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BMJ Clin Evid. 2007; 2007: 0912.
Published online 2007 August 1.
PMCID: PMC2943770

Chickenpox

Abstract

Introduction

Chickenpox is extremely contagious. Over 90% of unvaccinated people become infected, but infection occurs at different ages in different parts of the world — over 80% of people have been infected by the age of 10 years in the USA, the UK, and Japan, and by the age of 20-30 years in India, South East Asia, and the West Indies.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent chickenpox in healthy adults and children? What are the effects of interventions to prevent chickenpox in children exposed prenatally? What are the effects of interventions to prevent chickenpox in immunocompromised adults and children? What are the effects of treatments for chickenpox in healthy adults and children? What are the effects of treatments for chickenpox in immunocompromised adults and children? We searched: Medline, Embase, The Cochrane Library and other important databases up to March 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 13 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: acyclovir, famciclovir, live attenuated vaccine, valaciclovir, varicella zoster immunoglobulin, and zoster immunoglobulin.

Key Points

Chickenpox is caused by primary infection with varicella zoster virus. In healthy people, it is usually a mild, self-limiting illness, characterised by low-grade fever, malaise, and a generalised, itchy, vesicular rash.

  • Chickenpox is very contagious — in the UK, USA and Japan, over 80% of people have been infected by the age of 10 years.
  • The most common complications are bacterial skin sepsis in children under 5, acute cerebellar ataxia in older children, and varicella pneumonia in adults (which causes 20-30 hospital admissions per 10 000 adults).

Live attenuated varicella vaccine is effective at preventing chickenpox in healthy children.

  • The vaccine does not appear to reduce the incidence of chickenpox in postexposed children, although it does reduce severity of symptoms.

We haven't found any evidence that looks at the effect of the vaccine in healthy adults.

Newborns whose mothers' rashes appear in the last 5 days of pregnancy or within 2 days of birth have been reported, in small case series, to have a very high risk of severe chickenpox.

Overall, there is sparse evidence examining the effects of vaccines in immunocompromised adults and children.

Oral aciclovir also seems to effectively treat chickenpox if administered within 24 hours of onset of rash.

  • When given later than 24 hours after onset of rash, aciclovir doesn't appear to be so effective, although the evidence is sparse.
  • We haven't found any evidence assessing famciclovir or valaciclovir for treating chickenpox in healthy people.

In children with malignancy, intravenous aciclovir appears to reduce clinical deterioration from chickenpox.

About this condition

Definition

Chickenpox is caused by primary infection with varicella zoster virus. In healthy people, it is usually a mild, self limiting illness, characterised by low grade fever, malaise, and a generalised, itchy, vesicular rash.

Incidence/ Prevalence

Chickenpox is extremely contagious. Over 90% of unvaccinated people become infected, but infection occurs at different ages in different parts of the world — over 80% of people have been infected by the age of 10 years in the USA, the UK, and Japan, and by the age of 20-30 years in India, South East Asia, and the West Indies.

Aetiology/ Risk factors

Chickenpox is caused by exposure to varicella zoster virus.

Prognosis

Infants and children: In healthy children the illness is usually mild and self limiting. In the USA, mortality in infants and children (aged 1-14 years) with chickenpox is about 7/100,000 in infants, and 1.4/100,000 in children. In Australia, mortality from chickenpox is about 0.5-0.6/100 000 in children aged 1-11 years, and about 1.2/100,000 in infants. Bacterial skin sepsis is the most common complication in children under 5 years of age, and acute cerebellar ataxia is the most common complication in older children; both cause hospital admission in 2-3/10 000 children. Adults: Mortality in adults is higher, at about 31/100,000. Varicella pneumonia is the most common complication, causing 20-30 hospital admissions/10 000 adults. Activation of latent varicella zoster virus infection can cause herpes zoster, also known as shingles (see review on postherpetic neuralgia). Cancer chemotherapy: One case series (77 children with both cancer and chickenpox; 1 child received zoster immune globulin within 72 hours of exposure) found that more children receiving chemotherapy developed progressive chickenpox with multiple organ involvement compared with those in remission (19/60 [32%] of children receiving chemotherapy v 0/17 [0%] of children in remission), and more children died (4/60 [7%] of children receiving chemotherapy v 0/17 [0%] of children in remission). HIV infection: One retrospective case series (45 children with AIDS; no treatment reported) found that 1/4 (25%) children with AIDS who acquired chickenpox in hospital developed pneumonia, and 5% died. In a retrospective cohort study (73 children with HIV and chickenpox; 83% with symptomatic HIV; 14 children received varicella zoster immune globulin, 9 within 48 hours of exposure), infection beyond 2 months occurred in 10 children (14%), and recurrent varicella zoster virus infections occurred in 38 (55%). There was a strong association between an increasing number of recurrences and low CD4 cell counts. Half of recurrent infections involved generalised rashes, and the other half had zoster. Newborns: We found no cohort studies of untreated children with perinatal exposure to chickenpox. One cohort study (281 neonates receiving varicella zoster immune globulin because their mothers had developed a chickenpox rash during the month before or after delivery) found that 134 (48%) developed a chickenpox rash and 19 (14%) developed severe chickenpox. Sixteen (84%) of the 19 cases of severe chickenpox occurred in neonates of mothers whose rash had started between 4 days before and 2 days after delivery.

Aims of intervention

To prevent clinical chickenpox (characterised by a rash); to reduce the duration of illness and complications of chickenpox.

Outcomes

Development of clinical chickenpox; duration of illness (time to no new lesions, disappearance of fever); complications of chickenpox; mortality.

Methods

BMJ Clinical Evidence search and appraisal March 2007. The following databases were used to identify studies for this review: Medline 1966 to March 2007, Embase 1980 to March 2007, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2007, Issue 1. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and National Institute for Health and Clinical Excellence (NICE). Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the author for additional assessment, using pre-determined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews and RCTs in any language, at least single blinded, and containing more than 20 individuals of whom more than 80% were followed up. There was no minimum length of follow up required to include studies. We excluded all studies described as "open", "open label", or not blinded, unless blinding was impossible. We also searched for cohort studies on specific harms of named interventions. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the review as required. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ).

Table
GRADE evaluation of interventions for chickenpox

Glossary

High-quality evidence
Further research is very unlikely to change our confidence in the estimate of effect
Immune serum globulin (ISG)
Immunoglobulin prepared from pooled human plasma.
Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate
Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate
Varicella zoster immune globulin (VZIG)
Prepared from units of donor plasma selected for high titres of antibodies to varicella zoster virus.
Zoster immune globulin (ZIG)
Prepared from the plasma of donors convalescing from herpes zoster (sustainable supplies are difficult to obtain).

Notes

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

References

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17. Wise RP, Salive ME, Braun MM, et al. Postlicensure safety surveillance for varicella vaccine. JAMA 2000;284:1271–1279. [PubMed]
18. Ioannidis JP, Collier AC, Cooper DA, et al. Clinical efficacy of high-dose aciclovir in patients with human immunodeficiency virus infection: a meta-analysis of randomized individual patient data. J Infect Dis 1998;178:349–359. Search date not reported; primary sources Medline, hand searches of abstracts from meetings and trial directories, and communication with experts. [PubMed]
19. Zaia JA, Levin MJ, Preblud SR, et al. Evaluation of varicella-zoster immune globulin: protection of immunosuppressed children after household exposure to varicella. J Infect Dis 1983;147:737–743. [PubMed]
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27. Mor M, Harel L, Kahan E, et al. Efficacy of postexposure immunization with live attenuated varicella vaccine in the household setting - A pilot study. Vaccine 2004;23:325–328 [PubMed]
2007; 2007: 0912.
Published online 2007 August 1.

Live attenuated varicella vaccine in healthy children

Summary

INCIDENCE OF CHICKEN POX Compared with placebo: Live attenuated varicella vaccine reduces the incidence of chickenpox in healthy children after 9 months to 2 years ( high-quality evidence ).

Benefits

Live attenuated varicella vaccine in healthy children:

We found one systematic review (search date 2000, 2 RCTs), and one subsequent RCT. The first RCT identified by the review (914 healthy children aged 1–14 years, reported over 2 publications) found that live attenuated varicella vaccine significantly reduced clinical chickenpox at 9 months (0/468 [0%] with vaccine v 38/446 [9%] with placebo; ARR 8.5%, 95% CI 6.1% to 11.5%; protection level 100%) and at 2 years (1/163 [< 1%] with vaccine v 21/161 [13%] with placebo; OR 0.05, 95% CI 0.01 to 0.35). The second RCT identified by the review (327 healthy children aged 10–30 months) also found that live attenuated varicella vaccine significantly reduced clinical chickenpox after a mean of 29 months (AR: 5/166 [3%] with vaccine v 41/161 [25%] with placebo; RR 0.12, 95% CI 0.05 to 0.29). The subsequent RCT (42 children aged 12 months to 13 years, immunised within 72 hours of the first skin lesion appearing in a sibling) found no significant difference in the incidence of clinical chickenpox between live attenuated varicella vaccine and placebo at 28 days (AR: 9/22 [41%] with vaccine v 9/20 [45%] with placebo; RR 1.10, 95% CI 0.55 to 2.21). It found that significantly more children receiving placebo developed moderate or severe disease (1/9 [11%] with vaccine v 8/9 [89%] with placebo; RR of moderate to severe disease 8.00, 95% CI 1.21 to 51.51).

Harms

The systematic review found that the only reported adverse effect with varicella vaccine was a non-significant increase in varicella-like papules or vesicles (AR: 5.4% with vaccine v 3.7% with placebo; RR 1.45, 95% CI 0.53 to 4.0). No children had fever or constitutional symptoms. The subsequent RCT found no adverse effects with varicella vaccine. One postmarketing analysis of a database of 89,753 vaccinated adults and children found no associations with any rare serious adverse events. Another analysis found that the rate of serious adverse events was 2.9/100,000 doses.

Comment

Clinical guide

:

Chickenpox vaccine is a safe and effective vaccine against a usually mild disease in healthy children. The decision to use the vaccine depends on a trade-off between the potential benefits, harms, and cost. This trade-off will vary with the context.

Substantive changes

No new evidence

2007; 2007: 0912.
Published online 2007 August 1.

Live attenuated vaccine in healthy adults

Summary

We found no clinically important results about the effects of live attenuated varicella vaccine in healthy adults.

Benefits

Live attenuated varicella vaccine in healthy adults:

We found one systematic review. It found no RCTs assessing clinical outcomes in healthy adults.

Harms

We found no RCTs.

Comment

Clinical guide

:

Chickenpox vaccine is a safe and effective vaccine against a disease that is usually mild, at least in healthy children. The decision to use the vaccine depends on a trade-off between the potential benefits, harms, and cost. This trade-off will vary with the context.

Substantive changes

No new evidence

2007; 2007: 0912.
Published online 2007 August 1.

Aciclovir in children exposed prenatally

Summary

We found no clinically important results about the effects of aciclovir in prenatally exposed children.

Benefits

We found no systematic review or RCTs on the effects of aciclovir in prenatally exposed children.

Harms

We found no RCTs.

Comment

Clinical guide:

Newborns whose mothers' rashes appear in the last 5 days of pregnancy, or within 2 days of birth, have been reported in small case series to have a very high risk of severe chickenpox. On the basis of observational evidence and experience, most clinicians use varicella immunoglobulin in preference to aciclovir.

Substantive changes

No new evidence

2007; 2007: 0912.
Published online 2007 August 1.

Famciclovir in children exposed prenatally

Summary

We found no clinically important results about the effects of famciclovir for preventing chickenpox in prenatally exposed children.

Benefits

We found no systematic review or RCTs assessing famciclovir for preventing chickenpox in prenatally exposed children.

Harms

We found no RCTs.

Comment

None.

Substantive changes

Famciclovir for preventing chickenpox in prenatally exposed children New option. No systematic review or RCTs found. Categorisation: Unknown effectiveness

2007; 2007: 0912.
Published online 2007 August 1.

Valaciclovir in children exposed prenatally

Summary

We found no clinically important results about the effects of valaciclovir for preventing chickenpox in prenatally exposed children.

Benefits

We found no systematic review or RCTs assessing valaciclovir for preventing chickenpox in prenatally exposed children.

Harms

We found no RCTs.

Comment

None.

Substantive changes

Valaciclovir for preventing chickenpox in prenatally exposed children New option. No systematic review or RCTs found. Categorisation: Unknown effectiveness

2007; 2007: 0912.
Published online 2007 August 1.

Varicella zoster immunoglobulin in children exposed prenatally

Summary

We found no clinically important results about the effects of varicella zoster immunoglobulin in prenatally exposed children.

Benefits

We found no systematic review or RCTs assessing varicella zoster immunoglobulin (VZIG) in prenatally exposed children.

Harms

We found no RCTs.

Comment

None.

Substantive changes

Varicella zoster for preventing chickenpox in prenatally exposed children New option. No systematic review or RCTs found. Categorisation: Unknown effectiveness

2007; 2007: 0912.
Published online 2007 August 1.

Zoster immunoglobulin in children exposed prenatally

Summary

We found no clinically important results about the effects of zoster immunoglobulin in prenatally exposed children.

Benefits

We found no systematic review or RCTs on the effects of zoster immunoglobulin (ZIG) in prenatally exposed children.

Harms

We found no RCTs.

Comment

Clinical guide:

Newborns whose mothers' rashes appear in the last 5 days of pregnancy, or within 2 days of birth, have been reported in small case series to have a very high risk of severe chickenpox. Studies into the effects of zoster immunoglobulin have not been, and are unlikely to be, undertaken. Based on observational evidence and experience, most clinicians regard it as effective.

Substantive changes

No new evidence

2007; 2007: 0912.
Published online 2007 August 1.

Live attenuated varicella vaccine in immunocompromised people

Summary

We found no clinically important results about the effects of live attenuated varicella vaccine in immunocompromised adults or children.

Benefits

We found no systematic review or RCTs assessing clinical outcomes in people receiving cancer chemotherapy, or in people with HIV.

Harms

We found no RCTs.

Comment

The single antigen vaccine is licensed for use in the USA for HIV-infected children with CD4 counts greater than 15%, and in Europe for HIV-infected children with CD4 greater than 25%, and for immunocompromised people with more than 1200 lymphocytes per uL blood.

Substantive changes

No new evidence

2007; 2007: 0912.
Published online 2007 August 1.

Aciclovir, high dose (> 3200 mg/day) prevention in people with HIV infection

Summary

MORTALITY Compared with placebo: Aciclovir at doses of at least 3200 mg/day may reduce all-cause mortality over 22 months' treatment compared with placebo in people with HIV infection ( moderate-quality evidence ). INCIDENCE OF CHICKENPOX Compared with placebo: Aciclovir at doses of at least 3200 mg/day reduces the incidence of chickenpox compared with placebo in people with HIV infection ( high-quality evidence ).

Benefits

We found one systematic review (search date not reported, 8 RCTs, 1792 people with different stages of HIV, median CD4 count 34–607/mm3) comparing high dose aciclovir versus placebo. Three of the RCTs were unpublished, including two pharmaceutical company trials. The review found that aciclovir (at least 3200 mg/day for up to 22 months) significantly reduced clinical chickenpox (AR: 14/895 [2%] with aciclovir v 54/897 [6%] with placebo; OR 0.29, 95% CI 0.13 to 0.63; NNT 23, 95% CI 17 to 39). All cause mortality was also reduced (HR 0.78, 95% CI 0.65 to 0.93; OR 0.75, 95% CI 0.57 to 1.00). The treatment effect did not vary significantly with CD4 count. We found no RCTs of lower doses of aciclovir in people with HIV.

Harms

The systematic review gave no information on adverse effects (see harms under aciclovir for treatment).

Comment

None.

Substantive changes

No new evidence

2007; 2007: 0912.
Published online 2007 August 1.

Aciclovir prevention in people with immunocompromise other than HIV

Summary

We found no clinically important results about the effects of aciclovir in people with immunocompromise other than HIV.

Benefits

We found no systematic review or RCTs assessing aciclovir in adults or children with immunocompromise other than HIV.

Harms

We found no RCTs.

Comment

None.

Substantive changes

No new evidence

2007; 2007: 0912.
Published online 2007 August 1.

Famciclovir (prevention in immunocompromised people)

Summary

We found no clinically important results about the effects of famciclovir for chickenpox in immunocompromised people.

Benefits

We found no systematic review or RCTs assessing famciclovir for chickenpox in immunocompromised people.

Harms

We found no RCTs.

Comment

None.

Substantive changes

Famciclovir to prevent chickenpox in immunocompromised people New option. No systematic review or RCTs found. Categorisation: Unknown effectiveness

2007; 2007: 0912.
Published online 2007 August 1.

Valaciclovir (prevention in immunocompromised people)

Summary

We found no clinically important results about the effects of valaciclovir to prevent chickenpox in immunocompromised people.

Benefits

We found no systematic review or RCTs assessing valaciclovir to prevent chickenpox in immunocompromised people.

Harms

We found no RCTs.

Comment

None.

Substantive changes

Valaciclovir to prevent chickenpox in immunocompromised people New option. No systematic review or RCTs found. Categorisation: Unknown effectiveness

2007; 2007: 0912.
Published online 2007 August 1.

Varicella zoster immunoglobulin (prevention in immunocompromised people)

Summary

INCIDENCE OF CHICKENPOX Compared with zoster immunoglobulin (ZIG): Varicella zoster immunoglobulin is as effective as zoster immunoglobulin at preventing chickenpox in immunocompromised children ( moderate-quality evidence ). NOTE We found no direct information about whether varicella zoster immunoglobulin is better than no active treatment in immunocompromised children. We found no clinically important results about the effects of varicella zoster immunoglobulin compared with immune serum globulin in immunocompromised children or adults, or compared with zoster immunoglobulin in immunocompromised adults.

Benefits

Varicella zoster immunoglobulin versus placebo:

We found no systematic review or RCTs.

Varicella zoster immunoglobulin versus immune serum globulin in immunocompromised adults:

We found no systematic review or RCTs.

Varicella zoster immunoglobulin versus immune serum globulin in immunocompromised children:

We found no systematic review or RCTs.

Varicella zoster immunoglobulin versus zoster immunoglobulin in immunocompromised adults:

We found no systematic review or RCTs.

Varicella zoster immunoglobulin versus zoster immunoglobulin in immunocompromised children:

We found no systematic review. We found one RCT (164 immunocompromised children, mostly with leukaemia, exposed to a sibling with chickenpox) comparing varicella zoster immunoglobulin (VZIG) 1.25 mL/10 kg versus zoster immunoglobulin (ZIG) 1.25 mL/10 kg. It found no significant difference between VZIG and ZIG in the proportion of children with clinical chickenpox at 12 weeks (AR: 31/88 [37%] with ZIG v 36/81 [44%] with VZIG; RR 0.84, 95% CI 0.58 to 1.22).

Harms

The RCT gave no information on adverse effects.

Comment

Clinical guide:

Zoster immunoglobulin and varicella zoster immunoglobulin are frequently used to prevent chickenpox in exposed susceptible immunocompromised children, and sometimes in exposed pregnant women, preterm babies, adolescents, and adults.

Substantive changes

Varicella zoster immunoglobulin to prevent chickenpox in immunocompromised people New option. One RCT found no significant difference in clinical chickenpox with zoster immunoglobulin compared with varicella zoster immunoglobulin. Categorisation: Unknown effectiveness

2007; 2007: 0912.
Published online 2007 August 1.

Zoster immunoglobulin (prevention in immunocompromised people)

Summary

INCIDENCE OF CHICKENPOX Compared with varicella zoster immunoglobulin (VZIG): Zoster immunoglobulin is as effective as VZIG at preventing chickenpox in immunocompromised children ( moderate-quality evidence ). Compared with immune serum globulin: Zoster immunoglobulin may reduce the risk of developing chickenpox in healthy children after 20 days compared with immune serum globulin ( moderate-quality evidence ), but we found no clinically important information about their comparative effects in immunocompromised children. NOTE We found no direct information about whether or not zoster immunoglobulin is better than no active treatment in immunocompromised children. We found no clinically important results about the effects of zoster immunoglobulin compared with immune serum globulin or compared with varicella zoster immunoglobulin in immunocompromised adults.

Benefits

Zoster immunoglobulin versus placebo:

We found no systematic review or RCTs.

Zoster immunoglobulin versus immune serum globulin in immunocompromised adults:

We found no systematic review or RCTs.

Zoster immunoglobulin versus immune serum globulin in immunocompromised children:

We found no systematic review or RCTs.

Zoster immunoglobulin versus varicella zoster immunoglobulin in immunocompromised adults:

We found no systematic review or RCTs.

Zoster immunoglobulin versus varicella zoster immunoglobulin in immunocompromised children:

We found no systematic review. We found one RCT, see benefits of varicella zoster immunoglobulin.

Harms

The RCT gave no information on adverse effects.

Comment

Zoster immunoglobulin versus immune serum globulin in healthy children:

We found one small RCT (12 healthy susceptible children exposed to a sibling with recent onset of chickenpox) comparing ZIG (2 mL/10 kg) versus immune serum globulin (ISG) (2 mL/10 kg). It found that ZIG reduced the proportion of children with clinical chickenpox at 20 days (AR: 0/6 [0%] with ISG v 6/6 [100%] with ZIG). The RCT did not assess adverse effects. In the absence of evidence in immunocompromised people, data on effects in healthy people may be of some use, but the applicability of the findings to immunocompromised people is questionable.

Clinical guide:

Zoster immunoglobulin and varicella zoster immunoglobulin are frequently used to prevent chickenpox in exposed susceptible immunocompromised children, and sometimes in exposed pregnant women, preterm babies, adolescents, and adults.

Substantive changes

No new evidence

2007; 2007: 0912.
Published online 2007 August 1.

Aciclovir given within 24 hours after onset of rash in healthy people

Summary

DURATION OF FEVER Compared with placebo: Aciclovir given within 24 hours of onset of rash reduces the duration of fever compared with placebo in healthy children ( high-quality evidence ). DURATION OF RASH Compared with placebo: Aciclovir given within 24 hours of onset of rash does not reduce the duration of rash compared with placebo in healthy children (high-quality evidence). Aciclovir reduces the duration of rash in healthy adults if given within the first 24 hours of onset of rash compared with placebo ( moderate-quality evidence ).

Benefits

Aciclovir in healthy children:

We found one systematic review in children and adolescents (search date 2005, 3 RCTs, 979 children). The systematic review compared aciclovir versus placebo given within 24 hours of onset of rash in otherwise healthy children aged 0–18 years.It found no significant difference in time to no new lesions between aciclovir and placebo (WMD –0.8 days, 95% CI –1.6 days to +0.02 days). It found that aciclovir significantly reduced duration of fever compared with placebo (weighted mean reduction in duration of fever: 1.1 days, 95% CI 1.3 days to 0.9 days).

Aciclovir in healthy adults:

We found one systematic review (search date 1997, 3 RCTs). It did not perform a meta-analysis. The first RCT identified by the review (148 adults) compared early and late administration of aciclovir (800 mg 5 times/day) versus placebo. It found that aciclovir given within 24 hours of the onset of rash significantly reduced the maximum number of lesions (P < 0.01) and the time to full crusting of lesions (P = 0.001) compared with placebo. The two remaining RCTs (total of 168 healthy adults) only compared aciclovir given more than 24 hours after the onset of rash versus placebo.

Harms

The systematic review in children found no significant differences between treatment and control groups, or unfavourable trends in children taking aciclovir.

Comment

In healthy people who make an uneventful recovery without treatment, the effect on the measured outcomes was small and of questionable clinical importance.

Clinical guide:

Evidence is sparse, but symptomatic treatments are commonly used in practice, and may be beneficial. Paracetamol is used to reduce fever, topical calamine or crotamiton to soothe the skin and possibly relieve itching, and a sedating anithistamine at night to help sleep, and possibly break the itch-scratch-itch cycle. Should viral complications of chickenpox (e.g. pneumnia or encephalitis) develop in healthy people, aciclovir is indicated.

Substantive changes

No new evidence

2007; 2007: 0912.
Published online 2007 August 1.

Aciclovir treatment in healthy people given more than 24 hours after onset of rash

Summary

DURATION OF RASH Compared with placebo: Aciclovir may reduce the duration of rash in healthy children if started on the second day compared with the third day ( low-quality evidence ). Aciclovir does not reduce the duration of rash in healthy adults compared with placebo if started more than 24 hours after the onset of rash ( moderate-quality evidence ).

Benefits

Aciclovir in healthy children or adults:

We found one RCT that included children, adolescents, and adults (77 people). The RCT found that aciclovir started on the second day of the rash significantly reduced the time to no new lesions in children compared with starting on the third day (median: 4 days when started on second day v 5 days when started on third day; P < 0.04). It found no significant difference in time to new lesions between adolescents and adults. Earlier treatment significantly reduced the time to lowering of fever in adolescents (median: 2–3 days when started on second day v 3–4 days when started on third day; P < 0.02), but not in children and adults.

Aciclovir in healthy adults alone:

We found one systematic review (search date 1997, 3 RCTs). It did not perform a meta-analysis. The first RCT identified by the review (148 adults) compared early and late administration of aciclovir (800 mg 5 times/day) versus placebo. It found no significant difference in time to full crusting of lesions if aciclovir was given 24–72 hours after the rash (P > 0.2). The two remaining RCTs (total of 168 healthy adults) compared aciclovir given more than 24 hours after the onset of rash versus placebo. Neither found a significant difference in the time to no new lesions (P = 0.55 in 1 RCT, P values reported separately for different severities of eruption in the other RCT, all P > 0.05). They did not provide numerical information on the time to lowering of fever.

Harms

The systematic review in children found no significant differences between treatment and control groups, or unfavourable trends in children taking aciclovir.

Comment

Clinical guide:

Evidence is sparse, but symptomatic treatments are commonly used in practice, and may be beneficial. Paracetamol is used to reduce fever, topical calamine or crotamiton to soothe the skin and possibly relieve itching, and a sedating anithistamine at night to help sleep, and possibly break the itch-scratch-itch cycle. Should viral complications of chickenpox (e.g. pneumnia or encephalitis) develop in healthy people, aciclovir is indicated.

Substantive changes

No new evidence

2007; 2007: 0912.
Published online 2007 August 1.

Famciclovir (treatment in healthy people)

Summary

We found no clinically important results about the effects of famciclovir for treating chickenpox in healthy people.

Benefits

We found no systematic review or RCTs assessing famciclovir for treating chickenpox in healthy people.

Harms

We found no RCTs.

Comment

None.

Substantive changes

Famciclovir for treating chickenpox in healthy people New option. No systematic review or RCTs found. Categorisation: Unknown effectiveness.

2007; 2007: 0912.
Published online 2007 August 1.

Valaciclovir (treatment in healthy people)

Summary

We found no clinically important results about the effects of valaciclovir for treating chickenpox in healthy people.

Benefits

We found no systematic review or RCTs assessing valaciclovir for treating chickenpox in healthy people.

Harms

We found no RCTs.

Comment

None.

Substantive changes

Valaciclovir for treating chickenpox in healthy people New option. No systematic review or RCTs found. Categorisation: Unknown effectiveness.

2007; 2007: 0912.
Published online 2007 August 1.

Aciclovir treatment in immunocompromised adults

Summary

We found no clinically important results about the effects of aciclovir to treat chickenpox in immunocompromised adults.

Benefits

We found no systematic review or RCTs on the effects of aciclovir in immunocompromised adults.

Harms

We found no RCTs.

Comment

Despite scarce evidence, aciclovir is indicated in immunocompromised people, because of the poor prognosis without treatment, and the relatively minor harmful effects of the drug.

Substantive changes

No new evidence

2007; 2007: 0912.
Published online 2007 August 1.

Aciclovir (intravenous) for treatment of chickenpox in children with malignancy

Summary

SEVERITY OF ILLNESS Compared with placebo: Intravenous aciclovir may reduce the severity of illness compared with placebo in immunocompromised children ( low-quality evidence ) effective.

Benefits

We found two placebo controlled RCTs of intravenous aciclovir in children with cancer receiving chemotherapy. The largest RCT (50 children aged 1–14 years with chickenpox, 60% of whom had a rash for > 24 hours) found that significantly fewer children receiving aciclovir (500 mg/m2 of body surface area) deteriorated clinically and were transferred to open label aciclovir compared with placebo (1/25 [4%] with aciclovir v 12/25 [48%] with placebo; RR 0.08, 95% CI 0.01 to 0.59; NNT 3, 95% CI 2 to 4). Analysis of the remaining children not moved to open label aciclovir found that aciclovir significantly reduced the time to full crusting of lesions (mean: 5.7 days with aciclovir v 7.1 days with placebo; P < 0.013). It found no significant difference in lowering of fever. However, the exclusion from the subsequent analysis of children taking placebo who deteriorated clinically means that the effect of placebo may have been overestimated. The second RCT (20 children, mean age 6.4 years) comparing aciclovir (500 mg/m2 of body surface area) versus placebo found no significant difference in the proportion of children who deteriorated clinically and were moved to open label aciclovir (AR: 1/8 [12%] with aciclovir v 5/12 [42%] with placebo; RR 0.30, 95% CI 0.04 to 2.10). However, the RCT was too small to exclude a clinically important difference.

Harms

In the first RCT, 2/25 (8%) children on aciclovir developed transient elevated blood urea nitrogen levels, compared with two children with other transient minor adverse effects on placebo. In the second RCT, no adverse events were observed in the eight children receiving aciclovir, except one child with a self limiting maculopapular rash lasting 1 day.

Comment

Despite scarce evidence, aciclovir is indicated in immunocompromised people, because of the poor prognosis without treatment, and the relatively minor harmful effects of the drug.

Substantive changes

No new evidence

2007; 2007: 0912.
Published online 2007 August 1.

Famciclovir (treatment in immunocompromised people)

Summary

We found no clinically important results about the effects of famciclovir for treating chickenpox in immunocompromised people.

Benefits

We found no systematic review or RCTs assessing famciclovir for treating chickenpox in immunocompromised people.

Harms

We found no RCTs.

Comment

None.

Substantive changes

Famciclovir for treating chickenpox in immunocompromised people New option. No systematic review or RCTs found. Categorisation: Unknown effectiveness.

2007; 2007: 0912.
Published online 2007 August 1.

Valaciclovir (treatment in immunocompromised people)

Summary

We found no clinically important results about the effects of valaciclovir for treating chickenpox in immunocompromised people.

Benefits

We found no systematic review or RCTs assessing valaciclovir for treating chickenpox in immunocompromised people.

Harms

We found no RCTs.

Comment

None.

Substantive changes

Valaciclovir for treating chickenpox in immunocompromised people New option. No systematic review or RCTs found. Categorisation: Unknown effectiveness.


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