x

1
DH. Immunisation against infectious diseases – The Green book. Chapter 34. Varicella. Department of Health 2006. https://www.gov.uk/government/publications/varicella-the-green-book-chapter-34 Accessed 23.09.14. RATIONALE: Pregnant women are at greater risk of varicella pneumonia, and there is a risk to the fetus of congenital varicella syndrome if exposure occurs during the first 20 weeks of pregnancy, and severe disease in the neonate if varicella is contracted a week before delivery. Following infection in the second and third trimesters herpes zoster may present in otherwise healthy infants. Occasional cases of fetal damage comprising chorioretinal damage, microcephaly and skin scarring have been reported following maternal varicella infection between 20 and 28 weeks’ gestation but the risk is lower than for the first trimester. Neonates and immunocompromised individuals are at greater risk of disseminated or haemorrhagic varicella. Urgent specialist assessment is needed for all neonates, pregnant women, or immunocompromised individuals with varicella to assess the need for varicella immunoglobulin and antiviral treatment.

2
Klassen TP and Hartling L. Aciclovir for treating varicella in otherwise healthy children and adolescents. Cochrane Database of Systematic Reviews. 2005. Issue 4.
http://www.mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD002980/frame.html
Accessed 23.09.14. RATIONALE: Pooled data from three studies who enrolled participants within 24 hours of rash onset found that aciclovir was associated with a small reduction in the number of days with fever (-1.1, 95% CI -1.3 to -0.9) and in reducing the maximum number of lesions. Results were less supportive of a reduction in the number of days of itching. There were no differences in complication rates between those treated with aciclovir or placebo.

3
Swingler G. Chicken Pox. In: Clinical Evidence Concise. London. BMJ Publishing Group. 2006;15: 267-79. RATIONALE:One systematic review was identified that found one RCT (n = 148 adults) which compared early versus late administration of acyclovir 800mg five times a day compared with 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. 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).

4
Public Health England recommends that treatment with aciclovir should be considered (if it can be started within 24 hours of the rash) in those with severe chickenpox (including secondary cases) and in those at increased risk of complications (adults and adolescents aged 14 years and over, smokers, people on steroids).

5
Hope-Simpson RE. Postherpetic neuralgia.Brit J Gen Pract 1975; 25:571-75. RATIONALE:Study showing that incidence of post-herpetic neuralgia in a general practice population increases with age and is much more common in over 60 year olds

6
Wood MJ, Shukla S, Fiddian AP, Crooks RJ. Treatment of acute herpes zoster: effect of early (<48 h) versus late (48-72 h) therapy with acyclovir and valciclovir on prolonged pain. J Infect Dis 1998; 127(Suppl 1): S81-S84. RATIONALE:A study of two databases (n = 1076) found no difference in time to complete resolution of zoster-associated pain whether treatment was started within 48 hours or between 48 and 72 hours of the onset of cutaneous herpes zoster. Acyclovir HR 2.2, 95% CI1.03 to 4.71. Valaciclovir HR 1.40, 95% CI 1.04 to 1.87.

7
Wood MJ, Kay R, Dworkin RH, Soong S-J, Whitley RJ. Oral acyclovir therapy accelerates pain resolution in patients with herpes zoster: A meta-analysis of placebo-controlled trials. Clin Inf Dis 1996; 22: 341-7. Meta-analysis of four RCTs (n = 691) found greatest benefit in those aged over 50 years, in whom pain resolved twice as fast with acyclovir compared with placebo. Oral acyclovir also reduced the incidence of post herpetic neuralgia pain.

8
International Herpes Management Forum. Improving the management of varicella, herpes zoster, and zoster-associated pain. 2002. www.ihmf.org Accessed 23.09.14 RATIONALE: Antiviral treatment is recommended for ophthalmic shingles to prevent the potentially sight-threatening complications than can occur following herpes zoster involving the trigeminal nerve. Aciclovir, famciclovir, and valaciclovir have all been shown to reduce the complications of ophthalmic shingles in RCTs.

9
Dworkin RH, Johnson JW, Bruer J et al. Recommendations for the management of Herpes Zoster. Clin Infect Dis 2007;44(Suppl 1): S1-S26. RATIONALE: Expert opinion is that treatment of shingles should be considered for non-truncal involvement, people with moderate or severe pain, or those with moderate or severe rash. Evidence from RCTs supports treatment for all those over 50 years to prevent the incidence of post-herpetic neuralgia.

10
Beutner KR, Friedman DJ, Forszpaniak C, Anderson PL, Wood MJ. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother 1995; 39:1546-1553. RATIONALE:This randomized double-blind controlled trial (n = 1141) in people aged 50 years and over within 72 hours of onset of herpes zoster found that valaciclovir 1g three times a day for 7 or 14 days reduced the time to resolution of pain compared with acyclovir 800mg five times a day for 7 days. Median time to cessation of pain was 38 days for valaciclovir for 7 days compared with 51 days for acyclovir (p = 0.001), and was 44 days for valaciclovir for 14 days.

11
Shen MC, Lin HH, Lee SS, Chen YS, Chiang PC, Liu YC. Double-blind, randomized, acyclovir-controlled, parallel-group trial comparing the safety efficacy of famciclovir and acyclovir in patients with uncomplicated herpes zoster. J Microbiol Immunol Infect 2004; 37: 75-81.
RATIONALE: In this small study (n = 55), famciclovir and aciclovir were comparable in healing of lesions and cessation of acute-phase pain.

The POCAST project is funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at Imperial College London and by the Imperial College Healthcare Charity (Grant Ref No:7006/P36U).