Frances Keane

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.

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.

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 (abacavir–lamivudine once daily and lopinavir–ritonavir twice daily).

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.

Do users of the intrauterine system (Mirena) have different genital symptoms and vaginal flora than users of the intrauterine contraceptive device

The copper intrauterine contraceptive device (IUCD) is strongly associated with bacterial vaginosis (BV). Hormonal influences may play a role in the control of vaginal flora. It is unclear whether use of the progesterone-incorporated intrauterine system (IUS; Mirena) is associated with abnormal vaginal flora or genital symptoms. One hundred and seventy-two women were assessed for symptoms and abnormal vaginal flora prior to and at intervals after insertion of either a copper IUCD or an IUS. Women were significantly more likely to have developed an abnormal vaginal discharge 4–6 weeks after insertion of an IUCD compared with an IUS (27% cf. 14%, P = 0.04), although this trend was not significant six months postinsertion. More women with an IUCD developed BV compared with an IUS at 4–6 weeks and six months. However, there were insufficient numbers of women with BV to demonstrate any significant difference between the vaginal flora of the two groups.

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.

Who attends primary care services prior to attendance at genitourinary services and what level of care have they received

Objective: To determine the proportion of patients initially attending primary care services and describe the care received prior to attending genitourinary medicine (GUM) clinics. Method: A cross-sectional survey of 1000 new patients attending GUM services in Cornwall between June and December 2006. Patients were asked during consultation whether they had attended primary care before coming and what examination, investigation and management had been carried out there. Results: 35% (348/1000) of patients had attended primary care initially. Genital examination had been carried out in primary care on 60% (111/185) female and 58% (93/159) male patients (p = 0.78). Chlamydia testing had been carried out in 27% (46/171) female and 6% (8/139) male patients (p<0.005). 33% (100/301) patients seen in primary care had been offered treatment. 74% (68/92) patients with genital warts had been correctly diagnosed in primary care and 9% (8/92) of these offered treatment. Conclusions: The majority of these patients, including those given a diagnosis and/or offered treatment in primary care, had not had a chlamydia test or any other investigations. With the potential “fall out” of patients between primary care and GUM services, this may represent a missed opportunity to detect and appropriately manage sexually transmitted infections.

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.

Methods employed by genitourinary medicine clinics in the United Kingdom to diagnose bacterial vaginosis.

Objective: To determine the methods used by genitourinary medicine (GUM) clinics in the United Kingdom for the diagnosis of bacterial vaginosis (BV). Methods: A questionnaire survey of UK GUM clinics was conducted. Results: 148/221 (67%) clinics returned a questionnaire. 96/148 (64.9%) clinics reported using Amsel’s criteria to diagnose BV but only 29 (30.5%) of these used all four of the composite criteria. 139/148 (93.9%) clinics used the appearance of a Gram stained vaginal smear as an aid in BV diagnosis, although a variety of scoring methods was employed. In the majority of clinics, 92/148 (62.2%), one staff discipline provided the microscopy service, in 50 (33.8%) clinics two staff disciplines provided microscopy services. The bulk of microscopy services within UK GUM clinics is provided by nurses. Conclusions: Most UK GUM clinics utilise the appearance of a Gram stained vaginal smear for the diagnosis of BV although there is little consensus at present about the type of scoring method employed. Adaptation of a uniform scoring method would have enormous benefits, including consistency and reproducibility of results and the development of quality assurance schemes for BV diagnosis on a national basis. There are important issues to be addressed regarding the initial training and ongoing support for nurses providing microscopy services within UK GUM clinics.

The limits of health-care seeking behaviour: how long will patients travel for STI care? Evidence from England's ‘Patient Access and the Transmission of Sexually Transmitted Infections’ (‘PATSI’) study

The objective of this study was to identify factors associated with (i) longer patient travel time to genitourinary (GU) medicine clinics and (ii) not attending the nearest clinic. Questionnaires were completed by 4600 new attendees from seven sociodemographically and geographically different GU clinics across England between October 2004 and March 2005. These data were then linked to the routine clinic database. Median travel time was 25 minutes and varied significantly by clinic (P < 0.001) but not by gender (P = 0.96). Of all the respondents, 10% spent at least one hour getting to a GU clinic and this was significantly more likely in patients with less education, those who travelled by public transport and those who did not attend their closest clinic. Longer travel times were not associated with delays in seeking care. Patients reporting a previous sexually transmitted infection (STI) diagnosis were more likely not to go to their nearest GU clinic (P = 0.0006), as were those who used/tried to use other healthcare providers prior to attending the clinic (P = 0.007). To facilitate access to STI care, comprehensive local services need to be provided to avoid long journey times, especially for those who have to rely on public transport to get to clinic.