S h a r o n W o n g

P a e d i a t r i c i a n , W a i t e m a t a D i s t r i c t H e a l t h B o a r d

C l i n i c a l S e n i o r L e c t u r e r ,

D e p a r t m e n t o f P a e d i a t r i c s : C h i l d a n d Y o u t h H e a l t h , U n i v e r s i t y o f A u c k l a n d

The Preventable Reality of Varicella

Declaration of Conflict of Interest

• GlaxoSmithKline invited speaker

• GSK pneumococcal advisory board member

• Travel paid by GSK

• Research partially funded by Novartis

• Additional comments • 2 Varicella vaccine formulations

• Varilrix ® (GSK)

• Varivax® (MSD)

• Some slides provided by GSK

Chickenpox

The Great Chickenpox Quiz

Quiz Rules

• Buzzer must be pushed before answering

• Response must be given within 10 seconds of pushing buzzer

• 1 point for correct answer

• -1 point for an incorrect answer

• The judges decision is final

• Bribery will be accepted

Question

• How is varicella zoster virus transmitted?

Question

• How is varicella zoster virus transmitted?

• Respiratory route

• Direct contact with lesions

• Transplacental

Question

• If an individual is infected with chickenpox , when are they infectious?

Question

• If an individual is infected with chickenpox , when are they infectious?

• 2 days before onset of rash crusting of all lesions

Question

• What age group is chickenpox infection most common in New Zealand?

Varicella in New Zealand

• Most infection 1-9 years

• ? shift to younger age groups with preschool education

• Birth cohort

• 3% infected as infants

• 10% each year of childhood

• By 14 years <10% remain susceptible

• By 40 years >97% infected

Tobias M, Reid S, Lennon D et al. Chickenpox immunisation in New Zealand. NZ Med J 1998;111:274-81

Question

• How many cases of chickenpox occur in New Zealand each year?

Question

• How many cases of chickenpox occur in New Zealand each year?

• Chickenpox is not notifiable in New Zealand

• ~50,000 cases per year

• 250-300 hospital admissions

• 1-2 long term disability or death

Question

• What complications can result from varicella zoster virus infection?

Complications

• Bacterial super infection

• Group A beta haemolytic streptococci

• Central nervous system

• Acute cerebellar ataxia – 1 in 4000 children <15 years

• Encephalitis - 0.1-0.2%

• Aseptic meningitis

• Transverse myelitis

• Varicella pneumonitis

• More common in adults and immunocompromised

• Arthritis, glomerulonephritis, myocarditis

Question

• What type of vaccine is the varicella vaccine?

Varicella vaccine

• Live attenuated vaccine

• Developed in Japan (Oka strain)

• Varicella vaccines licensed and available in NZ

Varilrix® GSK • 9 months – 12 years 2 doses 6 weeks apart

• ≥13 years 2 doses 6 weeks apart

Varivax ® MSD • 1-12 years 1 dose

• ≥13 years 2 doses 4-8 weeks apart

Sam

5 year old boy

Attends Aotearoa Primary School. Another child in the class has just been diagnosed with chickenpox.

Sam was born in Australia and received the Varicella vaccine at 18 months of age

Is Sam is likely to become infected with chickenpox?

Immunogenicity

Highly immunogenic

Seroprotection • Healthy children >12 months

1 dose ~85%

2 doses ~100%

• Leukaemic children

1 dose 82%

2 doses 95%

Hamleton S, Gershon AA. Preventing Varicella-Zoster Disease. ClinMicrobiol Rev, 2005;18,70-80

Vaccine efficacy / effectiveness

Efficacy 1 dose 2 dose

• Against infection 70-90% 92-97%

• Against severe disease 95% 97-100%

Post licensure effectiveness studies similar for infection and severe disease

Dramatic decline reported in USA since 1995

• Active surveillance in Texas, California and Pennsylvania

74-84% decrease in cases

Annual hospitalisations

• 2.7-4.2 per 100,000 in 1995-1998 0.6 per 100,000 in 1999

Decreased incidence in nonvaccinated groups

Hamleton S, Gershon AA. Preventing Varicella-Zoster Disease. ClinMicrobiol Rev, 2005;18,70-80 Committee on Infectious Diseases. American Academy of Pediatrics. Red Book 28th ed. 2009; Varilrix® Data Sheet, GSKNZ

Break Through Varicella

• Occurs in ~10-20% vacinees

• Compared with natural infection

• Decreased incidence and severity of rash

• Most <50 lesions compared with >250 lesions in unimmunised

• Less fever

• Faster recovery

• Infectious

• Risk of transmission 1/3 of varicella in unimmunised

Break Through Varicella

Vazquez M, Shapiro ED. Varicella Vaccine and Infection with Varicella-Zoster Virus. NEJM 352;5 2005,439-440

Unvaccinated Adolescent Vaccinated Child

Peter

5 year old boy

Attends Aotearoa Primary School. Another child in the class has just been diagnosed with chickenpox.

Peter immigrated to NZ from the Philippines at the beginning of the year with his parents and 15 month old sister.

He has not had chickenpox or the Varicella vaccine

What would you recommend?

Post-exposure Immunisation

≥12 months of age without evidence of immunity

• Within 72 hours

• May prevent or modify disease

Committee on Infectious Diseases. American Academy of Pediatrics. Red Book 28th ed. 2009

Rest of Family

• Parents

• Tropical climates – different epidemiology

• Acquisition of disease at later ages

• Higher proportion of susceptible adults compared with temperate climates

• 15 month old sister

• Live attenuated vaccine

• Administer concurrently with other live vaccines (e.g. MMR) or separated by ≥1 month

Vaccine Safety

USA >55 million doses

Reactions generally mild

~20% minor injection site reactions

3-5% localised rash

3-5% generalised varicella-like rash

• 2-5 maculo-papular lesions

• Appear 1-3 weeks post-immunisation

Hamleton S, Gershon AA. Preventing Varicella-Zoster Disease. ClinMicrobiol Rev, 2005;18,70-80 Committee on Infectious Diseases. American Academy of Pediatrics. Red Book 28th ed. 2009

Vaccine Safety

SAE reports rare • Anaphylaxis

• Encephalitis, ataxia, seizures

• Thrombocytopenia

• Pneumonia

• Erythema multiforme, Stevens-Johnson syndrome

Most often in immuno-compromised children

SAE frequency lower than after natural infection

Hamleton S, Gershon AA. Preventing Varicella-Zoster Disease. ClinMicrobiol Rev, 2005;18,70-80 Committee on Infectious Diseases. American Academy of Pediatrics. Red Book 28th ed. 2009

Sophie

20 years old

Recently married and wants to start a family

What would you discuss with her with respect to varicella?

Congenital Varicella Syndrome

• Fetal infection after maternal varicella during first or early second trimester

• ~1-2% when infection <20 weeks gestation

• Fetal death

• Varicella embryopathy • Limb hypoplasia

• Cutaneous scarring

• Eye abnnormalities

• Central nervous system abnormalities

Jones KL. Smith’s Recognizable Patterns of Human Malformation. 5th ed. WB Saunders Company 1997

Congenital Varicella Syndrome

http://www.gfmer.ch/genetic_diseases_v2/gendis_detail_list.php?cat3=356

Question

• Who should receive the varicella vaccine?

Who Should Receive Varicella Vaccine?

NO prior history of varicella infection

Children likely to undergo solid organ transplant

Close contacts of immune suppressed patients

• “Ring fence” protection

Adults and adolescents

• From tropical countries

• Healthcare workers

• Women planning a family

Question

• What are the advantages of a 2 dose schedule of the varicella vaccine?

Question

• What are the advantages of a 2 dose schedule of the varicella vaccine?

• Maximise immune response

• Minimise primary vaccine failures

• Reduce waning of immunity

• Reduce the risk of later breakthrough disease

• But there is an impact on cost-effectiveness

Countries using Varilrix® in universal routine vaccination (URV) programmes

One-dose schedule Two-dose schedule

Rebublic of Korea:

URV since

2004 Italy:

URV since

2003

Saudi Arabia:

URV since

2008 Greece:

URV since

2006

Madrid/

Navarra:

URV since

2006

USA:

URV since

1995

2-dose

since 2007 Qatar:

URV since

2001

Australia:

URV since

2005

Taiwan:

URV since

2004

Uruguay:

URV since

1999

Canada:

URV since

2005

Updated: 12 May 2009

Latvia:

URV since

2008

Luxemburg:

URV 2-dose

since 2009

Germany:

URV since

2004

Israel:

URV since

2003

Summary

Chicken pox is highly infectious

• 90% chance of being infected by adolescence

• Numerous hospitalisations each year in NZ

• Children do die from chickenpox in NZ

An effective non funded vaccine is available and recommended

• Large amount of safety data

• Vaccine likely lessens the chance of shingles as adult

Complications

3 year old girl – chickenpox 1 week prior

Blood culture: Streptococcus pyogenes

Left forearm osteomyelitis – washouts

Pneumonia with empyema – surgical chest drainage

6 weeks IV penicillin

Varicella Pneumonitis

Complications

8 year old girl – chickenpox 1 week prior

• Orbital cellulitis

• Blood culture: Methicillin resistant Staphylococcus aureus

• MRI head: subdural empyema and cavernous sinus thrombosis

• 6 weeks IV antibiotics

• 3 months heparin anticoagulation

Complications

8 week old boy – chickenpox 1 week prior

• Blood culture: Streptococcus pyogenes

• Multiorgan failure, secondary DVT, left septic hip and femoral osteomyelitis

• 6 weeks IV penicillin

• 3 months SC heparin

Complications

3 year old girl – chickenpox 8 weeks prior

• Slurred speech and right sided weakness

• Acute haemorrhagic infarct of left basal ganglia, short segment stenosis of left middle cerebral artery

• Good recovery

• Residual deficits with attention and decreased cognition

Chicken Pox CJ Heck

Today I had fever

and I didn’t feel so good.

Daddy took me to the doctor

to get me better if me could.

The doctor looked at me and said,

“It’s only Chicken Pox.”

How come there’s such a fancy name

For plain ol’ itchin’ dots?

http://www.authorsden.com/visit/viewPoetry.asp?id=171993

Herpes Zoster (Shingles)

Herpes zoster after immunisation

• Virus reaches dorsal root ganglia through sensory nerves in skin lesions during primary infection

• Skin lesions in small percentage

Lower frequency and severity in vaccine recipients

Cost effectiveness

• Economic cost – benefit analysis for NZ in 1999

• For every $1 invested in immunisation programme

• Direct costs - $0.67 return

• Indirect costs - $2.79 return

Scuffham S et al. The cost-effectiveness of introducing a varicella vaccine to the New Zealand immunisation schedule. Soc Sc Med 49 (1999) 763-779

Future

New combined measles-mumps-rubella-varicella vaccine (MMRV)

Need for 2 dose schedule

• Maximise immune response

• Reduce waning of immunity

• Reduce risk of later breakthrough disease

Varilrix Product Information

•Varilrix® (live attenuated varicella vaccine) is available as an injection, 0.5mL per dose. Varilrix is a private-purchase prescription medicine for immunisation and prophylaxis against varicella (chickenpox) in adults and children older than 9 months. A prescription charge will apply. Children aged 13 years and older need two doses with an interval between doses of at least 6 weeks. Two doses at least six weeks apart are also recommended for children aged between 9 months and 12 years, to provide optimal immune responses against varicella virus. Contraindications: acute severe febrile illness, lack of cellular immunity (e.g. leukaemia, lymphoma, HIV infection, or immunosuppressive therapy), known systemic hypersensitivity to neomycin, or pregnancy. Pregnancy should also be avoided for 3 months after vaccination. Precautions: do not administer intradermally or intravenously. Ensure medical treatment is readily available in case of rare anaphylactic reaction following administration. Use caution in patients with serious chronic diseases (such as chronic renal failure, autoimmune diseases, collagen diseases, or severe bronchial asthma). Avoid salicylates for 6 weeks after vaccination. Vaccination should be delayed for at least 3 months after a patient has received immune globulins or a blood transfusion. If a measles vaccine is not given at the same time as Varilrix, it should be delayed by at least 1 month. Common side effects include mild rash; pain, redness and swelling at the injection site; and small numbers of papulo-vesicular eruptions. Uncommon side effects include fever, headache, cough, vomiting, lymphadenopathy, and arthralgia. Before prescribing Varilrix, please review the full Data Sheet at www.medsafe.govt.nz. Varilrix is a registered trade mark of the GlaxoSmithKline group of companies. Marketed by GlaxoSmithKline NZ Limited, Auckland. TAPS DA4311IG/11JL/255