RESUMEN
Varicella-zoster virus infections have increased globally, with complications such as postherpetic neuralgia and neurological sequelae. The recombinant vaccine against herpes zoster is proposed as a preventive strategy. This systematic review evaluates its effectiveness and safety in healthy and high-risk populations. A systematic review of randomized controlled trials comparing the effectiveness and safety of the vaccine was conducted. The search was carried out in Epistemonikos. Two researchers independently assessed the eligibility of the studies and the risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. A meta-analysis of homogeneous results was conducted, and the certainty of the evidence was evaluated using GRADE. A minimally contextualized approach was adopted using predetermined thresholds. Nine randomized controlled trials were selected. The vaccine demonstrated a significant reduction in the incidence of herpes zoster in high-risk populations (risk difference of 140 fewer per 1000) with high certainty. However, in healthy populations, the effect was trivial (28 fewer per 1000). No significant differences were observed in postherpetic neuralgia in any of the populations analyzed. Adverse events increased in both populations, though no discrepancies in serious adverse events were noted. In high-risk populations, where the incidence of herpes zoster and its complications is higher, the vaccine demonstrated effectiveness in lowering the incidence of the disease, though not in that of postherpetic neuralgia. Conversely, in healthy populations, the impact of the vaccine was trivial. Individualized and informed recommendations are crucial when considering this vaccine.
Las infecciones por el virus de la varicela-zóster han aumentado globalmente, con complicaciones como neuralgia postherpética y secuelas neurológicas. La vacuna recombinante contra el herpes zóster se propone como estrategia preventiva. Esta revisión sistemática evalúa su efectividad y seguridad en poblaciones sanas y de alto riesgo. Se realizó una revisión sistemática de ensayos controlados aleatorios que comparaban la efectividad y seguridad de la vacuna. La búsqueda se efectuó en Epistemonikos. Dos investigadores evaluaron independientemente la elegibilidad de los estudios y se evaluó el riesgo de sesgo con la herramienta Cochrane Risk of Bias 2. Se realizó un metanálisis de resultados homogéneos y se evaluó la certeza de la evidencia mediante GRADE. Se adoptó un enfoque mínimamente contextualizado utilizando umbrales predeterminados. Se seleccionaron 9 ensayos controlados aleatorios. La vacuna demostró una reducción significativa en la incidencia de herpes zóster en poblaciones de alto riesgo (diferencia de riesgo de 140 menos por 1000) con alta certeza. Sin embargo, en poblaciones sanas, el efecto fue trivial (28 menos por 1000). No se observaron diferencias significativas en la incidencia de neuralgia postherpética en ninguna de las poblaciones. En cuanto a la seguridad, se registró un aumento de eventos adversos en ambas poblaciones, aunque no se presentaron diferencias en los eventos adversos graves. En poblaciones de alto riesgo, donde la incidencia de herpes zóster y sus complicaciones es más alta, la vacuna demostró eficacia en la reducción de la incidencia de la enfermedad, aunque no en la de la neuralgia postherpética. Por otro lado, en población sana, el impacto de la vacuna fue trivial. Es crucial adoptar un enfoque individualizado e informado al recomendar esta vacuna.
Asunto(s)
Vacuna contra el Herpes Zóster , Herpes Zóster , Eficacia de las Vacunas , Humanos , Herpes Zóster/complicaciones , Herpes Zóster/epidemiología , Herpes Zóster/prevención & control , Vacuna contra el Herpes Zóster/efectos adversos , Vacuna contra el Herpes Zóster/administración & dosificación , Incidencia , Neuralgia Posherpética/epidemiología , Neuralgia Posherpética/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Eficacia de las Vacunas/estadística & datos numéricos , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/efectos adversosRESUMEN
BACKGROUND: Herpes zoster, commonly known as shingles, is a neurocutaneous disease caused by the reactivation of the virus that causes varicella (chickenpox). After resolution of the varicella episode, the virus can remain latent in the sensitive dorsal ganglia of the spine. Years later, with declining immunity, the varicella zoster virus (VZV) can reactivate and cause herpes zoster, an extremely painful condition that can last many weeks or months and significantly compromise the quality of life of the affected person. The natural process of ageing is associated with a reduction in cellular immunity, and this predisposes older adults to herpes zoster. Vaccination with an attenuated form of the VZV activates specific T-cell production avoiding viral reactivation. Two types of herpes zoster vaccines are currently available. One of them is the single-dose live attenuated zoster vaccine (LZV), which contains the same live attenuated virus used in the chickenpox vaccine, but it has over 14-fold more plaque-forming units of the attenuated virus per dose. The other is the recombinant zoster vaccine (RZV) which does not contain the live attenuated virus, but rather a small fraction of the virus that cannot replicate but can boost immunogenicity. The recommended schedule for the RZV is two doses two months apart. This is an update of a Cochrane Review first published in 2010, and updated in 2012, 2016, and 2019. OBJECTIVES: To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults. SEARCH METHODS: For this 2022 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2022, Issue 10), MEDLINE (1948 to October 2022), Embase (2010 to October 2022), CINAHL (1981 to October 2022), LILACS (1982 to October 2022), and three trial registries. SELECTION CRITERIA: We included studies involving healthy older adults (mean age 60 years or older). We included randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine (any dose and potency) versus any other type of intervention (e.g. varicella vaccine, antiviral medication), placebo, or no intervention (no vaccine). Outcomes were cumulative incidence of herpes zoster, adverse events (death, serious adverse events, systemic reactions, or local reaction occurring at any time after vaccination), and dropouts. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included two new studies involving 1736 participants in this update. The review now includes a total of 26 studies involving 90,259 healthy older adults with a mean age of 63.7 years. Only three studies assessed the cumulative incidence of herpes zoster in groups that received vaccines versus placebo. Most studies were conducted in high-income countries in Europe and North America and included healthy Caucasians (understood to be white participants) aged 60 years or over with no immunosuppressive comorbidities. Two studies were conducted in Japan and one study was conducted in the Republic of Korea. Sixteen studies used LZV. Ten studies tested an RZV. The overall certainty of the evidence was moderate, which indicates that the intervention probably works. Most data for the primary outcome (cumulative incidence of herpes zoster) and secondary outcomes (adverse events and dropouts) came from studies that had a low risk of bias and included a large number of participants. 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. 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). The vaccinated group had a higher cumulative incidence of one or more adverse events (RR 1.71, 95% CI 1.38 to 2.11; RD 23%; number needed to treat for an additional harmful outcome (NNTH) 4.3) and injection site adverse events (RR 3.73, 95% CI 1.93 to 7.21; RD 28%; NNTH 3.6; moderate-certainty evidence) of mild to moderate intensity. These data came from four studies with 6980 participants aged 60 years or older. Two studies (29,311 participants for safety evaluation and 22,022 participants for efficacy evaluation) compared RZV (two doses intramuscularly, two months apart) versus placebo. 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. 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). 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). Although most participants reported that their symptoms were of mild to moderate intensity, the risk of dropouts (participants not returning for the second dose, two months after the first dose) was higher in the vaccine group than in the placebo group (RR 1.25, 95% CI 1.13 to 1.39; RD 1%; NNTH 100, moderate-certainty evidence). Only one study reported funding from a non-commercial source (a university research foundation). All other included studies received funding from pharmaceutical companies. We did not conduct subgroup and sensitivity analyses AUTHORS' CONCLUSIONS: LZV (single dose) and RZV (two doses) are probably effective in preventing shingles disease for at least three years. To date, there are no data to recommend revaccination after receiving the basic schedule for each type of vaccine. Both vaccines produce systemic and injection site adverse events of mild to moderate intensity. The conclusions did not change in relation to the previous version of the systematic review.
Asunto(s)
Varicela , Vacuna contra el Herpes Zóster , Herpes Zóster , Humanos , Anciano , Persona de Mediana Edad , Herpesvirus Humano 3 , Vacuna contra el Herpes Zóster/efectos adversos , Varicela/inducido químicamente , Varicela/tratamiento farmacológico , Herpes Zóster/prevención & control , Herpes Zóster/inducido químicamente , Herpes Zóster/tratamiento farmacológico , Vacunas Atenuadas/efectos adversosRESUMEN
Allogeneic hematopoietic cell transplantation (HCT) recipients are at increased risk for varicella zoster virus (VZV) reactivation and associated complications. A nonlive adjuvanted recombinant zoster vaccine (RZV) has been developed to prevent herpes zoster (HZ), but there are no recommendations for use in this population. In this single-center prospective observational cohort study, we assessed the safety and reactogenicity of RZV, as well as incidence of graft-versus-host disease (GVHD) and confirmed cases of HZ after vaccination. Between December of 2018 and June of 2020, patients aged ≥18 years received 2 doses of RZV between 9 and 24 months after HCT, with the doses separated by ≥8 weeks. One hundred and fifty-eight patients (mean age, 55 years; 42% women) received ≥1 dose (total vaccinated cohort), and 150 patients (95%) received 2 doses (modified total vaccinated cohort). Solicited reactions occurred in 92.1% of patients (grade 3, 32.5%), owing mostly to injection site pain, which occurred in 86% (grade 3, 16%). The cumulative incidence of GVHD in the peri-vaccination period was no different than in historical controls (adjusted incidence rate ratio, 1.05; 95% confidence interval, 0.8-1.38). There were 4 cases of HZ in the total vaccinated cohort (2.5%) and 3 cases in the modified total vaccinated cohort (28.3/1000 person-years). Among recipients of allogeneic HCT, RZV was safe, tolerable, and did not increase rates of GVHD. Future clinical trials are needed to determine the immunogenicity and efficacy of RZV in this population.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Vacuna contra el Herpes Zóster , Herpes Zóster , Adolescente , Adulto , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpes Zóster/epidemiología , Herpes Zóster/prevención & control , Vacuna contra el Herpes Zóster/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Vacunas SintéticasRESUMEN
BACKGROUND: A trial involving adults 50 years of age or older (ZOE-50) showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01B adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older (ZOE-70). METHODS: This randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses of HZ/su or placebo (assigned in a 1:1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against herpes zoster and postherpetic neuralgia was assessed in participants from ZOE-70 and in participants pooled from ZOE-70 and ZOE-50. RESULTS: In ZOE-70, 13,900 participants who could be evaluated (mean age, 75.6 years) received either HZ/su (6950 participants) or placebo (6950 participants). During a mean follow-up period of 3.7 years, herpes zoster occurred in 23 HZ/su recipients and in 223 placebo recipients (0.9 vs. 9.2 per 1000 person-years). Vaccine efficacy against herpes zoster was 89.8% (95% confidence interval [CI], 84.2 to 93.7; P<0.001) and was similar in participants 70 to 79 years of age (90.0%) and participants 80 years of age or older (89.1%). In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001). Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients (79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two study groups. CONCLUSIONS: In our trial, HZ/su was found to reduce the risks of herpes zoster and postherpetic neuralgia among adults 70 years of age or older. (Funded by GlaxoSmithKline Biologicals; ZOE-50 and ZOE-70 ClinicalTrials.gov numbers, NCT01165177 and NCT01165229 .).
Asunto(s)
Vacuna contra el Herpes Zóster , Herpes Zóster/prevención & control , Neuralgia Posherpética/prevención & control , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Femenino , Herpes Zóster/inmunología , Vacuna contra el Herpes Zóster/efectos adversos , Vacuna contra el Herpes Zóster/inmunología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neuralgia Posherpética/epidemiología , Riesgo , Vacunas de Subunidad/efectos adversos , Vacunas de Subunidad/inmunologíaAsunto(s)
Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Vacuna contra el Herpes Zóster/inmunología , Herpes Zóster/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Adyuvantes Inmunológicos , Estudios Multicéntricos como Asunto , Vacunas de Subunidad/efectos adversos , Vacunas de Subunidad/inmunología , Neuralgia Posherpética/prevención & control , Vacuna contra el Herpes Zóster/administración & dosificación , Vacuna contra el Herpes Zóster/efectos adversos , Herpes Zóster/inmunologíaRESUMEN
BACKGROUND: Herpes zoster or, as it is commonly called, 'shingles' is a neurocutaneous disease characterised by the reactivation of varicella zoster virus (VZV), the virus that causes chickenpox, which is latent in the dorsal spinal ganglia when immunity to VZV declines. It is an extremely painful condition which can often last for many weeks or months, impairing the patient's quality of life. The natural aging process is associated with a reduction of cellular immunity which predisposes to herpes zoster. Vaccination with an attenuated form of VZV activates specific T cell production, therefore avoiding viral reactivation. A herpes zoster vaccine with an active virus has been approved for clinical use among older adults by the Food and Drug Administration and has been tested in large populations. OBJECTIVES: To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults. SEARCH METHODS: We searched the following sources for relevant studies: CENTRAL 2012, Issue 7, MEDLINE (1948 to July week 1, 2012), EMBASE (2010 to July 2012), LILACS (1982 to July 2012) and CINAHL (1981 to July 2012). We also reviewed reference lists of identified trials and reviews for additional studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine with placebo or no vaccine, to prevent herpes zoster in older adults (mean age > 60 years). DATA COLLECTION AND ANALYSIS: Two review authors independently collected and analysed data using a data extraction form. They also carried out an assessment of risk of bias. MAIN RESULTS: We identified eight RCTs with a total of 52,269 participants. Three studies were classified at low risk of bias. The main outcomes on effectiveness and safety were extracted from one clinical trial with a low risk of bias. Four studies compared zoster vaccine versus placebo; one study compared high-potency zoster vaccine versus low-potency zoster vaccine; one study compared refrigerated zoster vaccine versus frozen zoster vaccine; one study compared live zoster vaccine versus inactivated zoster vaccine and one study compared zoster vaccine versus pneumococcal polysaccharide vaccine (pneumo 23).Confirmed cases of herpes zoster were less frequent in patients who received the vaccine than in those who received a placebo: risk ratio (RR) 0.49 (95% confidence interval (CI) 0.43 to 0.56), with a risk difference (RD) of 2%, and number needed to treat to benefit (NNTB) of 50. Analyses according to age groups indicated a greater benefit in participants aged 60 to 69 years, RR 0.36 (95% CI 0.30 to 0.45) and in participants aged 70 years and over, RR 0.63 (95% CI 0.53 to 0.75). Vaccine-related systemic adverse effects were more frequent in the vaccinated group (RR 1.29, 95% CI 1.05 to 1.57, number needed to treat to harm (NNTH) = 100). The pooled data risk ratio for adverse effects for participants with one or more inoculation site adverse effect was RR 4.51 (95% CI 2.35 to 8.68), and the NNTH was 2.8 (95% CI 2.3 to 3.4). Side effects were more frequent in younger (60 to 69 years) than in older (70 years and over) participants. AUTHORS' CONCLUSIONS: Herpes zoster vaccine is effective in preventing herpes zoster disease. Although vaccine benefits are larger in the younger age group (60 to 69 years), this is also the age group with more adverse events. In general, zoster vaccine is well tolerated; it produces few systemic adverse events and injection site adverse effects of mild to moderate intensity.
Asunto(s)
Vacuna contra el Herpes Zóster/uso terapéutico , Herpes Zóster/prevención & control , Anciano , Vacuna contra el Herpes Zóster/efectos adversos , Humanos , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Vacunas Atenuadas/efectos adversos , Vacunas Atenuadas/uso terapéuticoRESUMEN
Multinodular fatty liver (MNFL) is a pattern of fatty infiltration of the liver characterized by multiple well-circumscribed nodules on hepatic imaging, often raising the concern of metastatic malignancy. Here we describe a case of MNFL and review the published literature. There is likely some association between traditional risk factors for hepatic steatosis (e.g. alcohol, rapid weight change, metabolic syndrome, medications, TPN) and MNFL. Further study and reporting of cases of MNFL are needed to better characterize its pathogenesis and natural history.