Since the first reports of hepatitis of unknown aetiology occurring in UK children, over 1000 cases have been reported worldwide, including 268 cases in the UK, with the majority younger than 6 years old. Using genomic, proteomic and immunohistochemical methods, we undertook extensive investigation of 28 cases and 136 control subjects. In five cases who underwent liver transplantation, we detected high levels of adeno-associated virus 2 (AAV2) in the explanted livers. AAV2 was also detected at high levels in blood from 10/11 non-transplanted cases. Low levels of Adenovirus (AdV) and Human Herpesvirus 6B (HHV-6B), both of which enable AAV2 lytic replication, were also found in the five explanted livers and blood from 15/17 and 6/9 respectively, of the 23 non-transplant cases tested. In contrast, AAV2 was detected at low titre in 6/100 whole bloods from child controls from cohorts with presence or absence of hepatitis and/or adenovirus infection. Our data show an association of AAV2 at high titre in blood or liver tissue, with unexplained hepatitis in children infected in the recent AdV-F41 outbreak. We were unable to find evidence by electron microscopy, immunohistochemistry or proteomics of AdV or AAV2 viral particles or proteins in explanted livers, suggesting that hepatic pathology is not due to direct lytic infection by either virus. The potential that AAV2, although not previously associated with disease, may, together with AdV-F41 and/or HHV6, be causally implicated in the outbreak of unexplained hepatitis, requires further investigation.

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Post-herpetic neuralgia (PHN) following acute herpes zoster remains a significant cause of neuropathic pain especially in the elderly. Early treatment of the zoster rash with antiviral agents, such as aciclovir remains one of the few measures proven to reduce the incidence and duration of PHN albeit only in a subset of patients. It is therefore crucial that the physician who first sees a case of zoster identifies those patients who are most likely to develop long-term pain and treats them accordingly. In particular, prodrugs such as famciclovir and valaciclvoir may be more beneficial in reducing PHN than the shorter acting aciclovir, but can be more expensive. Measures that could be used to predict patients likely to develop PHN would also facilitate the evaluation of early use of antiepileptic, anti-inflammatory and analgesic agents in the prevention of PHN. In a prospective study of 280 herpes zoster (HZ) cases seen by the general practitioner (GP) we evaluated the predictive value of five clinical factors identified in clinical trials as associated with a higher likelihood of PHN. A visual analogue score (VAS) over 5 and/or age over 50 correctly identified all subjects with PHN at 3 and 6 months, respectively. However, the specificity of this prediction was low because as many as 81% and 85% of those aged over 50 recovered within 3 and 6 months, respectively. Better methods are needed to identify patients over 50 at most risk of PHN that enable GPs to better allocate their resources with respect to HZ treatment.

BackgroundTrachoma, caused by ocular Chlamydia trachomatis, is the leading infectious cause of blindness worldwide. Sudan first reported trachoma in the 1930s and has since been consistently endemic. Ocular C. trachomatis previously isolated from trachoma patients in Sudan in 1963 was antigenically identical to an isolate from Saudi Arabia (A/SA1). No contemporary ocular C. trachomatis whole genome sequences have been reported from Sudan.MethodsThis study sequenced twenty ocular C. trachomatis isolates to improve understanding of pathogen diversity in North-East Africa and examine for genomic variation specific to Sudan, possibly related to the persistence of trachoma in surveyed communities. High quality, whole genome sequences were obtained from 12/20 isolates.ResultsAll isolates were serovar A and had tarP and trpA sequences typical of classical, ocular C. trachomatis isolates. The Sudanese isolates formed a closely related subclade within the T2-trachoma clade of C. trachomatis phylogeny distinct from geographically disparate ocular isolates, with little intra-population diversity. We found 333 SNPs that were conserved in Sudanese ocular isolates but rare compared to other ocular C. trachomatis populations, which were focused in two genomic loci (CTA0172-CTA0173 and CTA0482).ConclusionsLimited intra-population diversity and geographical clustering of ocular C. trachomatis suggests minimal transmission between and slow diversification within trachoma-endemic communities. However, diversity may have been higher pre-treatment in these communities. Over-representation of Sudan-specific SNPs in three genes suggests they may have an impact on C. trachomatis growth and transmission in this population.