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A 4 year old child is brought to the emergency department by her mother because of a rash that has developed over the preceding 24 hours. The rash is that of uncomplicated chickenpox infection and the history gives a good story of recent contact. The child has no medical history of note and is not immunocompromised. You wonder whether the prescribing of oral acyclovir would reduce the disease severity and duration compared to symptomatic control only.
Structured clinical question
In uncomplicated chickenpox infection in immunocompetent children [patient] is oral acyclovir [intervention] beneficial in reducing severity and duration of infection [outcome]?
Search strategy and outcome
Medline 1966–07/04 using the Ovid interface. The Cochrane Library Issue 2, 2004 [(aciclovir OR acyclovir).mp. AND (chickenpox OR chickenpox).mp.] LIMIT to human AND English language AND all child <0 to 18 years> AND randomised controlled trial.
Cochrane “aciclovir and chickenpox”.
The Medline search found 14 papers. Papers were excluded if they had no placebo group, which resulted in three relevant papers. These three papers have since been subject to a systematic review by the Cochrane Review Group. The review was first published in 1999 with the most recent substantive amendment made in February 2004.
See table 3.
Chickenpox (varicella) remains a common and highly contagious childhood illness among immunocompetent children. Although generally self-limiting, the infection usually presents with an itchy vesicular rash over the trunk and face, fever, and mild systemic upset. Disease complications include secondary bacterial infection of cutaneous lesions, encephalitis, cerebella ataxia, pneumonia, and otitis media. The economic burden is thought to come from the time taken off work by the child’s caregiver.
All three papers were randomised double blind placebo controlled trials carried out in the USA. Between them they looked at 988 patients aged between 2 and 18 years with either clinical of laboratory diagnoses of varicella.
Although the number of days to no new lesions and number of days to reduction of fever were reduced by one day in the acyclovir groups, the findings that one could consider to be more clinically relevant were less definite.
Reported adverse effects were similar in both groups and there was no significant difference between the treatment groups with respect to all skin, central nervous system, and respiratory complications arising from chickenpox infection.
Balfour and colleagues1 showed that the efficacy of acyclovir improves if treatment is initiated within 24 of rash onset, which in practical terms is a diagnostic window often difficult to achieve. Although Balfour et al also show that initiating treatment within 48 hours has greater benefit than 72 hours, one may ask oneself if the modest benefits in outcome, when weighed against the strict compliance required for four times daily medication over five days are of clinical worth.
Concerns have been raised regarding the development of resistance to acyclovir. The Cochrane Review concluded that there is evidence to suggest that strains of varicella resistant to acyclovir do not occur.
There is no published evidence to show a positive outcome in cost-benefit analysis and the Cochrane Review showed no reduction in the number of days missed from school between the treatment groups.
Possible issues with the studies were that all three had pharmaceutical sponsorship and other than the study of Dunkle and colleagues,2 they comprised relatively small patient numbers.
CLINICAL BOTTOM LINE
Oral acyclovir shortens time to fever reduction and time to no new lesions by one day but has no effect on complication rates secondary to infection. (Grade A)
These reductions were only seen if treatment was initiated with 24 hours of rash onset. (Grade B)
Use of acyclovir should not currently be recommended in immunocompetent children with chickenpox infection. (Grade A)
We thank The Cochrane Library for the use of the Database of Systematic Reviews.