Shingles (herpes zoster) vaccines — Vaccine Data Navigator

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Herpes zoster (shingles) Varicella zoster virus (reactivation)

Disease risks

Acute risks of the infection itself: complications, hospitalisation, ICU, death.

Outcome (O)	Population (P)	Comparator	Estimate	Design (S)	Source
Herpes zoster incidence in the general population severity: any case definition: Studies using prospective surveillance, electronic medical records or administrative data with record review	general population, all ages vaccination status: mixed country: North America, Europe and Asia-Pacific (130 studies in 26 countries) period: studies up to December 2013 All ages		3-5 incidence per 1,000 person-years (range across studies) per person-years	systematic review	Kawai et al. 2014 BMJ Open quote The incidence rate of HZ ranged between 3 and 5/1000 person-years in North America, Europe and Asia-Pacific, based on studies using prospective surveillance, electronic medical record data or administrative data with medical record review. abstract, RESULTS Range across high-quality study designs; incidence rises steeply with age within each population.
Hospitalisation for herpes zoster severity: hospitalisation case definition: HZ-associated hospitalisation in general-population studies	general population, higher rates among elderly vaccination status: mixed country: 26 countries period: studies up to December 2013 All ages		2-25 hospitalisation rate per 100,000 person-years (range across studies) per person-years in the population	systematic review	Kawai et al. 2014 BMJ Open quote Hospitalisation rates ranged from 2 to 25/100 000 person-years, with higher rates among elderly populations. abstract, RESULTS Population denominator, not per case. Do not combine with the per-case hospitalisation proportions in this file.
Recurrent herpes zoster severity: any case definition: Second episode of HZ in general-population studies	general population vaccination status: mixed country: 26 countries period: studies up to December 2013 All ages		1-6 proportion of zoster patients with recurrence (%) per zoster patient	systematic review	Kawai et al. 2014 BMJ Open quote The risk of recurrence of HZ ranged from 1% to 6%, with long-term follow-up studies showing higher risk (5-6%). abstract, RESULTS Long-term follow-up studies gave the higher end of the range.
Herpes zoster incidence in immunocompromised adults severity: any case definition: HZ in US studies of HCT, cancer, HIV and solid organ transplant patients	adults immune status: immunocompromised (HCT, haematological malignancy, SOT, solid tumours, HIV) vaccination status: not reported country: United States period: studies published after 1992 18-49y50-64y65+		9 to 92 incidence per 1,000 patient-years (range across populations) per patient-years	systematic review	McKay et al. 2020 Clin Infect Dis quote Incidence estimates ranged from 9 to 92 HZ cases/1000 patient-years and were highest in HCT, followed by hematologic malignancies, SOT, and solid tumor malignancies, and were lowest in people living with HIV. abstract, RESULTS Highest in HCT, then haematological malignancies, SOT, solid tumours; lowest in people living with HIV. Antiviral prophylaxis after HCT lowered incidence.
Hospitalisation for herpes zoster severity: hospitalisation case definition: Hospitalisation among HZ cases in Latin American and Caribbean studies	all ages vaccination status: not reported country: Latin America and Caribbean (mostly Brazil) setting: mixed, mostly higher-risk populations period: studies 2000-2020 All ages		3-35.7 proportion of zoster cases hospitalised (%) (range across studies) per zoster case	systematic review	Bardach et al. 2021 PLoS One quote Hospitalization rates ranged from 3%-35.7%. abstract Wide range because studies were mostly in higher-risk populations; no study reported general-population incidence.
In-hospital death with herpes zoster severity: death case definition: In-hospital mortality among hospitalised HZ patients in Latin American studies	all ages vaccination status: not reported country: Latin America and Caribbean setting: hospital period: studies 2000-2020 All ages		0-36 in-hospital mortality (%) (range across studies) per hospitalised zoster patient	systematic review	Bardach et al. 2021 PLoS One quote The in-hospital HZ mortality rate ranged from 0%-36%. abstract Upper end comes from small high-risk hospital series; not comparable to the population case-fatality rate in the Kaiser record.
Herpes zoster (shingles) over a lifetime severity: any case definition: Herpes zoster as described by CDC	all ages, lifetime vaccination status: not reported country: United States period: current (page dated 2024) All ages		1 in 3 lifetime risk (proportion of people) per person over a lifetime	expert body	cdc.gov quote About 1 in 3 people in the United States will develop herpes zoster during their lifetime. Who is at risk CDC summary figure, not a measured cohort estimate. The same page says most people have only one episode but recurrence occurs.
Herpes zoster incidence severity: any case definition: Herpes zoster as described by CDC	all ages, varies by age vaccination status: not reported country: United States period: current (page dated 2024) All ages		two to nine cases per 1,000 US population incidence per year (range across ages) per population per year	expert body	cdc.gov quote The incidence of herpes zoster varies by age and is approximately two to nine cases per 1,000 US population annually. Disease rates Range reflects the steep rise with age; the same page states about one million US cases annually.
Immunocompromise among people hospitalised with herpes zoster severity: hospitalisation case definition: Hospitalisation with herpes zoster	all ages vaccination status: not reported country: United States period: current (page dated 2024) All ages		30 proportion of hospitalised zoster patients who are immunocompromised (%) per hospitalised zoster patient	expert body	cdc.gov quote About 30% of people hospitalized with herpes zoster have compromised or suppressed immune systems. Who is at risk Describes who is hospitalised, not the risk of hospitalisation. Denominator is hospitalised patients.
Hospitalisation for herpes zoster severity: hospitalisation case definition: Zoster episodes as summarised by ACIP	all ages vaccination status: unvaccinated country: United States period: pre-vaccine era (ACIP 2008 statement) All ages		3 proportion of zoster patients hospitalised (%) per zoster patient	expert body	Harpaz et al. 2008 MMWR Recomm Rep quote Approximately 3% of patients with zoster are hospitalized; many of these episodes involved persons with one or more immunocompromising conditions. abstract ACIP summary; the same sentence notes many hospitalised episodes involved persons with immunocompromising conditions.
Herpes zoster ophthalmicus (eye involvement) severity: ocular complication case definition: Eye involvement in zoster episodes as summarised by ACIP	all ages vaccination status: unvaccinated country: United States period: pre-vaccine era (ACIP 2008 statement) All ages		10-25 proportion of zoster episodes with eye involvement (%) per zoster episode	expert body	Harpaz et al. 2008 MMWR Recomm Rep quote Another complication of zoster is eye involvement, which occurs in 10%-25% of zoster episodes and can result in prolonged or permanent pain, facial scarring, and loss of vision. abstract ACIP summary range; a population-based medical-record cohort in this file found a lower proportion with confirmed eye involvement.
Herpes zoster incidence, age-adjusted to the US adult population severity: any case definition: Confirmed HZ diagnosis by medical record review	adults 22 years and older vaccination status: unvaccinated country: United States (Olmsted County, Minnesota) setting: community period: 1996-2001, before zoster vaccine introduction n: 1669 adults with confirmed HZ 18-49y50-64y65+		3.6 (3.4–3.7) incidence per 1,000 person-years per person-years	cohort	Yawn et al. 2007 Mayo Clin Proc quote When adjusted to the US adult population, the incidence of HZ was 3.6 per 1000 person-years (95% confidence interval, 3.4-3.7), with a temporal increase from 3.2 to 4.1 per 1000 person-years from 1996 to 2001. abstract, RESULTS Pre-vaccine baseline; most patients were immunocompetent and the rate rose over the study years.
Any non-pain complication of herpes zoster severity: any complication case definition: HZ-related complications identified by medical record review	adults 22 years and older vaccination status: unvaccinated country: United States (Olmsted County, Minnesota) setting: community period: 1996-2001, before zoster vaccine introduction n: 1669 adults with confirmed HZ 18-49y50-64y65+		10 proportion of zoster patients with non-pain complications (%) per zoster patient	cohort	Yawn et al. 2007 Mayo Clin Proc quote Overall, 10% of all patients with HZ experienced 1 or more nonpain complications. abstract, RESULTS Excludes post-herpetic neuralgia, which is recorded separately in the PHN records. The authors summarise that about one patient in four had some HZ-related complication when pain is included.
Herpes zoster incidence severity: any case definition: Incident HZ diagnosis in electronic health records	adults 50 years and older immune status: immunocompetent vaccination status: unvaccinated country: United States (Kaiser Permanente Southern California) setting: community, integrated health system period: 2011-2015 50-64y65+		9.92 (9.82–10.01) incidence per 1,000 person-years per person-years	cohort	Tseng et al. 2020 J Infect Dis quote RESULTS: HZ incidence rate was 9.92/1000 person-years (95% confidence interval [CI], 9.82-10.01). abstract, RESULTS Restricted to immunocompetent adults unvaccinated with zoster vaccine live; this is the current unvaccinated baseline in a US managed-care population.
HZ-related hospitalisation severity: hospitalisation case definition: HZ-related hospitalisation among HZ patients diagnosed in 2015	adults 50 years and older immune status: immunocompetent vaccination status: unvaccinated country: United States (Kaiser Permanente Southern California) period: 2015 50-64y65+		0.86 proportion of zoster patients hospitalised (%) per zoster patient	cohort	Tseng et al. 2020 J Infect Dis quote Only 0.86% of patients had an HZ-related hospitalization. abstract, RESULTS Much lower than the ACIP summary figure, consistent with excluding immunocompromised patients.
Death related to herpes zoster severity: death case definition: HZ-related death determined from automated data and electronic health records	adults 50 years and older immune status: immunocompetent vaccination status: unvaccinated country: United States (Kaiser Permanente Southern California) period: 2011-2015 50-64y65+		0.04 CFR (%) per zoster patient	cohort	Tseng et al. 2020 J Infect Dis quote The case-fatality rate was 0.04%. abstract, RESULTS Immunocompetent population only; zoster deaths concentrate in immunocompromised patients, so this understates the all-population CFR.
Recurrent herpes zoster within 10 years severity: any case definition: Recurrent HZ in a cohort first diagnosed 2007-2008 and followed through 2016	adults 50 years and older immune status: immunocompetent vaccination status: unvaccinated country: United States (Kaiser Permanente Southern California) period: 2007-2016 50-64y65+		10.26 (9.36–11.23) 10-year cumulative risk of recurrence (%) per zoster patient follow-up: 10 years	cohort	Tseng et al. 2020 J Infect Dis quote Recurrence rate was 10.96/1000 person-years (95% CI, 10.18-11.79) with 10-year recurrence risk of 10.26% (95% CI, 9.36%-11.23%). abstract, RESULTS Higher than the range in the global systematic review record, reflecting longer follow-up.
Herpes zoster incidence severity: any case definition: ICD-10 coded HZ in statutory health insurance data	all ages vaccination status: unvaccinated country: Germany setting: community, insurance claims period: 2006-2009 n: 7 million insured members All ages		5.3-5.5 standardised incidence per 1,000 person-years (annual range) per person-years	cohort	Hillebrand et al. 2015 J Infect quote RESULTS: Annual standardized IRs ranged between 5.3 and 5.5 per 1000 person-years (PY) between 2006 and 2009 with higher IRs in females. abstract, RESULTS Claims-based ascertainment; higher in females. Zoster vaccine was not yet introduced in Germany during the study period.
Hospitalisation for herpes zoster severity: hospitalisation case definition: ICD-10 coded HZ in statutory health insurance data	all ages vaccination status: unvaccinated country: Germany period: 2009 All ages		3 proportion of zoster cases hospitalised (%) per zoster case	cohort	Hillebrand et al. 2015 J Infect quote About 3% of HZ cases were hospitalized. abstract, RESULTS Matches the ACIP summary figure. The same abstract reports the proportions with nervous system involvement and without complications.
Hospital-based (inpatient, outpatient or emergency) herpes zoster diagnosis severity: hospital-treated case definition: First-time hospital-based HZ diagnosis in the Danish National Patient Registry	50 years to 90 years and older vaccination status: not reported country: Denmark setting: hospital period: 1994-2012 50-64y65+		6 to 91.9 hospital-based diagnosis rate per 100,000 person-years (age 50 to 90+) per person-years in the population	cohort	Schmidt et al. 2016 BMC Infect Dis quote RESULTS: The diagnosis rate increased almost exponentially from 6 to 91.9 per 100,000 person-years between age 50 and ≥90 years. abstract, RESULTS Includes outpatient and emergency contacts, not only admissions. The steep age gradient is the main message.
All-cause mortality after hospital-based herpes zoster diagnosis severity: death case definition: Standardised mortality ratio using the Danish population as reference	all ages with hospital-based HZ diagnosis vaccination status: not reported country: Denmark setting: hospital period: 1994-2012 All ages	vs Danish general population	1.8 (1.7–1.8) SMR vs general population per hospital-diagnosed zoster patient	cohort	Schmidt et al. 2016 BMC Infect Dis quote HZ was associated with increased all-cause mortality overall (SMR 1.8, 95 % CI: 1.7-1.8), but not in analyses restricted to patients without comorbidity (SMR 1.0, 95 % CI: 0.9-1.0). abstract, RESULTS The same sentence reports no excess mortality in patients without comorbidity, so the excess reflects the comorbid, often immunocompromised, patients who reach hospital with zoster rather than zoster itself.
Hospitalisation with a diagnosis of herpes zoster or post-herpetic neuralgia severity: hospitalisation case definition: First hospitalisation with HZ or PHN diagnosis in the French hospital discharge database	adults 18 years and older; highest in those 80 years and older vaccination status: not reported country: France setting: hospital period: 2013-2020 n: 62,077 adults 18-49y50-64y65+		14.6-16.3 hospitalisations per 100,000 persons per year (range over years) per population per year	cohort	Loubet et al. 2024 J Infect quote HZ and/or PHN incidence ranged between 14.6 and 16.3 hospitalizations/100 000 persons and was highest in people aged ≥80 years (97.6 hospitalizations/100 000 persons). abstract, RESULTS The same sentence gives a much higher rate in people aged eighty and over; the authors summarise a six-fold rise with age.
In-patient death during hospitalisation for herpes zoster severity: death case definition: Death during a hospital stay with HZ diagnosis	adults 18 years and older immune status: immunocompromised vs non-immunocompromised vaccination status: not reported country: France setting: hospital period: 2013-2020 18-49y50-64y65+		8 vs 4 in-patient mortality (%), immunocompromised vs non-immunocompromised per hospitalised zoster patient	cohort	Loubet et al. 2024 J Infect quote IC patients had longer lengths of stay for HZ per episode compared with non-IC patients (15.5 ± 19.4 days vs 12.2 ± 13.5 days) and higher in-patient mortality (8% vs 4%). abstract, RESULTS Denominator is hospitalised patients, a severe subset. Deaths in hospital are not necessarily caused by zoster.
Herpes zoster incidence in haematopoietic stem cell transplant recipients severity: any case definition: HZ in primary care records linked to Hospital Episode Statistics	adults 18 years and older immune status: immunocompromised (HSCT recipients; range across 16 conditions) vaccination status: not reported country: England setting: primary care, CPRD period: 2000-2012 18-49y50-64y65+		5.3 to 41.7 incidence per 1,000 person-years (range across immunocompromising conditions) per person-years	cohort	Yanni et al. 2018 BMJ Open quote The overall IR of HZ varied across IC conditions, ranging from 5.3 (5.1-5.5) in psoriasis to 41.7/1000 PY (35.7-48.4) in HSCT. abstract, RESULTS HSCT is the highest-risk group; psoriasis the lowest of the conditions studied. Compare with the immunocompetent rate in the matched comparison record.
Herpes zoster incidence in people without immunocompromising conditions severity: any case definition: HZ in primary care records linked to Hospital Episode Statistics	adults 18 years and older, age and sex matched to the immunocompromised cohort immune status: immunocompetent vaccination status: not reported country: England setting: primary care, CPRD period: 2000-2012 18-49y50-64y65+		6.2 (6.1–6.3) incidence per 1,000 person-years per person-years	cohort	Yanni et al. 2018 BMJ Open quote This IR in the IC-free cohort was 6.2/1000 PY (6.1-6.3). abstract, RESULTS Matched comparison cohort; the immunocompromised cohort overall had a somewhat higher rate in the same abstract.
Herpes zoster eye involvement (ophthalmologist-confirmed) severity: ocular complication case definition: HZ confirmed by typical rash or laboratory testing, eye involvement confirmed by ophthalmologist	all ages; mean age 62.6 years among those with eye involvement vaccination status: not reported country: United States (Olmsted County, Minnesota) setting: community, medical record review period: 1980-2007 n: 2035 individuals with HZ All ages		9.0 proportion of zoster patients with eye involvement (%) per zoster patient	cohort	Yawn et al. 2013 Mayo Clin Proc quote RESULTS: Of the 2035 individuals with HZ in any dermatome, 184 (9.0%) had eye involvement. abstract, RESULTS Lower than the ACIP summary range because it requires ophthalmologist confirmation.
New vision loss to 20/200 or worse after zoster eye involvement severity: permanent vision loss case definition: Ophthalmologist-documented vision decrement	mean age 62.6 years vaccination status: not reported country: United States (Olmsted County, Minnesota) period: 1980-2007 n: 184 patients with HZ eye involvement All ages		3.3 proportion of patients with eye involvement developing vision 20/200 or worse (%) per zoster patient with eye involvement	cohort	Yawn et al. 2013 Mayo Clin Proc quote Outcomes included 6 patients (3.3%) with new vision decrements to 20/200 or worse. abstract, RESULTS Denominator is patients with eye involvement, not all zoster patients. Do not multiply by the eye-involvement proportion without noting the small numbers.
Death with herpes zoster as underlying cause severity: death case definition: Death certificates with herpes zoster as underlying cause	all ages; almost all deaths in older adults or the immunocompromised vaccination status: not reported country: United States period: as cited by CDC (death-certificate study 1979-2007) All ages		0.28-0.69 deaths per 1 million population per year (range) per population per year	surveillance	cdc.gov quote Death rates One study estimated 96 deaths occur each year where herpes zoster was the underlying cause (0.28–0.69 per 1 million population). Death rates Death-certificate based; the CDC page reports the figure as a single study estimate of about 96 deaths a year. Deaths from zoster are rare in people who are not immunocompromised.

Post-acute and long-term sequelae

What can follow the acute illness: chronic disease, disability, cancers, congenital syndromes, post-infectious conditions.

Outcome (O)	Population (P)	Comparator	Estimate	Design (S)	Source
Dementia after herpes zoster infection severity: dementia case definition: Dementia in controlled observational studies	adults vaccination status: not reported country: multiple All ages	vs people without herpes zoster	0.99 (0.92–1.08) pooled RR vs people without zoster	meta-analysis	Elhalag et al. 2023 Medicine (Baltimore) quote In the outcome of incidences of dementia and Alzheimer's disease, the pooled analysis showed no statistically significant difference between the HZV group and the incidence of dementia (RR = 0.99, 95% CI = 0.92-1.08, P = .89), (RR = 3.74, 95% CI = 0.22-62.70, P = .36) respectively. abstract, RESULTS Null overall. The same review reports a raised pooled estimate for herpes zoster ophthalmicus specifically, recorded separately, from few studies.
Dementia after herpes zoster ophthalmicus severity: dementia case definition: Dementia in controlled observational studies of HZO patients	adults vaccination status: not reported country: multiple All ages	vs people without herpes zoster ophthalmicus	6.26 (1.30–30.19) pooled RR vs people without HZO	meta-analysis	Elhalag et al. 2023 Medicine (Baltimore) quote In the outcome of incidences of Herpes Zoster ophthalmicus (HZO), the generic inverse variance showed a statistically significant association between patients who have HZO and increased incidence of dementia (RR = 6.26, 95% CI = 1.30-30.19, P = .02). abstract, RESULTS Very wide interval from a generic inverse-variance pooling of few studies; confounding by health-care contact and age is likely. Treat as hypothesis-generating.
All-cause dementia after herpes zoster severity: dementia case definition: Dementia from hospital diagnoses and prescription records in Danish registries	40 years and older; median 64 years vaccination status: not reported country: Denmark setting: nationwide registries period: 1997-2017 n: 247,305 people with zoster and 1,235,890 matched comparators 18-49y50-64y65+	vs matched general population comparators without zoster	0.98 then 0.93 (0.92–1.04) adjusted HR vs matched general population, first year vs thereafter follow-up: 0-1 year and 1-21 years	cohort	Schmidt et al. 2022 Neurology quote The HR of all-cause dementia was 0.98 (95% CI 0.92-1.04) during the first year and 0.93 (95% CI 0.90-0.95) thereafter in people with zoster vs matched comparators. abstract, RESULTS The interval entered is for the first-year HR 0.98; the later-period HR 0.93 carries its own narrower interval in the same sentence. No increased risk; the small decrease is unexplained and the authors advise considering systematic error. CNS zoster was the only subgroup with a raised point estimate.
Dementia after zoster with CNS involvement severity: dementia case definition: Dementia from hospital diagnoses and prescription records	40 years and older vaccination status: not reported country: Denmark setting: nationwide registries period: 1997-2017 18-49y50-64y65+	vs matched general population comparators without zoster	1.94 (0.78–4.80) adjusted HR vs matched general population follow-up: up to 21 years	cohort	Schmidt et al. 2022 Neurology quote We observed no increased long-term risk of dementia in subgroup analyses, except possibly in people with CNS infection (HR 1.94; 95% CI 0.78-4.80). abstract, RESULTS Wide interval crossing 1; a rare complication. The authors estimate the population attributable fraction of dementia from this complication at a tiny level.

Vaccine efficacy and effectiveness

Every estimate compiled, annotated by population (P), intervention (I), comparator (C), outcome (O) and study design (S).

Outcome (O)	Population (P)	Intervention / comparator	Estimate	Design (S)	Source
Herpes zoster incidence up to 21 months severity: any case definition: HZ in two RCTs of non-live zoster vaccines in haematological malignancies	adults 18 years and older immune status: immunocompromised (haematological malignancies) country: multiple n: 3067 participants 18-49y50-64y65+	non-live herpes zoster vaccines (RZV and inactivated zoster vaccine) platform: non-live (recombinant subunit or inactivated) doses: as given in the included trials vs placebo or no vaccine	0.40 (0.07–2.23) RR vs placebo or no vaccine follow-up: up to 21 months	meta-analysis GRADE: low 2 RCTs	Zorger et al. 2025 Cochrane Database Syst Rev quote Vaccines may reduce herpes zoster incidence up to 21 months post-vaccination, although the 95% CI includes the possibility of no effect (4% versus 6%; RR 0.40, 95% CI 0.07 to 2.23; 2 RCTs, 3067 participants; low-certainty evidence). abstract, MAIN RESULTS Cochrane review. The interval includes no effect; the two trials differ in vaccine (RZV vs an inactivated candidate), which drives the imprecision. The RZV trial's own post-hoc efficacy figure is not in its abstract and is listed as a gap.
Herpes zoster severity: any case definition: HZ in RCTs of RZV in immunocompromised adults	adults, all ages immune status: immunocompromised (transplant, cancer on chemotherapy, autoimmune disease, HIV) country: multiple 18-49y50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 vs placebo	81 (0.09–0.44 RR CI) VE (%) = 1 - RR	meta-analysis 7 RCTs	Marra et al. 2024 PLoS One quote Compared to placebo, RZV reduced the incidence of herpes zoster across all ages by 81% (RR: 0.19, 95%CI: 0.09, 0.44), with moderate heterogeneity across the studies (I2 = 60.49%; τ2 = 0.31; P = 0.07). abstract, RESULTS Moderate heterogeneity between trials. The interval is on the RR scale. Most events come from the HSCT trial.
Herpes zoster severity: any case definition: HZ in post-licensure cohort and case-control studies	adults 18 years and older immune status: immunocompetent country: multiple period: studies 2017-2025 18-49y50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: as given in included studies, mostly 2 vs unvaccinated	80.0 (74.1–84.5) pooled VE (%)	meta-analysis	Mbinta et al. 2026 Vaccine quote FINDINGS: A vaccine effectiveness of 80·0% (95% Confidence Intervals [CI]: 74·1-84·5) was found for immunocompetent adults and 64·3% (95 CI: 61·4-67·0) for immunocompromised adults. abstract, FINDINGS Substantial heterogeneity in many analyses. Same sentence gives the immunocompromised estimate, recorded separately.
Herpes zoster severity: any case definition: HZ in post-licensure observational studies	adults 18 years and older immune status: immunocompromised country: multiple period: studies 2017-2025 18-49y50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: as given in included studies vs unvaccinated	64.3 (61.4–67.0) pooled VE (%)	meta-analysis	Mbinta et al. 2026 Vaccine quote FINDINGS: A vaccine effectiveness of 80·0% (95% Confidence Intervals [CI]: 74·1-84·5) was found for immunocompetent adults and 64·3% (95 CI: 61·4-67·0) for immunocompromised adults. abstract, FINDINGS Materially lower than in immunocompetent adults; consistent with the Medicare and VSD subgroup findings.
Herpes zoster beyond 4 years after vaccination severity: any case definition: HZ in post-licensure observational studies with long follow-up	adults country: multiple 18-49y50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 time since vaccination: after 4 years vs unvaccinated	73.0 (68.0–76.0) pooled VE (%) after 4 years	meta-analysis	Mbinta et al. 2026 Vaccine quote Vaccine effectiveness after four years was 73·0% (68·0-76·0). abstract, FINDINGS Modest decline from the overall pooled figure.
Herpes zoster severity: any case definition: HZ in two US post-licensure cohort studies published after 2020	50 years and older country: United States 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 vs no vaccination	79.2 (57.6–89.7) pooled VE (%)	meta-analysis 2 studies (post-hoc analysis)	Mbinta et al. 2022 Lancet Healthy Longev quote In a post-hoc analysis of two studies from the USA published after 2020, the pooled vaccine effectiveness for RZV against herpes zoster in adults was 79·2% (57·6-89·7). abstract, FINDINGS Post-hoc pooling of two early studies; the later update of this review gives a tighter estimate.
Cumulative incidence of herpes zoster severity: any case definition: HZ in the included RCTs	healthy older adults, mean 60 years or older immune status: immunocompetent country: multiple n: 22,022 participants for efficacy 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 schedule: two months apart vs placebo	0.08 (0.03–0.23) RR vs placebo follow-up: 3.2 years	meta-analysis GRADE: moderate 2 RCTs	de et al. 2023 Cochrane Database Syst Rev quote Participants who received the new vaccine had a lower cumulative incidence of herpes zoster at 3.2 years follow-up (RR 0.08, 95% CI 0.03 to 0.23; RD 3%; NNTB 33; moderate-certainty evidence), probably indicating a favourable profile of the intervention. abstract, MAIN RESULTS Cochrane review. Risk difference and number needed to treat are in the same sentence. Dropout before the second dose was higher in the vaccine group.
Cumulative incidence of herpes zoster severity: any case definition: HZ in the Shingles Prevention Study	60 years and older immune status: immunocompetent country: United States n: 38,546 participants 50-64y65+	Zostavax (ZVL, live attenuated) platform: live attenuated doses: 1 vs placebo	0.49 (0.43–0.56) RR vs placebo follow-up: up to 3 years	meta-analysis GRADE: moderate 1 RCT (largest study)	de et al. 2023 Cochrane Database Syst Rev quote The cumulative incidence of herpes zoster at up to three years of follow-up was lower in participants who received the LZV (one dose subcutaneously) than in those who received placebo (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.43 to 0.56; risk difference (RD) 2%; number needed to treat for an additional beneficial outcome (NNTB) 50; moderate-certainty evidence) in the largest study, which included 38,546 participants. abstract, MAIN RESULTS Cochrane re-analysis of the SPS; risk difference and number needed to treat are in the same sentence.
Herpes zoster severity: any case definition: HZ in post-licensure observational studies	50 years and older country: USA, UK, Canada and Sweden period: studies 2006-2020 50-64y65+	Zostavax (ZVL, live attenuated) platform: live attenuated doses: 1 vs no vaccination	45.9 (42.2–49.4) pooled VE (%)	meta-analysis 7 studies	Mbinta et al. 2022 Lancet Healthy Longev quote The pooled vaccine effectiveness for ZVL against herpes zoster in adults was 45·9% (95% CI 42·2-49·4; seven studies). abstract, FINDINGS Overall quality of evidence rated very low by the review. Real-world ZVL effectiveness sits well below the SPS trial figure.
Confirmed herpes zoster severity: any case definition: Herpes zoster confirmed by PCR or clinical evaluation committee	50 years and older immune status: immunocompetent country: 18 countries n: 15,411 participants 50-64y65+	Shingrix (RZV, HZ/su: recombinant gE + AS01B) platform: adjuvanted recombinant subunit doses: 2 schedule: 0 and 2 months vs placebo	97.2 (93.7–99.0) VE (%) follow-up: mean 3.2 years	RCT	Lal et al. 2015 N Engl J Med quote Overall vaccine efficacy against herpes zoster was 97.2% (95% confidence interval [CI], 93.7 to 99.0; P<0.001). abstract, RESULTS The ZOE trial in adults fifty and older. The abstract also reports the incidence in each arm and much higher grade-three reactogenicity in the vaccine arm.
Confirmed herpes zoster severity: any case definition: Herpes zoster confirmed by PCR or clinical evaluation committee	age groups 50-59, 60-69 and 70 years and older immune status: immunocompetent country: 18 countries 50-64y65+	Shingrix (RZV, HZ/su) platform: adjuvanted recombinant subunit doses: 2 schedule: 0 and 2 months vs placebo	96.6-97.9 VE (%) (range across the three age strata) follow-up: mean 3.2 years	RCT	Lal et al. 2015 N Engl J Med quote Vaccine efficacy was between 96.6% and 97.9% for all age groups. abstract, RESULTS Age-stratified result of the ZOE trial in adults fifty and older: no fall in efficacy with age within this trial, unlike the live vaccine.
Confirmed herpes zoster severity: any case definition: Herpes zoster confirmed by PCR or clinical evaluation committee	70 years and older, mean 75.6 years immune status: immunocompetent country: 18 countries n: 13,900 participants 65+	Shingrix (RZV, HZ/su) platform: adjuvanted recombinant subunit doses: 2 schedule: 0 and 2 months vs placebo	89.8 (84.2–93.7) VE (%) follow-up: mean 3.7 years	RCT	Cunningham et al. 2016 N Engl J Med quote 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%). abstract, RESULTS ZOE-70 trial. The same sentence gives the two age strata; the oldest stratum is recorded separately.
Confirmed herpes zoster severity: any case definition: Herpes zoster confirmed by PCR or clinical evaluation committee	80 years and older immune status: immunocompetent country: 18 countries 65+	Shingrix (RZV, HZ/su) platform: adjuvanted recombinant subunit doses: 2 schedule: 0 and 2 months vs placebo	89.1 VE (%) follow-up: mean 3.7 years	RCT	Cunningham et al. 2016 N Engl J Med quote 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%). abstract, RESULTS ZOE-70 trial oldest stratum; no confidence interval in the abstract.
Confirmed herpes zoster severity: any case definition: Herpes zoster confirmed by PCR or clinical evaluation committee	70 years and older (pooled ZOE-50 and ZOE-70) immune status: immunocompetent country: 18 countries n: 16,596 participants 65+	Shingrix (RZV, HZ/su) platform: adjuvanted recombinant subunit doses: 2 schedule: 0 and 2 months vs placebo	91.3 (86.8–94.5) VE (%) follow-up: mean 3.7 years	RCT ZOE-50 and ZOE-70 participants aged 70 and older	Cunningham et al. 2016 N Engl J Med quote 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). abstract, RESULTS Pre-specified pooled analysis.
Herpes zoster severity: any case definition: Confirmed HZ in pooled ZOE-50/70	50 years and older, mean 68.8 years risk group: frailty subgroups (non-frail, pre-frail, frail) by frailty index immune status: immunocompetent country: multiple n: about 92% of 29,305 pooled participants 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 schedule: 0 and 2 months vs placebo	95.8 / 90.4 / 90.2 VE (%), non-frail / pre-frail / frail	RCT	Curran et al. 2021 J Am Geriatr Soc quote RZV vaccine efficacy against herpes zoster was >90% for all frailty subgroups (non-frail: 95.8% (95% confidence interval = 91.6-98.2), pre-frail: 90.4% (84.4-94.4), frail: 90.2% (75.4-97.0)). abstract, RESULTS Post-hoc frailty analysis of randomised data; each subgroup estimate has its own interval in the same sentence (non-frail 91.6-98.2, pre-frail 84.4-94.4, frail 75.4-97.0). Efficacy held above 90% even in frail participants.
Herpes zoster severity: any case definition: Confirmed HZ in ZOE-50 and ZOE-70	50 years and older; separate range for 70 and older immune status: immunocompetent country: across geographic regions (Europe, North America, Latin America, Asia-Australia) 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 schedule: 0 and 2 months vs placebo	95.7-97.2 VE (%) (range across geographic regions)	RCT	Willer et al. 2019 Vaccine quote Across geographic regions, efficacy against HZ ranged between 95.7 and 97.2% in ≥50-year-olds, and between 87.3% and 95.1% in ≥70-year-olds; efficacy against PHN ranged between 86.8 and 100% in ≥70-year-olds. abstract, RESULTS Post-hoc; the same sentence gives 87.3-95.1% across regions in those 70 and older. Trials were not powered for these subgroups.
Confirmed herpes zoster severity: any case definition: Confirmed HZ episodes in a phase IV observer-blind trial	50 years and older immune status: immunocompetent and medically stable country: China n: 6138 participants 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 schedule: 0 and 2 months vs placebo	100 (89.82–100) VE (%) follow-up: mean 15.2 months	RCT	Alexandra et al. 2024 Hum Vaccin Immunother quote During a mean follow-up period of 15.2 (±1.1) months, 31 HZ episodes were confirmed (RZV = 0; placebo = 31) for an incidence rate of 0.0 vs 8.2 per 1000 person-years and an overall VE of 100% (89.82-100). abstract Zero cases in the vaccine arm; short follow-up. The next sentence gives descriptive estimates by age category, both also at the ceiling with wide intervals.
Confirmed herpes zoster after autologous HSCT severity: any case definition: At least one confirmed HZ episode	18 years and older, mean 55 years immune status: immunocompromised (recent autologous haematopoietic stem cell transplant) country: 28 countries n: 1846 patients 18-49y50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 schedule: first dose 50-70 days after transplant, second 1-2 months later vs placebo	68.2 (0.22–0.44 IRR CI) VE (%) = 1 - IRR follow-up: median 21 months	RCT	Bastidas et al. 2019 JAMA quote During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P < .001), equivalent to 68.2% vaccine efficacy. abstract, RESULTS ZOE-HSCT. Incidence 30 vs 94 per 1,000 person-years. The interval is reported on the IRR scale, not the percentage scale.
Confirmed herpes zoster severity: any case definition: Herpes zoster diagnosed by clinical and laboratory criteria	60 years and older immune status: immunocompetent country: United States n: 38,546 adults 50-64y65+	Zostavax (ZVL, live attenuated Oka/Merck) platform: live attenuated doses: 1 vs placebo	51.3 VE (%) follow-up: median 3.12 years	RCT	Oxman et al. 2005 N Engl J Med quote 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). abstract, RESULTS Shingles Prevention Study. The same sentence reports the reductions in burden of illness and in PHN; PHN is recorded separately. No confidence intervals in the abstract.
PCR-confirmed herpes zoster severity: any case definition: HZ confirmed by PCR of lesion swabs	50-59 years immune status: immunocompetent country: North America and Europe n: 22,439 subjects 50-64y	Zostavax (ZVL, live attenuated) platform: live attenuated doses: 1 vs placebo	69.8 (54.1–80.6) VE (%) follow-up: mean 1.3 years	RCT	Schmader et al. 2012 Clin Infect Dis quote Vaccine efficacy for preventing HZ was 69.8% (95% confidence interval, 54.1-80.6). abstract, RESULTS ZEST trial. Higher than in the older SPS population, consistent with better efficacy at younger ages; short follow-up.
Herpes zoster severity: any case definition: Confirmed HZ in the long-term follow-up study	50 years and older at vaccination, mean 67.2 years immune status: immunocompetent country: multiple (ZOE-50/70 sites) n: 7277 participants 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 time since vaccination: years 6 to about 8 after vaccination vs historical control modelled from ZOE-50/70 placebo data	84.0 (75.9–89.8) VE (%), from start of follow-up study vs historical placebo follow-up: interim, mean 5.1-7.1 years post-vaccination	cohort	Boutry et al. 2022 Clin Infect Dis quote Efficacy of RZV against HZ through this interim analysis was 84.0% (95% confidence interval [CI], 75.9-89.8) from the start of this follow-up study and 90.9% (95% CI, 88.2-93.2) from vaccination in ZOE-50/70. abstract, RESULTS Open-label extension with no concurrent placebo; the comparator is modelled from earlier placebo incidence, so this is not a randomised comparison. Same sentence gives the cumulative estimate from vaccination, recorded separately.
Herpes zoster severity: any case definition: Confirmed HZ from vaccination through interim analysis	50 years and older at vaccination immune status: immunocompetent country: multiple n: 7277 participants 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 time since vaccination: from vaccination to about year 8 vs placebo during ZOE-50/70 then modelled historical control	90.9 (88.2–93.2) VE (%), cumulative from vaccination follow-up: about 8 years	cohort	Boutry et al. 2022 Clin Infect Dis quote Efficacy of RZV against HZ through this interim analysis was 84.0% (95% confidence interval [CI], 75.9-89.8) from the start of this follow-up study and 90.9% (95% CI, 88.2-93.2) from vaccination in ZOE-50/70. abstract, RESULTS Annual estimates stayed high and stable each year since vaccination at this interim.
Herpes zoster during years 6-11 severity: any case definition: Confirmed HZ during ZOE-LTFU	50 years and older at first vaccination, mean 67.3 years immune status: immunocompetent country: multiple n: 7273 participants 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 time since vaccination: years 6 to 11 after vaccination vs historical control constructed from ZOE-50/70 placebo data	79.8 (73.7–84.6) VE (%) during long-term follow-up (years 6-11) follow-up: 6 years of extension follow-up	cohort	Strezova et al. 2025 EClinicalMedicine quote During ZOE-LTFU, VE was 79·8% (95% confidence interval [CI]: 73·7, 84·6) and 73·2% (95% CI: 62·9, 80·9) against HZ in participants ≥50 and ≥70 years at first vaccination, respectively, and was 87·5% (95% CI: 64·8, 96·8) against PHN and 91·7% (95% CI: 43·7, 99·8) against other HZ-related complications in participants ≥50 years. abstract, FINDINGS Final ZOE-LTFU analysis. Same sentence gives the estimate for those seventy and older at vaccination, recorded separately. Non-randomised comparator.
Herpes zoster during years 6-11 severity: any case definition: Confirmed HZ during ZOE-LTFU	70 years and older at first vaccination immune status: immunocompetent country: multiple 65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 time since vaccination: years 6 to 11 after vaccination vs historical control constructed from ZOE-50/70 placebo data	73.2 (62.9–80.9) VE (%) during long-term follow-up (years 6-11) follow-up: 6 years of extension follow-up	cohort	Strezova et al. 2025 EClinicalMedicine quote During ZOE-LTFU, VE was 79·8% (95% confidence interval [CI]: 73·7, 84·6) and 73·2% (95% CI: 62·9, 80·9) against HZ in participants ≥50 and ≥70 years at first vaccination, respectively, and was 87·5% (95% CI: 64·8, 96·8) against PHN and 91·7% (95% CI: 43·7, 99·8) against other HZ-related complications in participants ≥50 years. abstract, FINDINGS Lower than the all-ages figure, showing some age-related decline in the long term that was not visible in the first 4 years.
Herpes zoster from 1 month after dose 2 to end of year 11 severity: any case definition: Confirmed HZ across ZOE-50/70 and ZOE-LTFU	50 years and older at first vaccination immune status: immunocompetent country: multiple 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 time since vaccination: 1 month post-dose 2 to 11 years vs placebo during ZOE-50/70 then historical control	87.7 (84.9–90.1) VE (%), cumulative over 11 years follow-up: 11 years	cohort	Strezova et al. 2025 EClinicalMedicine quote From 1 month post-dose 2 in ZOE-50/70 to the end of ZOE-LTFU, VE against HZ was 87·7% (95% CI: 84·9, 90·1) in participants ≥50 years and sustained at 82·0% (95% CI: 63·0, 92·2) in the eleventh year post-vaccination. abstract, FINDINGS Same sentence gives 82.0% (63.0-92.2) in the eleventh year alone, the longest single-year estimate available.
Herpes zoster in year 11 after vaccination severity: any case definition: Confirmed HZ during the eleventh year post-vaccination	50 years and older at first vaccination immune status: immunocompetent country: multiple 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 time since vaccination: 11 years vs historical control constructed from ZOE-50/70 placebo data	82.0 (63.0–92.2) VE (%) in year 11 follow-up: year 11 only	cohort	Strezova et al. 2025 EClinicalMedicine quote From 1 month post-dose 2 in ZOE-50/70 to the end of ZOE-LTFU, VE against HZ was 87·7% (95% CI: 84·9, 90·1) in participants ≥50 years and sustained at 82·0% (95% CI: 63·0, 92·2) in the eleventh year post-vaccination. abstract, FINDINGS Wide interval; the comparator is modelled, not concurrent.
Herpes zoster within 2 years of allogeneic HCT severity: any case definition: HZ incidence within 2 years after transplant	adults immune status: immunocompromised (allogeneic haematopoietic cell transplant) country: single tertiary transplant centre n: 506 recipients (152 vaccinated, 354 historical controls) 18-49y50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 vs historical unvaccinated allo-HCT recipients	0.287 (0.131–0.627) adjusted HR vs unvaccinated follow-up: 2 years after transplant	cohort	Lee et al. 2026 Transplant Cell Ther quote RZV significantly reduced HZ risk (aHR 0.287, 95% confidence interval [CI] 0.131 to 0.627), corresponding to 71.3% effectiveness, consistent across subgroup analyses. abstract Historical controls from a single centre; acyclovir prophylaxis modelled as time-varying. Equivalent to 71.3% effectiveness per the authors. No RCT of RZV exists in allogeneic HCT.
Herpes zoster (medical visit diagnosis with treatment) severity: any case definition: HZ office-visit diagnosis with antiviral treatment in Medicare claims	over 65 years country: United States (Medicare Part D) setting: community-dwelling beneficiaries period: first 2 years post-licensure 65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 vs unvaccinated beneficiaries (inverse probability weighted)	70.1 (68.6–71.5) VE (%), 2 doses	cohort	Izurieta et al. 2021 Clin Infect Dis quote RESULTS: We found a vaccine effectiveness of 70.1% (95% confidence interval [CI], 68.6-71.5) and 56.9% (95% CI, 55.0-58.8) for 2 and 1 doses, respectively. abstract, RESULTS Lower than trial efficacy, which the authors attribute to less specific outcome ascertainment. Same sentence gives the one-dose estimate, recorded separately.
Herpes zoster (medical visit diagnosis with treatment) severity: any case definition: HZ office-visit diagnosis with antiviral treatment in Medicare claims	over 65 years country: United States (Medicare Part D) period: first 2 years post-licensure 65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 1 vs unvaccinated beneficiaries (inverse probability weighted)	56.9 (55.0–58.8) VE (%), 1 dose only	cohort	Izurieta et al. 2021 Clin Infect Dis quote RESULTS: We found a vaccine effectiveness of 70.1% (95% confidence interval [CI], 68.6-71.5) and 56.9% (95% CI, 55.0-58.8) for 2 and 1 doses, respectively. abstract, RESULTS Single-dose effectiveness is materially lower than two-dose; second doses given later than the recommended window did not lose effectiveness.
Herpes zoster (diagnosis with antiviral prescription) severity: any case definition: Incident HZ diagnosis with an antiviral prescription	50 years and older country: United States (Vaccine Safety Datalink, four health systems) n: nearly 2.0 million persons, 7.6 million person-years 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 1 vs 2 vs unvaccinated persons	64 vs 76 VE (%), 1 dose vs 2 doses follow-up: up to 4 years	cohort	Zerbo et al. 2024 Ann Intern Med quote After adjustment, VE of 1 dose was 64% and VE of 2 doses was 76%. abstract, RESULTS No confidence intervals in the abstract. Outcome ascertainment less specific than in trials.
Herpes zoster (diagnosis with antiviral prescription) severity: any case definition: Incident HZ diagnosis with an antiviral prescription	50 years and older country: United States (Vaccine Safety Datalink) 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 time since vaccination: years 1, 2 and 3-4 after second dose vs unvaccinated persons	79 / 75 / 73 VE (%) by year since dose 2 (year 1 / year 2 / years 3-4) follow-up: 4 years	cohort	Zerbo et al. 2024 Ann Intern Med quote After 2 doses, VE was 79% during the first year, 75% during the second year, and 73% during the third and fourth years. abstract, RESULTS Little waning after two doses over 4 years. The one-dose series in the same abstract fell sharply after the first year, recorded separately.
Herpes zoster (diagnosis with antiviral prescription) severity: any case definition: Incident HZ diagnosis with an antiviral prescription	50 years and older country: United States (Vaccine Safety Datalink) 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 1 time since vaccination: years 1, 2, 3 and beyond after a single dose vs unvaccinated persons	70 / 45 / 48 / 52 VE (%) by year since the single dose (year 1 / year 2 / year 3 / after year 3) follow-up: 4 years	cohort	Zerbo et al. 2024 Ann Intern Med quote 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. abstract, RESULTS Substantial drop after the first year with a single dose, which is the argument for completing the series.
Herpes zoster (diagnosis with antiviral prescription) severity: any case definition: Incident HZ diagnosis with an antiviral prescription	50 years and older risk group: corticosteroid use before vaccination vs none country: United States (Vaccine Safety Datalink) 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 1 or 2 vs unvaccinated persons	65 vs 77 VE (%), corticosteroid users vs non-users	cohort	Zerbo et al. 2024 Ann Intern Med quote Vaccine effectiveness was 65% in persons who received corticosteroids before vaccination and 77% in those who did not. abstract, RESULTS Corticosteroid use is a proxy for immunosuppression; effectiveness is lower but still substantial.
Herpes zoster (diagnostic code plus antiviral within 7 days) severity: any case definition: HZ diagnostic codes B02.xx with antiviral within 7 days	50 years and older, median 68 years prior infection: 46.7% had previously received zoster vaccine live country: United States (Kaiser Permanente Southern California) period: vaccinated April 2018-December 2020, followed to December 2022 n: 102,766 two-dose recipients matched 1:4 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 schedule: 4 weeks to 6 months apart vs unvaccinated matched members	73.9 (71.8–75.8) adjusted VE (%), 2 doses follow-up: up to 4 years	cohort	Tseng et al. 2026 Clin Infect Dis quote RESULTS: Among N = 102 766 (median age 68 years) who received 2 RZV doses (4 weeks-6 months apart), 48 028 (46.7%) had previously received zoster vaccine live; aVE was 73.9% (95% CI: 71.8%-75.8%) for HZ and 83.7% (95% CI: 75.1%-89.3%) for PHN. abstract, RESULTS VE reported stable over 4 years. Same sentence gives the PHN estimate, recorded separately.
Herpes zoster (diagnostic code plus antiviral within 7 days) severity: any case definition: HZ diagnostic codes B02.xx with antiviral within 7 days	50 years and older country: United States (Kaiser Permanente Southern California) period: 2018-2022 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 1 vs unvaccinated matched members	60.3 (56.4–63.9) adjusted VE (%), 1 dose	cohort	Tseng et al. 2026 Clin Infect Dis quote One-dose VE was 60.3% (56.4%-63.9%) against HZ and 45.6% (11.4%-66.6%) against PHN. abstract, RESULTS Same sentence gives one-dose VE against PHN of 45.6% (11.4-66.6).
Herpes zoster ophthalmicus severity: ocular zoster case definition: HZO identified by natural language processing of clinical notes	50 years and older, median 68 years country: United States (Kaiser Permanente Southern California) period: 2018-2022 n: 102,766 vaccinated and 411,064 unvaccinated 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 vs unvaccinated matched members	72.9 (67.0–77.8) adjusted VE (%) against HZO	cohort	Rayens et al. 2025 Clin Infect Dis quote The adjusted RZV effectiveness against HZO was 72.9% (67.0%-77.8%). abstract, RESULTS Matched on age, sex, race/ethnicity and index date; healthy-vaccinee bias remains possible.
Herpes zoster incidence, 7-11 years after vaccination severity: any case definition: HZ by SPS surveillance and case determination	60 years and older at vaccination immune status: immunocompetent country: United States n: 6867 SPS vaccine recipients 50-64y65+	Zostavax (ZVL, live attenuated) platform: live attenuated doses: 1 time since vaccination: 7 to 11 years vs modelled reference placebo group from SPS and STPS placebo data	21.1 VE (%) in the long-term persistence substudy vs original SPS follow-up: up to 11 years	cohort	Morrison et al. 2015 Clin Infect Dis quote Compared to SPS, estimated vaccine efficacy in LTPS decreased from 61.1% to 37.3% for the herpes zoster (HZ) burden of illness (BOI), from 66.5% to 35.4% for incidence of postherpetic neuralgia, and from 51.3% to 21.1% for incidence of HZ, and declined for all 3 outcome measures from 7 through 11 years postvaccination. abstract, RESULTS No concurrent placebo; comparator modelled. Efficacy against HZ incidence was statistically greater than zero only through year 8. Same sentence gives PHN efficacy falling from 66.5% to 35.4% and burden of illness from 61.1% to 37.3%.
Herpes zoster severity: any case definition: HZ in Kaiser Permanente electronic records	60 years and older country: United States (Kaiser Permanente) n: 176,078 vaccinated and three matched unvaccinated each 50-64y65+	Zostavax (ZVL, live attenuated) platform: live attenuated doses: 1 time since vaccination: year 1 through year 8 vs matched unvaccinated members	68.7 then 4.2 (66.3–70.9) VE (%), year 1 vs year 8 after vaccination follow-up: 8 years	cohort	Tseng et al. 2016 J Infect Dis quote The effectiveness of HZ vaccine decreased from 68.7% (95% CI, 66.3%-70.9%) in the first year to 4.2% (95% CI, -24.0% to 25.9%) in the eighth year. abstract The interval entered is for year 1; year 8 effectiveness was 4.2% with an interval from -24.0% to 25.9%, indistinguishable from zero. The clearest real-world evidence of rapid waning of the live vaccine.
Herpes zoster severity: any case definition: Incident HZ in Kaiser Permanente records	60 years and older immune status: immunocompetent country: United States (Kaiser Permanente Southern California) setting: community-dwelling period: 2007-2009 n: 75,761 vaccinated, 227,283 unvaccinated 50-64y65+	Zostavax (ZVL, live attenuated) platform: live attenuated doses: 1 vs age-matched unvaccinated members	0.45 (0.42–0.48) adjusted HR vs unvaccinated	cohort	Tseng et al. 2011 JAMA quote In adjusted analysis, vaccination was associated with a reduced risk of herpes zoster (hazard ratio [HR], 0.45; 95% CI, 0.42-0.48); this reduction occurred in all age strata and among individuals with chronic diseases. abstract, RESULTS Incidence in each arm is in the abstract. Vaccinees were healthier and had more outpatient visits; the authors used unrelated conditions as a negative control.
Ophthalmic herpes zoster and hospitalisation coded as herpes zoster severity: ocular zoster and hospitalisation case definition: Coded ophthalmic HZ and HZ hospitalisations	60 years and older immune status: immunocompetent country: United States (Kaiser Permanente Southern California) period: 2007-2009 50-64y65+	Zostavax (ZVL, live attenuated) platform: live attenuated doses: 1 vs age-matched unvaccinated members	0.37 then 0.35 (0.23–0.61) adjusted HR vs unvaccinated, ophthalmic zoster then hospitalisation	cohort	Tseng et al. 2011 JAMA quote Ophthalmic herpes zoster (HR, 0.37; 95% CI, 0.23-0.61) and hospitalizations coded as herpes zoster (HR, 0.35; 95% CI, 0.24-0.51) were less likely among vaccine recipients. abstract, RESULTS The interval entered is for ophthalmic zoster; hospitalisation has its own interval (0.24-0.51) in the same sentence.
Incident herpes zoster severity: any case definition: Zoster in linked UK primary care records	70-79 years (born 1933-1946) country: United Kingdom setting: primary care, national programme period: 2013-2016 n: 516,547 individuals, 21% vaccinated 65+	Zostavax (ZVL, live attenuated) platform: live attenuated doses: 1 vs unvaccinated individuals	64 (60–68) adjusted VE (%) follow-up: first 3 years of the programme	cohort	Walker et al. 2018 Vaccine quote After adjustment, VE was 64% (95%CI = 60-68%) against incident zoster and 81% (95%CI = 61-91%) against PHN, with very similar VE estimates in the routine and catch-up cohorts. abstract, RESULTS Incidence in each arm is in the abstract. Same sentence gives the PHN estimate, recorded separately.
Incident herpes zoster severity: any case definition: Zoster in linked UK primary care records	70-79 years prior infection: previous history of zoster country: United Kingdom period: 2013-2016 65+	Zostavax (ZVL, live attenuated) platform: live attenuated doses: 1 vs unvaccinated individuals	47 vs 64 (31–58) adjusted VE (%), previous zoster vs no previous zoster	cohort	Walker et al. 2018 Vaccine quote VE against zoster was lower in those with a previous history of zoster: 47% (95%CI = 31-58%) versus 64% (95%CI = 60-68%) in those without previous zoster. abstract, RESULTS The interval entered is for the previous-zoster group; the no-previous-zoster group has 60-68 in the same sentence. Lower effectiveness in people who have already had zoster.
Incident herpes zoster severity: any case definition: Zoster in linked UK primary care records	70-79 years country: United Kingdom period: 2013-2016 65+	Zostavax (ZVL, live attenuated) platform: live attenuated doses: 1 time since vaccination: year 1 vs year 3 vs unvaccinated individuals	69 then 45 (65–74) adjusted VE (%), year 1 vs year 3 after vaccination follow-up: 3 years	cohort	Walker et al. 2018 Vaccine quote There was evidence of waning VE over time, from 69% (95%CI = 65-74%) in the first year after vaccination to 45% (95%CI = 29-57%) by the third year. abstract, RESULTS The interval entered is for year 1; year 3 is 45% (29-57) in the same sentence. Waning within 3 years is faster than in the SPS cohort.
Incident herpes zoster severity: any case definition: HZ in national health insurance claims	50 years and older, mean 61.5 years country: South Korea period: vaccinated 2012-2021, followed to January 2024 n: 910,602 individuals after overlap weighting 50-64y65+	live attenuated zoster vaccine platform: live attenuated doses: 1 vs unvaccinated individuals (overlap weighted)	0.48 (0.48–0.49) adjusted HR vs unvaccinated follow-up: up to 10 years	cohort	Yeo et al. 2025 Vaccine quote RESULTS: Among 910,602 individuals (mean age, 61.48 [SD, 2.53] years; 47.30 % males) after overlap weighting, vaccination was associated with significantly lower risks of herpes zoster (aHR, 0.48 [95 % CI 0.48-0.49]; RMST differences, 151.1 days), postherpetic neuralgia (0.47 [0.46-0.48]; 86.0 days), herpes zoster encephalitis (0.40 [0.25-0.63]; 0.20 days), and hospital admission for herpes zoster (0.33 [0.31-0.35]; 14.1 days). abstract, RESULTS Emulated target trial. Same sentence gives aHR 0.47 for PHN, 0.40 (0.25-0.63) for zoster encephalitis and 0.33 (0.31-0.35) for hospital admission. Protection waned but persisted for 8 years.
Hospital admission for herpes zoster severity: hospitalisation case definition: HZ admission in national health insurance claims	50 years and older country: South Korea period: 2012-2024 50-64y65+	live attenuated zoster vaccine platform: live attenuated doses: 1 vs unvaccinated individuals (overlap weighted)	0.33 (0.31–0.35) adjusted HR vs unvaccinated follow-up: up to 10 years	cohort	Yeo et al. 2025 Vaccine quote RESULTS: Among 910,602 individuals (mean age, 61.48 [SD, 2.53] years; 47.30 % males) after overlap weighting, vaccination was associated with significantly lower risks of herpes zoster (aHR, 0.48 [95 % CI 0.48-0.49]; RMST differences, 151.1 days), postherpetic neuralgia (0.47 [0.46-0.48]; 86.0 days), herpes zoster encephalitis (0.40 [0.25-0.63]; 0.20 days), and hospital admission for herpes zoster (0.33 [0.31-0.35]; 14.1 days). abstract, RESULTS Greater protection against severe (hospitalised) zoster than against any zoster, as seen with other zoster vaccines.

Vaccine safety and adverse events

Harms measured after vaccination against an unvaccinated or baseline comparator. Kept separate from post-acute sequelae, which follow the disease, not the vaccine.

Outcome (O)	Population (P)	Intervention / comparator	Estimate	Design (S)	Source
Serious adverse events after RZV severity: serious adverse event case definition: Serious adverse events in the included RCTs	healthy older adults, mean 60 years or older immune status: immunocompetent country: multiple n: 29,311 participants 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 vs placebo	0.97 (0.91–1.03) RR vs placebo	meta-analysis GRADE: moderate 2 RCTs	de et al. 2023 Cochrane Database Syst Rev quote There were no differences between the vaccinated and placebo groups in cumulative incidence of serious adverse events (RR 0.97, 95% CI 0.91 to 1.03) or deaths (RR 0.94, 95% CI 0.84 to 1.04; moderate-certainty evidence). abstract, MAIN RESULTS Cochrane review. Deaths are in the same sentence with no difference. Systemic and local symptoms were much more common with the vaccine, recorded separately.
Any systemic symptom after RZV severity: mild to moderate reactogenicity case definition: Solicited systemic symptoms in the included RCTs	healthy older adults immune status: immunocompetent country: multiple 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 vs placebo	2.23 (2.12–2.34) RR vs placebo	meta-analysis 2 RCTs	de et al. 2023 Cochrane Database Syst Rev quote The vaccinated group had a higher cumulative incidence of adverse events, any systemic symptom (RR 2.23, 95% CI 2.12 to 2.34; RD 33%; NNTH 3.0), and any local symptom (RR 6.89, 95% CI 6.37 to 7.45; RD 67%; NNTH 1.5). abstract, MAIN RESULTS Risk difference 33%, NNTH 3.0; any local symptom RR 6.89 (6.37-7.45), risk difference 67%, in the same sentence. Most participants reported mild to moderate intensity.
Serious adverse events after LZV severity: serious adverse event case definition: Serious adverse events in the included RCTs	60 years and older immune status: immunocompetent country: multiple 50-64y65+	Zostavax (ZVL, live attenuated) platform: live attenuated doses: 1 vs placebo	1.08 (0.95–1.21) RR vs placebo	meta-analysis GRADE: moderate	de et al. 2023 Cochrane Database Syst Rev quote There were no differences between the vaccinated and placebo groups for serious adverse events (RR 1.08, 95% CI 0.95 to 1.21) or deaths (RR 1.01, 95% CI 0.92 to 1.11; moderate-certainty evidence). abstract, MAIN RESULTS Cochrane review. Deaths are in the same sentence with no difference.

Post-herpetic neuralgia Varicella zoster virus (reactivation)

Post-acute and long-term sequelae

What can follow the acute illness: chronic disease, disability, cancers, congenital syndromes, post-infectious conditions.

Outcome (O)	Population (P)	Comparator	Estimate	Design (S)	Source
Post-herpetic neuralgia after zoster severity: chronic pain case definition: PHN as defined in the included studies	general population, varies by study age distribution vaccination status: mixed country: 26 countries period: studies up to December 2013 All ages	vs none (proportion of zoster cases)	5 to more than 30 proportion of zoster patients developing PHN (%) (range across studies) per zoster patient	systematic review	Kawai et al. 2014 BMJ Open quote The risk of developing PHN varied from 5% to more than 30%, depending on the type of study design, age distribution of study populations and definition. abstract, RESULTS The range depends on study design, age distribution and PHN definition. The next sentence of the abstract notes that more than 30% of PHN patients had pain for more than 1 year.
Pain persisting more than 1 year in patients with PHN severity: chronic pain over 1 year case definition: Persistent pain among PHN patients in included studies	general population vaccination status: mixed country: 26 countries period: studies up to December 2013 All ages	vs none (proportion of PHN cases)	more than 30 proportion of PHN patients with pain beyond 1 year (%) per PHN patient follow-up: more than 1 year	systematic review	Kawai et al. 2014 BMJ Open quote More than 30% of patients with PHN experienced persistent pain for more than 1 year. abstract, RESULTS Denominator is PHN patients, not all zoster patients.
Post-herpetic neuralgia after zoster severity: chronic pain case definition: Chronic pain persisting after zoster, as summarised by ACIP	all ages (risk rises with age) vaccination status: unvaccinated country: United States period: pre-vaccine era (ACIP 2008 statement) All ages	vs none (proportion of zoster cases)	10-18 proportion of zoster patients developing PHN (%) per zoster patient	expert body	Harpaz et al. 2008 MMWR Recomm Rep quote The risk for PHN in patients with zoster is 10%-18%. abstract ACIP summary range; definitions of PHN (pain persisting for different minimum durations) differ between studies and drive much of the spread.
Post-herpetic neuralgia after zoster severity: chronic pain case definition: PHN identified by medical record review	adults 22 years and older; separate figure for 79 years and older vaccination status: unvaccinated country: United States (Olmsted County, Minnesota) period: 1996-2001, before zoster vaccine introduction n: 1669 adults with confirmed HZ 18-49y50-64y65+	vs none (proportion of zoster cases)	18 vs 33 proportion of zoster patients with PHN (%), all adults vs aged 79 and older per zoster patient	cohort	Yawn et al. 2007 Mayo Clin Proc quote Postherpetic neuralgia occurred in 18% of adult patients with HZ and in 33% of those aged 79 years and older. abstract, RESULTS Shows the age gradient directly; PHN risk roughly doubles in the oldest patients.
Post-herpetic neuralgia after zoster severity: chronic pain case definition: Pain 90 days or more after zoster, based on diagnostic or prescription codes in primary care	all adult ages (risk rose steeply between 50 and 79 years) vaccination status: not reported country: United Kingdom setting: primary care, CPRD n: 119,413 zoster patients 18-49y50-64y65+	vs none (proportion of zoster cases)	5.8 proportion of zoster patients developing PHN (%) per zoster patient	cohort	Forbes et al. 2016 Neurology quote RESULTS: Of 119,413 zoster patients, 6,956 (5.8%) developed postherpetic neuralgia. abstract, RESULTS Primary-care coding of PHN gives a lower proportion than record-review studies. The adjusted odds of PHN rose steeply per decade of age in this cohort; that odds ratio is reported with a ninety-nine percent interval rather than a ninety-five percent one, so it is not entered as a value here.
Post-herpetic neuralgia after zoster in patients with leukaemia or lymphoma severity: chronic pain case definition: Pain 90 days or more after zoster, based on diagnostic or prescription codes	all adult ages immune status: severely immunosuppressed (leukaemia, lymphoma) vaccination status: not reported country: United Kingdom setting: primary care, CPRD 18-49y50-64y65+	vs zoster patients without these conditions (overall 5.8%)	13.7 vs 12.7 proportion of zoster patients developing PHN (%), leukaemia vs lymphoma per zoster patient	cohort	Forbes et al. 2016 Neurology quote Postherpetic neuralgia risk was higher in women (6.3% vs 5.1% in men: OR 1.19, 1.10-1.27) and those with severely immunosuppressive conditions, including leukemia (13.7%: 2.07, 1.08-3.96) and lymphoma (12.7%: 2.45, 1.53-3.92); autoimmune conditions, including rheumatoid arthritis (9.1%: 1.20, 0.99-1.46); and other comorbidities, including asthma and diabetes. abstract, RESULTS Roughly double the overall PHN proportion; the odds ratios in the same sentence are adjusted but reported with ninety-nine percent intervals.
Post-herpetic neuralgia after zoster severity: chronic pain case definition: ICD-10 coded PHN in statutory health insurance data	all ages, steady age-related increase vaccination status: unvaccinated country: Germany setting: insurance claims period: 2009 All ages	vs none (proportion of zoster cases)	15 proportion of zoster patients with PHN (%) per zoster patient	cohort	Hillebrand et al. 2015 J Infect quote The PHN proportion increased to 15% in 2009 with a steady age-related increase. abstract, RESULTS Claims-coded PHN; the proportion rose over the study years, which may reflect coding changes.
Post-herpetic neuralgia within 90 days of zoster onset severity: chronic pain case definition: PHN within 90 days of HZ onset in primary care and hospital records	adults 18 years and older immune status: immunocompromised vs immunocompetent vaccination status: not reported country: England setting: primary care, CPRD period: 2000-2012 18-49y50-64y65+	vs immunocompetent zoster patients	10.7 vs 9.1 proportion of zoster patients with PHN (%), immunocompromised vs immunocompetent per zoster patient	cohort	Yanni et al. 2018 BMJ Open quote The proportions of PHN and other HZ complications were 10.7% (10.2-11.1) and 2.9% (2.7-3.2) in the IC cohort, but 9.1% (8.7-9.5) and 2.3% (2.1-2.6) in the IC-free cohort, respectively. abstract, RESULTS Only a modest difference between immunocompromised and immunocompetent patients once zoster has occurred; the larger difference is in zoster incidence.

Vaccine efficacy and effectiveness

Every estimate compiled, annotated by population (P), intervention (I), comparator (C), outcome (O) and study design (S).

Outcome (O)	Population (P)	Intervention / comparator	Estimate	Design (S)	Source
Post-herpetic neuralgia severity: chronic pain case definition: PHN in post-licensure observational studies	adults immune status: immunocompetent vs immunocompromised country: multiple 18-49y50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 vs unvaccinated	84.7 (60.9–94.0) pooled VE (%), immunocompetent	meta-analysis	Mbinta et al. 2026 Vaccine quote Pooled vaccine effectiveness for postherpetic neuralgia for the immunocompetent population was 84·7% (95% CI 60·9-94·0) and for immunocompromised populations was 38·7% (95% CI 19·1-53·5). abstract, FINDINGS The same sentence gives 38.7% (19.1-53.5) for immunocompromised populations, a much lower and less certain estimate based on few studies.
Post-herpetic neuralgia severity: chronic pain case definition: PHN in post-licensure observational studies	50 years and older country: USA, UK, Canada and Sweden 50-64y65+	Zostavax (ZVL, live attenuated) platform: live attenuated doses: 1 vs no vaccination	59.7 (58.4–89.7) pooled VE (%)	meta-analysis 3 studies	Mbinta et al. 2022 Lancet Healthy Longev quote The vaccine effectiveness for ZVL against postherpetic neuralgia was 59·7% (58·4-89·7; three studies) and against herpes zoster ophthalmicus (in a fixed-effects model) was 30·0% (20·5-38·4; two studies). abstract, FINDINGS Same sentence gives 30.0% (20.5-38.4) against herpes zoster ophthalmicus from two studies in a fixed-effects model. The asymmetric interval is as reported.
Post-herpetic neuralgia severity: chronic pain case definition: PHN as defined in the trial protocol	70 years and older (pooled ZOE-50 and ZOE-70) immune status: immunocompetent country: 18 countries n: 16,596 participants 65+	Shingrix (RZV, HZ/su) platform: adjuvanted recombinant subunit doses: 2 schedule: 0 and 2 months vs placebo	88.8 (68.7–97.1) VE (%) follow-up: mean 3.7 years	RCT ZOE-50 and ZOE-70 participants aged 70 and older	Cunningham et al. 2016 N Engl J Med quote 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). abstract, RESULTS Wider interval because PHN is a rarer outcome; most of the PHN reduction comes from preventing zoster itself.
Post-herpetic neuralgia after autologous HSCT severity: chronic pain case definition: PHN as a prespecified secondary end point	18 years and older, mean 55 years immune status: immunocompromised (recent autologous HSCT) country: 28 countries n: 1846 patients 18-49y50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 vs placebo	0.1 (0.00–0.78) IRR vs placebo follow-up: median 21 months	RCT	Bastidas et al. 2019 JAMA quote Of 8 secondary end points, 3 showed significant reductions in incidence of postherpetic neuralgia (vaccine, n=1; placebo, n=9; IRR, 0.1; 95% CI, 0.00-0.78; P = .02) and of other prespecified herpes zoster-related complications (vaccine, n=3; placebo, n=13; IRR, 0.22; 95% CI, 0.04-0.81; P = .02) and in duration of severe worst herpes zoster-associated pain (vaccine, 892.0 days; placebo, 6275.0 days; hazard ratio, 0.62; 95% CI, 0.42-0.89; P = .01). abstract, RESULTS Based on 1 vs 9 cases, so the interval is very wide. Other HZ-related complications in the same sentence: IRR 0.22 (0.04-0.81).
Post-herpetic neuralgia severity: chronic pain case definition: PHN as a secondary end point, pain measured for six months	60 years and older immune status: immunocompetent country: United States n: 38,546 adults 50-64y65+	Zostavax (ZVL, live attenuated Oka/Merck) platform: live attenuated doses: 1 vs placebo	66.5 VE (%) follow-up: median 3.12 years	RCT	Oxman et al. 2005 N Engl J Med quote 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). abstract, RESULTS Based on few PHN cases. Higher than the efficacy against zoster itself, because the vaccine also reduces severity in breakthrough cases.
Post-herpetic neuralgia during years 6-11 severity: chronic pain case definition: PHN during ZOE-LTFU	50 years and older at first vaccination immune status: immunocompetent country: multiple 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 time since vaccination: years 6 to 11 after vaccination vs historical control constructed from ZOE-50/70 placebo data	87.5 (64.8–96.8) VE (%) during long-term follow-up follow-up: 6 years of extension follow-up	cohort	Strezova et al. 2025 EClinicalMedicine quote During ZOE-LTFU, VE was 79·8% (95% confidence interval [CI]: 73·7, 84·6) and 73·2% (95% CI: 62·9, 80·9) against HZ in participants ≥50 and ≥70 years at first vaccination, respectively, and was 87·5% (95% CI: 64·8, 96·8) against PHN and 91·7% (95% CI: 43·7, 99·8) against other HZ-related complications in participants ≥50 years. abstract, FINDINGS Same sentence reports 91.7% (43.7-99.8) against other HZ-related complications. Non-randomised comparator.
Post-herpetic neuralgia severity: chronic pain case definition: PHN identified by a validated claims algorithm	over 65 years country: United States (Medicare Part D) period: first 2 years post-licensure 65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 vs unvaccinated beneficiaries (inverse probability weighted)	76.0 (68.4–81.8) VE (%), 2 doses	cohort	Izurieta et al. 2021 Clin Infect Dis quote Two-dose vaccine effectiveness against postherpetic neuralgia was 76.0% (95% CI, 68.4-81.8). abstract, RESULTS The vaccine was also reported effective in beneficiaries with immunosuppressive and autoimmune conditions, without figures in the abstract.
Post-herpetic neuralgia (chart-reviewed pain beyond 3 months) severity: chronic pain case definition: HZ-related pain persisting more than 3 months on chart review	50 years and older, median 68 years country: United States (Kaiser Permanente Southern California) period: 2018-2022 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 vs unvaccinated matched members	83.7 (75.1–89.3) adjusted VE (%), 2 doses follow-up: up to 4 years	cohort	Tseng et al. 2026 Clin Infect Dis quote RESULTS: Among N = 102 766 (median age 68 years) who received 2 RZV doses (4 weeks-6 months apart), 48 028 (46.7%) had previously received zoster vaccine live; aVE was 73.9% (95% CI: 71.8%-75.8%) for HZ and 83.7% (95% CI: 75.1%-89.3%) for PHN. abstract, RESULTS Chart-reviewed PHN, a more specific outcome than claims-based PHN.
Post-herpetic neuralgia severity: chronic pain case definition: PHN in linked UK primary care records	70-79 years country: United Kingdom period: 2013-2016 65+	Zostavax (ZVL, live attenuated) platform: live attenuated doses: 1 vs unvaccinated individuals	81 (61–91) adjusted VE (%) follow-up: first 3 years of the programme	cohort	Walker et al. 2018 Vaccine quote After adjustment, VE was 64% (95%CI = 60-68%) against incident zoster and 81% (95%CI = 61-91%) against PHN, with very similar VE estimates in the routine and catch-up cohorts. abstract, RESULTS Protection against PHN exceeds protection against zoster, as in the SPS.

Stroke and myocardial infarction after herpes zoster Varicella zoster virus (reactivation)

Post-acute and long-term sequelae

What can follow the acute illness: chronic disease, disability, cancers, congenital syndromes, post-infectious conditions.

Outcome (O)	Population (P)	Comparator	Estimate	Design (S)	Source
Coronary heart disease after herpes zoster severity: coronary heart disease case definition: CHD as defined in included cohort and case-control studies	adults vaccination status: not reported country: multiple period: studies to July 2024 All ages	vs people without herpes zoster	1.12 (1.08–1.15) pooled adjusted RR vs people without zoster	meta-analysis	Kawai et al. 2025 J Am Heart Assoc quote Herpes zoster was also associated with an elevated risk of CHD (RR, 1.12 [95% CI, 1.08-1.15]) and stroke (RR, 1.18 [95% CI, 1.09-1.27]). abstract, RESULTS Pooled across between-person observational studies, so residual confounding by shared risk factors (age, immunosuppression, comorbidity) is likely. The same sentence gives the stroke estimate, recorded separately.
Stroke after herpes zoster severity: stroke case definition: Stroke as defined in included cohort and case-control studies	adults vaccination status: not reported country: multiple period: studies to July 2024 All ages	vs people without herpes zoster	1.18 (1.09–1.27) pooled adjusted RR vs people without zoster	meta-analysis	Kawai et al. 2025 J Am Heart Assoc quote Herpes zoster was also associated with an elevated risk of CHD (RR, 1.12 [95% CI, 1.08-1.15]) and stroke (RR, 1.18 [95% CI, 1.09-1.27]). abstract, RESULTS Long-run between-person estimate; the within-person SCCS estimates are larger because they capture the first weeks after zoster.
Ischaemic stroke in the first week after zoster diagnosis severity: stroke case definition: Ischaemic stroke in Medicare claims	65 years and older vaccination status: mixed country: United States (Medicare) period: 2006-2011 n: 42,954 beneficiaries with zoster and ischaemic stroke 65+	vs unexposed time periods within the same individuals	2.37 (2.17–2.59) incidence ratio vs unexposed periods within the same person follow-up: first week after zoster diagnosis, resolving over 6 months	SCCS	Minassian et al. 2015 PLoS Med quote We observed a marked increase in the rate of acute cardiovascular events in the first week after zoster diagnosis: a 2.4-fold increased ischemic stroke rate (IR 2.37, 95% CI 2.17-2.59) and a 1.7-fold increased MI rate (IR 1.68, 95% CI 1.47-1.92), followed by a gradual resolution over 6 mo. abstract, METHODS AND FINDINGS Within-person design removes fixed between-person confounding but not time-varying triggers; the same sentence gives the MI figure recorded in the next record. The authors found no evidence that zoster vaccination modified the association, with limited power.
Acute myocardial infarction in the first week after zoster diagnosis severity: myocardial infarction case definition: Acute MI in Medicare claims	65 years and older vaccination status: mixed country: United States (Medicare) period: 2006-2011 n: 24,237 beneficiaries with zoster and MI 65+	vs unexposed time periods within the same individuals	1.68 (1.47–1.92) incidence ratio vs unexposed periods within the same person follow-up: first week after zoster diagnosis, resolving over 6 months	SCCS	Minassian et al. 2015 PLoS Med quote We observed a marked increase in the rate of acute cardiovascular events in the first week after zoster diagnosis: a 2.4-fold increased ischemic stroke rate (IR 2.37, 95% CI 2.17-2.59) and a 1.7-fold increased MI rate (IR 1.68, 95% CI 1.47-1.92), followed by a gradual resolution over 6 mo. abstract, METHODS AND FINDINGS Same analysis as the stroke record. Health-care contact around the zoster diagnosis may increase detection of MI in the first week.
Stroke in weeks 1-4 after zoster severity: stroke case definition: First-ever stroke diagnosis in UK primary care records	adults with first zoster and stroke in the study period vaccination status: not reported country: United Kingdom setting: primary care, CPRD period: 1987-2012 n: 6584 individuals All ages	vs baseline unexposed periods within the same individuals	1.63 (1.32–2.02) age-adjusted incidence ratio vs baseline unexposed periods follow-up: weeks 1-4 after zoster	SCCS	Langan et al. 2014 Clin Infect Dis quote Stroke rate was increased following zoster compared with the baseline unexposed period, then gradually reduced over 6 months: weeks 1-4 (age-adjusted IR, 1.63; 95% CI, 1.32-2.02), weeks 5-12 (IR, 1.42; 95% CI, 1.21-1.68), and weeks 13-26 (IR, 1.23; 95% CI, 1.07-1.42), with no increase thereafter. abstract, RESULTS The same sentence reports the decline over the later periods, recorded separately. Antiviral-treated patients had lower ratios, and ophthalmic zoster carried a stronger effect.
Stroke in weeks 13-26 after zoster severity: stroke case definition: First-ever stroke diagnosis in UK primary care records	adults with first zoster and stroke in the study period vaccination status: not reported country: United Kingdom setting: primary care, CPRD period: 1987-2012 n: 6584 individuals All ages	vs baseline unexposed periods within the same individuals	1.23 (1.07–1.42) age-adjusted incidence ratio vs baseline unexposed periods follow-up: weeks 13-26 after zoster, no increase thereafter	SCCS	Langan et al. 2014 Clin Infect Dis quote Stroke rate was increased following zoster compared with the baseline unexposed period, then gradually reduced over 6 months: weeks 1-4 (age-adjusted IR, 1.63; 95% CI, 1.32-2.02), weeks 5-12 (IR, 1.42; 95% CI, 1.21-1.68), and weeks 13-26 (IR, 1.23; 95% CI, 1.07-1.42), with no increase thereafter. abstract, RESULTS Shows the excess fading by 6 months. Within-person design; time-varying confounders such as acute illness contact are not removed.

Vaccine efficacy and effectiveness

Every estimate compiled, annotated by population (P), intervention (I), comparator (C), outcome (O) and study design (S).

Outcome (O)	Population (P)	Intervention / comparator	Estimate	Design (S)	Source
Hospitalised acute myocardial infarction and hospitalised stroke severity: hospitalised cardiovascular event case definition: ICD-10 coded hospitalised AMI and stroke	50 years and older, median 68 years country: United States (Kaiser Permanente Southern California) period: 2018-2022 50-64y65+	Shingrix (RZV) platform: adjuvanted recombinant subunit doses: 2 vs unvaccinated matched members	0.720 then 0.575 (0.588–0.881) adjusted HR vs unvaccinated, AMI then stroke	cohort	Rayens et al. 2025 Clin Infect Dis quote The aHRs (95% CI) of HZO, hospitalized AMI, and hospitalized stroke comparing RZV-vaccinated and unvaccinated individuals were 0.271 (95% CI: 0.222, 0.330), 0.720 (0.588-0.881), and 0.575 (0.533-0.619), respectively. abstract, RESULTS The interval entered is for AMI; stroke has its own interval (0.533-0.619) in the same sentence. These are associations in a vaccinated-vs-unvaccinated cohort and are vulnerable to healthy-vaccinee bias; the effect sizes are larger than the zoster-attributable fraction of cardiovascular events would predict.
Overall cardiovascular events severity: any cardiovascular event case definition: ICD-10 coded cardiovascular diagnoses	50 years and older, mean 61.3 years country: South Korea period: 2012-2024 n: 1,271,922 in overlap-weighted cohort 50-64y65+	live attenuated zoster vaccine platform: live attenuated doses: 1 vs unvaccinated individuals (propensity overlap weighted)	0.77 (0.76–0.78) HR vs unvaccinated follow-up: median 6.0 years	cohort	Lee et al. 2025 Eur Heart J quote Live zoster vaccination was associated with lower risks of overall cardiovascular events [HR 0.77, 95% confidence interval (CI) 0.76-0.78], particularly major adverse cardiovascular events [0.74 (0.71-0.77)], heart failure [0.74 (0.70-0.77)], cerebrovascular disorders [0.76 (0.74-0.78)], ischaemic heart disease [0.78 (0.76-0.80)], thrombotic disorders [0.78 (0.74-0.83)], and dysrhythmia [0.79 (0.77-0.81)]. abstract, RESULTS Observational; healthy-vaccinee bias is the main concern because a reduction of this size in all cardiovascular events exceeds what preventing zoster alone could plausibly deliver given the modest zoster-cardiovascular association in the post-acute records.

Gaps

The ZOE-HM trial in haematological malignancies (PMID 31399377) reports a post-hoc efficacy estimate only in the full text, not the abstract; the Lancet Infectious Diseases full text was not snapshotted, so the haematological-malignancy efficacy here comes from the Cochrane 2025 pooling (shingles-eff-019) and the immunocompromised RZV meta-analysis (shingles-eff-020).
No RCT efficacy data for RZV in solid organ transplant, HIV, or on biologic/JAK-inhibitor therapy was compiled; the Marra meta-analysis pools them but the abstract does not break them out.
ZOE-50 age-stratified efficacy is recorded only as the abstract's range (96.6-97.9%); per-stratum confidence intervals for 50-59, 60-69 and 70+ are in the full text, not cached.
Shingles Prevention Study confidence intervals for the 51.3% and 66.5% efficacy figures are in the full text, not the abstract, so they are absent here.
No head-to-head randomised comparison of RZV versus ZVL exists; the only comparative real-world study found (PMID 41910420, chronic inflammatory skin disease) was not cached. Comparison rests on separate placebo-controlled trials and separate cohorts.
PHN proportion by narrow age band (e.g. 50-59, 60-69, 70-79) with confidence intervals was not found in any cached abstract; Yawn 2007 gives all adults vs 79+, Forbes 2016 gives an odds ratio per decade with a 99% interval.
No zoster burden data from low-income countries in Africa or South Asia were found; the LMIC-adjacent evidence is the Latin America review (shingles-bur-027/028), which itself found no general-population incidence study.
Herpes zoster ophthalmicus specific long-term outcomes (chronic ocular disease, recurrence) beyond the Olmsted cohort were not compiled.
Zoster vaccine effect on dementia (Welsh natural experiment, Eyting 2025 and related studies) was deliberately not compiled: it is a vaccine-outcome claim outside the disease-burden scope of this file and needs its own review.
Pre-licensure efficacy of RZV against herpes zoster ophthalmicus and against disseminated/visceral zoster was not found in cached abstracts.

Flags for review

Comparator for RZV long-term follow-up (shingles-eff-007 to eff-013) and for the ZVL long-term persistence substudy (shingles-eff-044) is a modelled historical placebo group, not a concurrent randomised control; design is set to cohort for those records even though the parent studies were RCTs. A reviewer should decide whether to present them alongside the RCT estimates.
shingles-pa-015, eff-033, eff-045, eff-047, eff-050 and eff-051 each carry two point estimates from a single sentence but only one confidence interval field; the second interval is stated in notes=. If the renderer cannot show that, split them into separate records with duplicate find= fragments.
shingles-eff-056 (live zoster vaccine and 23% lower cardiovascular events, Korea) and shingles-eff-033 (RZV and 28-43% lower AMI/stroke, Kaiser) are observational associations much larger than the zoster-attributable cardiovascular risk would predict; healthy-vaccinee bias is likely. Present with the caveat or consider omitting from a benefit summary.
Forbes 2016 (shingles-pa-005/006) reports odds ratios with 99% confidence intervals; they were not entered as ci_low/ci_high because the schema assumes 95% bounds.
Real-world RZV effectiveness (70-80%) is consistently below trial efficacy (90-97%); the Medicare and VSD authors attribute this to less specific outcome ascertainment in claims data. The two sets should not be presented as conflicting without that explanation.
The Danish SMR 1.8 after hospital-based zoster (shingles-bur-019) reflects comorbid patients; the same sentence shows no excess in patients without comorbidity. Do not present it as a zoster case-fatality figure.
The Cochrane 2025 haematological-malignancy pooling (shingles-eff-019, RR 0.40, CI 0.07-2.23) combines RZV with an inactivated candidate vaccine; the interval includes no effect. Do not cite it as evidence that RZV does not work in haematological malignancy.
The dementia records (shingles-pa-015 to pa-018) show no overall association between zoster and dementia; only HZO and CNS zoster subgroups show raised, imprecise estimates. Surprising relative to popular claims; include the null.

Search log (34 searches)

herpes zoster incidence systematic review lifetime risk · PubMed → Found PMID 38767209 (Asia-Pacific SLR, no numbers in abstract; cached but not used).
herpes zoster incidence complications systematic review Kawai · PubMed → Found PMID 24916088 (Kawai 2014 global systematic review); compiled as shingles-bur-007 to bur-009, pa-003, pa-004.
adjuvanted recombinant zoster vaccine efficacy randomized ZOE-50 older adults · PubMed → Found PMID 27626517 (ZOE-70), 38838170 (China RZV RCT), 31537443 (region/sex post hoc), 33197294 (frailty); compiled as shingles-eff-003 to eff-006, eff-014 to eff-016.
Lal herpes zoster subunit vaccine efficacy adults 50 years or older 2015 · PubMed → Found PMID 25916341 (ZOE-50); compiled as shingles-eff-001, eff-002.
recombinant zoster vaccine long-term efficacy follow-up ZOE-LTFU · PubMed → Found PMID 40630610 (final ZOE-LTFU 11 years); compiled as shingles-eff-009 to eff-013.
recombinant zoster vaccine autologous hematopoietic stem cell transplant randomized efficacy · PubMed → Found PMID 31287523 (ZOE-HSCT); compiled as shingles-eff-017, eff-018.
recombinant zoster vaccine hematological malignancies randomized placebo-controlled efficacy · PubMed → Found PMID 31399377 (ZOE-HM); abstract has immunogenicity only, efficacy listed as a gap.
Shingles Prevention Study live attenuated zoster vaccine Oxman postherpetic neuralgia older adults · PubMed → Found PMID 15930418 (SPS); compiled as shingles-eff-040, eff-041.
zoster vaccine live waning effectiveness long-term persistence Morrison Tseng · PubMed → No results on first phrasing; re-run below.
long-term persistence of zoster vaccine efficacy Shingles Prevention Study · PubMed → Found PMID 25416754 (Morrison LTPS) and 34283213 (Boutry interim ZOE-LTFU); compiled as shingles-eff-044, eff-007, eff-008.
declining effectiveness of herpes zoster vaccine in adults aged 60 years · PubMed → Found PMID 26908728 (Tseng 2016), 29555217 (Walker UK VE), 41082816 (Korea ZVL target trial); compiled as shingles-eff-045, eff-048 to eff-051, eff-054, eff-055.
postherpetic neuralgia proportion herpes zoster patients age cohort incidence · PubMed → Found PMID 25230396 (Germany) and 29880565 (England immunocompromised cohort); compiled as shingles-bur-016, bur-017, bur-022, bur-023, pa-007, pa-008.
postherpetic neuralgia risk factors cohort Forbes UK primary care · PubMed → Found PMID 27287218 (Forbes 2016); compiled as shingles-pa-005, pa-006.
herpes zoster stroke myocardial infarction self-controlled case series risk · PubMed → Found PMID 26671338 (Minassian SCCS), 28749981 (Erskine meta-analysis, no numbers in abstract), 41160032 (Kawai 2025 meta-analysis); compiled as shingles-pa-009, pa-010, pa-013, pa-014.
herpes zoster stroke self-controlled case series Langan UK · PubMed → Found PMID 24700656 (Langan 2014); compiled as shingles-pa-011, pa-012.
Cochrane vaccines for preventing herpes zoster in older adults · PubMed → Found PMID 37781954 (Cochrane 2023) and 36098300 (Mbinta 2022 post-licensure meta-analysis); compiled as shingles-eff-039, eff-042, saf-001 to saf-003, eff-038, eff-052, eff-053.
recombinant zoster vaccine effectiveness Medicare beneficiaries cohort real-world · PubMed → Found PMID 33580242 (Izurieta 2021); compiled as shingles-eff-022 to eff-024.
herpes zoster ophthalmicus incidence complications cohort · PubMed → Found PMID 23664666 (Yawn 2013 eye complications), 40795767 (Rayens RZV HZO/AMI/stroke), 35676090 (Danish zoster-dementia cohort); compiled as shingles-bur-025, bur-026, eff-032, eff-033, pa-015, pa-016.
herpes zoster risk immunocompromised systematic review meta-analysis incidence · PubMed → Found PMID 39585863 (Marra RZV in immunocompromised meta-analysis), 34383851 (Latin America review), 40396505 (Cochrane haematological malignancy vaccines); compiled as shingles-eff-020, bur-027, bur-028, eff-019.
herpes zoster dementia risk cohort meta-analysis · PubMed → Found PMID 37904465 (Elhalag meta-analysis); compiled as shingles-pa-017, pa-018.
herpes zoster hospitalization mortality rate population-based older adults · PubMed → Found PMID 26932311 (Denmark hospital-based HZ), 39505070 (France hospitalisations), 40324473 (Korea ZVL cardiovascular); compiled as shingles-bur-018 to bur-021, eff-056.
recombinant zoster vaccine versus live zoster vaccine effectiveness comparison cohort · PubMed → Found only PMID 41910420 (skin disease cohort), not cached; no head-to-head RCT exists (gap).
Izurieta recombinant zoster vaccine effectiveness Medicare · PubMed → Confirmed PMID 33580242.
herpes zoster vaccine and risk of postherpetic neuralgia Tseng JAMA 2011 · PubMed → No results on this phrasing; re-run below.
Herpes zoster vaccine in older adults and the risk of subsequent herpes zoster disease · PubMed → Found PMID 21224457 (Tseng 2011 JAMA); compiled as shingles-eff-046, eff-047.
Yawn population-based study incidence complication rates herpes zoster before zoster vaccine Olmsted · PubMed → Found PMID 17976353 (Yawn 2007); compiled as shingles-bur-010, bur-011, pa-002.
Recommendations of the Advisory Committee on Immunization Practices for use of herpes zoster vaccines MMWR 2018 · PubMed → Found PMID 29370152 (Dooling 2018, cached; abstract carries no efficacy numbers, not used).
herpes zoster lifetime risk one in three Harpaz prevention MMWR 2008 · PubMed → Found PMID 18528318 (ACIP 2008); compiled as shingles-bur-005, bur-006, pa-001.
recombinant zoster vaccine effectiveness immunocompromised adults cohort real-world · PubMed → Found PMID 40581370 (Tseng 2026 KPSC), 42308980 (Mbinta 2026 meta-analysis), 41397551 (allo-HCT cohort); compiled as shingles-eff-029 to eff-031, eff-034 to eff-037, eff-021.
recombinant zoster vaccine effectiveness waning time since vaccination cohort 2023 · PubMed → Found PMID 38190712 (Zerbo 2024 VSD); compiled as shingles-eff-025 to eff-028.
herpes zoster case fatality mortality rate deaths United States · PubMed → Found PMID 31830250 (Tseng 2020 unvaccinated immunocompetent epidemiology); compiled as shingles-bur-012 to bur-015.
zoster vaccine live efficacy adults 50-59 years ZEST trial · PubMed → No result on first phrasing; re-run as Schmader search below.
Schmader efficacy safety tolerability zoster vaccine persons aged 50-59 years · PubMed → Found PMID 22291101 (ZEST); compiled as shingles-eff-043.
CDC Clinical Overview of Shingles (Herpes Zoster) · websource → Cached as web cdc-gov-23a18fec05; compiled as shingles-bur-001 to bur-004.