Implementing routine blood-borne virus testing for HCV, HBV and HIV at a London Emergency Department - uncovering the iceberg?

UK guidelines recommend routine HIV testing in high prevalence emergency departments (ED) and targeted testing for HBV and HCV. The 'Going Viral' campaign implemented opt-out blood-borne virus (BBV) testing in adults in a high prevalence ED, to assess seroprevalence, uptake, linkage to care (LTC) rates and staff time taken to achieve LTC. Diagnosis status (new/known/unknown), current engagement in care, and severity of disease was established. LTC was defined as patient informed plus ⩾1 clinic visit. A total of 6211/24 981 ED attendees were tested (uptake 25%); 257 (4.1%) were BBV positive (15 co-infected), 84 (33%) required LTC. 100/147 (68%) HCV positives were viraemic; 44 (30%) required LTC (13 new, 16 disengaged). 26/54 (48%) HBV required LTC (seven new, 11 disengaged). 16/71 (23%) HIV required LTC (10 new, five disengaged). 26/84 (31%) patients requiring LTC had advanced disease (CD4 1, Fibroscan F3/F4 or liver cancer), including five with AIDS-defining conditions and three hepatocellular carcinomas. There were five BBV-related deaths. BBV prevalence was high (4.1%); most were HCV (2.4%). HIV patients were more successfully and quickly LTC than HBV or HCV patients. ED testing was valuable as one-third of those requiring LTC (new, disengaged or unknown status patients) had advanced disease.

Incorporating HIV/hepatitis B virus/hepatitis C virus combined testing into routine blood tests in nine UK Emergency Departments: the "Going Viral" campaign.

OBJECTIVES: Routine HIV screening is recommended in those UK hospitals and primary care settings where the HIV prevalence is > 0.2%. For hepatitis B virus (HBV) and hepatitis C virus (HCV), however, testing is targeted at at-risk groups. We investigated the prevalence of these blood-borne viruses (BBVs) during a routine testing pilot in UK Emergency Departments (EDs). METHODS: During the "Going Viral" campaign (13-19 October 2014), nine UK EDs in areas of high HIV prevalence offered routine tests for HIV, HBV and HCV to adults having blood taken as part of routine care. Patients who tested positive were linked to care. RESULTS: A total of 7807 patients had blood taken during their ED visit; of these, 2118 (27%) were tested for BBVs (range 9-65%). Seventy-one BBV tests were positive (3.4%) with 32 (45.1%) new diagnoses. There were 39 HCV infections (15 newly diagnosed), 17 HIV infections (six newly diagnosed), and 15 HBV infections (11 newly diagnosed). Those aged 25-54 years had the highest prevalence: 2.46% for HCV, 1.36% for HIV and 1.09% for HBV. Assuming the cost per diagnosis is £7, the cost per new case detected would be £988 for HCV, £1351 for HBV and £2478 for HIV. CONCLUSIONS: In the first study in the UK to report prospectively on BBV prevalence in the ED, we identified a high number of new viral hepatitis diagnoses, especially hepatitis C, in addition to the HIV diagnoses. Testing for HIV alone would have missed 54 viral hepatitis diagnoses (26 new), supporting further evaluation of routine BBV testing in UK EDs.

Immune deficiency: changing spectrum of pathogens.

Current UK national standards recommend routine bacteriology surveillance in severe antibody-deficient patients, but less guidance exists on virology screening and viral infections in these patients. In this retrospective audit, we assessed the proportion of positive virology or bacteriology respiratory and stool samples from patients with severe, partial or no immune deficiency during a 2-year period. Medical notes were reviewed to identify symptomatic viral infections and to describe the course of persistent viral infections. During the 2-year period, 31 of 78 (39·7%) severe immune-deficient patients tested had a positive virology result and 89 of 160 (55.6%) had a positive bacteriology result. The most commonly detected pathogens were rhinovirus (12 patients), norovirus (6), Haemophilus influenzae (24), Pseudomonas spp. (22) and Staphylococcus aureus (21). Ninety-seven per cent of positive viral detection samples were from patients who were symptomatic. Low serum immunoglobulin IgA levels were more prevalent in patients with a positive virology sample compared to the total cohort (P = 0·0078). Three patients had persistent norovirus infection with sequential positive isolates for 9, 30 and 16 months. Virology screening of symptomatic antibody-deficient patients may be useful as a guide to anti-microbial treatment. A proportion of these patients may experience persistent viral infections with significant morbidity.

High prevalence of hepatitis C (HCV) in the emergency department (ED) of a London hospital: should we be screening for HCV in ED attendees?

An unlinked anonymous study was conducted to estimate the prevalence of hepatitis C virus (HCV) infection in emergency department (ED) attendees at a London Hospital. Nine hundred and ninety-seven samples collected over a 12-day period were tested for HCV antibody (Ab) and reactive samples were further tested for HCV RNA. The HCV seroprevalence was 2·6% (26/997) with 1·2% (12/997) HCV RNA positive. A peak HCV RNA-positive prevalence of 4·8% (3/63) was found in males aged 35-44 years, this was compared to 0% (0/136) in males aged <35 years (P = 0·0614) and 1·4% (4/278) in males aged ⩾45 years (P = 0·2415). Assuming the cost for HCV Ab is £6 and HCV RNA is £40 per test, screening ED attendees aged 25-54 years would cost £360 per viraemic infection and identify 82% of those who were HCV RNA positive, yielding the most favourable cost/benefit ratio. HCV screening of ED attendees aged 25-54 years in this population could be an effective way of identifying patients and limit onward transmission.

Diagnosing HIV infection in patients presenting with glandular fever-like illness in primary care: are we missing primary HIV infection?

OBJECTIVES: The aim of the study was to examine the prevalence of HIV infection in patients presenting in primary care with glandular fever (GF)-like illness. METHODS: Samples from primary care submitted for a GF screen between April 2009 and June 2010 were identified. Samples without an HIV request were anonymized and retrospectively tested using a 4th-generation HIV antigen/antibody screening test. Reactive samples were further confirmed by an HIV antibody only test, with or without a p24 antigen assay. Antibody avidity testing based on the Recent HIV Infection Testing Algorithm (RITA) was used to identify individuals with evidence of recent acquisition (within 4-5 months). RESULTS: Of 1046 GF screening requests, concomitant HIV requests were made in 119 patients. Excluding one known positive patient, 2.5% (three of 118) tested HIV positive. Forty-five (4.3%) had a subsequent HIV test through another consultation within 1 year; of these, 4.4% (two of 45) tested positive. Of the remaining 882 patients, 694 (78.7%) had samples available for unlinked anonymous HIV testing, of which six (0.9%) tested positive. The overall HIV prevalence was 1.3% (11 of 857), with 72.7% (eight of 11) of cases missed at initial primary care presentation. Four of the nine (44.4%) available positive samples had evidence of recent acquisition, with three (75.0%) missed at initial primary care presentation. CONCLUSION: Low levels of HIV testing in patients presenting in primary care with GF-like illness are resulting in a significant number of missed HIV and seroconversion diagnoses. Local policy should consider adopting an opt-out strategy to include HIV testing routinely within the GF-screening investigation panel.

Performance of the GeneXpert CT/NG assay compared to that of the Aptima AC2 assay for detection of rectal Chlamydia trachomatis and Neisseria gonorrhoeae by use of residual Aptima Samples.

There are currently no commercially available molecular assays for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae in rectal swabs with regulatory approval. We compared the Cepheid GeneXpert CT/NG assay with the GenProbe Aptima Combo2 assay, using 409 rectal swabs. Using Aptima as the gold standard, the sensitivity, specificity, and positive and negative predictive values of GeneXpert for the detection of C. trachomatis and N. gonorrhoeae were 86%, 99.2%, 92.5%, and 98.4% and 91.1%, 100%, 100%, and 98.6%, respectively. Despite significant dilution of samples prior to GeneXpert testing, the assay performed well with excellent specificity.

New therapies for chronic hepatitis C infection: a systematic review of evidence from clinical trials.

INTRODUCTION: Hepatitis C virus (HCV) affects approximately 3% of the world population. The current standard of care for treatment of HCV is a combination of pegylated interferon and ribavirin. Approximately 10% of patients will stop treatment and 30% of patients require dose reduction because of side effects. For genotype 1 HCV-infected patients, only 40% of patients will achieve undetectable viral load 26 weeks posttreatment. AIMS: The objectives of this review were to identify new treatments that are in clinical trials. These include boceprevir and telaprevir which are in routine clinical use and form part of the American Association for the Study of Liver Diseases (AASLD) 2011 guidelines as well as drugs based on observational studies, improving/modifying ribavirin or interferon-based therapies, modifying the host response and finally the use of direct-acting antiviral agents (DAA). MATERIALS AND METHODS: MEDLINE and EMBASE databases were searched from 2008 to 2011 for treatments for hepatitis C. Furthermore, abstracts and poster presentations for the annual European Association Study of the Liver, AASLD, Digestive Disease Week and Asian Pacific Association for the study of the Liver were searched for relevant material. RESULTS: All four classes of DAA; NS3/NS4a serine protease inhibitors, cyclophilin inhibitors, NS5b polymerase inhibitors and NS5a inhibitors, show good success rates. Trials have been performed without ribavirin or interferon and demonstrate good antiviral activity with a decreased side effect profile. Combinations of DAA are a promising area of research with a high success rate. CONCLUSIONS: Clinical trials show that future HCV therapy could be personalised, achieve higher success rates with decreased adverse incidents.

Clinical utility of genotypic resistance tests for HIV-1-infected patients with low-level virological failure.

The usefulness of genotypic resistance tests (GRT) among HIV-1 patients with low-level virological failure (LLVF) was evaluated. Up to 78% of samples with <1,000 copies/ml were sequenced successfully. For samples with 50 to 200 copies/ml, the success rate was as high as 69%. LLVF should not deter clinicians from requesting GRT.

Multicentric Castleman's disease in HIV infection.

Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder. The precise incidence is unknown, although it is more common in HIV-positive than HIV-negative individuals. The pathological features of MCD strongly suggest a chronic antigen stimulation response, and human herpes virus 8 (HHV8) has been found to be universal in cases of HIV-related MCD. The presentation is non-specific with a wide differential diagnosis, which often results in a significant delay in its diagnosis. Diagnosis is made on the clinical presentation of a lymphoproliferative disorder, with evidence of multisystem involvement with classical histopathology on lymph node biopsy. Although no standard of care has been established for its treatment, symptomatic recurrences are often treated with corticosteroids and chemotherapy. The contribution of highly active antiretroviral treatment to the treatment of MCD remains debated. Novel treatments targeted at HHV8 show promising results, although evidence is currently limited to case reports. Randomized control trials assessing whether 'prophylactic' treatment with ganciclovir may prevent flares as currently used against cytomegalovirus disease in transplant patients are proposed. The prognosis of MCD in HIV-positive patients remains generally poor with a median survival of 48 months from diagnosis, and a 15-fold increased risk of non-Hodgkin's lymphoma.

Genital ulcers: it is not always simplex .

Patients with vulval aphthae, also termed Lipschütz ulcers, often present to genitourinary medicine clinics. Typically, these ulcers present as acute, painful, vulval ulcers in young women and adolescents. The aetiology is unknown, and often these ulcers are accompanied by flu-like symptoms. Previous case reports have linked such lesions to acute viral infections such as Epstein-Barr virus, cytomegalovirus and influenza A. We report the first case of influenza B virus and adenovirus infections associated with this presentation.

Analysis of a potential cluster of rhinovirus infections in patients and staff on two haemato-oncology wards.

BACKGROUND: Human rhinoviruses (HRV) cause the common cold, increased mortality in patients attending elderly care facilities and significant morbidity as well as mortality in the post-transplantation setting. OBJECTIVES: The aim of the study was to determine if there had been a breakdown in infection control practice in a large haemato-oncology centre. Molecular techniques had detected increased numbers of HRV in respiratory samples from patients and staff over a 6-week period. Typing was performed to investigate the possibility of transmission between individuals. STUDY DESIGN: This was a retrospective study having detected HRV RNA in combined nose and throat swab samples that were collected from 13 individuals: 8 patients and 5 staff members, in the haemato-oncology wards of a tertiary referral centre in January and February 2011. The 5'NTR and the VP4/VP2 region were used for HRV typing. RESULTS: All 3 HRV species were detected with 7 HRV-A, 1 HRV-B, 4 HRV-C and 1 untyped. None of the individuals were infected by the same HRV serotype. Three individuals had multiple samples collected: 1 patient had an HRV-B infection over a 4-week period, 1 patient had an HRV-A infection over 3 months and 1 staff member had an HRV-C infection over 1 week, each shedding an unchanged serotype throughout the whole period. CONCLUSION: Nucleotide sequence analysis confirmed that there was no breakdown in infection control measures. No transmission incidents had occurred between patients and/or between staff and patients.

Hepatitis B virus carrier rate, prevalence and susceptibility and impact of immunization program among households in the city of Taiz, Yemen.

OBJECTIVE: To examine the carrier rate, prevalence and susceptibility to hepatitis B virus infection in the city of Taiz, Yemen. METHODS: In a community-based household survey 521 subjects from 98 randomly selected households were enrolled. Carrier rate, prevalence and susceptibility of hepatitis B virus infection in the city of Taiz, Yemen were examined. RESULTS: The median age of the subjects was 19 years (range <1-85 years), 219 (42.0%) of whom were males and 305 (58.0%) were females. The HBsAg carrier rate was 4.2% (22/521), the prevalence was 16.9% (88/521) and the susceptibility rate was 57.5% (287/499). Male vs female carrier rate, prevalence and susceptibility rate were comparable. Children (age ≤ 18 years) vs adults had carrier rates of 2.7% vs 5.7% (odds ratio=2.2) and a prevalence of 5.1% vs 28.4% (OR: 5.6). The carrier rate, prevalence and immunity to HBV among subjects who reported vaccination vs those unvaccinated was; 2.1% vs 5.5%, 11.3 vs 20.8% and 53.1% vs 18.8%. A proportion of 47.2% of subjects who aged ≤ 10 years had isolated anti-HBs. Of 142 of the cohort born after full implementation of vaccination program (age:≤ 9 years) 72 (50.7%) were immune and 70 (49.3%) were susceptible whereas of 357 subjects borne before program implementation (Age:≥ 10 years) 140 (39.2%) were immune and 217 (60.8%) were susceptible (p<0.02 (Pearson) OR: 1.6 CI=0.42-0.93). CONCLUSIONS: An intermediate endimicity was identified in Taiz city. Vaccination reduced carrier rate prevalence and susceptibility among vaccinated subjects. The high rate of subjects with isolated anti- HBs together with the reduced susceptibility rate among the cohort born after inclusion of HBV vaccine to EPI reflects impact of the program. Improving vaccination coverage will further reduce susceptibility rate.

Vaccination against hepatitis B in an HIV outpatients' department: an audit against national vaccination guidelines.

Practice related to hepatitis B vaccination of HIV outpatients in a London teaching hospital was audited against the British HIV Association (BHIVA) immunization guidelines 2004 and 2008, both before and after the implementation of a vaccination record sheet in the patients' notes. Adherence to the guidelines in the original audit was poor - only 67% of patients requiring vaccination for hepatitis B received a full course of vaccination. Following the introduction of the vaccination record sheet, this vaccination completion rate increased to 79% (BHIVA target 95%). Overall the percentage of patients managed according to BHIVA guidelines, including those who did not require vaccination, improved from 33% in the original audit to 61% in the re-audit. Introduction of a simple hepatitis B vaccination record sheet improved the quality of care for our HIV outpatients. Further modification of this system is warranted, perhaps by the introduction of a computerized reminder system.

Seven days of doxycycline is an effective treatment for asymptomatic rectal Chlamydia trachomatis infection.

There are no evidence-based guidelines for the specific management of rectal Chlamydia trachomatis (CT) infection. All men who have sex with men (MSM) diagnosed with asymptomatic rectal CT by nucleic acid amplification test (NAAT) at a large London genitourinary (GU) medicine clinic between September 2006 and September 2009 were offered oral doxycycline 100 mg twice daily for seven days and invited for a test of cure (TOC) by CT NAAT four weeks after treatment. A total of 487 asymptomatic rectal CT infections were diagnosed and analysis was restricted to 165 TOCs from men whose only treatment had been doxycycline for seven days. The median time post-treatment for TOC was 45 days (interquartile range [IQR], 34-88). Only two patients tested CT-positive at follow-up. One had taken doxycycline only for three days; the other attended for TOC 240 days after the completion of doxycycline treatment and at this time presented with new symptoms in the context of ongoing high sexual risk. Our findings show that doxycycline 100 mg twice daily for seven days is highly effective treatment for asymptomatic rectal CT infection, achieving clearance of CT in 98.8% (163/165; 95% CI 95.4-99.9%) of cases. We advocate doxycycline for seven days as first-line therapy for asymptomatic rectal CT.

Transmission of syphilis by solid organ transplantation.

Two organ recipients developed serologic evidence of syphilis infection after renal transplantation from a common deceased donor with a history of treated syphilis. Testing of donor serum for syphilis, which occurred after transplantation, gave results interpreted as consistent with past infection. However, subsequent serologic results in the recipients suggested transmission of infection at transplantation due to active infection of the donor. This may be explained by recent donor re-infection in view of the current syphilis epidemic in the United Kingdom. An initial error in the treatment of recipients further served to highlight unfamiliarity in managing this resurgent infection in the context of organ transplantation.

Genotyping of B and non-B subtypes of human immunodeficiency virus type 1.

Current HIV-1 genotyping assays were developed using subtype B viruses prevalent in Western countries. It is not clear whether these assays are appropriate for use among African patients, who are likely to be infected with non-B subtypes. We evaluated the Bayer TRUGENE HIV-1 genotyping (TG) assay using prospectively collected samples from HIV-1-infected individuals who acquired infection in either sub-Saharan Africa or the West (Europe, North America, and Australia). Plasma samples from 208 individuals with an HIV-1 viral load of >1,000 copies/ml were tested using version 1 primers supplied with the TG assay. If these failed, an alternative primer set version 1.5 was used. Of the 208 individuals, the likely origin of infection was Africa (n = 104), Western (n = 87) and "Others" (i.e., all other geographic locations or origin not certain; n = 17). Among the three groups, the version 1 primers were successful in 85 (82%), 77 (89%), and 13 (76%) individuals, respectively (P = 0.1). Of the remaining 32 samples, 30 were successfully amplified by using the version 1.5 primers. HIV-1 subtypes deduced from the reverse transcriptase sequences correlated with the likely origin of infection: Africa (28A, 3B, 33C, 13D, 6G, 4J, 2K, 5CRF01_AE, and 10CRF02_AG), Western (86B and 1K), and Others (1A and 16B). The success of the version 1 primers correlated with viral load (P < 0.014) and not with HIV-1 subtypes. A protocol based on version 1 primers, followed by 1.5 primers, was successful in sequencing 99% of the samples in this cohort.

Prevalence of blood-borne viral hepatitis in different communities in Yemen.

It is generally believed that hepatitis B (HBV) and C (HCV) viruses are highly prevalent in the Republic of Yemen. This study investigated the prevalence of HBV and HCV markers in 494 blood donors from Aden, 493 blood donors from Sana'a, 97 residents from an African ethnic minority in Sana'a and 99 residents of Soqotra Island. There were significant differences in the prevalence of HBV carriage (HBsAg: 6.7, 15, 19.6 and 26.3% respectively; P < 0.001); past HBV infection (anti-HBc: 17.4, 18.5, 30.9 and 59.6% respectively; P < 0.001); susceptibility to HBV (absence of HBV markers: 73.3, 61.9, 38.1 and 9.1% respectively; P < 0.001), infectivity of HBV carriers (HBV DNA: 51.5, 33.8, 52.6 and 65.4% respectively; P = 0.028) and HCV antibodies (RIBA confirmed or indeterminate: 0.6, 0.2, 5.2 and 5.1% respectively; P < 0.001). A significant difference in HBV carrier rate and a borderline significant difference in the prevalence of natural infection was observed between males and females in the African community (P = 0.02 and 0.06 respectively). In contrast, in Soqotra Island, there was no significant sex difference in HBV carrier rate but susceptibility was significantly more prevalent in males (P = 0.03). This study illustrates that significant difference in prevalence and epidemiology exists among different communities within the same country, reflecting political, geographical and social differences. Control strategies should take these differences into account.