Guidelines for Adult Immunisation

Available Vaccines

Varicella

Introduction

Varicella or chickenpox presents as fever, vesicular rash, itching and tiredness. It is caused by the varicella-zoster virus (VZV), also known as human herpesvirus 3 (HHV-3). It undergoes latency after primary infection and later reactivates as herpes zoster (HZ, shingles). Seroconversion in tropical countries occurs at a later age than in temperate countries making varicella common in adolescents and adults. The spectrum of varicella varies from mild in some people, to significant morbidity and some mortality in previously healthy persons. The live attenuated varicella vaccine (Oka strain) was developed by Takahashi in 1974, and it was registered in Japan in 1986. Since then monovalent varicella vaccines have been made available throughout the world for the prevention of infection in healthy children, adolescents and adults. Combination vaccines for the prevention of measles, mumps, rubella, and varicella became available in 2005.

VZV is transmitted by the airborne route or direct contact with vesicular fluid. It is highly contagious with secondary attack rates in susceptible household contacts ranging from 61-100%. VZV can also be transmitted to susceptible persons from patients with HZ.  Studies suggest that the risk of viral transmission is considerably less from HZ than from varicella.

In an immunocompetent person, malaise and fever occur 1 or 2 days before the onset of rash. Patients with varicella typically have a generalised vesicular rash concentrated on the head and trunk. The rash appears in crops; each crop usually progresses within 24 hours from macules to papules, vesicles, pustules and finally crusts. New lesions occur in crops over the next few days, with various stages of healing. The lesions are pruritic and may cause scars.  Adults with varicella have significantly higher morbidity than varicella in children.

VZV has the capacity to persist in the body after primary infection as latent infection in sensory nerve ganglia. VZV specific cell mediated immunity (CMI) plays import role in limiting reactivation of latent VZV. Decline in CMI leads to reactivation of VZV and herpes zoster.

The two-dose varicella vaccination programme has lowered the varicella incidence, outbreaks and hospitalisations, and has squashed concerns that routine childhood vaccination could lead to increase in HZ.

Varicella may be more severe in pregnant women (especially in the last trimester). Foetal morbidity is increased in maternal varicella. Varicella during pregnancy may damage the foetal central nervous system (CNS), resulting in permanent scarring of the skin, aplasia of extremities, chorioretinitis, microphthalmia, optic atrophy, cataract, Horner’s syndrome, blindness, mental retardation, foetal demise, and a high incidence of zoster and death in infancy. This constellation of problems in infants whose mothers had varicella in pregnancy is clinically diagnostic of the congenital varicella syndrome.

Maternal varicella that develops within 5 days before or 2 days after delivery, is potentially most serious for the newborn. Maternal antibodies to VZV may not have been formed or crossed the placenta and VZV may infect the baby before or after delivery. Immaturity of the infant’s cellular immunity, put the infant at risk for severe varicella. The infected infant may develop haemorrhagic skin lesions and primary varicella pneumonia. Severe varicella can usually be avoided with prophylactic administration of passive immunisation and acyclovir (ACV) therapy. Vaccination of women before pregnancy is the preferable strategy.

Vaccines Available in Malaysia

 

1. Varilrix® (Live attenuated Oka strain of varicella-zoster virus)
GlaxoSmithKline Pharmaceuticals Sdn Bhd/GlaxoSmithKline Biologicals, Belgium

2. Varivax® (Live attenuated Oka/Merck strain of varicella-zoster virus)
Merck Sharp & Dohme (M) Sdn Bhd/ Merck Sharp & Dohme Vaccine, US contains processed porcine gelatine

Mode of Administration

 
  • The vaccine is administered subcutaneously. Although data on the intramuscular route are limited, it too seems to be safe and effective. All manufactured varicella vaccines are lyophilised; both refrigerator-stable and frozen vaccine formulations are available.

  • Persons 13 years and older without evidence of immunity should receive 2 doses of monovalent varicella vaccine, 4-8 weeks apart. If an interval longer than 8 weeks elapses after the 1st dose, the 2nd dose can be administered without restarting the schedule.

  • Monovalent vaccines are to be used in adults as MMRV vaccine is approved for use in children 12 months through 12 years of age.

Contraindications and Adverse Effects

 
  • Although no infants with congenital varicella syndrome secondary to vaccine type virus have been reported, vaccination in pregnancy is contraindicated.

  • To date, the reported adverse events for varicella vaccine received by the National Pharmaceutical Regulatory Agency (NPRA) are varicella-like rashes occurring 7-23 days post vaccination and fever.

Varicella-containing vaccine should be given at least 2 weeks before the administration of blood products. In subjects who have received immune globulins or a blood transfusion, immunisation should be delayed for at least three months because of the likelihood of vaccine failure due  to passively acquired varicella antibodies.

    Target Groups in Malaysia

    • Adults who have no history of previous varicella infection. Because varicella infection is more severe among adolescents and adults, vaccination is important for them. Monovalent vaccines are to be used in adults as MMRV vaccine is approved for children 12 months through 12 years of age.

    • Vaccinating adult groups at high risk of exposure/transmission or close contact with persons at high risk of severe varicella should be a priority. These groups include students in schools, colleges and universities, international travelers, and healthcare workers.

    • To prevent congenital varicella, women who do not have previous natural infection or vaccination are advised to receive varicella vaccination before they start a family and they should avoid pregnancy for 3 months following vaccination. If already pregnant, they should be vaccinated postnatally.

    Implications for Healthcare Workers (HCWs)

    • Nosocomial transmission of VZV is a well-recognised medical problem. Because of their high risk of exposure to varicella or HZ and close contact with persons at high risk for serious complications, healthcare workers should be routinely vaccinated with two doses of varicella vaccine unless they have other evidence of immunity. Serologic testing after vaccination is not recommended unless a sensitive and specific test can be used. Available commercial assays are not sensitive enough to detect low levels of antibody after vaccination.

    • Varicella vaccine is recommended for post-exposure vaccination, for outbreak control, and for certain groups in whom there is adequate data on vaccine safety and immunogenicity or efficacy.

    Evidence for Effectiveness

     
    • The National Institute for Allergy and Infectious Diseases (NIAID) conducted a collaborative study on 350 healthy adults in 1980-1990 in which most of them were given 2 doses. Their fluorescent antibody to membrane antigen (FAMA) seroconversion rate was 82 % after one dose and 90% after two doses. Thirteen years after vaccination, 60-90% were positive by FAMA or latex agglutination antibody tests. In subsequent follow-up studies of a subset of these vaccine recipients (120 healthcare workers), 31% lost detectable FAMA antibodies, on average 8 years later. Twelve (10%) developed varicella; all had mild infections despite loss of detectable VZV antibodies.

    • In a multicentre study using Oka/Merck in 539 adolescents and adults, 75% seroconverted after first dose and 99% after second dose. A second multicentre Oka/Merck study involving 142 adolescents and adults showed 94% seroconversion after first dose and 99% after second dose.

    References

    1. Gershon, A.A., Marin, M. J. F., Seward, J.F. (2018) Varicella vaccine. In Plotkin S.A., Orenstein W.A., Offit, P.A., Edwards K.M.(Eds) Vaccines. (7th Edition) Saunders Elsevier.
    2. MSD. Varivax® Refrigerated Local Product Circular
    3. National Pharmaceutical Regulatory Agency (NPRA), Ministry of Health Malaysia. Senarai Produk Vaksin Berdaftar Dengan Pihak Berkuasa Kawalan Dadah. Updated 5 September, 2019
    4. The Malaysian National Centre of Adverse Drug Reactions Database [Accessed: 10 October, 2019]
    5. Wang, L., Zhu, L , Zhu, H. (2016) Efficacy of varicella vaccination: an update for the clinicians. Ther Adv Vaccines,4,20-31