Deaths from chickenpox in England and Wales 1995-7: analysis of routine mortality data
BMJ 2001; 323 doi: https://doi.org/10.1136/bmj.323.7321.1091 (Published 10 November 2001) Cite this as: BMJ 2001;323:1091
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The following statistics, although more than a decade old, (1) are
relevant to the paper(2) by Rawson et al:-
Incidence of pneumonia in adult varicella;- 0.3 to 1.8%;42 to 47% in
smokers; mortality in varicella pneumonia 11% but 35% in pregnant patients.
I therefore suggested (3) that when chickenpox is diagnosed or
suspected the attendant medical staff should enquire about contacts,
particularly adult contacts who have not had chickenpox, especially those
who smoke or who are pregnant. For these contacts (and for other immune
supressed patients) prophylaxis with varicella-zoster immunoglobulin or
anti-viral drugs shoujld be considered.
For patients who can't recall a history of varicella-zoster,
microbiology laboratories can readily check their immunity by estimating
the serm VZIgG.
(1) Haake DA,ZSakowski PC, Haaka DL,Bryson YJ. Rev Infect Dis
1990:12:788-796
(2) Rawson H, Campin A, Noah N BMJ 2001 323: 1091-3 (3 November)
(3) Gunstone RF J.Infect 1994 29 235-6
Competing interests: No competing interests
Chickenpox associated morbidity
Editor
We read the paper published by Rawson et al1 with interest (1). It
has previously been recorded that chickenpox in healthy adults has a 25
fold greater risk of complications than in a childhood (2). The paper by
Rawson et al demonstrates a significant mortality of chicken pox in
England and Wales but is not able to address the question as to the
associated morbidity - certainly a very important issue when addressing
the value of immunisation on a population. We recently performed a
prospectively study on respiratory function in adult patients with
chickenpox hospitalised in a subregional infectious diseases unit in a UK
hospital over a period of 29 months (3).
Sixty six adult patients with chickenpox were hospitalised during the
period, 4 of whom were immunocompromised. Thirty eight patients fulfilled
the study protocol and of these, fifty percent had radiological evidence
of pneumonia (all immunocompetent)3. Three female patients required
admission to intensive care unit, two of whom were pregnant. One patient
presented with chickenpox encephalitis and five had superimposed bacterial
skin infections.
Severe respiratory disease was associated with the presence of new
respiratory symptoms, close contact with the index case and a history of
current smoking. On follow up at a year post infection, 37% of patients
with radiological pneumonia and 10.6% of those without pneumonia continued
to have reduced single breath carbon monoxide transfer factor (TLCO).
This effect was independent from the effect of smoking and may indicate
permanent lung damage. It may therefore be that the morbidity relates not
only to the acute infection and admission but also longer term effects on
the lung function but the exact clinical relavance of our findings are
uncertain at present. However the study does indicate that chicken pox
causes significant morbidity in adults which may be seen increasingly in
the future. Accurate data on morbidity as well as mortality are required
to inform the debate on the value of mass vaccination for chickenpox in
the UK.
No competing interest.
Dr Abdul H Mohsen, MD, MRCP, DTM&H
Clinical Research Fellow, Infectious Disease,
Weston Education Centre,
GKT School of Medicine,
King's College,
University of London,
e-mail: Abdul.Mohsen@kcl.ac.uk
M W McKendrick FRCP
North Trent Department of Infection and Tropical Medicine
Consultant Physician,
Royal Hallamshire Hospital
Sheffield S10 2JF
References
1. RawsonH, Crampin A, and Noah N. Deaths from chickenpox in England
and Wales 1995-7: analysis of routine mortality data. BMJ 2001;323: 1091-
1093.
2. Centre for Disease Control. Varicella-zoster immune globulin for the
prevention of chickenpox. MMWR 1984;33:84-90.
3. Mohsen AH, Peck R J, Mason Z, Mattock L, McKendrick MW. Lung function
tests and risk factors for pneumonia in adults with chicken pox. Thorax
200; 56:796-799.
Competing interests: No competing interests
Deaths from Chicken Pox- the role of ECMO.
EDITOR- We applaud Rawson 1 for highlighting the potentially devastating effects of varicella infection, particularly the fact
that adults in the UK are dying from this disease and these deaths are increasing in number. We know the pneumonitits caused
by varicella infection can lead to respiratory failure that is often the cause of death in these patients. Antiviral therapy may help
in such patients but only if their severely compromised physiology can be adequately supported until they recover.
Extra Corporeal Membrane Oxygenation (ECMO) has been reported to be used successfully in cases of adult respiratory
failure due to varicella pneumonia 2-5 and we would like to bring the results of such intervention to the attention of Rawson and
colleagues. We have treated 15 adults with ECMO for confirmed varicella pneumonitis in Leicester between August 1992 and
December 1999. These 15 patients had a mean age of 36 years with range 24-61, and were significantly hypoxic on referral
with a ratio arterial oxygen tension to fraction of inspired oxygen (PaO2/FIO2) of 8.09 KPa. The overall survival in these
patients was 60%. However of the 11 patients we treated with veno-venous ECMO the survival was 75% (compared to zero
for the four patients treated via veno-arterial ECMO).
It seems likely, therefore, that ECMO is a treatment that should be considered for fulminant varicella pneumonitis, but the
numbers treated so far are too few to be sure of the effectiveness of this invasive treatment . To resolve this uncertainty,
currently all such cases in the UK can be referred for entry into the CESAR trial (Conventional ventilation or ECMO for
Severe Adult Respiratory failure) Suitable patients will be randomised to receive either ECMO or continued conventional
ventilation. Further details about the trial are available from www.cesar-trial.org.
Neil Roberts Clinical ECMO fellow. Heartlink ECMO centre, Glenfield Hospital Leicester, LE3 9QQ.
Neilrob52@hotmail.com.
Giles J Peek Lecturer in Cardiac Surgery, Division of Cardiac Surgery, University of Leicester, Principal Investigator
CESAR
(Corresponding Author, e mail: ycq57@dial.pipex.com)
Nikki Jones Research Fellow in Cardiac Surgery, Division of Cardiac Surgery, University of Leicester, CESAR Trial
Research Fellow
Richard K Firmin ECMO Director and Consultant Cardiac Surgeon, Glenfield Hospital Leicester LE3 9QQ, Principal
Investigator CESAR
Diana Elbourne Head of Medical Statistics Unit, LSHTM, Principal Investigator CESAR
1.Rawson H, Crampin A, Noah N. Deaths from chickenpox in England and Wales 1995-7: analysis of routine mortality
data. BMJ 2001; 323: 1091-3.
2.Marriage S, Lyall EG, Nadel S, Britto J. Prolonged extracorporeal life support for varicella pneumonia. Crit Care Med.1998 Jun;26(6):1138-9.
3.Lee AW, Kolla S, Schreiner RJ Jr, Hirschl RB, Bartlett RH. Prolonged extracorporeal life support (ECLS) for varicella pneumonia. Crit Care Med. 1997 Jun;25(6):977-82.
4.Claydon AH, Nicholson KG, Wiselka MJ, Firmin RK. Varicella pneumonitis: a role for extra-corporeal membrane
oxygenation? J Infect. 1994 Jan;28(1):65-7.
5.Peek GJ, Moore HM, Moore N, Sosnowski AW, Firmin RK. Extracorporeal Membrane Oxygenation for adult
respiratory failure.Chest.1997;112:759-64.
Competing interests: No competing interests
If one were to cost a chicken pox vaccination programme – say £3 per
course for say 500,000 children per year = £9,000,000 for 25 lives
saved. (Cost per life = £360,000.)
If one were to buy say rehydration sachets at 33p per unit, one could
buy 27,000,000.
If these were used on children with diarrhoea in the third world, one
could save (I’m guessing wildly here) 500 lives. (Cost per life = £18,000)
Therefore one would obviously spend the money on saving 500 lives.
The problem would be convincing the government to part with its money. Or
do we actually agree that in a global situation, it is permissible to be
racist?
Competing interests: No competing interests
I'm pleased to see that your results do not on their own provide
sufficient evidence for mass vaccination, because this would surely be a
very expensive route. How many of these cases received treatment in the
form of VZIG or acyclovir? I had chickenpox at the beginning of the year
while 27 weeks pregnant and cannot fault the care of my GPs in the rapid
response they provided. My four year old son started chickenpox on
Christmas Day, I saw the GP on Boxing Day and because I'd requested to be
tested for immunity at my initial pregnancy blood test, she knew
immediately that I was not immune, so arranged for the VZIG the next day.
My two year old son then came down with it about 10 days later and I
followed on 6th January. I started the acyclovir within two hours of the
spots first appearing and they were completely gone within 36 hours.
While I was ill for the next few days, I have no doubt that I had it very
mildly due to the medication. But I get the feeling that if I had not
been pregnant, nothing would have been done. Why can't adults be treated
for chickenpox this way as standard? Surely this would be much cheaper
than mass vaccination? I suppose the downside is that while treatment may
prevent nearly all deaths, it wouldn't produce a large profit for Pasteur-
Merieux.
Competing interests: No competing interests
There are 10 deaths per day on British roads.
I think that there needs to be a sense of proportion in disease prevention. Disease is a normal part of life. To prevent disease may alter our perception of life, maybe depriving our children and society of the experience of how to cope with and respond to disease.(All that will be left will be colds and cancer!!)
With the current fears over MMR, the interrest arround 'Gulf War Syndrome' I think it would be difficult to get enough parental support for mass vaccination.
Maybe the message from this article is that we should have a low threshold to use aciclovir in paople over 45 with chickenpox?
How about more on road safety - 10 death per day is an awful death toll - unremarked in the press and yet a bigger killer than menngitis etc etc?
Competing interests: No competing interests
Editor--Three year mortality attributable to chicken pox in England and Wales during the period 1995-1997, as reviewed by Rawson and colleagues (9 November, p1091)1, points to the maximum deaths among those aged less than 4 years or those above 65 years of age. Though chickenpox vaccine is yet not fully licensed in the United Kingdom, antivirals like acyclovir, famciclovir and valciclovir have been marketed for several years. Antiviral should be used to address the annual chickenpox mortality of at least 25 in England and Wales.
Randomized, double blind, placebo-controlled trials with oral acyclovir were encouraging in adolescents and adults with chickenpox. Adolescents were less likely to have residual hypopigmented skin lesions after four weeks. That indicated that acyclovir therapy reduced the spread of virus to deeper layers in dermis2. The usual recipe, to start within 24 hours of appearance of rash, is of acyclovir, 20mg/kg, four times a day for five days3. Furthermore, adults with varicella pneumonia have also been treated effectively with intravenous acyclovir. Acyclovir did not affect host response to virus4.
Recently, acyclovir has been formulated in a twice-daily controlled formulation that has an extended time of absorption from small intestine5. Such a formulation that would not require medication four time a day would indeed be an asset and eventually replace the current four times a day schedule3.
Postexposure antiviral prophylaxis has been introduced against those exposed to HIV. Likewise, close contacts of those afflicted with varicella might be protected through a prophylaxis recipe with acyclovir. That would emerge as a valuable armory against chickenpox mortality till chickenpox awaiting availability of fully licensed chickenpox vaccine in the England and Wales.
Subhash C Arya, MBBS, PhD
Research Physician
Centre for Logistical Research and Innovation,
M-122 Greater Kailash- Part 2,
New Delhi- 110048, India
Email subhashji@hotmail.com
References
1. Rawson H, Amelia A, Noah N. Deaths from chickenpox in England and Wales 1995-7: analysis of routine mortality data. BMJ 2001; 323:1091-3
2. Wallace MR, Bowler MA, Murray NB, et al. Treatment of adult varicella with oral acyclovir: a randomized, placebo-controlled trial. Ann Int Med 1992;117:358-363
3. Physicians' Desk reference. 53rd edition. Medical Economics Company. Montvale. 1999. PP 1273
4. Haake DA, Zakowski PC, Haake DL, Bryson YJ. Early treatment with acyclovir for varicella pneumonia in otherwise healthy adults: retrospective controlled study and review. Rev Infect Dis 1990;12:788-798
5. Barnard DL. Genvir (Flanel Technologies). Curr Opin Investig Drugs 2001;2(5):622-3
Competing interests: No competing interests
Rawson et al found that chickenpox was a definite or contributory
cause of death in 75 cases in England and Wales 1995-7 (BMJ 2001;323:1091-
1093).
They found that a high proprtion of elderly (> 65 years) people died
from the disease, whereas only one of the children had HIV.
However, I would like to know the proportion of children (and adults)
who were immune-deficient /-compromised due to cancer treatment, or
whether these patients were excluded.
Competing interests: No competing interests
The authors conclude that there are not persuasive arguments for mass
vaccination. In fact, I think that their data provide persuasive argument
against such mass vaccination programs as we have here in the USA.
The study demonstrates that 19% of the cases, but 81% of the deaths,
are in adults, which is consistent with earlier data. Varicella is much
more likely to be lethal among adults than among children.
As with other vaccines, one would expect the immunity from V-Z
vaccine to wane in 15-20 years. Thus, if we vaccinate children we will
have a large cohort of young adults who are not immune to chickenpox,
unless they all come in to get boosters. This seems unlikely, given the
low likelihood of regular doctor visits for people in their 20's. However,
there will still be a large reservoir of potential exposure to the virus
in the form of Herpes Zoster. Thus, there is the potential for large-scale
exposure of non-immune young adults to the varicella-zoster virus if there
is a large vaccination program.
It would be far preferable for people to be exposed naturally to
chickenpox and perhaps reserve the vaccine for those who reach young
adulthood without getting chickenpox.
Competing interests: No competing interests
Varicella in adults - do not forget health care workers
We agree with the conclusion of Rawson et al that although deaths in
adults from chickenpox have increased in number and proportion, this does
not justify mass immunisation with varicella vaccine.1 However, one
population that would clearly benefit from vaccination is susceptible
healthcare workers. At St George's Hospital, prospectively collected data
over the past three years has identified a total of 25 cases of chickenpox
in staff and students. We were able to determine the country of birth in
22 of these individuals and found that the majority of cases, 13/22 (59%)
occurred in people born outside the United Kingdom. This figure was
higher than expected since only 39% of the St George's workforce who have
patient contact are black or from an ethnic minority. Since Rawson et al
found that there was a disproportionately higher mortality among such
people compared with those born here, it would be interesting to know if
occupations, such as those in healthcare with a higher likelihood of
exposure, were over-represented amongst the cases of fatal varicella.
Live attenuated varicella vaccine has been in use now for over 2
decades.2 Moreover, it has had a license for use in susceptible
individuals in the USA since 1995, and has an excellent safety and
efficacy record.3 We believe that the increased mortality from chickenpox
in adults of working age of between 1:1000 and 1:5000 demonstrated by
Rawson may make it indefensible for NHS Trusts not to offer varicella
vaccine to their susceptible staff for two reasons: personal safety at
work and nosocomial chickenpox. Indeed, if only medical and nursing
staff and students had been vaccinated in the last three years at St
George's, 85% of chickenpox cases in hospital staff would have been
prevented.
Devi R, Muir D, Rice P.
Department of Medical Microbiology, St George's Hospital, Blackshaw
Road, London SW17 0QT
References
1. Rawson H, Crampin A, Noah N. Deaths from chickenpox in England and
Wales 1995-7 analysis of routine mortality data. BMJ 2001; 323: 1091-93
2. Asano Y, Suga S, Yoshikawa T, et al. Experience and reason: twenty year
follow-up of protective immunity of the Oka strain live varicella vaccine.
Paediatrics 1994; 94: 524-6
3. Vazquez M, La Russa P S, Gershon AA, et al. The effectiveness of the
varicella vaccine in clinical practice. N Engl J Med 2001; 344: 955-60
Competing interests: No competing interests