Varicella zoster

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Contents

Introduction

Herpes Zoster (or Zoster, or Shingles) is a painful blistering rash owing to reactivation of the virus persisting from previous (childhood) chickenpox, which is one of the traditionally recognised childhood exanthems. Zoster sine herpete (dermatone distribution pain without rash) is known.

History

Isolates obtained from varicella and zoster in the same person are identical, as shown by molecular genetics since then, despite there being differences between individual strains of the Varicella Zoster virus (VZV).

Aetiology

Reactivation of Varicella zoster virus - a large DNA Herpes virus - Human herpesvirus 3.

Clinical

LogoKeyPointsBox.pngAlthough missing the diagnosis in the presence of the rash is embarrassing it must be remembered that zoster sine herpete is more common early and late
A painful blistering rash, usually restricted to one or two adjacent dermatones.

The Varicella Zoster virus (VZV) remains dormant in the dorsal root ganglion and is reactivated, perhaps owing to stress, infection, sunlight, immunodeficiency or other intercurrent illness. This appears as a vesicular rash along the dermatome supplied by the the dorsal root nerve root. The rash tends to appear most predominately on the trunk and chest and sometimes also on the face where the eye can become involved. It can cause severe pain.

Since PCR testing has become available the virus has been identified as one of the most common viruses causing CNS disease and it has become evident that this disease includes a wide spectrum of different CNS manifestations. The most evaluated CNS manifestations are encephalitis which is associated with both varicella and herpes zoster and, cerebellitis which occurs predominantly in children with varicella.[11]

Clinical complications

Urinary retention

Urinary retention can result from sacral dermatone involvement.

CNS vasculitis

The risk of stroke is increased following an attack of shingles, especially after an attack of opththalmic shingles.[12]. This is due to large vessel vasculitis and can occur without shingles or many months after the attack of shingles.

Confusion can be a problematical complication in the very old with a differential diagnosis including drugs (analgesics and aciclovir), zoster encephalitis and stroke as above. However many cases are probably small vessel vasculitis.[13] The role of antivirals and steroids in such presentations are unclear.

VZV in the immune suppressed

In the immune suppressed a more widespread - but often less painful - eruption may occur. Organs may also be affected. Viral shedding is more profuse and persistent.

Ophthalmic shingles

Zoster of the fifth cranial nerve is a special case and should involve a timely specialist opinion. There is a risk of blindness.

Investigations

A clinical diagnosis, although virus may be isolated from lesions.

Blood tests

Blood tests are not usually required, useful or performed.

Treatment

Medical

Varicella Zoster virus is one of the few viruses for which we have a safe effective drug available. Aciclovir and other drugs in that group are somewhat effective in attenuating the disease. Treatment is traditionally reserved for those who are believed to be at greater risk, particularly if they have a history of steroid treatment recently, but if shingles is seen early treating it seems likely to be beneficial. The effect of anti-viral treatment of the initial illness on post-herpetic neuralgia (PHN) is unclear, although a recent review stated that:[14]

"Meta-analyses and randomised controlled trials suggest that the oral antiviral agents aciclovir, famcicolovir, and valaciclovir started within 72 hours of the onset of rash reduce both the severity and the duration of acute pain, as well as the incidence of postherpetic neuralgia. The nucleoside analogue brivudin has been shown to be as effective as famciclovir but superior to aciclovir in both healing acute lesions and reducing postherpetic neuralgia. The pharmacokinetics of oral antivirals differ considerably, so the patient's ability to adhere to a multiple dosing regimen should be considered when selecting an agent for treatment. Antiviral treatment is effective at an early stage when viral replication is still occurring. It should be given to patients who present within 72 hours of the onset of rash and to those aged over 50 with new vesicle formation or complications whenever they present. Published guidelines advise that herpes zoster ophthalmicus should always be treated with antivirals and the advice of an ophthalmologist sought. Likewise, visceral herpes zoster requires prompt admission to hospital and use of intravenous aciclovir (10 mg/kg, eight hourly)."

(The use of the word "suggest" rather than "show" implies that the results of the studies referred to are not clear cut.)

Prevention

Although the virus is present in the blisters, shingles is minimally infectious. It can cause chickenpox - but the virus has to be inhaled or ingested. As long as the blisters can be kept covered, staff and school-children need not be excluded from work or school to prevent the infection of others. (In contrast, patients with chickenpox excrete the virus in respiratory secretions, so it can be spread by coughing.)

Immunisation

Primary infection (Chickenpox) can be safely and effectively prevented by vaccination, but the vaccine is not part of the routine UK policy - see information on chickenpox page for more details. It is likely that chickenpox vaccination would prevent future cases of shingles - although, as a live attenuated virus is used, there is a possibility that the vaccine virus might cause shingles, though if it does, it might be milder than with wild virus.

LogoWarningBox4.pngVaricella and Zoster vaccines have different concentrations of virus and are for different indications. Check carefully

There is also a licensed vaccine for zoster - it's the same live attenuated virus as for varicella, but a higher concentration is used.[15] In the USA this vaccine is recommended for everybody age 60+.[16][17] The JCVI's varicella subgroup recommended in 2009 that herpes zoster vaccination should be introduced to people aged 70 years and over; and on January 31 2010 the main JCVI endorsed this decision.[18][19][20][21]

The 2013/14 General Medical Services (GMS) contract states:

"The new shingles immunisation programme is being introduced from 1 September 2013 comprising a single injection to last a lifetime, offered routinely to patients who are aged 70 and the initial stages of catch-up programme for patients aged 71–79 (as at 1 September 2013) likely to commence with patients aged 79 (and any remaining vaccines supplies used to catch up patients aged 78)."[22]

A programme was introduced as described in the contract. Under this programme:

  • People will be offered the vaccine when they turn 70 - or more specifically, people who were 70 on the previous 1st September will be offered the vaccine (and any who miss it or decline it then will presumably be entitled to it subsequently).
  • A catch-up programme will be offered, with people who turned 79 on the previous 1st September being offered the vaccine.

The issue is resource prioritisation as at 3 years zoster vaccine reduced the shingles related burden of illness by 61%, the incidence of herpes zoster by 51% and the incidence of postherpetic neuralgia by 67%[10][23]. It works for at least 7 years in those with normal immunity for age[24]. Various articles have suggested that the vaccine may be cost-effective.[25][26][27]

In theory the catch-up programme could proceed more rapidly; but the issue here is supplies. Production of live virus vaccines is far from trivial - it takes at least 5 years to build and commission a plant, and the bio-security implications (ensuring no infections get in) are immense. The amount of virus in shingles vaccine is considerably greater than in chickenpox vaccine (it is the same attenuated vaccine virus). There is limited manufacturing capacity; and manufacturers are still (in November 2013 struggling to produce enough vaccine for the target groups in the programme.

Again, in theory GPs may prescribe (or purchase) and administer shingles vaccine on the NHS for people in whom it is "clinically indicated"; and vaccine may be available from private clinics. However, nearly all (if not all) of the stock available in the UK has been bought by the NHS for the national programme, so the vaccine may not be available for prescription of purchase of people outwith the programme. It would be illegal (quite likely a criminal offense) to use vaccines provided for the programme for other purposes.

It may have been sensible - were it permitted, and were sufficient supplies available - to offer the vaccine to certain individuals who don't meet the strict criteria for vaccination. If there were adequate supplies it might make sense to vaccinate people who were over 70 but less than 79 on the previous 1 September opportunistically, for example.

There is an interesting point here about the NHS Constitution and in particular the Health Protection (Vaccination) Regulations 2009. If the JCVI recommendation was that everybody age 70-79 would benefit from the vaccine, it could be argued that (subject to availability of a cost-effective vaccine) everybody in this age range is entitled to the vaccine. At present At the time of writing this (November 2013) there clearly isn't vaccine available for everybody in this range; and it seems unlikely that this will change in the near future. Should, however, more manufacturing capacity come on stream, however, this might change; in which case the legality of denying the vaccine to people in this age range who are not included in the national programme might reasonably be challenged.

Vaccine efficacy following an attack of shingles may be poor (the attack of shingles may already have boosted immunity); and data on the value (or otherwise) of additional boosters is limited.

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, Director of Immunisation at the Department of Health, said that this would be logical, but that, because of the higher morbidity and mortality associated with shingles, Zoster vaccine was a higher priority.

David Salisbury also announced on this radio programme that zoster vaccine would be introduced in autumn 2013. From then, the vaccine would be offered to everybody age 70. In addition, in the first year the vaccine would also be offered to everybody aged 79; in the second year it would also be offered to those age 78 and 79, and a catch-up programme would continue, with different cohorts covered each year, until everybody who had been 70-79 years old at the time the vaccine was introduced had been offered the vaccine.

This appears to have been the first announcement of any detail about this proposal. There had been no formal announcement from JCVI since 2010;[28] the document describing the new NHS Commissioning Board's public health functions refers to the introduction of a zoster vaccine in 2013,[29] but with no details; and a letter from the Department of Health proposing changes to the General Practice contract included the paragraph (Annex A, para 43):[30]

  • "We propose to introduce a new item of service fee of £7.63 to make payments for routine shingles immunisation for patients aged 70. The NHS CB will be responsible for introducing any confirmed catch up programme for patients aged 71 to 79."

Other shingles vaccines

Sub-unit vaccines

In 2017 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.[31]

Post exposure prophylaxis

See chickenpox page.

Notification

Since shingles is a (usually late) sequela of chickenpox, there would be little point in making it notifiable. Chickenpox is not currently notifiable (although if a decision is made to move to using MMRV vaccine in the UK - as is current policy in North America - this might change).

External links and references

References

  1. Von Bokay, J, l~ber den aetiologischen Zusammenhang der Varizellen mit gewissen Fällen yon Herpes zoster, Wein. klin. woch. 1909;22:1323
  2. Kundratitz K. Experimentelle Übertragung von Herpes Zoster auf den Menschen und die Beziehungen von Herpes Zoster zu Varicellen. Monatsshrift Kinderheilkd 1925;29: 516–522.
  3. Brain, R T, The relationship between the viruses of zoster and varicella as demonstrated by the complement fixation reaction, Brit. J. Exp. Path. 1933;14:67
  4. Rake, G, Blank, H, Coriell, L L, Nagler, F P O, and Scott, T F M, The relationship of varicella and herpes zoster: Electron microscope studies, J. Bact. 1948;56:293
  5. Weller T H, Witton H M. The etiologic agents of varicella and herpes zoster: Serological studies with viruses as propagated in vitro. J Experimental Medicine 1958;108:869-890
  6. Hope-Simpson RE. Postherpetic neuralgia. The Journal of the Royal College of General Practitioners. 1975 Aug; 25(157):571-5.
  7. HOPE-SIMPSON RE. THE NATURE OF HERPES ZOSTER. The Practitioner. 1964 Aug; 193:217-9.
  8. 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.
  9. Edmunds WJ, Brisson M. The Effect of Vaccination on the Epidemiology of Varicella Zoster Virus. Journal of Infection 2002;44(4):211-219
  10. a b Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, Arbeit RD, Simberkoff MS, Gershon AA, Davis LE, Weinberg A, Boardman KD, Williams HM, Zhang JH, Peduzzi PN, Beisel CE, Morrison VA, Guatelli JC, Brooks PA, Kauffman CA, Pachucki CT, Neuzil KM, Betts RF, Wright PF, Griffin MR, Brunell P, Soto NE, Marques AR, Keay SK, Goodman RP, Cotton DJ, Gnann JW, Loutit J, Holodniy M, Keitel WA, Crawford GE, Yeh SS, Lobo Z, Toney JF, Greenberg RN, Keller PM, Harbecke R, Hayward AR, Irwin MR, Kyriakides TC, Chan CY, Chan IS, Wang WW, Annunziato PW, Silber JL. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. The New England journal of medicine. 2005 Jun 2; 352(22):2271-84.(Link to article – subscription may be required.)
  11. Grahn A, Studahl M. Varicella-zoster virus infections of the central nervous system - Prognosis, diagnostics and treatment. ;;J Infect 2015;71(3):281-93 PMID: 26073188.
  12. Kang JH, Ho JD, Chen YH, Lin HC. Increased Risk of Stroke After a Herpes Zoster Attack. A Population-Based Follow-Up Study. Stroke; a journal of cerebral circulation. 2009 Oct 8.(Epub ahead of print) (Link to article – subscription may be required.)
  13. Nagel MA, Cohrs RJ, Mahalingam R, Wellish MC, Forghani B, Schiller A, Safdieh JE, Kamenkovich E, Ostrow LW, Levy M, Greenberg B, Russman AN, Katzan I, Gardner CJ, Häusler M, Nau R, Saraya T, Wada H, Goto H, de Martino M, Ueno M, Brown WD, Terborg C, Gilden DH. The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features. Neurology. 2008 Mar 11; 70(11):853-60.(Link to article – subscription may be required.)
  14. Wareham DW, Breuer J. Herpes zoster. Br Med J 2007;334(7605):1211-1215. (May require subscription)
  15. 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
  16. R Harpaz, IR Ortega-Sanchez, JF Seward. Prevention of Herpes Zoster: Recommendations of the Advisory Committee on Immunization Practices (ACIP). 2008 (June 6) 57(05);1-30.
  17. Vaccines and Preventable Diseases: Shingles (Herpes Zoster) Vaccination. CDC web site. Last modified January 25, 2008. Last viewed February 3, 2008.
  18. Joint Committee on Vaccination and Immunisation (JCVI). Minutes of the Minutes of the JCVI Meeting held on 14 October 2009.
  19. Joint Committee on Vaccination and Immunisation (JCVI). JCVI short statement on Herpes zoster vaccines. London: Joint Committee on Vaccination and Immunisation, 2010
  20. Department of Health. Press release: Shingles vaccine moves a step closer. 2010; Updated 29 January 2010 Accessed: 2010 (1 February)
  21. Anonymous. Joint Committee on Vaccination and Immunisation Statement on varicella and herpes zoster vaccines: Joint Committee on Vaccination and Immunisation (JCVI), Undated
  22. NHS Employers, NHS England. 2013/14 General Medical Services (GMS) contract - Guidance and audit requirements for new and amended services Leeds: NHS Employers and NHS England, 2013 (April); 1-41
  23. Oxman MN, Levin MJ. Vaccination against Herpes Zoster and Postherpetic Neuralgia. The Journal of infectious diseases. 2008 Mar 1; 197 Suppl 2:S228-36.(Link to article – subscription may be required.)
  24. Sanford M, Keating GM. Zoster vaccine (zostavax(r)): a review of its use in preventing herpes zoster and postherpetic neuralgia in older adults. Drugs & aging. 2010; 27(2):159-76.(Link to article – subscription may be required.)
  25. Pellissier JM, Brisson M, Levin MJ. Evaluation of the cost-effectiveness in the United States of a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. Vaccine. 2007 Nov 28; 25(49):8326-37.(Link to article – subscription may be required.)
  26. Bilcke J, Marais C, Ogunjimi B, Willem L, Hens N, Beutels P. Cost-effectiveness of vaccination against herpes zoster in adults aged over 60 years in Belgium. Vaccine. 2012 Jan 11; 30(3):675-84.(Link to article – subscription may be required.)
  27. de Boer PT, Pouwels KB, Cox JM, Hak E, Wilschut JC, Postma MJ. Cost-effectiveness of vaccination of the elderly against herpes zoster in The Netherlands. Vaccine. 2013 Feb 18; 31(9):1276-83.(Link to article – subscription may be required.)
  28. Joint Committee on Vaccination and Immunisation (JCVI). Joint Committee on Vaccination and Immunisation Statement on varicella and herpes zoster vaccines. London: Joint Committee on Vaccination and Immunisation (JCVI), 2010 (29 March)
  29. 1. DH, PH, PHPSU. Public health functions to be exercised by the NHS Commissioning Board. London: Department of Health, 2012 (15 November); 1-26
  30. Armstrong R. General Medical Services – Contractual Changes 2013/2014. Leeds: Department of Health, 2012 (6 December)
  31. 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
  32. Wareham DW, Breuer J. Herpes zoster. Br Med J 2007;334(7605):1211-1215. (May require subscription)
  33. Martin J Wood. History of Varicella Zoster Virus. International Herpes Management Forum Journal 2000:7(3);60-65

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