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Over 90% of the population are infected with varicella zoster virus (VZV) but only some develop shingles - caused when the virus reactivates from latency, and only some shingles patients develop post-herpetic neuralgia (PHN), defined as pain continuing for more than about 4 months. Epstein Barr virus (EBV) similarly infects over 90% of the population; some of those infected during teenage or young adult years develop infectious mononucleosis (IM). The reason for these disparities between numbers infected and numbers affected by illness is unknown, but presumably reflects host factor(s). Our previous results showed that apolipoprotein E (APOE) genotype determines susceptibility to, or outcome of, infection in the case of several diseases of known infectious cause. Therefore, we investigated APOE genotypes of shingles, PHN, and IM patients. Our rationale for the previous studies and for investigating VZV was that these micro-organisms use for cell binding and entry the same sites in the cell surface as does the protein apoE, and that consequently, competition with apoE could affect the pathogen's extent of entry and hence extent of the damage caused. The APOE genotypes of shingles and PHN sufferers, and of IM sufferers were determined using restriction fragment length polymorphism. In females, epsilon4 homozygosity confers a risk of shingles and also of IM, and the APOE-epsilon4 allele is protective against PHN whereas APOE-epsilon3 allele is a risk. Our results showing that a host genetic factor influences the development of shingles and PHN in females have clinical significance: they could lead to identification of those (female) patients at greater risk of PHN, thus enabling these people to be targeted for treatment with the most effective drugs.

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We analysed prospectively the medical, societal and economic burden among patients from 18 general practices in East London, serving 158,716 patients who presented to their general practitioners with acute Herpes Zoster over an 8-month period. One hundred and eighty-six patients with HZ were seen by GPs during the study period, of whom 96 were referred, 70 enrolled and 65 completed. PHN occurred in 13.4% of patients. The average overall cost of HZ in the first 6 months was calculated at pound524 per patient. Medical costs were highest in those aged over 65 and societal costs highest in those aged under 65 years.

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Strains of Varicella zoster virus (VZV) have been described recently in which a single base mutation in the gE epitope abrogates binding of the 3B3 monoclonal antibody, which is widely used for virus detection in diagnostic laboratories. These strains, named VZV-MSP, are associated with a distinct phenotype in both in vitro culture and in SCID-hu mice. We investigated the possibility that negative direct immunofluorescence results, using the 3B3 antibody, where the presence of virus was confirmed by polymerase chain reaction (PCR) or tissue culture are due in some cases to the MSP strain of VZV. A total of 249 vesicle fluid specimens from people with suspected shingles were examined using direct immunofluorescence, tissue culture and a nested multiplex PCR for VZV, herpes simplex virus type 1 (HSV-1) and 2 (HSV-2). VZV was detected in 218 of 249 (87.6%) cases. Forty-five confirmed VZV specimens, but with negative (30) or indeterminate (15) immunofluorescence results, were analysed further. PCR was used to amplify a fragment in ORF 68 that encodes the VZV gE ectodmain recognised by 3B3 antibody. The fragments were sequenced and analysed for the single base change G448A (D150N), which is present in VZV-MSP as compared with the reference Dumas strain. No VZV gE mutant (MSP/MSP-like) was detected. Overall, PCR was found to be the most sensitive method of confirming VZV infection. False negative VZV immunofluorescence results are unlikely to be due to virus variants.

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The incidence of post-herpetic neuralgia following shingles and the factors that are known to predict it were examined in a prospective observational community study of patients with acute shingles presenting to their family doctors. The detection of viral DNA in the blood at presentation as a prognostic indicator for pain was also evaluated. Patients were followed for one year and the persistence of pain following rash assessed. Among 165 patients who had completed 6 months, and 139 one-year follow-up, the prevalence of post herpetic neuralgia was 30% at 6 weeks 27% at 12 weeks, 15.9% at 6 months, and 9% at one year. Age and severity of pain were significantly associated with the persistence of pain beyond 3 months. Viremia at presentation was detected in 66% of patients and was significantly associated with the presence of pain at six months or beyond. Antiviral agents were administered to only 50% of those at highest risk of post-herpetic neuralgia (PHN) mainly because of presentation longer than 72 hours after the onset of rash. Few patients were prescribed the more potent prodrugs, Valaciclovir and Famciclovir. In conclusion, treatment of acute shingles in this observational community-based study was suboptimal in 50% of cases. More accurate prediction of which subset of elderly patients are most at risk of PHN may enable targeted prescribing of the most potent drugs to those most likely to benefit.

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Of 75 varicella-zoster virus (VZV) isolates obtained from patients in Africa, Asia, and the Far East, 74 (98.6%) were found to be positive for a BglI restriction site in gene 54. By contrast, <22% of strains from patients in the United Kingdom and in North and South America were positive for the BglI restriction site. Viruses positive for BglI were significantly more common in zoster occurring in patients of nonwhite origin (P<.05). Irrespective of the country in which the sample was obtained, 98% of strains positive for BglI clustered within a single phylogenetic group, which we termed "group A"; the exception was 1 strain that appeared to be recombinant genotype C/A. We used the BglI site to examine both the spread of type A viruses in the United Kingdom and the patterns of VZV infections within persons from different ethnic groups who grew up in the United Kingdom or abroad.

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