= Varicella (Latin). One of the traditionally recognised childhood exanthems, caused by Herpes varicella-zoster virus, a systemic viral illness characterised by widespread vesicles. Like other herpes viruses, it retains the ability to lie dormant in ganglions after initial infection, possibly reactivating in the future as Herpes Zoster (aka shingles).
It is regarded as a 'trivial' (though not for the sufferer!), self-limiting childhood illness, but is often complicated by secondary bacterial infection of the vesicles, and can itself cause severe disease in both immunocompetent and immunocompromised eg encephalitis and pneumonitis. The question is important in considering the merits of the vaccine.
Age and immunodeficiency are the most important predictors of severity, with adults and infants having more severe disease. Cellular rather than humoral immunodeficiency is associated with more severe disease. Numerically, most cases of severe disease (and 90% of the deaths) occur in previously healthy people. Anecdotally, varicella in pregnancy is more severe; the fetus is at risk of severe disease.
The impact of later Herpes Zoster (aka shingles) must also be considered.
A Herpes virus - Varicella zoster virus, or human herpesvirus 3. As such, it lies dormant in the dorsal root ganglion after primary infection, with sporadic reactivation leading to localized herpes zoster (shingles).
There are 3 genotypes but they are virtually identical, and only 1 circulates in Europe; it remains theoretically possible, therefore, to get chickenpox twice!
The incubation period is 10-21 days, usually 10-14. A low fever may precede briefly the appearance of the spots. The visible disease starts as 2mm pale red spots often around the neck and trunk, spreading over the trunk within 24 hr. Within 24-48 hours the classic pustules develop in the centre of these patches which may grow to 3-4mm in size. The pox are very thin walled and burst to leave a scab which falls off after 4-5 days. There may be several crops of these blisters which follow the same pattern. The classical distribution is on the trunk but lesions can be widespread and can affect the mouth, the eyes and the urethra.
Onset of the rash is often associated with fever and other systemic symptoms. The disease can however be subclinical in some cases. Secondary cases in a household on the other hand tend to be more severe, probably due to increased viral load.
Old lesions may leave hypopigmentation or scars.
In times past the differentiation between chickenpox and smallpox was made clinically on the basis of smallpox blisters all being at the same stage and more likely to spread all over the body particularly the face and hands. Compare the differing sizes of blisters in the picture above with the WHO recognition card on the smallpox page.
In the immunocompromised, symptoms may occur at the time of initial viraemia, around day 7 of the incubation period eg abdominal pain, hyponatraemia (possibly from SIADH).
The clinical picture is such that investigations are not usually required. If in doubt, PCR can be done on skin scrapings (particularly from the base of lesions, but potentially also from the crust) or from other sites eg CSF.
IgM can be positive from as early as 1-2 days after appearance of the rash. But serology is not 100% sensitive. Antibodies persist lifelong and are useful for indicating previous exposure and hence immunity; they may however be passed on passively through transfusion. Not very good for confirming response to vaccination, as levels are 10 times lower than after disease.
If pneumonia is suspected a chest X-ray is required. If encephalitis is considered then admission and CAT scan may be required.
Usually expectant (Doctor speak for "Keep it till it gets better").
Chickenpox can be treated with aciclovir or drugs of that group. It is regarded as unusual to so treat a normally healthy child, and there is not consensus that all adults should be treated, but it is a common view. Oral aciclovir in the healthy child reduces fever by 1 day and symptoms by 15-30%; not clear if complications are reduced. If medical treatment is undertaken, it will be most effective if given intravenously within 72 hours of onset of the rash.
The most common complication is bacterial superinfection of the rash, potentially leading to cellulitis. Streptococcal infections are more common after chickenpox, and not just in the skin. VZV itself can have serious complications in the immunocompetent, as well as the immunocompromised including pneumonia/pneumonitis (much more common in smokers ), haemorrhage, encephalitis, hepatitis and glomerulonephritis. Encephalitis usually occurs a week into the illness, and can be acute or gradual in onset. It can however develop before onset of the rash. Other CNS manifestations are benign cerebellar ataxia and vasculitis (potentially leading to stroke, possibly months after disease).
If a pregnant woman has had chicken pox previously, or is immune as a consequence of vaccination, this is not a risk.
If a pregnant woman is not already immune, however, the fetus may be infected. If infected during the first trimester (risk extend to 20th week), a fetus has a 1% chance of developing widespread scarring, hypoplastic limbs, cataracts and brain lesions. Affected infants have a poor neurodevelopmental outlook.
If chickenpox is contracted in the week prior to delivery, the infant is at risk of developing severe disseminated neonatal varicella disease.
- HPA guidelines "Guidance on the management of, and exposure to, rash illness in pregnancy".
- Royal College of Obstetricians & Gynaecologists Chickenpox in pregnancy guidelines.
Transmission & Prevention
Incubation period is 10-21 days, typically 14 days. Infectivity (by aerosol spread) begins up to 48 hours before onset of the rash and persists until all lesions have dried ("crusted"), usually 1-2 weeks but may be longer in the immunocompromised.
In theory transmission from a moist spot can occur but infection is generally by virus escaping by the respiratory route.
Chickenpox can be safely and effectively prevented by vaccination, and the US was one of the first countries to introduce a universal vaccination programme; and in Australia the vaccine has been recommended since 2003, and publicly funded since 2005. It is not currently part of the routine UK immunisation schedule, although the possibility of adding it - whether as a universal vaccine, or for subgroups - is under active consideration.
- Susceptible (non-immune) health care workers
- Healthy susceptible contacts of immunocompromised where continuing close contact is likely
It is licensed in Europe for:
- HIV patients with age-specific CD4 above 25%
- Immunocompromised patients with lymphocyte count greater than 1200x10e9/L.
Because the risk of complications of chickenpox increase after adolescence, some countries recommend vaccination of adolescents who have not had chickenpox. The JCVI is considering recommending that the UK adopt this policy.
The vaccine is a live attenuated Oka strain. The regimen is 2 doses at least 4 weeks apart, usually given in the second year. More than 50 million doses have been given in US since 1995, serious reactions are rare (hepatitis, pneumonia, possibly encephalitis).
Break through varicella in the immunized is milder but can still be transmitted, and if more than 50 lesions after vaccine then the transmission risk is the same as for wild type. Zoster due to vaccine does occur but more rarely than in wild type virus infection.
Post-licensure in the US, vaccine achieves 80% prevention of moderate/severe disease in outbreaks cf over 90% prevention in prospective studies. There is also a reduction of disease in infants and adults by herd effect. Mean age of disease has become higher, so potentially more severe, but is still less frequent than the previous age-specific rate.
The main concern about universal immunisation is whether lack of exposure to varicella in the community will reduce adult immunity, leading to more cases in older groups (who get more severe disease) and more cases of zoster, due to lack of natural immune boosting.
- Preliminary data suggests 1 dose is cost-effective in terms of medical care for varicella, but not if a zoster increase is confirmed (see below). 2 doses would only be cost-effective if MMRV is used instead of the single-valent vaccine.
- No change in zoster rates has yet been seen at surveillance sites but baseline data was poor, so it will need years more data to see if any change has occurred; from HMO data, no change has been seen over 11 years. Some increase has been seen in other studies but this probably reflects a secular upwards trend preceding vaccine introduction. Several studies in progress.
- Vaccine programmes are now being implemented in Germany, Canada, Australia.
- Partially vaccinated populations may have quite different epidemiology.
- Introduction of stronger Zoster vaccine may counteract this effect.
- In 2007 a 10 year followup included 1080 subjects who had had breakthrough disease. THe annual rate of breaktrhough rose from 1.6 to 58.2 cases per thousand person-years within 1 and 9 years of vaccination respectively.
The rationale for not introducing routine VZV vaccination in the UK at present is interesting, and includes the following:
- Cost. Chickenpox is not, usually a very severe illness. It's very sad if your child dies from chicken pox; but the cost to society of vaccinating everybody against chickenpox would be considerable. The usual economic arguments apply. Of course, if we, like the USians were to use MMRV, the marginal cost would be lower than if we were to use a separate vaccine.
- Hope-Simpson hypothesis See below.
- Antivaxxers. Following the ill-founded scares about MMR vaccine - and the outbreaks of measles that are now occurring as a result - there is a concern that switching from MMR to MMRV might excite another wave of anti-vaccine publicity, and possibility of the sort of anti-vaccine hysteria that caused the drop in MMR uptake. It is possible - though there is no evidence for this - that this might have been an important consideration for DH when considering whether to swap MMR for MMRV.
Some also worry about possible vaccine-related complications. The live attenuated vaccine can - like the wild virus - persist in dorsal route ganglia and in some cases it can cause shingles. We know that some vaccine recipients get vaccine-virus related zoster: probably not as many, and not as serious, as from wild infection. But we don’t really know – the main burden of zoster disease is in older people, and until we’ve been using the vaccine for 80 years or more, we really won’t know what its effects will be.
In the meantime, there is a possibility that other vaccines will be developed that do not have this possibility. In 2017, for example, an adjuvanted Herpes zoster sub-unit (hence its short generic name "HZ/su") vaccine was endorsed by a US advisory committee - suggesting that it might soon be licensed to prevent shingles. It is conceivable that the vaccine might be adapted for use in infants and children to prevent chickenpox. As it is not a live virus vaccine, this is unlikely to pose any subsequent risk of vaccine-type shingles. Other vaccines may also be in development - a chimeric vaccine, for example, in which the DNA for the viral antigens is presented by a safe vaccine, without including the parts of the virus that make it pathogenic.
UPDATE, February 2013
Zoster vaccine was discussed on BBC Radio4's "Inside Health" programme on 12 February 2013. Adam Finn, a paediatrician with a particular interest in vaccination said that he would like to see varicella vaccination introduced in the UK; and David Salisbury, head of the Department of Health's Immunisation team said that this would be logical, but that, because of the higher morbidity and mortality associated with shingles, Zoster vaccine was a higher priority.
The Hope-Simpson hypothesis
- Chicken pox is a disease with a relatively low mortality and morbidity
- Shingles has far greater morbidity
- Once somebody has had chicken pox they acquire immunity to it. This prevents them getting chicken pox again. The immunity is insufficient, however, to prevent the virus from persisting in sites where it is protected from the immune system - in particular in the dorsal root ganglia. If the level of immunity to chicken pox falls sufficiently, the virus can spread down the nerves and cause shingles. (We now know it is specifically cellular immunity that matters.)
- Having shingles effectively exposes a patient to the virus, boosting their immunity - this is referred to as endogenous boosting. (People seldom have shingles twice.)
- Exposure to the cases of chicken pox exposes the immune system to the virus, hypothetically stimulating the immune system to enhance the level of immunity to the virus. This natural or exogenous boosting, in turn, prevents or delays the drop in immunity that permits shingles to develop.
- Vaccine virus is of extremely low infectivity, and this natural (or exogenous) boosting effect is therefore not likely to arise if children are vaccinated and do not get chickenpox
- Until vaccinated individuals outnumber individuals with natural immunity there will be this risk of increased morbidity from shingles. This transition will take some 60 years or so.
On the other hand:
- 90% varicella deaths occur in healthy people ie nonimmunocompromised!
- About 50% deaths are in children (historically, about 50 per year in US, perhaps 5 per year in UK?).
- Congenital varicella disease still occurs.
- Introduction of Zoster vaccine may prevent risk of zoster.
This raises all sorts of interesting ethical issues: vaccination is usually something which benefits society as well as the individual vaccinated, as the herd immunity generated also protects individuals who are not themselves immunised. Indeed, the benefit of such herd effect may in some cases exceed the benefit to vaccine recipients. In the case of VZV vaccine, there is a sort of reversed herd effect, where vaccinating individuals while potentially protecting them from disease may increase the risk to non-vaccinees.
The experience of countries who are already offering universal vaccination will show whether the hypothesis above is correct, and - if the concerns of increased mortality from shingles do not happen in reality - the UK may well follow suit. In the opinion of at least one ganfyd editor, the evidence for the Hope-Simpson hypothesis having a significant effect on shingles rates is poor. There is evidence of no effect; yet other studies, often with less reliable methodology, seem to show at most a very small effect. Indeed, some researchers suggest that there is so little (if any) evidence of a real-world Hope-Simpon hypothesis effect (of chickenpox vaccination increasing the burden of shingles disease), that this should not be considered a reason not to vaccinate children against chickenpox.
If the Hope-Simpson effect were to remain a concern, options to address it would include vaccinating adolescents, rather than infants (which would have little effect on "natural boosting", but would have a significant effect on morbidity and mortality due to chickenpox); and a policy of offering both chickenpox vaccination in infancy and shingles vaccination for older people. Financial issues (cost-effectiveness) will eventually sway the argument.
There are also licensed vaccines for zoster - one has been in use since the early 21st century - it is the same live attenuated virus as for varicella, but using a higher concentration. In the USA this vaccine has been recommended for everybody age 60+ since 2005 or thereabouts. A vaccination programme for shingles was introduced in the UK in September 2013, for people aged 70-79 years. More recently an attenuated subunit vaccine has been licensed, although it is not yet in widespread use in the UK. See the section on vaccination on the shingles page for more information.
The Joint Committee on Vaccination and Immunisation (JCVI) is the body which advises the Department of Health on vaccination issues, and the committees minutes (published at its website) often provide the earliest indication of likely changes in vaccination policy. Current vaccination policy is described in the Green Book.
Chickenpox vaccine developments
There seems to be little movement towards developing a new vaccine for chickenpox. The licensure in 2017 of an adjuvanted, subunit vaccine for Shingles, however, raises the prospect that a version of this new vaccine might be created, to prevent chickenpox.
The potential advantages of such a vaccine include:
- Can be used safely in immune-suppressed individuals.
- No risk of subsequent vaccine-virus associated shingles disease.
- We know that the live-virus chickenpox vaccines can cause shingles in some individuals - although the incidence seems to be lower, and the severity less than with wild-type vaccine.
- The incidence of shingles increases with age, with most cases arising in people aged 65, and complications being even commoner at older ages.
- The live-virus chickenpox vaccine has not been used long enough to know what the natural history of the vaccine virus will be in people of this age.
- A subunit vaccine, however, carries no risk of later shingles disease.
Infectious or isolation period is until all lesions crusted, or else 5 days after the last spot appears. UK guidance is available on exclusion from school or nursery on health grounds.
Infectivity can persist in the immunocompromised for up to several weeks.
Post exposure prophylaxis
Post-exposure prophylaxis is required for at risk groups who have had significant exposure. This includes pregnant women, children and adults with compromised immunity (except those receiving regular normal immunoglobulin), and susceptible neonates exposed up to 7 days after birth. Neonates should also receive prophylaxis if mum develops chickenpox up to 7 days before or after birth, or if they require intensive or prolonged special care.
Specific Varicella Zoster Immunoglobulin (VZIG) is effective at reducing the likelihood of disease, and where disease occurs it tends to be less severe. It is an intramuscular product and should be given within 10 days of exposure. Protection lasts 3 weeks, after which a further dose should be considered if re-exposure occurs and antibody has not persisted.
There is guidance on this in the HPA "Immunoglobulin Handbook - Indications and dosage for normal and specific immunoglobulin preparations issued by the HPA" available here, and in the Varicella chapter of the Immunisation "Green Book". Guidance on the management of women exposed to chickenpox while pregnant is available at the HPA website.
There is evidence that varicella vaccine can be used up to 3 days after exposure to prevent disease, and Varivax is licensed for this indication. This is not, however, policy although active immunisation should be considered for anyone in whom ongoing exposure is likely.
Why chicken? It may come from a word for an old small coin, which also gives us the word sequin. Even smaller than "small", to distinguish it from smallpox; and smallpox is small in comparison to the Great Pox (syphilis). THis is further discussed with alternative explanations at http://www.bmj.com/content/321/7262/682.full
- Lancet seminar.
- HPA information on chickenpox
- Guidelines "Guidance on the management of, and exposure to, rash illness in pregnancy" from the HPA website.
- Green Book chapter on varicella (covers vaccination, and post-exposure prophylaxis with immunoglobulin).
- BMJ Learning module. "Shingles: diagnosis and management of herpes zoster and postherpetic neuralgia". (Membership/subscription may be required.)
- ↑ Dunkle LM, Arvin AM, Whitley RJ, Rotbart HA, Feder HM, Feldman S, et al. A controlled trial of acyclovir for chickenpox in normal children. The New England journal of medicine 1991;325(22):1539-44.
- ↑ Jones AM, Thomas N, Wilkins EG. Outcome of varicella pneumonitis in immunocompetent adults requiring treatment in a high dependency unit. The Journal of infection 2001;43:135-9. (Direct link – subscription may be required.)
- ↑ Mohsen AH, Peck RJ, Mason Z, Mattock L, McKendrick MW. Lung function tests and risk factors for pneumonia in adults with chickenpox. Thorax. 2001 Oct;56(10):796-9.
- ↑ Byrne B, on behalf of the Guidelines and Audit Committee of the Royal College of Obstetricians and Gynaecologists. Green-top Guideline No. 13: Chickenpox in pregnancy: Royal College of Obstetricians and Gynaecologists, 2007:1-11
- ↑ Ward K, Dey A, Hull B, Quinn HE, Macartney K, Menzies R. Evaluation of Australia's varicella vaccination program for children and adolescents. Vaccine 2013;2(12):01839-7 PMID: 23290837.
- ↑ Joint Committee on Vaccination and Immunisation (JCVI). Minutes of the Minutes of the JCVI Meeting held on 14 October 2009.
- ↑ Joint Committee on Vaccination and Immunisation (JCVI) Varicella / Herpes Zoster sub-group. Minutes of the Varicella / Herpes Zoster sub-group - 4 December 2007. London: Joint Committee on Vaccination and Immunisation (JCVI), 2007
- ↑ Anonymous. Government considers varicella screening for pregnant women. Pulse 2008;Accessed: 2008(11 March 2008)
- ↑ Farlow A. Childhood immunisation against varicella zoster virus. BMJ (Clinical research ed.). 2008; 337:a1164.(Epub)
- ↑ Chaves SS, Gargiullo P, Zhang JX, Civen R, Guris D, Mascola L, Seward JF. Loss of vaccine-induced immunity to varicella over time. NEJM 2007, Mar 15;356(11):1121-9. (or here)
- ↑ Anonymous. Joint Committee on Vaccination and Immunisation Statement on varicella and herpes zoster vaccines: Joint Committee on Vaccination and Immunisation (JCVI), Undated
- ↑ Tanuseputro P, Zagorski B, Chan KJ, Kwong JC. Population-based incidence of herpes zoster after introduction of a publicly funded varicella vaccination program. Vaccine. 2011 Sep 20.(Epub ahead of print) (Link to article – subscription may be required.)
- ↑ N Engl J Med 2007; 356: 1121-9
- ↑ GlaxoSmithKline plc. FDA Advisory Committee votes unanimously for Shingrix (HZ/su) in the US for prevention of herpes zoster (shingles) in adults ages 50 and over. Press releases 2017; Updated 13 September 2017; Accessed: (2017): 22 September
- ↑ Hope-Simpson RE. Postherpetic neuralgia. The Journal of the Royal College of General Practitioners. 1975 Aug; 25(157):571-5.
- ↑ HOPE-SIMPSON RE. THE NATURE OF HERPES ZOSTER. The Practitioner. 1964 Aug; 193:217-9.
- ↑ HOPE-SIMPSON RE. THE NATURE OF HERPES ZOSTER: A LONG-TERM STUDY AND A NEW HYPOTHESIS. Proceedings of the Royal Society of Medicine. 1965 Jan; 58:9-20.
- ↑ Edmunds WJ, Brisson M. The Effect of Vaccination on the Epidemiology of Varicella Zoster Virus. Journal of Infection 2002;44(4):211-219
- ↑ Oxman MN. Advances and Controversies in Our Understanding of Herpes Zoster—Introduction. J Infect Dis 2018;218(suppl_2):S55-S56, DOI: 10.1093/infdis/jiy156 (https://academic.oup.com/jid/article/218/suppl_2/S55/5105947).
- ↑ Laing KJ, Ouwendijk WJD, Koelle DM, Verjans GMGM. Immunobiology of Varicella-Zoster Virus Infection. J Infect Dis 2018;218(suppl_2):S68-S74, DOI: 10.1093/infdis/jiy403 (https://academic.oup.com/jid/article/218/suppl_2/S68/5105954).
- ↑ Harpaz R, van Hoek AJ. Point–Counterpoint: The Hope-Simpson Hypothesis and Its Implications Regarding an Effect of Routine Varicella Vaccination on Herpes Zoster Incidence. J Infect Dis 2018;218(suppl_2):S57-S62, DOI: 10.1093/infdis/jiy418 (https://academic.oup.com/jid/article/218/suppl_2/S57/5105961).
- ↑ Wutzler P, Casabona G, Cnops J, Akpo EIH, Safadi MAP. Herpes zoster in the context of varicella vaccination – An equation with several variables. Vaccine 2018, DOI: https://doi.org/10.1016/j.vaccine.2018.09.013 (http://www.sciencedirect.com/science/article/pii/S0264410X18312623).
- ↑ Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, et al. A Vaccine to Prevent Herpes Zoster and Postherpetic Neuralgia in Older Adults. N Engl J Med 2005;352(22):2271-84
- ↑ Harpaz R, Ortega-Sanchez IR, Seward JF. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 2008 Jun 6; 57(RR-5):1-30; quiz CE2-4.
- ↑ Vaccines and Preventable Diseases: Shingles (Herpes Zoster) Vaccination. CDC web site. Last modified January 25, 2008. Last viewed February 3, 2008.
- ↑ Rozenbaum MH, van Hoek AJ, Vegter S, Postma MJ. Cost-effectiveness of varicella vaccination programs: an update of the literature. Expert Rev Vaccines 2008;7(6):753-82
- ↑ Heininger U, Seward JF. Varicella. Lancet 2006;368(9544):1365-76. (Direct link – subscription may be required.)