Q Could you tell me the side effects of the new chickenpox vaccine, which doctors are now recommending for babies? - EH, Santa Fe, NM.
A A year ago, the US Food and Drug Administration approved the license of Varivax, by Merck, Sharp & Dohme, and in November 1995, the American Academy of Pediatrics announced that it should be given to all American children between the ages of one and 18 who haven't had chickenpox. The FDA recommends a single injection for children between 12 months and 12 years and two shots, four to eight weeks apart, for teenagers and adults.
Although Merck has been reported to be considering a licence in Britain, so far the drug company hasn't applied. One possible reason is that it is currently only made in frozen form, and freezers aren't generally available in the surgeries of British GPs. At the moment, Japan and Korea have also licensed similar products using the same strain (Oka) of the live, attenuated (weakened) virus, and several other countries have licensed it for children at risk (those with lowered immunity).
The arguments behind the approval of the chickenpox vaccine carry an air of desperation - a vaccine searching for a rationale. There's no doubt that chickenpox in a healthy child is only a minor nuisance. Four million cases occur in the US, according to the US Centers for Disease Control and Prevention usually among children under 15. Most reported cases of chickenpox in children under 10 are mild, and death is rare. However, the CDC points out that some 9000 people with chickenpox are hospitalized, and 50 to 100 of those catching the disease - mostly young children with lowered immunity - die.
The main population at risk of complications are children with leukemia who are having chemotherapy, which depresses the immune system, as are children and adults taking drugs like steroids for asthma or other illnesses with a similar kind of effect on the immune system.
Besides the immune-compromised, babies and adults can suffer from more severe side effects, such as pneumona, bacterial superinfection, encephalitis, arthritis, hepatitis and glomerulonephritis (an inflammation of the kidneys). If pregnant women contract the virus in the first two trimesters of pregnancy, it can cause birth defects of the skin, limbs, eyes and nervous system; in the last trimester of pregnancy, the baby can contract chickenpox, which has up to a 30 per cent mortality in this age group (BMJ, January 7, 1995).
Since most children get chickenpox at some point and most don't suffer from it if they get it while they're small, there's no appreciable benefit to them, but only for those who have lowered immunity. However, if this is the case, parents at large are being asked to subject their healthy children to the vaccine's side effects solely for the benefit of a small population at risk. In fact, since we can't guarantee how long the vaccine will last, we're asking parents to put their children at risk of contracting more serious disease as adults.
The largest reason for launching the jab appears to be economics. Because the medical costs of chickenpox cases are low, it is more expensive to immunize, which costs $39 per dose, than it is to treat chickenpox. In fact, the entire vaccine programme would cost $162 million a year in the US. But to make the cost-benefit equation add up, the authorities have thrown in as a cost the amount of parental income or work time lost because a child had to stay home with chickenpox. Several researchers have attempted to quantify this loss as equalling $293 per family, or $183 per chickenpox cases (Pediatr Infect Dis J, 1994; 13: 173-7). The days lost are often more than the child actually needs because many schools have policies forcing children to stay at home well past the communicable stage.
Therefore, the net theoretical benefit of this vaccination is to save some $6.6 million of lost income in the US alone (J Pediatr, June 1994). Other journals have somehow blown this into a $400 million savings (The Lancet, April 16,1994). Of course, this highly theoretical figure doesn't take into account the many thousands of parents who will be able to claim paid leave. It also doesn't take into account the high cost of vaccinating adolescents ($329 per chickenpox case prevented), which actually doesn't make economic sense (Pediatrics, May 1995). Many questions remain about the effect of vaccinating a population against a disease that doesn't really do much harm. The CDC has admitted that 'considerable uncertainty' exists about a wholesale vaccination of preschoolers (JAMA, June 22-29, 1994.) The first and most obvious question is why we aren't simply vaccinating children at risk (or, better yet, looking for alternate ways of treating diseases like leukemia that don't involve suppressing the immune system). But ironically, the Merck vaccine is not supposed to be used in the very population it is meant to protect - those on immunosuppressive drugs. Merck warns that vaccination with the live chickenpox virus can result in a 'more extensive vaccine-associated rash or disseminated disease in individuals on immunosuppressant doses of corticosteroids.'
Even for children with leukemia who are on an experimental protocol, the vaccine hasn't proved effective enough; 5 to 10 per cent have developed a mild infection during vaccination and about 10 per cent had breakthrough chickenpox within three years (Public Citizen's Health Letter, August 1995). In one study, 40-50 per cent of children with leukemia developed a vaccine-associated rash, although the study said 90 per cent were protected (Rev Infect Dis (Nov-Dec 1991). In another study, this protection lasted eight to 10 years (J Infect Dis, August 1992).
The big question in everyone's mind is how long the vaccine lasts, and Merck doesn't have any more answers than anyone else. In its handout on the drug, Merck admits 'the duration of protection from varicella infection after vaccination with VARIVAX is unknown.' Although those in favour of the vaccine argue that children show evidence of antibodies for at least six years (J Infect Dis, January 1994), and that booster shots can always be given, the vaccine doesn't work as well among adults, conferring only 70 per cent protection (Rev Infect Dis, 1991;13 Suppl 11: 5957-9).
However, all that any scientific study can do is to measure antibody levels, which may not be a true picture of whether someone is adequately protected. In one study of 14 healthy children who'd contracted chickenpox naturally, three lost any evidence of antibodies or immunity (Pediatr Infect Dis J, 1991; 10: 569-75). In another study of 21 pregnant women, four developed the disease even though they'd had prior evidence of antibodies from naturally occurring chickenpox. The study concluded that thee criteria for determining immunity from the chickenpox zoster virus 'remain ill-defined' (J Infect Dis,1994;170: 991-5).
We also have no idea at what point children require boosters so that a repeat of the US situation with measles doesn't occur. In the late 1980s and early 1990s, epidemics of measles occurred among college-age teenagers and young adults, most of whom had been vaccinated against measles as children because the vaccine wore off. Furthermore, it's thought that even immunized patients require reexposure to natural chickenpox or reimmunization in order to boost long-term immunity. Although it is planned that this vaccine will be given with the measles-mumps-rubella triple jab, it has been shown not to work as well when given at the same time as the Hib vaccine.
The problem with waning immunity, of course, is that giving this vaccine may create a population of adults at greater risk of serious illness than they would have been if they'd got chickenpox as children. It could turn what is largely a benign childhood disease into a source of major illness and hospitalization. Indeed, in one study of the vaccine, the number of cases of chickenpox in adults did increase (cited in JAMA, June 22/29,1994).
Another concern is the effect of injecting into one-year-old babies and children a live virus which has a tendency to lie latent in the nervous system and reactivate many years later. A majority of patients who have had chickenpox as children may go on to develop herpes zoster, commonly known as shingles, later in life. This condition causes painful and highly sensitive blisters on the skin along the nerves infected by the virus, often on only one side of the body. The severe pain may last from two to five weeks and in older patients, this jabbing pain can go on for several months.
There is some evidence that the live chickenpox vaccine can incubate in the body, causing shingles in later life. At least three cases of shingles have been reported in healthy children given the vaccine (J Infect Dis, May 1989), and one in a healthy adult (J Infect Dis, September 1989). It's also developed in children with leukemia (The Lancet, May 28, 1994). This, of course, means that the vaccine cannot accomplish its stated aim - to wipe out the zoster virus altogether. In one small study, 11 children developing a rash after vaccination were found to have the shingles virus (Pediatrics, May 1991).
We also don't know whether the live vaccine virus is itself contagious. According to Merck's information sheet: 'Individuals vaccinated with VARIVAX may potentially be capable of transmitting the vaccine virus to close contacts.' Perhaps the greatest worry is the likelihood that future babies will be more susceptible to chickenpox once this generation of vaccinated girls is unable to pass on maternal immunity. With measles in 1990, the largest increases in the incidence rates of the disease occurred among babies under one (137 per cent) and adults over 25 (130 per cent) (JAMA, June 26,1991).
Although many studies demonstrate a very high take-up rate among children - 70-90 per cent or more demonstrate antibodies to the disease - there is also a high incidence of what has been termed 'breakthrough cases' - that is, vaccinated children who have gone on to develop chickenpox. In one study, one-fifth of vaccinated children went on to develop chickenpox, although it was a more mild form of the illness. In another study, conducted by Merck itself, 12 per cent of 3303 children caught chickenpox when exposed to it at home (Pediatrics, May 1991). As for adults, 27 per cent of a Merck-studied group which received two doses of VARIVAX developed chickenpox when exposed to it in the household over two years.
Much has been made of the minor side effects of this jab. Merck says that about a fifth have swelling, rash or the like at the injection site, 15 per cent have a fever of 30 degrees C or higher, and about 7 per cent have a chickenpox rash at the injection site or locally. Otherwise, 21 per cent of patients reported an adverse reaction, including (in decreasing order of frequency): upper respiratory illness, cough, irritability/ nervousness, fatigue, disturbed sleep, diarrhea, lost of appetite, vomiting, ear infection, diaper rash or contact rash, headache, teething, malaise, abdominal pain, nausea, eye complaints, chills, enlargement of the lymph nodes, myalgia, lower respiratory illness, allergic reactions (including allergic rash and hives), stiff neck, heat rash, prickly heat, arthralgia, eczema, dry skin or dermatitis, conspitation and itching. Adults have reported similar side effects, albeit with far less frequency.
However, what doctors don't tell you is that around 1 in every 100 of children vaccinated with VARIVAX have gone on to develop pneumonia, and some one in 1000 children have febrile seizures. In one study of 3303 children, one 16-month-old baby was hospitalized with rash, fever, swelling of the right knee 16 days after the vaccine (Pediatrics, May 1991), and one adult developed a severe kidney inflammation after the jab (Clin Infect Dis,1993;17:1079).
Furthermore, these reactions, including fever and rash, can happen at any point for six weeks after vaccination and last for six days or more - which would tend to rebuke the notion that parents are going to save time off work by vaccination (Pediatrics, Sept 1991).
It may make sense for children and adults at risk to consider the vaccine, although acyclovir and varicella immunoglobulin have demonstrated some effectiveness in preventing the illness in at-risk children exposed to the virus. Otherwise, healthy children, who are already 'pin cushons' for nine diseases, may be trading a mild childhood illness for a load of adult problems without much appreciable gain.