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At the heart of general practice since 1960

3GPs' views

GPs have an important role in managing this infection that can have life-threatening complications

­ Professor Judith Breuer advises

Chickenpox in the UK is for the most part a childhood infection. In the majority of children, chickenpox is an inconvenience without serious complications. Hospitalisation occurs in 0.1 per cent of children and one child in 50,000 develops serious complications, usually as a result of secondary bacterial infection, pneumonitis or encephalitis.

The situation in adults, however, is more serious. The hospitalisation rate is 10 times higher in healthy adults aged over 15 with primary chickenpox and hospitalisation increases to one in 30 cases aged over 65.

Smokers and pregnant women have a 10 per cent risk of severe complications and mortality is on average 20 times higher in adults compared with children.

The most common complication is life-threatening varicella zoster virus pneumonitis. Contrary to popular belief, the virus itself is directly responsible for the severity of disease and in most cases there is no bacterial superinfection.

Adults are also 10 times more likely to develop encephalitis.

Immunosuppressed adults ­ which includes those taking oral steroids, patients with HIV, bone marrow and solid organ transplant recipients and anyone on chemotherapy or within six months ­ are in an even worse position. Mortality can be as high as 30 per cent even if treatment is started. In this situation the overwhelming viral infection can lead to disseminated intravascular coagulation, hepatitis and multi-organ failure.

How common is adult varicella in the UK?

Some 95 per cent of adults who have grown up in the UK will have immunity to chickenpox. Most of us will have been exposed as school children, but the growing trend for pre-school children to attend nursery education means more and more outbreaks are occurring before children even start school.

The situation in warmer more tropical climates is different. Here chickenpox transmission occurs later in life. In St Lucia in the 1970s up to 60 per cent of adults aged 40 were found not to be immune to chickenpox1. Similar findings have been reported in Singapore, the whole Indian subcontinent and Sri Lanka2,3,4.

The reasons for these differences are not clear but it may reflect the higher ambient temperatures in these countries as well as social differences including lower rates of pre-school attendance, and less inclination to encourage mixing of infected children with their peers.

Interestingly, part of the last attitude may reflect the old precautions that were taken in these areas for smallpox for which chickenpox is the commonest differential diagnosis4.

Whatever the reasons, adult chickenpox is likely to occur twice as commonly in adults over the age of 20 who have grown up in Asia, the West Indies or the Far East than those who have spent all their life in temperate climates such as the UK5.

Chickenpox is not notifiable in England and Wales. However, data from Scotland, where a passive notification system operates, suggests the numbers of cases occurring in adults is around three in 5,000 per annum which represents 20-30 per cent of the tota · 6.

Data from the RCGP sentinel surveillance suggests the average GP will see a case of adult chickenpox every two-three years, but this figure may be higher in areas with high numbers of first-generation immigrants from tropical areas7. Interestingly, all the evidence suggests children born in the UK to immigrants from high-risk areas are at the same risk as the rest of the UK.

Adults who develop chickenpox commonly give a history of having caught the infection from their own children.

Can we treat chickenpox?

The virus is sensitive to the antiviral agent aciclovir and its analogues famciclovir and valaciclovir. Research has shown a reduction in viral shedding and accelerated rash healing in adults started within 24 hours of rash onset on aciclovir 800mg five times per day8.

The study was not powered to show an improvement in complication rates. Nor was there earlier improvement in symptoms if aciclovir was started later than 24 hours. However, small studies of varicella pneumonitis show a better outcome the earlier intravenous aciclovir is started9. Famciclovir 250mg tds and valaciclovir1g tds, although currently not licensed for chickenpox, are increasingly being used, and are generally held to be a safe alternative.

So whom should we treat? The big problem is predicting who will develop complications.

Immunocompromised patients, including those taking oral steroids, must be referred immediately, whenever they present, for treatment with intravenous aciclovir. Smokers and those with underlying lung disease such as asthma should also always be treated.

Aciclovir is not licensed in pregnancy. Nonetheless it has been extensively used in pregnant women without any teratogenic effects. Pregnant women who are at more than 20 weeks' gestation and present within 24 hours of onset of chickenpox should be treated10.

Some virologists would advise more caution, because of the theoretical risks, when a pregnant woman presents more than 24 hours after onset of rash or the pregnancy is less than 20 weeks gestation. But any sign that the chickenpox is progressive should override such caution.

What are the signs of progressive and potentially severe chickenpox?

Unfortunately there are no really good predictors, especially early on, of which adults will develop complications, other than low oxygen saturation. For this reason many of us adopt a safe approach and advise treatment with aciclovir for all adults who present within 24 hours.

Clinically, in those who present later than 24 hours, treatment is warranted in patients of an older age, with a high fever and a high density of lesions, but are otherwise heathy. Any signs or symptoms of lung involvement, continued cropping after five days, drowsiness or haemorrhage should prompt a rapid referral for treatment with intravenous aciclovir10. Patients with chickenpox should be cautioned against taking aspirin because of the risk of Reye's syndrome.

How should GPs manage adults

in contact with chickenpox?

Establishing whether there has been direct contact is an imprtant first step in identifying whether a patient is at risk. Household contact with the patient's own child or direct contact with a known case is a definite risk factor for transmission. Indirect contact with a child who is in the same class as another child with chickenpox is not.

A history of chickenpox is a good positive predictor of immunity if the person at risk grew up in the UK but less reliable if the person grew up in the tropics. Immunosuppressed patients in whom chickenpox is most likely to be lethal should always be tested for antibodies to varicella zoster virus.

Patients who give a negative history or are unsure if they have previously had the infection also need to be tested.

There may also be a case for testing any patient who has grown up abroad irrespective of history. Seronegative immunosuppressed patients, pregnant women and babies born to mothers with chickenpox within seven days either side of their delivery date need to be given zoster immune globulin within 10 days of contact with the infectious case11.

Advice on this is available from virology or microbiology laboratories and from the Health Protection Agency.

Post-exposure prophylactic aciclovir 400mg bd given seven-nine days after contact for one week has been shown to prevent varicella in susceptible children in contact with an infectious case. But there is no data on its use in healthy or immunosuppressed adults.

The Oka vaccine is also used post-exposure to prevent chickenpox in susceptible adults in the USA. However, although it is licensed for use in anyone aged over 13 in the UK, no funding has been made available.

What about future developments?

The UK has recently introduced immunisation against varicella for seronegative health care workers including those in general practice. The vaccine is much safer than ordinary chickenpox in adults but is not available in the UK for other seronegative adults.

Unlike the USA, immunisation of toddlers is not likely to be introduced in the foreseeable future as it is not seen as cost-effective in the UK.

However, immunising adolescents has been shown to be cost-effective, as has post-partum immunisation of seronegative pregnant women. The advantage of the first strategy is that it would prevent 75 per cent of all complications and mortality in adults and would virtually abolish the need to administer blood products (VZIG) to pregnant women and infants. Also cost saving would be prevention of zoster by immunisation and a study to evaluate whether this is possible in patients over the age of 60 is ongoing in the USA and will report shortly.

In summary, chickenpox in adults is potentially life-threatening. Current advice is to treat all adults who present within 24 hours and anyone who is at risk of progressive chickenpox including smokers, those with lung disease, pregnant women and those with severe infections.

Any immunocompromised patient with chickenpox requires immediate hospitalisation for intravenous aciclovir.

Judith Breuer is professor of virology at

St Barts and the London Hospital

Medical Schools

Take-home points

·Adult chickenpox is a rare but potentially serious infection

·Adult chickenpox is more common in people who grew up in tropical countries

·Healthy adults who smoke, have underlying respiratory problems or who are pregnant are at higher risk of complications

·Aciclovir 800mg five times a day for five days is safe to give and particularly effective if given within 24 hours

·Immunosuppressed patients with chickenpox, including those on steroids, must be referred for IV aciclovir

·Immunosuppressed and pregnant patients in contact with chickenpox who do not think they have had the infection should be tested urgently for varicella zoster antibodies and, if negative, offered ZIG

·Advice on the management of chickenpox or contact with chickenpox is available from local virology or microbiology laboratories

References

01 Garnett GP et al. The age of infection with varicella-zoster virus in St Lucia, West Indies. Epidemiol Infect. 1993; 110(2): 361-72

02 Ooi PL et al. Prevalence of varicella-zoster virus infection in Singapore. Southeast Asian J Trop Med Public Health 1992; 23(1): 22-5

03 Venkitaraman AR et al. Infections due to the human

herpesviruses in southern India: a seroepidemiological survey.

Int J Epidemiol. 1986; 15(4):561-6

04 Saha SK et al. Seroepidemiology of varicella-zoster virus in Bangladesh. Ann Trop Paediatr. 2002; 22(4):341-5

05 Breuer J. Vaccination to prevent varicella and shingles.

J Clin Pathol. 2001; 54(10):743-7

06 SCIEH, Chickenpox. 2004, Scottish NHS

07 Fairley CK, Miller E. Varicella-zoster virus epidemiology ­

a changing scene? J Infect Dis. 1996; 174 Suppl 3:S314-9

08 Wallace MR et al. Treatment of adult varicella with oral acyclovir. A randomised, placebo-controlled trial.

Ann Intern Med. 1992 Sep 1;117(5):358-63

09 Haake DA et al. Early treatment with acyclovir for varicella pneumonia in otherwise healthy adults: retrospective controlled study and review. Rev Infect Dis. 1990; 12(5): 788-98

10 Wilkins EG et al. Management of chickenpox in the adult.

A review prepared for the UK Advisory Group on Chickenpox on behalf of the British Society for the Study of Infection.

J Infect. 1998; 36 Suppl 1: 49-58

11 Immuisation against infectious disease1996 HMSO.

Varicella pp (updated 2004)

12 Brisson M, Edmunds WJ. Varicella vaccination in England and Wales: cost-utility analysis. Arch Dis Child. 2003; 88(10): 862-9

Two common dilemmas for GPs

Q An adult presents with the lesions of chickenpox more than 24 hours after the onset and insists he/she wants something. Is there any evidence to show that some patients may benefit from antivirals after 24 hours?

A There is no evidence that aciclovir given to adults more than 24 hours after onset has any effect on virus shedding or duration or rash. Studies were not powered to show effect on preventing complications. My advice is that any adult with risk factors for severe chickenpox, for instance, smoking, respiratory disease including asthma, dense rash, haemorrhage, low O2 sats should be offered aciclovir by their GP. The drug is safe and inexpensive and resistance

does not occur.

Q A patient asks to be checked to see if he/she is immune against varicella and is not, and so asks to be vaccinated. Can we give immunisation? Can they have it privately and pay for it?

A This is a complex situation. The Department of Health advises immunisation of close family members of immunosuppressed children or adults and health workers who have not had chickenpox. But, the department adds, that as with any treatment, it is up to the GP to decide what is the best treatment for an individual patient. If a patient is given the vaccine, the GP is reimbursed under the vaccination and immunisation additional service money. On the issue of private prescription, the MDU says GPs are obliged to use an NHS script for any drugs needed for treatment, and so cannot prescribe the vaccine privately to their NHS patients.

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