Chickenpox (Varicella)

Definition

Problem Statement (Global and Indian Burden)

• Globally, chickenpox causes 4.2 million severe complications leading to hospitalization and 4,200 deaths annually (conservative estimates).
• In the pre-vaccine era, the case fatality rate in high-income countries was about 3 per lakh cases (compared to 1-3 per 1,000 for measles).
• Factors influencing severity include: proportion of cases in infants, pregnant women, and adults; prevalence of immunocompromising conditions (including HIV); and access to appropriate treatment.
• The incidence and severity of herpes zoster increases with age, markedly after 50 years - about half of those who reach 85 years will suffer at least one episode.
• India (2018): 66,963 cases reported with 50 deaths; CFR ~0.074%. Kerala had the highest case count (34,785); West Bengal had the most deaths (31).

Epidemiological Determinants

1. Agent Factors

• V-Z virus = "Human (alpha) herpes virus 3"
• Primary infection causes chickenpox
• After recovery, the virus establishes latent infection in cranial nerve ganglia, sensory ganglia, and spinal dorsal root ganglia - sometimes for decades
• When cell-mediated immunity wanes (with age or immunosuppressive therapy), the virus reactivates causing herpes zoster in 10-30% of persons - a painful, vesicular, pustular eruption in the distribution of one or more sensory nerve roots
• The virus can be grown in tissue culture

• Usually a case of chickenpox
• Virus present in oropharyngeal secretions and skin/mucosal lesions
• Rarely, a patient with herpes zoster can be the source
• Virus can be isolated from vesicular fluid during the first 3 days of illness
• Scabs are NOT infective

• Ranges from 1-2 days before the appearance of rash to 4-5 days after
• The virus tends to die out before the pustular stage
• The patient ceases to be infectious once the lesions have crusted

• Varicella is highly contagious with a secondary attack rate of approximately 85% (range 61-100%) in susceptible household contacts
• Herpes zoster is approximately 20% as infectious as chickenpox

2. Host Factors

• Occurs primarily in children under 10 years of age
• Few escape infection until adulthood
• Disease can be severe in normal adults

• One attack gives durable (lifelong) immunity; second attacks are rare
• Maternal antibodies protect infants during the first few months of life
• IgG antibodies persist for life and correlate with protection
• Cell-mediated immunity is important in recovery from V-Z infections and in preventing reactivation of latent V-Z virus

• Infection during pregnancy presents risk of congenital varicella syndrome
• Occurs in 0.4-2.0% of children born to mothers infected with VZV during the first 20 weeks of gestation
• Infants whose mothers had chickenpox during pregnancy have a higher risk of developing herpes zoster in the first years of life

3. Environmental Factors

• Seasonal trend: peak incidence during winter and spring in temperate settings, and in the coolest, driest months in the tropics
• Periodic large outbreaks with an inter-epidemic cycle of 2-5 years
• VZV is heat labile - survives only a few hours (occasionally a day or two) in the external environment
• Readily inactivated by lipid solvents, detergents, and proteases

Transmission

• Person-to-person by droplet infection and droplet nuclei
• Most patients infected by "face-to-face" (personal) contact
• Portal of entry: upper respiratory tract or the conjunctiva
• Since the virus is extremely labile, fomites play no significant role in transmission
• Contact infection is important when a herpes zoster patient is the index case
• The virus can cross the placental barrier causing congenital varicella

Incubation Period

• Ranges from 10-21 days (usually 14-16 days)

Clinical Features

• The rash begins on the trunk, spreading centrifugally to the face and extremities
• Lesions progress through stages: macule → papule → vesicle → pustule → scab
• A characteristic feature is pleomorphism - lesions in all stages simultaneously
• In most cases, it is a mild, self-limiting disease
• Mortality less than 1% in uncomplicated cases

Complications

• Haemorrhagic varicella
• Pneumonia (rare in healthy children; most common serious complication in neonates, adults, and immunocompromised patients - responsible for many varicella-related deaths)
• Encephalitis
• Acute cerebellar ataxia
• Reye's syndrome (acute encephalopathy with fatty degeneration of viscera, especially liver)

• Maternal varicella can cause: cutaneous scars, atrophied limbs, microcephaly, low birth weight, cataract, microphthalmia, chorioretinitis, deafness, cerebro-cortical atrophy
• If varicella develops in a mother within 5 days after delivery, the newborn is at risk of disseminated disease and should receive varicella-zoster immunoglobulin (VZIG)

• VZV is the major virus associated with acute retinal necrosis and progressive outer retinal necrosis - increased frequency in AIDS patients

• Secondary infection with Group A beta-haemolytic streptococci and Staphylococcus aureus is common
• Can cause: cellulitis, erysipelas, epiglottitis, osteomyelitis, scarlet fever, and rarely meningitis
• Pitted scars are frequent sequelae

• Highest risk group includes patients with malignancies, organ transplants, HIV infection, or those on high-dose corticosteroids
• Disseminated intravascular coagulation (DIC) may occur - rapidly fatal
• Children with leukaemia especially prone to severe disseminated VZV disease

Laboratory Diagnosis

• Clinical signs are usually clear-cut and laboratory confirmation is rarely required
• PCR (detecting VZV DNA) from vesicular fluid, crusts, saliva, or CSF - method of choice
• Viral isolation in cell culture from vesicular fluid
• Direct immunofluorescence - rapid but lower sensitivity than PCR
• VZV-specific serum IgM - considerably less sensitive than PCR, not preferred
• Serum IgG antibodies - used to assess immunity/susceptibility in unvaccinated persons (e.g., healthcare workers)

Control Measures

• Notification (notifiable disease)
• Isolation of cases for about 6 days after onset of rash
• Disinfection of articles soiled by nose and throat discharges

• Acyclovir, valaciclovir, famciclovir, and foscarnet are effective
• Acyclovir can prevent systemic disease in immunosuppressed patients and halt progression of zoster in adults
• Acyclovir does not appear to prevent post-herpetic neuralgia

• Varicella-Zoster Immunoglobulin (VZIG) - for passive immunization
• Indicated for: susceptible immunocompromised persons, neonates of mothers who develop varicella within 5 days before or 2 days after delivery, susceptible pregnant women exposed to varicella
• Must be given within 96 hours of exposure (preferably within 72 hours); effective for ~3 weeks

• Varicella vaccine is a live attenuated preparation derived from the Oka strain of VZV
• Available as monovalent vaccine, or combined as MMR-V (measles-mumps-rubella-varicella)
• WHO (2014) recommends a 2-dose schedule
• First dose: 12-18 months; Second dose: 4-6 years of age (or at least 3 months after first dose)
• Efficacy: 1 dose = ~80-85% against all varicella, >95% against severe disease; 2 doses = >98%
• Post-exposure vaccination within 3-5 days of exposure is effective in healthy individuals
• Contraindicated in: immunocompromised patients (including HIV with CD4 <200), pregnant women, patients on high-dose corticosteroids
• Outstanding questions include: whether universal childhood vaccination will shift disease incidence to adolescence/adulthood, and whether vaccination prevents herpes zoster development