M R Lokeshwar
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 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. Administration of aspirin to children with varicella is postulated to cause Reye's syndrome.

Use of systemic antiviral therapy is usual 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 lesion 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 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 anti-viral therapy is indicated for 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 Vidarabine has proven efficacy in treating varicella infections but it has been replaced by acyclovir .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.

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

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

Is it true that the varicella vaccine in extremely sensitive to temperature changes?
Varicella vaccine that was initially introduced was highly sensitive to temperature changes. It required to be stored at -20 degree 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 studies 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 polio vaccine and vaccine against measles, mumps, rubella, hepatitis-A, hepatitis-B, and H.influenzae type B. Such an administration does not interfere with 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 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, varicella vaccine should not be administered. Presence of acute febrile illness in healthy subjects , the presence of a minor infection is not a contra-indication 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 varicella vaccine, one must ensure that the woman is not pregnant. The lady should be advised to avoid pregnancy for next 3 months after vaccination.

What are the side effects of varicella vaccine?
Varicella vaccine has a low reactogenicity and most of the children and adults tolerate the vaccine well. Detailed follow-up studies done for 6 weeks after vaccination have revealed very few side-effects and these are transient and of low severity. These have included pain at the site of injection, fever and papulo-vesicular 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 papulo-vesicular 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 rash. There is no evidence to suggest reversion to virulence of the vaccine strain during transmission. Persons acquiring vaccine virus may have mild rash or subclinical infection resulting in seroconversion. Due to the possibility of transmission of vaccine virus, vaccinees with rash should avoid contact with susceptible pregnant women and immuno-compromised person.

How can one determine if a child is protected against varicella after vaccination?
Antibody titre against varicella can be determined 6 weeks after immunization. A titre in excess of or equal to 4 is considered protective. However, routine demonstration of the titre 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 history of having suffered from varicella previously, may be considered as non-immune and vaccinated. In case of adults, however, recommendation 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, American Academy of pediatrics (AAP) and Advisory committee on Immunization practices (ACIP) have provided certain recommendation 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 circulation of wild virus will decrease in view of 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 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 occurrence of Reye's syndrome in children and aspirin administration to children who have varicella infection. So far, there is no evidence that administration of 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, administration of a live, attenuated vaccine like varicella vaccine is contra-indicated in children with acute leukemia. Leukemia children should receive vaccine if they have no history of disease or are found to be seronegative. This can be undertaken only when they are in complete 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 case of varicella vaccine. A combination vaccine combining this vaccine with 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 varicella vaccine can boost cellular immunity of older individuals so that herpes zoster can be prevented. Further studies are required to judge the need for booster immunization.

VZIG or varicella zoster immunoglobulin is prepared by selection of serum containing high titres 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 gestational age of less 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 sub clinical 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. 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.

VZV is highly contagious and VZV infection may be life-threatening in certain patient populations. Nosocomial transmission of VZV infection occurs due to air-borne 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 relaxed 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 negative or uncertain history of previous VZV infection, determine exposure history. No further follow-up is require if there were no exposure. Those with negative or uncertain history of previous VZV infection but with 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 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 require in immune individuals.
* The exposed staff member who has no history of pervious VZV infection should undergo serological testing. Susceptible among them should be re-assigned to low-risk area for at least 21 days after exposure. Immune staff member do not require any reassignment or follow-up.

Chickenpox Chickenpox 2/4/2002
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