Charles Grose, M.D.
Professor and Director of Infectious Disease,
Department of Pediatrics, Iowa Children's Hospital
First Published by the UI Center for Disabilities and Development: 1999
Last
Revised: January 2003
Peer Review Status: Internally Peer Reviewed
Smallpox and Vaccination in the 21st Century
People in the Middle Ages identified three pox illnesses:
Smallpox, a life-threatening illness with a fatality rate of 10-20%, continued through the early 20th century. Then a massive, worldwide effort was undertaken, and in the 1960-70s, this disease was eradicated. But the vaccination of healthy children was not without risk. Every year from seven to nine small children in the United States died from complications directly related to vaccination. Children with immunosuppressive disease who were vaccinated in error would almost invariably die. For these reasons, routine childhood vaccinia (the milder vaccine form of variola) vaccination was discontinued in the 1970s.
The eradication campaign was successful because there was a potent vaccine. Today, it is a lyophilized (rapidly frozen and then dehydrated under high vacuum conditions) preparation of live vaccinia virus. After eradication of smallpox, vaccine production ended except for a limited use with military personnel. In the year 2002, all people in the United States who have never received vaccinia vaccine are susceptible to smallpox. Older individuals who were vaccinated during childhood (before 1970) may have some residual immune protection.
With the advent of bioterrorism, such as that using anthrax, concerns have increased about the intentional release of smallpox virus in the general population. As a direct result, the federal government has expressed a renewed interest in smallpox vaccination. Pharmaceutical companies are producing more of the traditional vaccine. In addition, they are also developing new smallpox vaccine products.
The traditional vaccine is produced using calf lymph. One of the new vaccine products is being prepared in human cell cultures, in a manner similar to that used in the preparation of rubella vaccine. Because it is produced in human cell cultures, it will probably cause fewer reactions, and thus fewer deaths. Phase 1 vaccine trials are being designed to evaluate the safety and effectiveness of these newer candidate vaccines.
If these clinical trials are successful, the pediatric community will be asked again to consider universal vaccination for smallpox. One strategy may include immunization only of 4-6 year old children, to avoid vaccination of younger children with as yet undiagnosed immunosuppressive conditions. In addition to vaccination, antiviral medications are also being developed to treat vaccinia virus infection.
Varicella vaccine was approved for use in the USA on St. Patrick's Day, 1995. No vaccine has ever had a longer series of clinical trials, beginning in Japan in the late 1970s. In March 1998 in Atlanta, a consensus meeting brought together the experts to discuss varicella-zoster (VZV) virus and the varicella vaccine.
At that meeting, a review of three years of US data shows that the immunization rates for varicella virus in children 1-2 years old is about 25%. In the upper Midwest, Minnesota has one of the highest rates, at about 30%.
The good news is that no previously unrecognized sequelae of vaccination have appeared. The vaccine is effective in preventing chickenpox. Epidemiologists from Texas emphasized the value of varicella vaccination to prevent severe streptococcal skin infection, which has recently re-emerged as one of the most feared complications of childhood chickenpox.
Further information provided at the meeting demonstrated that immunization within 2-3 days of exposure can prevent chickenpox in a healthy child. This strategy could be used to curb chickenpox outbreaks within a classroom or a family.
Based on several studies, about 20% of children will develop a mild rash 2-3 weeks following vaccination. The rash will be minimal, usually about 20 vesicles. Casual contact with these children has not been shown to be contagious, even in daycare settings.
A handful of cases have occurred in which the virus is transmitted to family members by a recently vaccinated child. Transmission of the virus following vaccination correlates with the severity of the rash that appears post-immunization. Contact must be very close, and persist over several days. The infection that results is very mild. It is important to note that a vaccination-induced rash never occurs during the first week following immunization. If a child develops a rash during that first week, he or she has contracted wild-type chickenpox coincident with the vaccination.
The final issue that was discussed concerned "catch up" vaccination for older children and adolescents who never contracted chickenpox during childhood. Very few of these children are being vaccinated. This may be because most insurance plans do not reimburse for varicella immunization in older children (however, the Vaccine for Children [VFC] program provides varicella vaccine for eligible children born on or after January 1, 1983 and children younger than 19 who are family members of immunocompromised persons). Children older than 12 years require two doses of varicella vaccine, at a cost of more than $100. As a result, there are many older children in the US who are susceptible to chickenpox, which often produces more severe illness in them than in young children.
Acyclovir for Children at Risk
I recommend that all adolescents who contract chickenpox be treated with oral acyclovir upon diagnosis. The dosage for anyone weighing 100 pounds or more is 4 grams daily, given over four intervals, in doses of 800mg, 800mg, 800mg, 1600mg. In most cases, five days of acyclovir treatment is sufficient.
Because acyclovir is now available as a generic drug, the cost should be less than $2 per tablet. The only contraindication to acyclovir treatment is impaired renal function. In most cases, five days of acyclovir treatment is sufficient. No acyclovir-resistant strains of varicella have appeared following the treatment of healthy children.
One other age group is at high risk from varicella infection: Infants during the first year of life, who have a mortality rate 3 times that of older children. For this reason, I recommend oral acyclovir treatment for all infants from 4-12 months of age who contract chickenpox. The dosage is 20mg/kg every 6 hours (80mg/kg/day), for 5 days.
The Redbook recommends that all one-month-olds with chickenpox be considered candidates for intravenous acyclovir, a treatment recommendation which I support. Infants 2-3 months of age may require a combination of intravenous and oral acyclovir treatment.
On the other hand, there is no reason to delay vaccination of older children who have a sibling younger than a year old in the household. Just ask the parents to discourage the newly immunized sibling from holding or caring for the infant for 3 weeks.
A closing thought: This month I read of yet another case in which an adult died from wild-type chickenpox contracted from his 4-year-old son. Let's make a special effort to immunize the children in our care, and their parents as well when necessary.
See related Provider Textbooks about Pediatrics or Preventive Medicine.
See related Provider Topics Chickenpox, Child and Teen Health, Food, Nutrition and Metabolism, Immune System/AIDS, Immunization/Vaccination, Infections, Pediatrics, Poisoning, Toxicology, Environmental Health, Preventive Medicine or Smallpox.
See related Patient Textbooks about or Pediatrics.
See related Patient Topics Chickenpox, Child and Teen Health, Food, Nutrition and Metabolism, Immune System/AIDS, Immunization/Vaccination, Infections, Pediatrics or Poisoning, Toxicology, Environmental Health.
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