The herpes zoster vaccine, Zostavax, was launched by Merck, Sharpe and Dohme in Malaysia in November 2013. The MSGM aims to provide accurate information on new health technology for older people by producing position statements that summarizes the available literature and interpretating them based on the local context. It has therefore produced its first position paper in response to the recent availability of the zoster vaccine.

Summary recommendations:

  • HZV vaccine can be offered to those 60 years and older with previous shingles
  • HZV vaccine can still be offered to patients without a history of chicken pox
  • HZV vaccine should not be recommended in over 80s due to reduced effectiveness
  • Younger patients may not be covered after 7.5yrs
  • HZV vaccine is most cost effective in 70-79 yr olds
  • Over 50s may choose to have the vaccine after considering the data

We would like to thank Dr George Taye, Dr Loh Pei Chong and Dr Pauline Bailey for so readily agreeing to this challenge, and to producing this guidance in a timely fashion.

Note: An update to the recommendation will be available soon on the porcine gelatine content of the vaccine. There is currently no non-porcine alternative for the vaccine.

The Malaysian Society of Geriatric Medicine Position Statement on Vaccination against the Herpes Zoster Virus in Older Adults (updated June 2014)

Prepared by

  • Dr George Taye Wei Chun, Mahkota Hospital, Melaka (chair)
  • Dr Loh Pei Chong, Lam Wah Ee Hospital, Penang
  • Dr Pauline Bailey, Newcastle University Medicine Malaysia, Johor

Summary Recommendations

  • Vaccination against herpes zoster infection can be offered to patients ≥60 years of age including patients who report a previous episode of zoster infection
  • The vaccine can still be offered to patients without a clinical history of chickenpox
  • The vaccine should not be recommended in patients >80 years old as its effectiveness is reduced in this group of patients
  • Younger patients may not be adequately covered after 7.5 years (the estimated duration of vaccine effectiveness)
  • The vaccine is most cost effective in patients aged 70-79 years old.
  • Patients >50 years may choose to have the vaccine after considering the data above.

Introduction

Infection by the Varicella-zoster virus (VZV) may lead to two types of disease: varicella (or chickenpox- usually during childhood) and zoster (or shingles- due to the reactivation of the initial latent virus in the dosal root ganglia during the later stages of life, usually rarely < 50 years old)

It is estimated that nearly 1 in 3 persons will experience zoster during their lifetimes (1). There is a substantial increase in risk of shingles (8- to 10-fold) in late life, presumably due to the decline in VZV-specific cell-mediated immunity (2) and up to 1% had at least two attacks (3) and are more common in immunocompromised patients (4)

Complications, which usually are also more frequent in the older aged patients, include post herpetic neuralgia (PHN), eye problems such as retinal necrosis, meningitis, encephalitis and muscle paralysis which may mimic stoke syndromes. Although shingles and its adverse sequale are rarely fatal, these complications may have an adverse impact of the patient, mentally, physically and emotionally.

Vaccine

A vaccine for immunocompetent adults 60 years old and above given approval by the FDA (US) in 2006 to prevent herpes zoster (5) as well as in the European Union (age >50) as well as the MOH Malaysia. The Advisory Committee on Immunization Practices (ACIP) CDC recommends zoster vaccination for all immunocompetent persons age 60 years and above, regardless of history of varicella (chickenpox) or documentation of varicella immunity (1).Although it was also given FDA approval in 2011 for patients aged 50-59, the ACIP does not recommend the vaccine for this age group (6). This was mainly due to the limited supply of the materials used to make the vaccine, which is also used in the varicella vaccine. The zoster vaccine contains more than 14 times more potent than the Oka/Merck varicella vaccine for prevention of varicella (1) and there for it is not interchangeable with the varicella vaccine.

The indication for the vaccine varies from country to country, for example in Malaysia, the vaccine is approved in patients 50 years or older for Herpes Zoster, Post Herpetic Neuralgia and Burden of Illness (eg acute and chronic zoster pain) reduction. In Singapore, it is only licensed for the prevention of herpes zoster. We are mindful about these approved indications when taking into account the recomendations of the various health authorities with regards to the vaccine's usage.

Vaccine Data
The Shingles Prevention Study (SPS) (11), a placebo-controlled clinical trial of 38,546 adults 60 years of age or older was conducted to determine if the zoster vaccine would decrease the incidence and severity of zoster and PNH. Results:

  • Confirmed herpes zoster occurred in 957 (2.5 %)
  • Immunization decreased the incidence of zoster by 51 %compared with placebo
  • In those who did develop zoster, the median duration of pain was modestly reduced in the vaccine group than in the placebo group (21 versus 24 days, respectively).
  • PNHincidence was reduced by 67 % in the vaccine group (0.46 versus 1.38 cases per 1000 person-years).
  • The degree of benefit was > in patients ≥70 years of age (0.2 vs0.6 percent overall [0.71 vs 2.13 cases per 1000 person-years]).
  • Increases in cell mediated immunity persisted during the 3 years of follow-up, although the magnitude of the responses declined over time.
  • A follow-up study, the Short-Term Persistence Sub-Study (STPS) (13), re-enrolled 7320 vaccine recipients and 6950 placebo recipients and followed them through year 7 after vaccination; In the STPS as compared to the SPS, there were no statistically significant differences in vaccine efficacy for herpes zoster burden of illness, vaccine efficacy for the incidence of post-herpetic neuralgia, or vaccine efficacy for the incidence of herpes zoster.
  • Vaccine efficacy for the incidence of herpes zoster and for the burden of herpes zoster illness remained statistically significant through year 5.

A 2012 meta-analysis evaluated the vaccine efficacy in 8 randomized trials that included 52,269 individuals 60 years of age or older, A similar reduction in herpes zoster was observed as was seen in the SPS. For herpes zoster incidence, a greater benefit was observed in individuals aged 60 to 69 years (RR 0.36, 95% CI 0.30-0.45) than in participants aged 70 years and over (RR 0.63, 95% CI 0.53-0.75).

The vaccine is generally well tolerated (14), with the most common side effect being injection site symptoms eg pain, erythema, pruritus and warmth (up to 48%) . Other side effects includeflu like syndromes (2%), diarrhea (2%) , fever (2%) and myalgia (<1%). Side effects are more common in the patients 60-69 years old compared to those >70 years old.

Recommendations

We are mindful that there are differences in the suggestions of certain other countries with regards to this vaccine's usage:

The ACIP, the Australian and New Zealand Society for Geriatric Medicine (7) and theNational Advisory Committee on Immunization(9) (Canada)recommend the following:

  1. Routine vaccination of all patients ≥60 years of age including patients who report a previous episode of zoster
  2. The ACIP further recommends that the following patients be considered for vaccination as well
  3. Patients with chronic medical conditions (eg, chronic renal failure, diabetes mellitus, rheumatoid arthritis, chronic pulmonary disease) without contraindications
  4. and residents of nursing homes without contraindications (1)

NACI (Canada) additionally states that patients aged >50 years old can be considered for this vaccine

In the UK, the Joint Committee on Vaccines and Immunisation, JCVI (8) has initiated a universal vaccinationprogramme to provide the vaccine to adults aged 70–79 years. This was based on a cost effective analysis involving various age groups. The benefit of vaccination is greatest in this age group due to the following factors:

  1. An increase in the burden of shingles disease with age (making it less cost effective in the younger age groups)
  2. A decrease in the effectiveness of the vaccine with age (making it less cost effective in the older age groups)
  3. The duration of protection of the vaccine (estimated to be around 7.5 years)
  4. The lack of knowledge about the effectiveness of a second dose of vaccine

In Canada, an additional suggestion noted that the vaccine may be used in patients aged>50 years old.

Note that only the UK has a universtal zoster vaccination programme.

Our Recommendations

As there is no universal vaccination programme in Malaysia for the zoster vaccine, we suggest the following:

  1. vaccination can be offered to patients ≥60 years of age including patients who report a previous episode of zoster
  2. The vaccine can still be offered to patients without a clinical history of chickenpox (varicella)
  3. Despite the vaccine being licensed for use in patients >50 years old, it is suggested that the vaccine not be recommended in patients >80 years old as its effectiveness is reduced in this group of patients.
  4. Furthermore, as the duration of effectiveness is estimated to be around 7.5 years based on current data (serological studies), younger patients may not be adequately covered after this period plus the issue of a booster or revaccination has also not been adequately addressed (13)
  5. The vaccine is most cost effective in patients aged 70-79 years old.
  6. Patients not in this age group, but is more than 50 years old and wish to have the vaccine administered may still do so, bearing in mind the data above.

Note on Vaccine Component

The zoster vaccine contains elements of gelatine of porcine origin in the hydrolyzed form. This serves as a stabiliser and helps maintain the vaccine’s effectiveness. Due to cultural sensitivities in Malaysia, it is suggested that this fact be discussed before hand with the patient, especially those of the Muslim faith.

There is some guidance with regards to this issue in the form of a letter written in July 2001 by the Regional Office of the World Health Organization (WHO) for the Eastern Mediterranean where more than one hundred Islamic legal scholars at a seminar convened by the Islamic Organization for Medical Sciences on the topic "The Judicially Prohibited and Impure Substances in Foodstuff and Drugs." (15, 16)

Quoting from a statement issued by the scholars, the letter states the following: "The seminar issued a number of recommendations, included in the attached statement, stipulating that 'Transformation which means the conversion of a substance into another substance, different in characteristics, changes substances that are judicially impure . . . into pure substances, and changes substances that are prohibited into lawful and permissible substances'."

Consequently, the scholars determined that the transformation of pork products into gelatin alters them sufficiently to make it permissible for observant Muslims to receive vaccines containing pork gelatin and to take medicine packaged in gelatin capsules.

Other health agencies in the UK (17) and Australia (18) have similar views. In Malaysia, the Jabatan Kemajuan Islam Malaysia (JAKIM) position statement on gelatin in medicine is as follows (19):

"The 8th Muzakarah (Conference) of the Fatwa Committee of the National Council for Islamic Religious Affairs Malaysia held on 24th -25th September 1984 has discussed gelatine in medicine. The Committee decided that gelatine in medicine is permissible because of necessity (darura). If there is any other alternative substance that can prevent medicine from easily deteriorating, hence the gelatine is no longer permitted"

Currently, there is however, no alternative to the current zoster vaccine.

Contraindications

We agree with the ACIP and Joint Committee on Vaccines and Immunisation UK, recommendations that the following immunocompromised patients should not receive zoster vaccine (1, 10):

  1. Patients undergoing hematopoietic stem cell transplant (limited data; assess risk:benefit, if needed, administer ≥24 months after transplantation)
  2. Hypersensitivity to any component of the vaccine
  3. Patients receiving recombinant human immune modulators, particularly antitumor necrosis factor agents (eg, adalimumab, infliximab, etanercept).
  4. Has primary or acquired immunodeficiency state due to conditions such as: acute and chronic leukaemias; lymphoma; other conditions affecting the bone marrow or lymphatic system; immunosuppression due to HIV/AIDS ; cellular immune deficiencies
  5. Those receiving immunosuppressive therapy (including high dose steriods)

Therapy with low-doses of methotrexate (<0.4 mg/Kg/week), azathioprine (<3.0 mg/Kg/day), or 6mercaptopurine (<1.5 mg/Kg/day) for treatment of rheumatoid arthritis, psoriasis, polymyositis, sarcoidosis, inflammatory bowel disease, and other conditions are not considered sufficiently immunosuppressive and are not contraindications for administration of zoster vaccine (10)

Patients of any age who have received the varicella vaccine is not recommended to have the zoster vaccine. It is not used for the treatment of shingles itself.

References

  1. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). Harpaz R, Ortega-Sanchez IR, Seward JF, CDC SOMMWR Recomm Rep. 2008;57(RR-5):1.
  2. Varicella-zoster vaccine for the prevention of herpes zoster.Kimberlin DW, Whitley RJ Engl J Med. 2007;356(13):1338.
  3. Hope-Simpson RE (1965). "The nature of herpes zoster; a long-term study and a new hypothesis". Proceedings of the Royal Society of Medicine 58 (1): 9–20
  4. Herpes zoster recurrences more frequent than previously reported. Yawn BP, Wollan PC, Kurland MJ, St Sauver JL, Saddier P Mayo Clin Proc. 2011;86(2):88.
  5. FDA approves shingles vaccine: herpes zoster vaccine targets older adults. Mitka M JAMA. 2006;296(2):157.
  6. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6044a5.htm
  7. Australian and New Zealand Society for Geriatric Medicine Position Statement No. 7 Immunisation of Older People – Revision Number 2, 2011
  8. Joint Committee on Vaccination and Immunisation. Statement on varicella and herpes zoster vaccines. 29 March 2010 (updated April 2011).
  9. National Advisory Committee on Immunization. Canada Communicable Disease Report. 2010;36:1–19
  10. Department of Health, 2013 Immunisation against infectious diseases: Shingles Chapter, TSO Publishing, Crown Copyright. http://immunisation.dh.gov.uk/green-book-chapters
  11. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.Oxman MN, Levin MJ, Johnson GR, Shingles Prevention Study Group N Engl J Med. 2005;352(22):2271.
  12. Vaccines for preventing herpes zoster in older adults. Gagliardi AM, Gomes Silva BN, Torloni MR, Soares BG Cochrane Database Syst Rev. 2012;10:CD008858.
  13. Persistence of the efficacy of zoster vaccine in the shingles prevention study and the short-term persistence substudy. Schmader KE, Oxman MN,, Shingles Prevention Study Group Clin Infect Dis. 2012 Nov;55(10):1320-8. Epub 2012 Sep 12.
  14. Safety of herpes zoster vaccine in the shingles prevention study : a randomised trial. Simberkoff MS, Arbeit RD et al. Ann Intern Med 2010; 152:545
  15. http://www.vaccinesafety.edu/Porcine-vaccineapproval.htm
  16. http://www.immunize.org/concerns/porcine.pdf
  17. https://www.gov.uk/government/news/vaccines-and-gelatine-phe-response
  18. http://www.ncirs.edu.au/immunisation/fact-sheets/vaccine-components-fact-sheet.pdf
  19. http://www.e-fatwa.gov.my/fatwa-kebangsaan/gelatin-dalam-ubat