Chickenpox

Treatment In Otherwise Healthy Children With VZV Infection

Symptomatic treatment is the mainstay of therapy in immunocompetent individuals suffering from varicella infection. Pruritus can be managed by application of a drying lotion such as calamine or occasionally anti-histaminic preparations that may be required for relieving itching. Aluminum acetate or soaks with burrow solution can be both soothing and cleansing in patients with herpes zoster. The fingernails should be trimmed to reduce the damage done by scratching. Daily bathing must be advised to decrease the probability of secondary skin infections. One should avoid using aspirin for treating fever in these children. The administration of aspirin to children with varicella is postulated to cause Reye's syndrome.

The use of systemic antiviral therapy is usually not necessary, although oral acyclovir has been used in the treatment of both chickenpox and herpes zoster in normal children. Such a therapy shortens the duration of lesion formation by about one day, reduces the total number of new lesions by about 25%, and improves constitutional symptoms in one-third of patients. The American Academy of Pediatrics recommends therapy of adolescents and high-risk groups such as children with bronchopulmonary dysplasia within 24 hours of the onset of disease. Oral acyclovir therapy of herpes zoster in the normal host accelerates cutaneous healing and reduce acute neuritis. Its effect on post-herpetic neuralgia is marginal if any.

Parenteral Antiviral Therapy In The Management of Chickenpox and Herpes Zoster

Parenteral anti-viral therapy is indicated for the treatment of varicella infections (chickenpox as well as herpes zoster) in immunocompromised patients. They should also be used in immunocompetent individuals when visceral complications such as varicella pneumonitis appear. Vidarabine has proven efficacy in treating varicella infections but it has been replaced by acyclovir. Acyclovir is not only potent but has fewer side-effects than vidarabine and has a high degree of selectivity for the inhibition of VZV replication.

Preventing Varicella

Varicella infection can be prevented by:

• avoiding contact with cases of varicella,
• providing passive immunization against varicella e.g. varicella zoster immune globulin,
• administering vaccination against VZV

Varicella Vaccine

A live-attenuated varicella virus vaccine is available for protecting children, adolescents, and adults from the varicella vaccine. An attenuated Oka strain is used in the vaccine.

Is it true that the varicella vaccine in extremely sensitive to temperature changes?

The varicella vaccine that was initially introduced was highly sensitive to temperature changes. It required to be stored at -20 degrees Celsius like most other vaccines. At these temperatures, the vaccine has a shelf-life of 2 years.

How effective is varicella vaccine in children, adolescents and adults?

Varicella vaccine is highly immunogenic. Seroconversion rates at 6 weeks following complete immunization in adults and children are as high as 92-98%. Its clinical efficacy has been studied extensively. Studies have shown that it provides protection from classical chickenpox to the extent of 100%.

What is the dosage schedule for administration of varicella vaccine?

The varicella vaccine has been cleared for use in children over the age of 12 months. Children up to the age of 12 years require only one dose, which has to be administered subcutaneously. In contrast, individuals above the age of 12 years are advised two doses of the vaccine, which are administered 6-10 weeks apart.

Can varicella vaccine be administered simultaneously with other vaccines?

Varicella vaccine can be administered simultaneously with other immunizing agents such as the polio vaccine and vaccine against measles, mumps, rubella, hepatitis-A, hepatitis-B, and H.influenzae type B. Such an administration does not interfere with the immunogenicity of these vaccines nor does it increase the incidence or severity of complications. However, in such situations, the injections should be given at different sites and the different vaccine preparations should not be mixed together.

What are the contraindications to the use of varicella vaccine?

Being a live-viral vaccine, its use is contraindicated during pregnancy. The vaccine contains neomycin and hence the history of systemic pre-sensitivity to neomycin is a definite contra-indication. If a child's total lymphocyte count is less then 1200/mm3 or if there is evidence of lack of cellular immune competence, the varicella vaccine should not be administered. The presence of acute febrile illness in healthy subjects, the presence of a minor infection is not a contraindication for vaccination.

What precautions would you take while immunizing a woman of the child-bearing age group?

Pregnancy being an absolute contra-indication to the use of the varicella vaccine, one must ensure that the woman is not pregnant. The lady should be advised to avoid pregnancy for the next 3 months after vaccination.

What are the side effects of varicella vaccine?

Varicella vaccine has low reactogenicity and most of the children and adults tolerate the vaccine well. Detailed follow-up studies were done for 6 weeks after vaccination has revealed very few side-effects and these are transient and of low severity. These have included pain at the site of injection, fever, and papulovesicular eruptions. In a four weeks follow-up, double-blind placebo-controlled study; there was no significant difference in the nature or incidence of symptoms in children (aged 12-30 months) receiving the vaccine or placebo. The high-risk patients tend to develop papulovesicular eruptions that are sometimes accompanied by moderate fever.

A major concern has been whether the risk of zoster in children immunized with the vaccine would be increased. However, in both healthy and leukemic children, the rate of zoster has been similar to or lower than that expected after natural chickenpox. The vaccine strain of the virus is transmissible but primarily from vaccinees with a rash. There is no evidence to suggest a reversion to virulence of the vaccine strain during transmission. Persons acquiring vaccine virus may have a mild rash or subclinical infection resulting in seroconversion. Due to the possibility of transmission of the vaccine viruses, vaccinees with a rash should avoid contact with susceptible pregnant women and immunocompromised persons.

How can one determine if a child is protected against varicella after vaccination?

Antibody titer against varicella can be determined 6 weeks after immunization. A titer in excess of or equal to 4 is considered protective. However, a routine demonstration of the titer is not necessary.

Is it mandatory to do serological testing children and adults prior to vaccination?

While answering this question, the following facts need to be noted:

• Varicella has a characteristic rash and is easily diagnosed even by family members.
• One attack of chickenpox gives life-long immunity against varicella infection.
• Giving varicella vaccine to an immune individual does not increase the severity or frequency of side-effects, though it may amount to waste of vaccine.
• Studies carried out in the United States have shown than given a positive history of varicella infection, 93% of children were immune. However, even when there was no history of varicella, as many as 60% were immune. Even when there was no history of previous varicella infection: most adults were still immune to varicella.

Based on these facts, it may be recommended that children who have a definite history of varicella may be considered as immune while those children who have a doubtful history or on the history of having suffered from varicella previously, may be considered as non-immune and vaccinated. In the case of adults, however, recommendations regarding serological testing will depend upon relative costs of testing and vaccination.

What are the indications for the use of varicella vaccine?

Varicella vaccine is not a part of routine immunization in children in India. However, the American Academy of Pediatrics (AAP) and the Advisory Committee on Immunization Practices (ACIP) have provided certain recommendations in this regard. These guidelines are on the background of most infections occurring in childhood in that country, where varicella infections are likely to be milder with lesser frequency and severity of complications. AAP recommends that all infants aged 12-18 months be routinely immunized against varicella.

What benefit will occur if routine childhood immunization against varicella is implemented?

Routine varicella vaccination will prevent morbidity and mortality associated with varicella. It will also offer protection to high-risk individuals as the circulation of the wild viruses will decrease in view of the reduced number of susceptible individuals. Whenever a child suffers from varicella he is likely to miss the school and the care-giver is likely to stay at home to look after the child. Routine immunization will lead to saving, as direct (expenses on medications and hospitalization) and indirect (loss of school attendance, absence at the workplace, loss of wages) costs will be saved.

Can one administer varicella vaccine to a child for rheumatoid arthritis on chronic aspirin therapy?

There is an association between the occurrence of Reye's syndrome in children and aspirin administration to children who have varicella infection. So far, there is no evidence that the administration of the varicella vaccine to a child who receives aspirin leads to Reye's syndrome. However, as a measure of abundant precaution, it is advised that aspirin should not be given for 6 weeks following varicella vaccination. In a child on chronic aspirin therapy, the risks of precipitation of Reye's syndrome due to infection by wild varicella virus and that following vaccination are weighed. The child should be monitored closely if vaccination is administered.

Can a child suffering from leukemia be immunized against varicella?

Children with acute leukemia are at an enhanced risk of developing progressive varicella infection and severe complications if they come in contact with a case of varicella. This is due to their immunocompromised state. However, for the same reason, the administration of a live, attenuated vaccine-like the varicella vaccine is contraindicated in children with acute leukemia. Leukemia children should receive a vaccine if they have no history of the disease or are found to be seronegative. This can be undertaken only when they are incomplete hematological remission, the total lymphocyte count is at least 1200 per mm, and when there is no other evidence of lack of cellular immune competence. While vaccinating such children, it is advised that maintenance therapy be withheld one week before and after the immunization. Patients under radiotherapy should normally not be vaccinated during the treatment phase.

What future developments can one expect with regards to varicella vaccine?

Exciting developments are awaited in the case of the varicella vaccine. A combination vaccine combining this vaccine with the MMR vaccine is likely to be developed. This will decrease the number of injections received by a child. Studies are being undertaken to see if the varicella vaccine can boost the cellular immunity of older individuals so that herpes zoster can be prevented. Further studies are required to judge the need for booster immunization.

What Is VZIG?

VZIG or varicella-zoster immunoglobulin is prepared by the selection of serum containing high titers of varicella-zoster antibodies. It is available for intramuscular injection and provides passive immunity against varicella-zoster to the recipients.

What are the indications for using VZIG?

VZIG provides immediate protection from varicella infection if it is administered to susceptible individuals within 96 hours of exposure. To derive maximum benefit it should be given as soon after exposure as possible. The possible indication for its use include:

• Susceptible immunocompromised individuals who have been recently been exposed to a case of varicella
• Newborn to a mother who has developed varicella within 5 days before to 48 hours after the delivery
• Premature infants of the gestational age of fewer than 28 weeks
• Susceptible pregnant women exposed to varicella.

Some believe that it may also be useful in ameliorating the expression of varicella in susceptible adults, who are at increased risk of complications from varicella infection. VZIG may not prevent infection; however, if infection occurs it is usually subclinical or mild.

What are the limitations of using VZIG?

The limitations of using VZIG are as follows:

• VZIG offers passive immunity, which lasts for only about 3 weeks. It does not provide long-lasting immunity. The individual at high risk from developing complications of varicella will require VZIG every 3-4 weeks to have complete protection
• For it to be effective, VZIG has to be administered soon after exposure and definitely within 72-96 hours.
• It may not be able to provide complete protection. The incidence of disease in immunocompromised children who have received VZIG after household exposure is still 33-50%.

• Its administration may prolong the incubation period. Hence, recipients could be infectious for as many as 10-28 days after exposure.
• The product is difficult to procure and is extremely expensive.

How is VZIG administered?

VZIG is administered intramuscularly in the dose of 125 u/10 kg body weight. The minimum dose is 125 u while the maximum dose is 625 u. For it to be effective, it has to be given soon after exposure. It is hardly of any use if its administration is delayed by more than 96 hours after exposure.

How Does One Prevent Nosocomial Spread of VZV Infection?

VZV is highly contagious and VZV infection may be life-threatening in certain patient populations. Nosocomial transmission of VZV infection occurs due to airborne transmission from an index case of varicella or due to direct contact with lesions from a patient with dermatomal zoster.

The following recommendations have been made to avoid or limit the nosocomial spread of VZV infection:

• Avoid admitting a patient with VZV infection
• If an immunocompetent patient with dermatomal zoster has to be admitted, he should be put on drainage and secretion precaution and people who haven't had chickenpox should not be allowed to enter the room.
• Severely immunocompromised persons who develop dermatomal zoster carry a higher risk of dissemination. Hence, they should be placed under strict isolation precautions. These may be related to drainage and secretion procedure once the primary dermatomal begins to heal.
• Patients with varicella or disseminated zoster should be placed on strict isolation precautions.
• VZV transmission can also be prevented by using negative pressure ventilation rooms.
• If a case is detected to have developed chickenpox after admission to the hospital, patient-related and staff-related epidemiological investigations are begun:
  * Obtain an in-hospital travel history from the index case.

  * Examine records of appropriate areas to determine patient-population at risk

  * Among the population at risk, those who have had VZV infection in past do not require any further work-up.

  * Amongst those with a negative or uncertain history of previous VZV infection, determine exposure history. No further follow-up is required if there were no exposure. Those with a negative or uncertain history of previous VZV infection but with a history of exposure to the index case in the hospital should have their blood drawn for serological testing. Immunocompromised individuals amongst them should also receive appropriate doses of VZIG as early as possible. All these patients should be discharged as early as possible. If the discharge is not possible, those found susceptible on the basis of serological testing should continue to be isolated for 21 days while no follow-up is required in immune individuals.

  * The exposed staff member who has no history of previous VZV infection should undergo serological testing. Susceptible among them should be re-assigned to the low-risk areas for at least 21 days after exposure. Immune staff members do not require any reassignment or follow-up.

What are the complications of chickenpox?

The commonest complication of chickenpox is a secondary bacterial infection of the skin lesions. Pruritus and scratching associated with chickenpox and practice of not bathing the infected child with rash contribute to the occurrence of this complication. These infections are usually caused by the invasion of varicella lesions by staphylococcus aureus or streptococcus pyogenes.

Of the complications unrelated to the varicella rash, the most common complication of varicella infection is acute cerebellar ataxia. This condition is characterized by nystagmus, headache, nausea, vertigo, vomiting, altered speech, and neck stiffness. It develops any time between 10 days before and 21 days after the onset of rash. Most sufferers recover completely. An association has been described between the use of aspirin in febrile children with varicella and Reye's syndrome. Other CNS complications of varicella in immunocompetent children include varicella encephalitis, aseptic meningitis, Guillain-Barre syndrome, Ramsay Hunt syndrome, and Bell's palsy.