Vaksin untuk mencegah herpes zoster (kayap) dalam kalangan orang tua
Abstract
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.
PICOs
Ringkasan bahasa mudah
Vaksin untuk mencegah kayap dalam kalangan orang tua
Mesej utama
Vaksin boleh mencegah kayap pada orang tua yg sihat.
Apakah herpes zoster?
Herpes zoster ialah pengaktifan semula virus varicella zoster. Virus varicella zoster menyebabkan cacar air dan boleh kekal tidak aktif di dalam sel‐sel saraf selama bertahun‐tahun. Virus ini boleh menjadi aktif semula, bergerak melalui saraf ke kulit dan menghasilkan lepuh di sepanjang perjalanan saraf. Keadaan ini dipanggil kayap (herpes zoster), dan kerap terjadi pada orang yang mempunyai imuniti yang rendah, seperti orang tua. Sebelum lepuh muncul, gejala yang mungkin termasuklah kegatalan, kebas, atau sakit setempat. Kayap menyebabkan keradangan saraf dan kesakitan yang teruk yang boleh menjejaskan kualiti hidup. Kadar kejadian kayap berkisar dari 2.08 kes kepada 6.20 kes bagi setiap 1000 orang‐tahun (iaitu bilangan kes baru bagi setiap penduduk berisiko, dalam tempoh masa tertentu). Bilangan ini semakin meningkat, sebahagiannya disebabkan orang hidup lebih lama.
Apa yang kami ingin tahu?
Kami ingin mengetahui sama ada orang tua yang sihat yang menerima vaksin virus herpes zoster kurang berkemungkinan menghidap penyakit ini berbanding orang tua yang sihat yang menerima 'vaksin palsu' (iaitu plasebo, suntikan yang tidak menyebabkan sebarang kesan berkaitan herpes zoster). Kami juga ingin mengetahui sama ada vaksin, berbanding dengan vaksin palsu, menyebabkan sebarang kesan yang tidak diingini.
Apakah yang kami lakukan?
Kami mencari kajian yang menyiasat dan membandingkan orang tua yang sihat (purata umur peserta 60 tahun dan ke atas) yang menerima vaksin melindungi daripada herpes zoster, dengan orang tua sihat yang menerima vaksin palsu.
Kami membandingkan dan merumuskan penemuan, dan menilai keyakinan kami terhadap bukti berdasarkan saiz kajian, tentang cara data dibentangkan, dan mengenai risiko bias (kemungkinan ciri reka bentuk kajian atau pengendalian kajian akan membawa kepada keputusan yang salah).
Apakah yang telah kami temui?
Ini adalah kemas kini ulasan sistematik, dan kami menemui dua kajian baharu, menjadikan jumlah keseluruhan kepada 26 kajian yang dimasukkan (90,259 peserta). Kajian ini menguji dua jenis vaksin yang telah diluluskan kegunaannya. Enam belas kajian menguji vaksin virus hidup yang dilemahkan (LZV) dan memasukkan 55,975 peserta (dos tunggal); 10 kajian menguji vaksin zoster rekombinan (RZV), dan memasukkan 34,284 peserta (dua dos dengan selang dua bulan antara mereka).
Semua kajian melibatkan pesakit luar. Kebanyakan peserta kajian adalah Caucasian (bangsa kulit putih).
Keputusan utama
Keberkesanan vaksin
LZV (dos tunggal)
Peserta yang menerima LZV mempunyai kadar kayap yang lebih rendah berbanding mereka yang menerima vaksin palsu. Oleh itu, LZV mungkin berkesan kerana kepastian bukti adalah sederhana. Adalah perlu untuk memvaksin 50 orang tua yang sihat dengan LVZ untuk mengelakkan satu episod kayap.
RZV (dua dos)
Vaksinasi dengan RZV juga mungkin berkesan (bukti berkepastian sederhana), dan mungkin lebih berkesan daripada vaksinasi dengan LZV, kerana keputusan menunjukkan bahawa adalah perlu untuk memberi vaksin kepada 33 orang tua yang sihat untuk mengelakkan satu episod kayap.
Keselamatan
Kedua‐dua vaksin mungkin selamat (bukti berkepastian sederhana) untuk kesan yang tidak diingini.
Dalam kajian yang menguji RZV, yang memerlukan dos kedua dua bulan kemudiannya, kadar keciciran (bilangan orang yang tidak menerima dos kedua) adalah lebih tinggi dalam kumpulan yang menerima vaksin sebenar berbanding kumpulan yang menerima vaksin palsu. Ini boleh dikira sedemikian rupa sehingga bagi setiap 100 orang tua yang sihat yang divaksinasi dengan dua dos vaksin sebenar, seorang tua yang menerima dos pertama vaksin ini tidak menerima dos kedua. Kereaktifan (kesan sampingan) dos pertama vaksin mungkin telah menyumbang kepada kelakuan ini.
Kesimpulan
LZV (dos tunggal) dan RZV (dua dos) mungkin berkesan dalam mencegah penyakit kayap selama sekurang‐kurangnya tiga tahun. Bagi kedua‐dua vaksin, kepastian bukti adalah sederhana dari segi keberkesanan dan keselamatan sekurang‐kurangnya tiga tahun.
Apakah batasan bukti?
Kami mempunyai bukti kepastian sederhana untuk semua titik akhir keberkesanan dan keselamatan, berdasarkan kajian yang memasukkan sebilangan besar orang tua yang sihat berumur 60 tahun atau lebih.
Sejauh manakah bukti ini terkini?
Bukti adalah terkini sehingga 21 Oktober 2022.
