“Overview of varicella disease and role of vaccination” BD/VAR/0002/18
“Overview of varicella disease and role of vaccination” Dr. Raunak Parikh. MBBS, MD (Micro.), Dip. Pharm. Med. Senior Medical Advisor (Vaccines) GSK Pharmaceuticals India.
The varicella-zoster virus (VZV) causes varicella and HZ Varicella Varicella-zoster HZ (shingles) (chicken pox) virions Secondary disease that Secondary disease that Without vaccination, Without vaccination, occurs when dormant >90% of children are VZV reactivates in seropositive by previously infected adolescence in individuals 3 temperate countries 1,2
Varicella: a substantial burden of disease The WHO estimated that 4.2 million severe complications of varicella worldwide result in hospitalisation and 4200 deaths per year 1 Hospitalisation rates in children aged <17 years range from 0.82–22.7 per 100,000 across Europe 2,3 from 0.82–22.7 per 100,000 across Europe 2,3 Economic cost of varicella can be substantial, 4-8 due to both societal costs and direct medical costs 4,7,8 * WHO, World Health Organization. *Societal costs include work hours lost due to care of sick children; Direct costs include visits to primary care physicians, hospitalisations, medication costs and diagnostic examinations. 1. World Health Organization. Wkly Epidemiol Rec 2014; 89 : 265–87; 2. Cameron JC et al. Arch Dis Child 2007; 92 : 1062–6; 3. Bonsignori F et al. Infection 2007; 35 : 444–50; 4. Banz K et al. Eur J Health Econ 2004; 5 : 46–53; 5. Carapetis JR et al. Vaccine 2004; 23 : 755–61; 6. Edgar BL et al. Can Commun Dis Rep 2007; 33 : 1–15; 7. Somekh E et al. J Infect 2002; 45 : 233–6; 8. Vally H et al. Aust N Z J Public Health 2007; 31 : 113–9.
Chickenpox (Varicella) – Primary infection with Varicella-zoster virus – Benign, self-limiting disease in children – Severe disease more likely in neonates, infants, pregnant women, adults, and immunocompromised persons – Fever, malaise, and a generalized vesicular rash – Fever, malaise, and a generalized vesicular rash [especially concentrated on the head and trunk] – Highly transmissible by the airborne route – infecting virus coming predominately from vesicular skin lesions 1. Varicella and herpes zoster vaccines: WHO position paper, June 2014. Weekly epidemiological record 2014;89:265-288 5
Varicella Rash pruritic erythematous Starting on face and trunk, and spread to macules extremities in a so-called “centripetal spread.” New batches of lesions appear every few days for 5-7 days. 2 papular stage hrs 2 Vesicles at various stages of evolution are Vesicles at various stages of evolution are 24-48 hr found on the skin. 2 clear, fluid-filled vesicles Varicella lesions are superficial and crusts fall off after 1–2 weeks. 3 Spots of hypopigmentation that can remain for Crusting of the several months or leave persistent scars. 3 lesions 1. Leonid I, et al. J Clin Aesthet Dermatol. 2009 Aug; 2(8): 36–38. 2. Varicella and herpes zoster vaccines: WHO position paper, June 2014. Weekly 6 epidemiological record 2014;89:265-288. Heininger U, et al. Lancet 2006;368:1365-76.
Complications – Vast majority of complications occur in healthy individuals. 1 – Cannot predict which patients will experience complications. 1 – Central nervous system: 2 – Cerebellar ataxia (1 in ~4000 cases) – Encephalitis (1 in 33 000–50 000 cases) – Vasculitis, stroke (most frequently in children) – Vasculitis, stroke (most frequently in children) – Secondary bacterial infections: 2 – most common complication in children – group A β -haemolytic streptococci or Staphylococcus aureus – Usually affect skin and underlying soft tissue – Invasive infections (pneumonia, arthritis, osteomyelitis, necrotizing fasciitis, and sepsis) – Pneumonia; usually viral (most common complication in adults). 2 1. Bonanni P, et al. BMC Med. 2009 May 28;7:26. 2. Varicella and herpes zoster vaccines: WHO position paper, June 2014. Weekly epidemiological 7 record 2014;89:265-288
Comparative incidence of varicella complications Estimates, Germany Complications requiring Complications hospitalization Bacterial superinfec Other Bacterial tion/scarri complicati superinfec ng on Acute tion/scarri neurologic ng al disorder Other complicati on on Otitis media Acute neurologic al disorder Pneumoni Pneumoni a/bronchiti a/bronchiti s s Model estimates based on input data mainly from a retrospective epidemiological survey of 1,334 varicella cases in Germany. Base case analysis the model predicted approx.740,000 varicella cases per year with 39,700 complications and 5,740 hospitalization and 22 deaths. 1. Banz K, et al. Eur J Health Econom 2004;5:46–53.
Immunity during varicella infection Innate and adaptive immune responses VZV-specific T cells: Essential to terminate viremic phase and enable Severity of infection inversely correlated with T - cell recovery response VZV-specific antibodies: Not associated with reduced clinical severity of May prevent a second infection if immune individual infection exposed to virus After resolution of initial infection, VZV establishes latency in sensory ganglia, where it persists lifelong VZV reactivation: Attributed to declining T cell, rather than humoral immunity Warren-Gash C, et al. Expert Review of Vaccines, 16:12 1191-1201 9
Varicella vaccines development 1970s: early Development of first Further development marketed vaccine development of OKA strain strain • New stabiliser added to • Varilrix : lyophilised Varilrix in 1994 to allow formula not less than 10 3.3 PFU ( ≥ ~1995 storage at 2–8°C 2 • Varicella virus isolated 1 • Merck Varicella vaccines PFU); launched • Attenuated using three cell lines to create the launched in 1995 by GSK in 1984 2,3 Oka strain 1 • Combined MMRV vaccines launched in 2000s PFU, plaque-forming units; Virus image courtesy of the CDC. 1. Takahashi M. Infect Dis Clin North Am 1996; 10 : 469–88; 2. GlaxoSmithKline. Varilrix Summary of product characteristics 2016; 3. Kreth HW et al . BioDrugs 2008; 22 : 387–402; .
Question related to varicella vaccination?? 1 vs. 2 doses ? Timing of first Timing of first dose? Vaccinate against varicella? 11
Vaccination can reduce incidence of OPD visits related to varicalla Uruguay: varicella URV for 1 ‒ 2 year olds introduced in 1999 1000 2005 vs. 1997-9 87% decline tion (log scale) ricella cases / (all age groups) [p<0.001] 100 Number of varic 1000 populatio 10 1 1997 1998 1999 2000 2001 2002 2003 2004 2005 Year <1 1–4 5–9 10–14 Varicella vaccination introduced end of 1999 for children aged 12 months. Estimated to exceed 90%. Information on medical consultations for varicella 12 was collected from two private health insurance systems. Ambulatory visits for varicella compared between 1999 and 2005 and 1997 and 1999 Quian J et al. Arch Dis Child 2008; 93 : 845 ‒ 50.
Vaccination can reduce varicella related hospitalization Rate Number Hospitalisation 7 1200 rates declined by alisation rate pitalisations 21.4% per 6 ual number population 1000 annum 5 800 per 100,000 po Annual hospitali Annua of hospi 4 4 600 3 400 2 200 1 0 0 Vaccine Vaccine Vaccine Pre-vaccine funded licensed recommended (before 1999) (2006–2010) (2000–2003) (2004–2005) Principal or any coded varicella or HZ hospitalizations were retrieved from the national hospital morbidity database from 1998 to 2010. Incidence rate 13 ratios (IRR) were calculated between periods before and after implementation of immunization programme funding. Varicella vaccine coverage ~ 75% in children aged 24 months and> 80% in children aged 60 months. Heywood AE et al. Bull World Health Organ 2014; 92 : 593–604.
Vaccination can reduce varicella related mortality Annual varicella-related deaths in the USA, national vital statistics system data, 1990–2011 2 120 aths per year Pre-vaccine period Implementation of a Implementation of a one-dose schedule two-dose schedule 100 80 80 Average number of deat 60 40 20 0 1990–1994 2005–2007 2008–2011 Varicella listed as underlying cause of death Varicella listed as contributing cause of death Data on varicella deaths for 2008–2011 using the Mortality Multiple Cause-of Death public use records from the National Center for Health Statistics and and calculated rates to compare with the prevaccine and mature 1-dose varicella vaccination program eras Leung J, et al. Hum Vaccin Immunother 2015; 11 : 662–8.
Optimal age for 1 st varicella vaccination – Knowledge of kinetics of maternal antibodies is important in order to properly estimate the optimal age of vaccination. – When live attenuated vaccines are injected, the presence of maternal IgG antibodies may neutralize vaccine viruses, thereby inhibiting the vaccine-specific immune viruses, thereby inhibiting the vaccine-specific immune response. – Reduce the gap of immunity between the disappearance of transmitted maternal antibodies and the age of initiation of active immunization can decrease burden of varicella disease in infants Pinquier D, et al. Clin Vaccine Immunol. 2009 Apr; 16(4): 484–487. 15
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