Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus-host recombinant.

The RNA virus, hepatitis E virus (HEV) is the most or second-most important cause of acute clinical hepatitis in adults throughout much of Asia, the Middle East, and Africa. In these regions it is an important cause of acute liver failure, especially in pregnant women who have a mortality rate of 20-30%. Until recently, hepatitis E was rarely identified in industrialized countries, but Hepatitis E now is reported increasingly throughout Western Europe, some Eastern European countries, and Japan. Most of these cases are caused by genotype 3, which is endemic in swine, and these cases are thought to be zoonotically acquired. However, transmission routes are not well understood. HEV that infect humans are divided into nonzoonotic (types 1, 2) and zoonotic (types 3, 4) genotypes. HEV cell culture is inefficient and limited, and thus far HEV has been cultured only in human cell lines. The HEV strain Kernow-C1 (genotype 3) isolated from a chronically infected patient was used to identify human, pig, and deer cell lines permissive for infection. Cross-species infections by genotypes 1 and 3 were studied with this set of cultures. Adaptation of the Kernow-C1 strain to growth in human hepatoma cells selected for a rare virus recombinant that contained an insertion of 174 ribonucleotides (58 amino acids) of a human ribosomal protein gene.

Serial monogamy and biologic concurrency: measurement of the gaps between sexual partners to inform targeted strategies.

Having multiple sexual partners concurrently increases the risk of transmission of a sexually transmitted infection. Even if partnerships do not overlap, transmission potential exists when the gap between partnerships is shorter than the remaining infectious period. In the present article, we quantify the gap between partners to assess transmission potential using data collected by a cross-sectional survey of 2,203 genitourinary medicine clinic patients in England in 2009. Questionnaires asked about patients' 3 most recent partnerships. Gaps were calculated as time (days) between the last sexual encounter with a former partner and the first sexual encounter with the next partner. Among 1,875 patients who reported 1 or more partners in the previous 3 months, 47.6% of men and 27.7% of women reported 2 or more partners. Forty-two percent of the gaps were negative (i.e., partnerships that were concurrent); the median gaps were -7 and -17 days for men and women, respectively (i.e., overlaps were 7 and 17 days for men and women, respectively). Although half of the gaps were positive (serially monogamous partnerships), many were of short duration; the median gaps were 14 and 24 days for men and women, respectively. In over half of the gaps, condoms were used inconsistently with one or both partners, and in one-quarter, condoms were never used with either partner. There is thus a high potential for sexually transmitted infections, as even if partnerships are not behaviorally concurrent, they may be biologically concurrent. These data have important implications for designing and targeting effective health promotion messages.

Building the bypass--implications of improved access to sexual healthcare: evidence from surveys of patients attending contrasting genitourinary medicine clinics across England in 2004/2005 and 2009.

OBJECTIVE: The objective of this study was to examine changes in patient routes into genitourinary medicine (GUM) clinics since policy changes in England sought to improve access to sexual healthcare. METHODS: Cross-sectional patient surveys at contrasting GUM clinics in England in 2004/2005 (seven clinics, 4600 patients) and 2009 (four clinics, 1504 patients). Patients completed a short pen-and-paper questionnaire that was then linked to an extract of their clinical data. RESULTS: Symptoms remained the most common reason patients cited for attending GUM (46% in both surveys), yet the proportion of patients having sexually transmitted infection (STI) diagnosis/es declined between 2004/2005 and 2009: 38%-29% of men and 28%-17% of women. Patients in 2009 waited less time before seeking care: median 7 days (2004/2005) versus 3 days (2009), in line with shorter GUM waiting times (median 7 vs 0 days, respectively). Fewer GUM patients in 2009 first sought care elsewhere (23% vs 39% in 2004/2005), largely from general practice, extending their time to attending GUM by a median of 2 days in 2009 (vs 5 days in 2004/2005). Patients with symptoms in 2009 were less likely than patients in 2004/2005 to report sex since recognising a need to seek care, but this was still reported by 25% of men and 38% of women (vs 44% and 58%, respectively, in 2004/2005). CONCLUSIONS: Patient routes to GUM shortened between 2004/2005 and 2009. While GUM patients in 2009 were less likely overall to have STIs diagnosed, perhaps reflecting lower risk behaviour, there remains a substantial proportion of high-risk individuals requiring comprehensive care. Behavioural surveillance across all STI services is therefore essential to monitor and maximise their public health impact.

Treatment of chronic hepatitis E in a patient with HIV infection.

BACKGROUND: Hepatitis E virus (HEV) infections in immunosuppressed patients can result in chronic hepatitis that rapidly progresses to cirrhosis (1, 2). When immunosuppressed transplant recipients are treated with pegylated -interferon and ribavirin, HEV clears and liver histology improves (2). However, we are not aware of reports about how this therapy works in patients with HIV infection. OBJECTIVE: To describe the clinical and laboratory response to antiviral therapy for chronic HEV infection in a patient also infected with HIV. CASE REPORT: We studied a 48-year-old bisexual male with HIV- 1 infection who was chronically infected with HEV genotype 3a and had several years of painful sensory neuropathy of uncertain cause in the lower limbs (3). He had malaise, persistently abnormal liver function tests, and active inflammation and cirrhosis on liver biopsy (Figure).Before beginning anti-HEV therapy, the patient had an undetectable HIV viral load and a CD4 cell count between 30 and 150 cells/mL for the previous 2 years while receiving combination antiretroviral therapy (abacavir­lamivudine once daily and lopinavir­ritonavir twice daily).

Hepatitis E virus and neurologic disorders.

Information about the spectrum of disease caused by hepatitis E virus (HEV) genotype 3 is emerging. During 2004-2009, at 2 hospitals in the United Kingdom and France, among 126 patients with locally acquired acute and chronic HEV genotype 3 infection, neurologic complications developed in 7 (5.5%): inflammatory polyradiculopathy (n = 3), Guillain-Barre syndrome (n = 1), bilateral brachial neuritis (n = 1), encephalitis (n = 1), and ataxia/proximal myopathy (n = 1). Three cases occurred in nonimmunocompromised patients with acute HEV infection, and 4 were in immunocompromised patients with chronic HEV infection. HEV RNA was detected in cerebrospinal fluid of all 4 patients with chronic HEV infection but not in that of 2 patients with acute HEV infection. Neurologic outcomes were complete resolution (n = 3), improvement with residual neurologic deficit (n = 3), and no improvement (n = 1). Neurologic disorders are an emerging extrahepatic manifestation of HEV infection.

Rationale and development of a survey tool for describing and auditing the composition of, and flows between, specialist and community clinical services for sexually transmitted infections.

BACKGROUND: National health strategies have called for an expansion of the role of primary care in England to increase access to sexual health services. However, there is little guidance for service planners and commissioners as to the public health impact of different combinations of specialist genitourinary medicine (GUM) clinics and primary care based services for local populations. Service planning for infectious diseases like sexually transmitted infections (STI) is further complicated because the goal of early detection and treatment is not only to improve the health of the individual, but to benefit the wider population and reduce future treatment costs by preventing onward transmission. Therefore, we are developing a survey tool that will enable service planners to better understand the needs of their local STI care-seeking population and which will help inform evidence-based decision-making about current and future service configurations. Here we describe the rationale and development of this survey tool. METHODS/DESIGN: A pen-and-paper questionnaire asking about sociodemographics, reasons for attendance, care pathways, and recent sexual risk behaviours, is being developed for patients to complete in waiting rooms of diverse clinical services, including GUM clinics and primary-care based services in sociodemographically- and geographically-contrasting populations in England. The questionnaire was cognitively tested before being piloted. In the pilot, 67% of patients participated, of whom 84% consented to our linking their questionnaire to data on STI testing and diagnosis and partner notification outcomes from their clinical records. DISCUSSION: The pilot study suggests that both the questionnaire and its linkage to routinely-collected clinical data are likely to be acceptable to patients. By supplementing existing surveillance, data gathered by the survey tool will inform service planners' and providers' understanding of the needs and care-pathways of their patients, facilitating improved services and greater public health benefit.

Sexualized drug use and specialist service experience among MSM attending urban and rural sexual health clinics in England and Scotland.

Background: To date, evidence on whether sexualized drug use (SDU) and chemsex occur less frequently in rural compared to urban areas in Britain has been conflicting. This study aimed to better measure and understand whether attending urban versus rural sexual health clinics in the United Kingdom was associated with a difference in men who have sex with men's (MSM) experience of SDU or their access to SDU support. Methods: Men from 29 sexual health services across England and Scotland were recruited by self-completing a waiting room survey. Results: A total of 2655 men (864 MSM) took part. There was no statistically significant difference in recent SDU or chemsex identified in MSM attending rural compared to urban clinics. Gamma-Hydroxybutyrate/Gamma-Butyrolactone (GHB/GBL) was the most commonly reported chemsex drug used in a sexual setting, with equal prevalence of use in urban and rural MSM attendees. Distance travelled for SDU was not significantly different for rural compared to urban MSM. Rural MSM reported a higher rate of unmet need for SDU specific services, although this difference was not statistically significant. Conclusion: Within this sample of MSM, there were no significant differences in sexualized drug use behaviours between those attending rural compared to urban sexual health settings.

Chlamydia screening in a rural population: access, outcomes and health-care planning.

During the first year of a screening programme in Cornwall, a rural area of southwest England, 5024 young people were screened for genital Chlamydia trachomatis infection. We used mapping software to assess the prevalence of genital chlamydial infection and access to genitourinary medicine services among 16-25 year olds. Using this data, we calculated that attendance at genitourinary medicine clinics in Cornwall varies between 20/1000 and 83/1000 in this age group. Similarly, the rate of positive results varies between 2.9 and 27.4%, depending on place of residence and testing site. The highest rates of infection were noted in two areas with poor access to existing genitourinary medicine clinics. This information can be used to better plan sexual health services.

How much do delayed healthcare seeking, delayed care provision, and diversion from primary care contribute to the transmission of STIs?

OBJECTIVES: To quantify the contribution of patient delay, provider delay, and diversion between services to delayed access to genitourinary medicine (GUM) clinics. To describe the factors associated with delay, and their contribution to STI transmission. METHODS: Cross-sectional survey of 3184 consecutive new patients attending four GUM clinics purposively selected from across England to represent different types of population. Patients completed a short written questionnaire that collected data on sociodemographics, access, and health-seeking behaviour. Questionnaires were then linked to routinely collected individual-level demographic and diagnostic data. RESULTS: Patient delay is a median of 7 days, and does not vary by demographic or social characteristics, or by clinic. However, attendance at a walk-in appointment was associated with a marked reduction in patient delay and provider delay. Among symptomatics, 44.8% of men and 58.0% of women continued to have sex while awaiting treatment, with 7.0% reporting sex with >1 partner; 4.2% of symptomatic patients reported sex without using condoms with new partner(s) since their symptoms had begun. Approximately 25% of all patients had already sought or received care in general practice, and these patients experienced greater provider delay. CONCLUSIONS: Walk-in services are associated with a reduction in patient and provider delay, and should be available to all populations. Patients attending primary care require clear care pathways when referred on to GUM clinics. Health promotion should encourage symptomatic patients to seek care quickly, and to avoid sexual contact before treatment.