Chickenpox

Just recently, chickenpox was a harmless childhood disease, but it becomes more dangerous each year, and soon will come the time when it will become more dangerous than measles, which is already more dangerous than Ebola.

Chickenpox (varicella) is caused by the varicella-zoster virus. The same virus that causes shingles.
Chickenpox in adults is more severe and the risk of complications is higher. Children suffering from lymphoma, leukemia and HIV also face a higher risk of complications.
Prior to introduction of vaccination, death rate for varicella among children of 1-14 years of age was 1:100,000, and 2.7 in every 100,000 for 15-19 year-olds. Varicella mortality rate among adults was 25.2 in every 100,000. Adults accounted for 5% of the chickenpox cases, but 35% of deaths.
Varicella is highly contagious; less than measles, but more than mumps and rubella.
Chickenpox during pregnancy can cause birth defects. The risk of congenital varicella syndrome due to mother’s infection is less than 2%. [1]
Chickenpox during labor is very dangerous for the infant and its mortality rate is 30%.
Varicella vaccine was developed in the 70s and licensed in USA in 1995. The virus for the vaccine was attenuated by consecutive passages through embryonic lung cells, embryonic guinea pig fibroblasts and human diploid cells (WI-38). The Merck vaccine virus was also consecutively passed 31 times through MRC-5 diploid cells. The vaccine also contains fetal bovine serum. The vaccine produces less antibodies than disease exposure.
In the early 2000s, varicella outbreaks were registered in schools where almost all children have been vaccinated. Therefore, a second dose of the vaccine was added in 2006.
Combination measles-mumps-rubella-varicella vaccine was licensed on the basis on immunogenicity (antibodies level), and not clinical efficacy.
Varicella vaccine was 2.5 times less effective for those who received it within 30 days of getting MMR vaccine.
Reye syndrome is a rare, but very dangerous disease that occurs as a result of treating varicella (and other viral diseases) with aspirin. Therefore, it is not recommended to take aspirin for 6 weeks after vaccination.

For many years, medicine did not pay much attention to varicella, which was perceived as a kind of childhood rite of passage, but we cannot continue to treat it so carelessly. Varicella can be a serious, and even deadly disease. Fortunately, we have vaccines and antiviral drugs.
Varicella resembles poliomyelitis, in a sense that a serious disease is partially a consequence of the progress in developed countries. The nature of the disease changed radically after Sydney Farber invented chemotherapy. The joy of the success was tainted when a boy, who survived chemotherapy, was killed by varicella, which can be deadly under conditions of immunodeficiency. When drugs that weaken immunity became widely used, varicella could no longer be considered a harmless rite of childhood. It became a disease that was feared and avoided. The first steps towards solving this iatrogenic problem were taken by Thomas Weller, who isolated the virus. This feat was a prerequisite for developing a vaccine.
As chemotherapy, steroids and antimetabolites, which are used to treat autoimmune diseases or to suppress immunity for organ transplantation, became more common, and the life expectancy increased, not only varicella, but also the shingles, turned into a significant clinical problem. Thus came the necessity to control the varicella virus, which was becoming more and more dangerous.

Vaccine strain of the virus is produced by sequential passages through animal cell cultures, which attenuates the virus. But how can one be sure that this procedure truly attenuates the virus?
The hypothesis that chickenpox and shingles are caused by the same virus was proposed in 1909. To test it, researchers extracted fluid from the blisters of shingles patients, and injected it to children who have not been exposed to varicella, in 1925 and 1932. 50% of the children got infected with chickenpox, but the rash was less severe than usual. That is, if an airborne virus is administered by injection, it causes an atypical disease. Therefore, it is impossible to conclude that the vaccine strain of the virus is attenuated, only on the basis of it having caused mild symptoms. It is also possible, that the injected dose of the virus was not enough to cause the usual symptoms.
In this study, the authors vaccinated children with leukemia and examined how often they infected their healthy siblings. It turned out that only 17% of the siblings got infected. Since the wild strain of the virus infects 80%-90%, the authors concluded that the vaccine strain indeed is attenuated.

Vaccine’s effectiveness in the first year after vaccination is 97%, which later decreases to 84%. Vaccination at the age under 15 months is less effective. [1].

Vaccination at the age under 14 months is 3 times less effective than vaccination at the age over 14 months.
Nonetheless, most countries vaccinate at 12 months old.

Vaccine effectiveness in South Korea was 54%, and despite the 97% vaccination coverage, it had almost no effect on varicella incidence, unlike in other countries. Most varicella cases are reported among the vaccinated. Vaccine had no effect on the course of the disease.

Varicella outbreak in daycare, where 66% of children had been vaccinated.
Vaccine efficacy was 44%. After three years the effectiveness decreased by 2.6 times. Vaccinated children had less rash than those unvaccinated.
The outbreak began with a vaccinated boy, who infected half of his class, who had no previous varicella exposure. The boy himself got infected by his 11 years old sister, who was suffering from shingles.
Vaccine efficacy was much lower than was determined during clinical trials. That is, most probably, due to the fact that in clinical trials, children who did not develop antibodies got repeat vaccination or were excluded from the efficacy analysis, or were analyzed separately, which is what led to an overestimated effectiveness rate.
Here is a meta-analysis of 14 studies of chickenpox outbreaks. The effectiveness of one dose was 72.5%.

Varicella outbreak in a school, where 97% of children had been vaccinated (with one dose). Vaccine effectiveness was 72% (CI:3-87). Children vaccinated over 5 years prior to the outbreak got infected 6.7 times more often than those vaccinated less than 5 years ago. More: [1], [2], [3].

Varicella outbreak in a school, where 97% of children had been vaccinated (39% of them with two doses). The effectiveness of one dose and two doses was almost the same.

Varicella outbreak in a school, where 98.6% of children had been vaccinated (63% of them with two doses).
Of the unvaccinated children, 14% got infected, of those vaccinated with one dose – 1.6%, and of those vaccinated with two doses – 2%.
The authors conclude that higher two-dose vaccination coverage is needed to prevent outbreaks.

After the MMRV vaccine, much less varicella antibodies are produced than after a separate vaccine, but more measles antibodies, as compared to MMR. [1].

62% of 10-year-old unvaccinated children, who have not been exposed to chickenpox (or did not know about it), had antibodies.

After the infection, varicella virus remains in the neurons of the spinal ganglia in an inactive form, and a few decades later, due to the weakening of cellular immunity, it can re-activate and cause herpes zoster.
Hope Simpson in 1965 was the first one to suggest that being in contact with chickenpox patients reduces the risk of shingles. This phenomenon is called exogenous boosting. Incidentally, this is the same Hope-Simpson that first suggested that the epidemiology of influenza depends more on the sun, than on the virus.
One of the dangers of vaccination, which is usually disregarded, is that if being in contact with varicella patients actually reduces the risk of re-activation of the virus, then the mass vaccination will cause an increase in the incidence of shingles.
A study conducted in England in 1991 revealed that the incidence of herpes zoster is 25% lower among adults living with children. This figure is most likely underestimated, since many participants of the study that did not live with children at the moment, did so until recently. Exposure to varicella is estimated to provide protection from the shingles for an average of 20 years.
Based on this data, the authors built a mathematical model, and concluded that mass vaccination will cause a shingles epidemic, which will last 30-50 years. 50% of people aged 10 to 44 years will get shingles, and only 46 years later the incidence of shingles will decrease to the level of pre-vaccine era.

Contact with varicella patients is associated with a decrease in risk of herpes zoster by 71%. This figure is probably underestimated, since varicella is contagious before the onset of the rash.
Contact with shingles patients does not decrease the risk of shingles, because shingles is less contagious than chickenpox.
Pediatricians suffer from herpes zoster much less frequently than dermatologists and psychiatrists.

15. Pediatricians and family doctors suffer from shingles 50%-87% less often than general population.

Herpes zoster ophthalmicus (HZO) accounts for 15% of all herpes zoster cases.
The number of HZO cases in Boston increased by 2.7 times between 2007 and 2013. The average age of patients decreased from 61.2 to 55.8 years, while the number of patients at the clinic during the same years has not changed.
The same was found in another study in Oklahoma, where the average age of HZO patients decreased by 8 years, from 65.5 to 58.9 years. Smokers got sick 11.5 years earlier than non-smokers.

The incidence of varicella in Massachusetts decreased by 79% between 1998 and 2003, but the incidence of herpes zoster increased by 90%, and 161% in the 25-44 years age group.
The incidence of herpes zoster in Minnesota increased by 28% between 1996 and 2001.
The incidence of herpes zoster among children under 10 years of age in California decreased by 55%, but increased by 63% among teenagers of 10-19 years of age.

The incidence of varicella decreased from 7.14 to 0.76 per 1,000 in Taiwan from 2001 to 2009, and the incidence of herpes zoster increased from 4.04 to 6.24 per 1,000.
The incidence of chickenpox is higher during the winter months, while the incidence of shingles, on the contrary, is higher during the summer months.

After the introduction of vaccination, the incidence of herpes zoster increased by 2%-6% annually in Australia among adults over 20 years of age.

The incidence of herpes zoster in Australia doubled among those under 50 years of age, and tripled among those over the age of 50 years.

The incidence of varicella fell 4-fold, and hospital costs associated with it decreased by $100 million per annum. However, hospital costs associated with herpes zoster increased by $700 million per annum by 2004.

For years CDC refused to admit that the incidence of herpes zoster increased after the introduction of vaccination, and threatened to sue the researcher, who wanted to publish this data.

69% of the 32 shingles patients were infected with the vaccine strain of the virus. [1].

UK does vaccinate against varicella for the following reasons:
1) Chickenpox is more dangerous in adulthood than in childhood. Mortality, as well as the risk of pneumonia and encephalitis due to varicella increases with age.
2) Vaccination will lead to an increase in neonatal and congenital varicella (since mothers would not get exposure in childhood).
3) Vaccination can lead to an increase in the incidence of shingles. It is known that an increase in chickenpox incidence among children under 5 years is associated with a decrease of shingles incidence among 15-44 years age group.
Therefore, UK is being cautious, and waits to see what happens in the countries that do vaccinate.
Most other European countries also do not vaccinate against varicella.

Herpes zoster is much more painful than varicella. The number of lost years of quality life are 10 times higher for shingles patients that for chickenpox patients. Thus, an increase in shingles incidence will bring serious consequences to public health, and will eliminate the benefits of reduced varicella incidence.

Due to an increase in the herpes zoster incidence, a vaccine against it was licensed in 2006. It contains the same virus as varicella vaccine, but it has 14 times more virus particles. The effectiveness is 70% for 50-year-olds, 64% for 60-year-olds, and 18% for 80-year-olds for 3 years. How long the protective effect lasts is unknown.

Shingles vaccine is ineffective for people over 80 years of age, and more than doubles the risk of serious side effects.
The risk of serious side effects among people over 60 years of age is increased by 36%.
Among those vaccinated against shingles, the risk of arthritis was increased by 2.2 times, and the risk of alopecia was increased by 2.7 times.
The vaccine also increases the risk of heart failure and giant cell arteritis.

Since due to the effect of exogenous boosting, a decrease in the varicella incidence causes an increase in the herpes zoster incidence, mass vaccinations raises an ethical question. Advancing the health of one population group damages the health of another group.
Although mass varicella vaccination program was launched in a few countries, while other countries wait for the final research results of the exogenous boosting effect, there has not been an attempt for an ethical analysis of vaccination.
The issue of vaccination cannot be solved by simple ethical rules, such as “respect for autonomy” (vaccinate) or “do no harm to others” (do not vaccinate). It requires a balance between competing interests of different groups, and thus, requires a more complex ethical approach.
The authors address this ethical issue through two fundamental ethical approaches: classic utilitarianism and contractualism.
The utilitarianism approach is based on two premises: (1) effect of the choice on the wellbeing (happiness and health) is the only aspect that really matters, and (2) the wellbeing of everyone is equally important. That is, increase in the average level of wellbeing is what’s important when choosing alternatives.
Therefore, in case of the chickenpox, the question is whether vaccination will cause an overall decrease in varicella incidence. Despite the fact that empirical data from USA indicates an 88% decrease in chickenpox hospitalization rates and 74% decrease in chickenpox mortality rates, this data does not take into account the effect on the elderly. If it is taken into account, vaccination becomes less attractive, since it is estimated that the increase in the shingles incidence will exceed the decrease in the chickenpox incidence.
Therefore, according to classic utilitarianism, mass vaccination is undesirable.

From the contractualism point of view, an ethical decision is not determined by the consequences, but rather by the justification in terms of principles and rules arising from the hypothetical ‘social contract.’ This contract is concluded between all people, and it defines the fundamental rules that should govern society.
That is, unlike the utilitarianism approach, what’s important is not the quantitative benefit of the vaccination, but whether its introduction can be justified by the generally accepted principles. These principles should also be acceptable to those who stand to be disadvantaged by them – adults and elderly.
The following considerations are examined:
1) Freedom to protect one’s health (through vaccination).
2) Responsibility. Elderly can vaccinate against shingles. This vaccine is considered to be safe.
3) Unacceptable sacrifice. Some elderly would not be able to get protection against shingles (since the vaccine is not effective enough or contraindicated). These people would be sacrificed for the benefit of a large group of children. However, since the herpes zoster is rarely lethal, this sacrifice is acceptable.
4) Uncertainly. Although exogenous boosting exists, its effect on the incidence of herpes zoster is less known than the effect of vaccination on varicella incidence. Therefore, it is possible to demand giving more importance to something already determined, that something that is not fully known yet.
Thus, from the contractualism point of view, mass vaccination is fully justified, since it is not clear why children should protect the elderly. Contractualism emphasizes impartial a priori rules, and not the a posteriori consequences, and therefore, depends less on the quantitative evaluations of these consequences.
The authors conclude that the decision to introduce vaccination should be based not only on quantitative data and research, but also on the ethical premises.

Several studies were cited in the measles section. According to them, varicella in childhood is associated with a 33% decrease in the risk of heart attack, 47%-50% decrease in the risk of lymphoma, 34% decrease in the risk of ovarian cancer, and 34% decrease in the risk of other types of cancer. Chickenpox also decreases the risk of Parkinson’s disease. Here are some more studies.

Varicella at the age under 8 years is associated with the decrease in the risk of asthma by 88%, allergic rhinoconjunctivitis by 84%, atopic dermatitis by 43%, allergic sensitization by 89%.
In those who have been sick with varicella, the level of IgE (antibodies responsible for allergic reactions) remains low for more than 10 years after the disease.
9% of children in USA suffer from asthma, and 17% suffer from atopic dermatitis.

Varicella in childhood is associated with a 45% decrease in the risk of atopic dermatitis, and 96% for severe atopic dermatitis.
Children, who suffered from atopic dermatitis despite having had varicella in childhood, see a doctor for dermatitis 83% less.
Varicella vaccine, despite it being a live one, does not provide protection from asthma or allergies.
The authors conclude that varicella vaccine might have contributed to a sharp increase in the incidence of atopic dermatitis.
Studies proving economic benefits of varicella vaccination did not take into account an increase in the incidence of atopic dermatitis. Since the protective effect of chickenpox against atopic dermatitis lasts about 8-10 years, it might be worthwhile waiting to vaccinate until that age, which would increase the economic benefit of vaccination, providing herd immunity at the same time.

Having a herpes type infection (including varicella) in the first 3 years of life is associated with a 50% decrease in the risk of asthma.
Having 5-7 viral infections in the first 3 years of life is associated with a 68% decrease in the risk of asthma, and 84% decrease in case of 8 and more viral infections.
Having rhinitis two or more times during the first year of life decreases the risk of asthma by 48%, and the risk of wheeze by 40%. Having rhinitis also decreases the risk of allergies.

Varicella in childhood is associated with a decrease in the risk of cancer by 34%. Having three common colds per year decreases the risk of cancer by 77%-82%. Viral gastroenteritis – by 57%. High frequency of infections decreases the risk of cancer by 53%. Measles, mumps and rubella also decrease the risk of cancer by 17%-39%, but the result was not statistically significant.

Varicella is associated with a 47% decrease in the risk of glioma (brain tumor) among people under the age of 40 years, and a 21% for people of all ages.

Varicella is associated with a 60% decrease in the risk of glioma, and herpes zoster with a 50% decrease..

Presence of varicella antibodies is associated with 59% decrease in the risk of glioma. More: [1], [2], [3] , [4], [5].

Varicella virus kills cancer cells in vitro, and could probably be used as an oncolytic virus. [1].

- Since the overwhelming majority of varicella cases in childhood are very mild, varicella vaccination was introduced not to reduce the insignificant mortality or hospitalization rates, but rather to prevent parents from missing work on the days when the child cannot attend school or daycare due to the disease.
- Economic feasibility of vaccination was based on the following assumptions:
1) The price of the vaccine is $35, and another $35 to administer it.
However, after licensing, the price doubled.
2) Single dose of the vaccine gives a lifelong immunity.
It later turned out that it is not the case, and a second dose was recommended.
3) Vaccine efficacy is 85%-95%, while side effects are insignificant.
High vaccine efficiency was ensued by exogenous boosting (i.e. contact with patients). When, due to vaccination, contact with patients became rare, the effectiveness of the vaccine decreased to 80% and lower.
4) Mass vaccination does not affect the shingles incidence.
It turned out, that the shingles incidence increased.
5) Annual cost of vaccination program was estimated at $162 million, while savings on varicella medical expenses were $80 million. That is, the cost of vaccination program was twice the amount of estimated savings. However, taking into account the need for parents to miss work (which cost $392 million per annum), one-dose vaccination was economically justifiable.
A 2005 study found that two-dose vaccination program might not be economically feasible.
- Only 25% of medical expenses associated with varicella virus are due to varicella itself, and 75% are due to shingles.
- Clinical studies of the vaccine effectiveness are overestimated, because children who got the infection, but whose PCR analysis did not prove the presence of the virus, and whose sample did not meet the requirements, were excluded from the study.
- The UK Department of Health concluded that two-dose vaccination might be economically justified, but only 80-100 years after the introduction of vaccination.

39. When a child gets chickenpox, their parents usually miss half a workday on average.

Most parents do not think that vaccination is justified, if its only benefit is to prevent them from missing work, but they think it is justified if it prevents rare complications.
It is also reported that parents, whose children are under 18 months old, are more positive about vaccination than parents of older children. Therefore, the authors conclude, that infant vaccination should be promoted.

Paracetamol extends varicella for one day.

Taking NSAIDs (Nonsteroidal anti-inflammatory drug) in a month prior to chickenpox is associated with a five times higher risk of complications. Paracetamol is associated with a 50% increase in the risk of complications.
Other studies determined that:
1) Taking ibuprofen in a month prior to varicella is associated with a three times higher risk of skin superinfections.
2) Ibuprofen is associated with an 11.5 times increase in the risk of necrotizing fasciitis.
3) Ibuprofen is associated with a 3.9 times increase in the risk of group A streptococcal infections. [1]

I recently graduated from a medical school and in the 6 years of studying, despite repeated encounters with varicella, I have never heard that anti-inflammatory drugs complicate the course of chickenpox. So I did not take the Daily Mail article, warning against the use of ibuprofen during chickenpox, seriously.
However, I learned that the Ministry of Health and other medical associations really do recommend avoiding ibuprofen during varicella.
It is strange that no one warned me about it during the whole period of my studies. Of course, the information is available, if you go looking for it, but since ibuprofen is such a common medicine, it would be beneficial to have this information covered more widely.

Klenner reports that his daughter had been cured of varicella within 24 hour of an intravenous injection of 1g of vitamin C. 24 g taken orally, however, had no effect.

Vaccine strain of the virus remains in the body and re-activates periodically upon a decrease in immunity. This could have negative long-term consequences.
The virus re-activates with a probability of 19% in children with low titers, and 41% for children constantly low titers. Wild strain of the virus re-activates with the same probability in people with very weak immunity.
Since immunity against the virus provided by the vaccination is weaker than from the actual disease, long-term effect of frequent virus re-activation on singles and other consequences is unknown. For instance, it is unclear how re-activation of vaccine virus will affect those with weakened immunity against chickenpox, or those whose immunity will be suppressed in adulthood.

MMRV increases the risk of febrile seizures 7-10 days post vaccination by 2, as compared to separate vaccines (MMR and varicella).
MMRV increases the risk of febrile seizures by 7.6 times, MMR+V by 4 times, and MMR separately by 3.7 times. (USA)

MMRV increases the risk of febrile seizures by 6.5 times, and MMR+V by 3.3 times. (Canada)

The same was found in Germany, where a different vaccine was used (Priorix-Tetra). MMRV is associated with a four times increase in the risk of febrile seizures as compared to MMR, and 3.5 increase as compared to MMR+V.

12 months old boy was vaccinated, and as a result he got sick with the vaccine strain of varicella, and infected his pregnant mother, who had to have an abortion.
The opposite is reported, when a mother, who got vaccinated right after childbirth, infected the infant, even though she did not get sick herself.
(CDC recommends vaccinating women, who have not had chickenpox, right after childbirth, despite the fact that the virus is excreted in the breast milk.
A case of two brothers is reported here. After getting vaccinated, one of them got shingles from the vaccine, and then infected his vaccinated brother, who got varicella.
More cases of infection with the vaccine strain of the varicella virus from those who had been vaccinated: [1], [2], [3], [4], [5], [6], [7].

Analysis of the literature for chickenpox complication in those who got infected despite being vaccinated. The authors found a description of 52-60 such cases, only 6 of them lethal.

Some children develop shingles at the vaccination site several years after vaccination.

It is usually argued that vaccines are completely safe and that serious side effects occur in one in a million vaccinated individuals. How is such statistics obtained? Here is an example for chickenpox.
The authors (from FDA and CDC) analyze VAERS from 1995 to 1998. 14 deaths were recorded in this period. To calculate the probability of death after vaccination, they use the number of vaccines sold for this period (9.7 million), and conclude that the probability of death is 1 in one million (they round it up a little, as in fact it come up to 1 in 700,000).
It does not take into account that:
1) Only 1%-10% of all side effects get registered with VAERS.
2) The number of vaccine doses sold does not equal to the number of doses administered. Moreover, 9.7 millions doses sold is not an exact figure, but a CDC estimate.
A total of 6,574 adverse events have been registered with VAERS, 4% of which were serious. However, among children under 4 years of age there were 6.3% serious adverse events, among children under 3 years of age – 9.2%, and among children under one year of age, who got vaccinated by mistake – 14%.
A total of 271 serious adverse event have been registered, that is, 1 in every 36,000. These figures should be multiplied by 10-100 (that is, the real number is between 1:3600 and 1:360), and considering that the quantity of administered doses was lower than the quantity of sold doses, which is quite possibly overestimated, they should be multiplied by an additional factor.

According to VAERS, 140 people died after vaccination over the last 20 years (129 of them were children under 12 years of age), and 534 people became disabled (444 children).
Considering that VAERS registers 1%-10% of all side effects, it turns out that 64 to 640 children die each year after vaccination, and 220-2,220 become disabled.
Given that 4 million children are born each year, and the vaccination coverage is about 90%, the probability of death after vaccination is 1:5,600 to 1:56,000, and the probability of disability is 1:1,600 to 1:16,000.
Before the introduction of vaccination, the probability of child’s death due to varicella was 1:100,000, and this required medically damaged immune system.