The impact, effectiveness and outcomes of targeted screening thresholds for programmatic latent tuberculosis infection testing in HIV.

BACKGROUND: Screening and treatment for latent tuberculosis infection (LTBI) are key for TB control. In the UK, the National Institute for Health and Care Excellence (NICE) and the British HIV Association (BHIVA) give conflicting guidance on which groups of people with HIV (PWH) should be screened, and previous national analysis demonstrated heterogeneity in how guidance is applied. There is an urgent need for a firmer clinical effectiveness evidence base on which to build screening policy. METHODS: We conducted a systematic, programmatic LTBI-screening intervention for all PWH receiving care in Leicester, UK. We compared yields (percentage IGRA positive) and number of tests required when applying the NICE and BHIVA testing strategies, as well as strategies targeting screening by TB incidence in patients' countries of birth. RESULTS: Of 1053 PWH tested, 118 were IGRA-positive (11.2%). Positivity was associated with higher TB incidence in country-of-birth [adjusted odds ratio, 50-149 cases compared with <50 cases/100 000: 11.6; 95% confidence interval (CI) 4.79-28.10)]. There was high testing uptake (1053/1069, 98.5%). Appropriate chemoprophylaxis was commenced in 100 of 117 (85.5%) patients diagnosed with LTBI, of whom 96 of 100 (96.0%) completed treatment. Delivering targeted testing to PWH from countries with TB incidence greater than 150 per 100 000 population or any sub-Saharan African country, would have correctly identified 89.8% of all LTBI cases while cutting tests required by 46.1% compared with NICE guidance, performing as well as BHIVA 2018 guidance. CONCLUSION: Targeting screening to higher risk PWH increases yield and reduces the number requiring testing. Our proposed 'PWH-LTBI streamlined guidance' offers a simplified approach, with the potential to improve national LTBI-screening implementation.

Latent tuberculosis screening and treatment in HIV: highly acceptable in a prospective cohort study.

Background: People living with HIV (PLWH) are at increased risk of re-activation of latent tuberculosis infection (LTBI). Although UK and international guidelines identify this group as a priority for LTBI screening and treatment, data on attitudes of PLWH to this policy recommendation are lacking. Methods: A five-point, Likert-style questionnaire was administered to PLWH to assess views and intentions towards accepting LTBI screening and treatment. Subsequent interferon-γ release assay (IGRA) testing was offered, and chemoprophylaxis if required. Influencing demographic and psychological associations with planned, and actual, testing and treatment uptake were assessed using multivariable logistic regression. Results: 444 out of 716 (62%) patients responded. 417 out of 437 (95.4%) expressed intention to accept LTBI testing. The only significant association was the perceived importance of testing to the individual (adjusted odds ratio (aOR) 8.98, 95% CI 2.55-31.67). 390 out of 393 (99.2%) accepted appropriate IGRA screening; 41 out of 390 (10.5%) were positive. 397 out of 431 (92.1%) expressed intention to accept chemoprophylaxis, associated with perceived importance of treatment (aOR 3.52, 95% CI 1.46-8.51), a desire to have treatment for LTBI (aOR 1.77, 95% CI 0.99-3.15) and confidence in taking treatment (aOR 3.77, 95% CI 1.84-7.72). Of those offered chemoprophylaxis, 36 out of 37 (97.3%) accepted and 34 out of 36 (94.4%) completed treatment. There were no correlates with actual screening acceptance. Conclusions: LTBI is common amongst PLWH, highlighting the importance of robust screening and treatment programmes. This study shows that screening and treatment for LTBI is highly acceptable to PLWH and provides strong, objective evidence for policy-makers developing guidelines in this cohort.

Rectal cancer mimic: a rare case of syphilitic proctitis.

Syphilitic proctitis is a rare presentation of sexually transmitted infection that poses a diagnostic challenge as it mimics rectal cancer clinically, radiologically and endoscopically. We report a case of a 66-year-old male patient with a background of HIV infection presenting with obstructive bowel symptoms and initial diagnosis of rectal cancer on CT. Sigmoidoscopy and histopathology were non-diagnostic. A diagnosis of secondary syphilis was suspected after obtaining sexual history and diagnostic serology, avoiding planned surgical intervention.

Community-based testing of migrants for infectious diseases (COMBAT-ID): impact, acceptability and cost-effectiveness of identifying infectious diseases among migrants in primary care: protocol for an interrupted time-series, qualitative and health economic analysis.

BACKGROUND: Migration is a major global driver of population change. Certain migrants may be at increased risk of infectious diseases, including tuberculosis (TB), HIV, hepatitis B and hepatitis C, and have poorer outcomes. Early diagnosis and management of these infections can reduce morbidity, mortality and onward transmission and is supported by national guidelines. To date, screening initiatives have been sporadic and focused on individual diseases; systematic routine testing of migrant groups for multiple infections is rarely undertaken and its impact is unknown. We describe the protocol for the evaluation of acceptability, effectiveness and cost-effectiveness of an integrated approach to screening migrants for a range of infectious diseases in primary care. METHODS AND ANALYSIS: We will conduct a mixed-methods study which includes an observational cohort with interrupted time-series analysis before and after the introduction of routine screening of migrants for infectious diseases (latent TB, HIV, hepatitis B and hepatitis C) when first registering with primary care within Leicester, UK. We will assess trends in the monthly number and rate of testing and diagnosis for latent TB, HIV, hepatitis B and hepatitis C to determine the effect of the policy change using segmented regression analyses at monthly time-points. Concurrently, we will undertake an integrated qualitative sub-study to understand the views of migrants and healthcare professionals to the new testing policy in primary care. Finally, we will evaluate the cost-effectiveness of combined infection testing for migrants in primary care. ETHICS AND DISSEMINATION: The study has received HRA and NHS approvals for both the interrupted time-series analysis (16/SC/0127) and the qualitative sub-study (16/EM/0159). For the interrupted time-series analysis we will only use fully anonymised data. For the qualitative sub-study, we will gain written, informed, consent. Dissemination of the results will be through local and national meetings/conferences as well as publications in peer-reviewed journals.

Hypogonadism in the HIV-Infected Man.

Low testosterone levels are frequently observed among men with treated and untreated HIV infection. However, the interpretations of biochemical measurements of testicular function are challenging and need to be considered in the context of the clinical presentation and scenario. The distinction between primary and secondary hypogonadism and determination of the underlying clinical pathophysiology are not always straightforward. Early recognition of clinical hypogonadism and appropriate treatment may improve clinical outcomes and quality of life for affected individuals. A principal aim of testosterone replacement is to maintain serum testosterone concentrations in the normal physiological range and should be considered in clinically symptomatic patients.

Latent tuberculosis infection screening and treatment in HIV: insights from evaluation of UK practice.

Latent TB infection (LTBI) screening and treatment in HIV-positive individuals in the UK is advocated by the British HIV Association (BHIVA) and National Institute for Health and Care Excellence (NICE), although each recommends differing strategies. We undertook an evaluation of UK practice, relating the responses to the local HIV/TB disease burden. 162 of 188 (86%) UK geographical areas responded; only 93/162 (57.4%) offer LTBI testing with considerable heterogeneity in practice, and no difference in HIV/TB burden between areas offering testing and those who do not. Only 33/93 (35.5%) and 6/93 (6.5%) reported full compliance with BHIVA and NICE guidance respectively. A uniform national guideline is required.

Multi-centre observational study of transplacental transmission of influenza antibodies following vaccination with AS03(A)-adjuvanted H1N1 2009 vaccine.

INTRODUCTION: Illness and death from influenza increase during pregnancy. In the United Kingdom pregnant women were targeted in a national programme for vaccination during the H1N1 2009-10 pandemic. METHODS: In this study, pregnant women were recruited in labour from November 9, 2009 to March 10, 2010. Pandemic vaccination status was determined. Venous cord blood collected at delivery was evaluated for transplacental transfer of antibodies by measurement of haemagglutination inhibition and microneutralization titres. RESULTS: Samples were collected from 77 vaccinated and 27 unvaccinated women. Seroprotection (HI titre ≥1:40) was detected in 58 (75.3%, 95% CI 64.2-84.4) cord blood samples from vaccinated women and 5 (18.5%, 95% CI 6.3-38.1) from unvaccinated women (P<0.0001). There was evidence of transplacental seroprotection 8 days after maternal immunization (77.9%, 95 CI 66.2-87.1), maintained in most cases for at least 16 weeks. DISCUSSION: Immunization of pregnant women with AS03(A)-adjuvanted vaccine is followed by transplacental transfer of passive immunity at titres consistent with clinical protection in three-quarters of new-born infants. The findings support national and international pandemic H1N1 2009 recommendations for immunization during pregnancy.

Reproducibility of serology assays for pandemic influenza H1N1: collaborative study to evaluate a candidate WHO International Standard.

Haemagglutination-inhibition (HI) and virus neutralisation (VN) assays are used to evaluate immunogenicity of pandemic H1N1 vaccines; however these bioassays are poorly standardised leading to inter-laboratory variation. A candidate International Standard (IS) for antibody to H1N1 pdm virus (09/194) was prepared from pooled sera of subjects who had either recovered from H1N1 pdm infection or who had been immunised with an adjuvanted subunit vaccine prepared from reassortant virus NYMC X-179A (derived from A/California/7/2009 virus). Ten laboratories from seven countries tested the candidate IS, 09/194 and a panel of human sera by HI and VN using the A/California/7/2009 virus (six laboratories) and/or the reassortant virus NYMC X-179A (ten laboratories). As expected, the inter-laboratory variability for HI and VN assay results was high. For results of antibody tests to NYMC X-179A, the % geometric coefficient of variation (%GCV) for 09/194 between laboratories was 83% for HI and 192% for VN. For tests of all sera, the median %GCV ranged from 95 to 345% for HI (80-fold variation) and 204 to 383% for VN (109-fold variation), but for the titres relative to 09/194 the median %GCV was much reduced (HI 34-231%; VN 44-214%). For tests of antibody to the A/California/7/2009 wild type virus there were similar reductions in %GCV when 09/194 was used. These results suggest that 09/194 will be of use to standardise assays of antibody to A/California/7/2009 vaccine and 09/194 has now been established by WHO as an IS for antibody to A/California/7/2009 with an assigned potency of 1300 IU per ml.

Seasonal influenza vaccination predicts pandemic H1N1 vaccination uptake among healthcare workers in three countries.

The aim of this study was to identify the common barriers and facilitators for acceptance of pandemic influenza vaccination across different countries. This study utilized a standardized, anonymous, self-completed questionnaire-based survey recording the demographics and professional practice, previous experience and perceived risk and severity of influenza, infection control practices, information of H1N1 vaccination, acceptance of the H1N1 vaccination and reasons of their choices and opinions on mandatory vaccination. Hospital-based doctors, nurses and allied healthcare workers in Hong Kong (HK), Singapore (SG) and Leicester, United Kingdom (UK) were recruited. A total of 6318 (HK: 5743, SG: 300, UK: 275) questionnaires were distributed, with response rates of 27.1% (HK), 94.7% (SG) and 94.5% (UK). The uptake rates for monovalent 2009 pandemic H1N1 vaccine were 13.5% (HK), 36.2% (SG) and 41.3% (UK). The single common factor associated with vaccine acceptance across all sites was having seasonal influenza vaccination in 2009. In UK and HK, overestimation of side effect reduced vaccination acceptance; and fear of side effect was a significant barrier in all sites. In HK, healthcare workers with more patient contact were more reluctant to accept vaccination. Drivers for vaccination in UK and HK were concern about catching the infection and following advice from health authority. Only a small proportion of respondents agreed with mandatory pandemic influenza vaccination (HK: 25% and UK: 42%), except in Singapore where 75.3% were in agreement. Few respondents (<5%) chose scientific publications as their primary source of information, but this group was more likely to receive vaccination. The acceptance of pandemic vaccine among healthcare workers was poor (13-41% of respondents). Breaking barriers to accept seasonal influenza vaccination should be part of the influenza pandemic preparedness plan. Mandatory vaccination even during pandemic is likely to arouse substantial discontent.

Report of the fourth meeting on 'Influenza vaccines that induce broad spectrum and long-lasting immune responses', World Health Organization and Wellcome Trust, London, United Kingdom, 9-10 November 2009.

Current influenza vaccines are limited by the need for annual immunisation, frequent antigenic updating to match the evolution of circulating influenza virus strains, and reduced efficacy in elderly persons. On 9-10 November 2009, the Initiative for Vaccine Research of the World Health Organization convened jointly with the Wellcome Trust in London, United Kingdom, the fourth meeting on 'Influenza vaccines that induce broad spectrum and long-lasting immune responses'. Presentations were made by representatives from industry, academia, governmental and non-governmental organisations. The objectives of the meeting were to update the progress of research in the field of influenza vaccine strategies able to generate cross protection against divergent influenza virus strains. Improvements in existing strategies including live attenuated influenza vaccines and adjuvantation of inactivated vaccines were summarised. Developments in novel antigen production methods, new routes of vaccine delivery and administration, and vaccine approaches based on conserved virus antigens were explored. In addition, correlates of immune protection and regulatory issues for the evaluation and approval of future novel vaccine strategies were discussed.

Enteric fever in a UK regional infectious diseases unit: a 10 year retrospective review.

INTRODUCTION: Enteric fever is an increasingly common diagnosis in returning travellers in the UK. METHODS: We performed a retrospective descriptive study of culture-confirmed cases of enteric fever admitted to University Hospitals Leicester, UK between January 1999 and April 2009. RESULTS: 100 cases of enteric fever were identified in adults (n = 76) and children (n = 24). The median age of adult subjects was 38 (range 18-71) and 55% were male. Of the 61 adult cases with notes available, 60 (98.3%) were of Asian ethnicity and 56 (92%) had a recent travel history, principally to the Indian Subcontinent. Symptoms included fever (100%), headache (62%), diarrhoea (59%) and abdominal pain (44%). Common examination findings included pyrexia and mild generalized abdominal tenderness. Mild hyponatraemia, transaminitis and a normal white cell count were commonly identified. Reduced ciprofloxacin sensitivity was common and increased over the study period. Median fever clearance time was 6 days, and treatment failure occurred in 20% of cases. Relapse occurred in 2 patients. Complications were unusual, and one patient died. DISCUSSION: Patients with enteric fever presented with a non-specific febrile illness within one month after returning from travel, and most had an uncomplicated clinical course. Increasing ciprofloxacin insensitivity was the likely explanation for a high treatment failure rate and this agent can no longer recommended as empirical treatment.