding infection rates after vaccination are lacking.
CONCLUSION: Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases.
Copyright © 2024. Published by Elsevier Inc.
American College of Rheumatology. 2022 Guideline for Vaccinations in Patients with Rheumatic and Musculoskeletal Diseases. 2023.
Anna Maria Geretti. British HIV Association guidelines on the use of vaccines in HIV-positive adults 2015. British HIV Association. 2015.
Ladhani SN, Fernandes S, Garg M, Borrow R, de Lusignan S, Bolton-Maggs PHB; BSH Guidelines Committee.
Prevention and treatment of infection in patients with an absent or hypofunctional spleen: A British Society for Haematology guideline.
Br J Haematol. 2024 May;204(5):1672-1686. doi: 10.1111/bjh.19361. Epub 2024 Apr 10.
Abstract/Text
Guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen were published by the British Committee for Standards in Haematology in 1996 and updated in 2002 and 2011. With advances in vaccinations and changes in patterns of infection, the guidelines required updating. Key aspects included in this guideline are the identification of patients at risk of infection, patient education and information and immunisation schedules. This guideline does not address the non-infective complications of splenectomy or functional hyposplenism (FH). This replaces previous guidelines and significantly revises the recommendations related to immunisation. Patients at risk include those who have undergone surgical removal of the spleen, including partial splenectomy and splenic embolisation, and those with medical conditions that predispose to FH. Immunisations should include those against Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus) and influenza. Haemophilus influenzae type b (Hib) is part of the infant immunisation schedule and is no longer required for older hyposplenic patients. Treatment of suspected or proven infections should be based on local protocols and consider relevant anti-microbial resistance patterns. The education of patients and their medical practitioners is essential, particularly in relation to the risk of serious infection and its prevention. Further research is required to establish the effectiveness of vaccinations in hyposplenic patients; infective episodes should be regularly audited. There is no single group ideally placed to conduct audits into complications arising from hyposplenism, highlighting a need for a national registry, as has proved very successful in Australia or alternatively, the establishment of appropriate multidisciplinary networks.
© 2024 British Society for Haematology and John Wiley & Sons Ltd.
Ahmed F, Lindley MC, Allred N, Weinbaum CM, Grohskopf L.
Effect of influenza vaccination of healthcare personnel on morbidity and mortality among patients: systematic review and grading of evidence.
Clin Infect Dis. 2014 Jan;58(1):50-7. doi: 10.1093/cid/cit580. Epub 2013 Sep 17.
Abstract/Text
BACKGROUND: Influenza vaccination of healthcare personnel (HCP) is recommended in >40 countries. However, there is controversy surrounding the evidence that HCP vaccination reduces morbidity and mortality among patients. Key factors for developing evidence-based recommendations include quality of evidence, balance of benefits and harms, and values and preferences.
METHODS: We conducted a systematic review of randomized trials, cohort studies, and case-control studies published through June 2012 to evaluate the effect of HCP influenza vaccination on mortality, hospitalization, and influenza cases in patients of healthcare facilities. We pooled trial results using meta-analysis and assessed evidence quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS: We identified 4 cluster randomized trials and 4 observational studies conducted in long-term care or hospital settings. Pooled risk ratios across trials for all-cause mortality and influenza-like illness were 0.71 (95% confidence interval [CI], .59-.85) and 0.58 (95% CI, .46-.73), respectively; pooled estimates for all-cause hospitalization and laboratory-confirmed influenza were not statistically significant. The cohort and case-control studies indicated significant protective associations for influenza-like illness and laboratory-confirmed influenza. No studies reported harms to patients. Using GRADE, the quality of the evidence for the effect of HCP vaccination on mortality and influenza cases in patients was moderate and low, respectively. The evidence quality for the effect of HCP vaccination on patient hospitalization was low. The overall evidence quality was moderate.
CONCLUSIONS: The quality of evidence is higher for mortality than for other outcomes. HCP influenza vaccination can enhance patient safety.
