Anna Riddell

Comparison of interferon-{gamma} release assays and tuberculin skin test in predicting active tuberculosis (TB) in children in the UK: a paediatric TB network study

Background The value of interferon-γ release assays (IGRA) to diagnose active tuberculosis (TB) in children is not established, but these assays are being widely used for this purpose. The authors examined the sensitivity of commercially available IGRA to diagnose active TB in children in the UK compared with the tuberculin skin test (TST). Methods The authors established a paediatric tuberculosis network and conducted a retrospective analysis of data from children investigated for active TB at six large UK paediatric centres. All centres had used TST and at least one of the commercially available IGRA (T-Spot.TB or Quantiferon-Gold in Tube) in the diagnostic work-up for active TB. Data were available from 333 children aged 2 months to 16 years. The authors measured the sensitivity of TST and IGRA in definite (culture confirmed) and probable TB in children, agreement between TST and either IGRA, and their combined sensitivity. Results Of 333 children, 49 fulfilled the criteria of definite TB, and 146 had probable TB. Within the definite cohort, TST had a sensitivity of 82%, Quantiferon-Gold in tube (QFT-IT) had a sensitivity of 78% and T-Spot.TB of 66%. Neither IGRA performed significantly better than a TST with a cut-off of 15 mm. Combining the results of TST and IGRA increased the sensitivity to 96% for TST plus T-Spot.TB and 91% for TST plus QFG-IT in the definite TB cohort. Conclusions A negative IGRA does not exclude active TB disease, but a combination of TST and IGRA increases the sensitivity for identifying children with active TB.

Gag-specific CD4+ T-cell responses are associated with virological control of paediatric HIV-1 infection

HIV-specific Elispot responses were investigated in 57 antiretroviral therapy-naive children, of median age 9.9 years. CD8+ T-cell responses were detected in 96% children; Nef was the immunodominant protein. Responses broadened over time, but there was no association between magnitude, breadth or specificity of response and viraemia. Gag-specific CD4+ T-cell responses, detectable in 26% children, correlated inversely with viraemia (R = −0.43, P < 0.001), suggesting that preservation of this cell population may be an important goal of therapeutic/vaccine strategies.

The impact of BCG vaccination on tuberculin skin test responses in children is age dependent: evidence to be considered when screening children for tuberculosis infection

Background Following exposure to TB, contacts are screened to target preventive treatment at those at high risk of developing TB. The UK has recently revised its recommendations for screening and now advises a 5 mm tuberculin skin test (TST) cut-off irrespective of age or BCG status. We sought to evaluate the impact of BCG on TST responses in UK children exposed to TB and the performance of different TST cut-offs to predict interferon γ release assay (IGRA) positivity. Methods Children <15 years old were recruited from 11 sites in the UK between January 2011 and December 2014 if exposed in their home to a source case with sputum smear or culture positive TB. Demographic details were collected and TST and IGRA undertaken. The impact of BCG vaccination on TST positivity was evaluated in IGRA-negative children, as was the performance of different TST cut-offs to predict IGRA positivity. Results Of 422 children recruited (median age 69 months; IQR: 32–113 months), 300 (71%) had been vaccinated with BCG. BCG vaccination affected the TST response in IGRA-negative children less than 5 years old but not in older children. A 5 mm TST cut-off demonstrated good sensitivity and specificity in BCG-unvaccinated children, and an excellent negative predictive value but was associated with low specificity (62.7%; 95% CI 56.1% to 69.0%) in BCG-vaccinated children. For BCG-vaccinated children, a 10 mm cut-off provided a high negative predictive value (97.7%; 95% CI 94.2% to 99.4%) with the positive predictive value increasing with increasing age of the child. Discussion BCG vaccination had little impact on TST size in children over 5 years of age. The revised TST cut-off recommended in the recent revision to the UK TB guidelines demonstrates good sensitivity but is associated with impaired specificity in BCG-vaccinated children.

Management of sharps injuries in the healthcare setting

#### The bottom line Sharps injuries are common in the healthcare setting. Between 2004 and 2013 a total of 4830 healthcare associated occupational exposures to body fluid were reported in the UK, 71% of these for percutaneous injuries.1 As the reporting system is likely to have recorded only cases with an important exposure, the actual burden of sharps injuries is likely to be much higher. Healthcare workers need to be familiar with immediate management both for themselves if they become injured and for assisting injured colleagues. Many healthcare workers do not know how to manage a sharps injury,2 particularly if this occurs out of hours. This review presents a summary of the immediate management of sharps injuries and outlines the risk assessment and management strategies to prevent the transmission of HIV, hepatitis B virus, and hepatitis C virus. #### Sources and selection criteria We searched PubMed and the Cochrane Library for articles published over the past 20 years using the terms “sharps injury”, “needle stick injury”, and “body fluid exposure” and hand selected the most relevant and appropriate articles. To search for relevant UK national guidelines we also accessed the UK Department of Health and Public Health England …

Management and outcome of Bacille Calmette-Guérin vaccine adverse reactions

Highlights • BCG vaccine is the one of the most widely used vaccines globally.• Local complications are commonly seen but approach to management varies.• Injection site reactions and non-suppurative lymphadenitis can be managed conservatively.• Aspiration may be beneficial in suppurative lymphadenitis.• Antimicrobials and surgery are rarely required except for non-resolving cases.

Management of paediatric tuberculosis in leading UK centres: unveiling consensus and discrepancies.

SETTING Large specialist paediatric TB clinics in the UK. OBJECTIVE To evaluate clinical practice and compare with national and international guidelines. DESIGN A survey based on an electronic questionnaire on the management of latent tuberculous infection (LTBI) and tuberculosis (TB) disease was conducted in 13 specialist paediatric TB clinics. The consensus and discrepancies were evaluated by descriptive analysis. RESULTS Practice was reportedly different when choosing age limits for preventive treatment for TB contacts with initially negative tuberculin skin tests (TSTs), interpretation of TST results and use of interferon-gamma release assays (IGRAs) in the context of LTBI. In relation to management of children with TB disease, practices varied for duration of treatment of osteoarticular TB, monitoring for ethambutol ocular toxicity and use of pyridoxine. There was limited experience with multidrug-resistant TB (MDR-TB), and over half of the clinics monitored MDR-TB contacts without giving preventive treatment. CONCLUSIONS The survey showed heterogeneity in several aspects of clinical care for children with TB. Available paediatric TB guidelines differ substantially, explaining the wide variations in management of childhood TB. Prospective paediatric studies are urgently required to inform and standardise clinical practice, especially in the context of evolving drug resistance.

The impact of out-of-hospital models of care on paediatric emergency department presentations

Objective To estimate the potential impact of enhanced primary care and new out-of-hospital models (OOHMs) on emergency department (ED) presentations by children and young people (CYP). Design Observational study. Patients & setting Data collected prospectively on 3020 CYP 0–17.9 years from 6 London EDs during 14 days by 25 supernumerary clinicians. CYP with transient acute illness, exacerbation of long-term condition (LTC), complex LTC/disability and injury/trauma were considered manageable within OOHM. OOHMs assessed included nurse-led services, multispecialty community provider (MCP), primary and acute care system (PACS) plus current and enhanced primary care. Measures Diagnosis, severity; record of investigations, management and outcome that occurred; objective assessment of clinical need and potential alternative management options/destinations. Results Of the patients 95.6% had diagnoses appropriate for OOHM. Most presentations required assessment by a clinician with skills in assessing illness (39.6%) or injuries (30.9%). One thousand two hundred and ninety-one (42.75%) required no investigations and 1007 (33.3%) were provided only with reassurance. Of the presentations 42.2% were judged to have been totally avoidable if the family had had better health education. Of the patients 26.1% were judged appropriate for current primary care (community pharmacy or general practice) with 31.5% appropriate for the combination of enhanced general practice and community pharmacy. Proportions suitable for new models were 14.1% for the nurse-led acute illness team, MCP 25.7%, GP federation CYP service 44.6%, comprehensive walk-in centre for CYP 64.3% and 75.5% for a PACS. Conclusions High proportions of ED presentations by CYP could potentially be managed in new OOHMs or by enhancement of existing primary care.

Evaluating UK National Guidance for Screening of Children for Tuberculosis. A Prospective Multicenter Study

Rationale: To identify infected contacts of tuberculosis (TB) cases, the UK National Institute for Health and Care Excellence (NICE) recommended the addition of IFN‐&ggr; release assays (IGRA) to the tuberculin skin test (TST) in its 2006 TB guidelines. Treatment for TB infection was no longer recommended for children who screened TST‐positive but IGRA‐negative. Objectives: We performed a cohort study to evaluate the risk of TB disease in this group. Methods: Children exposed to an infectious case of TB in their household were recruited from 11 pediatric TB clinics. TST and IGRA were performed at baseline, with IGRA repeated at 8 weeks and TST repeated if initially negative. Children were treated according to 2006 NICE guidelines and followed for 24 months. Measurements and Main Results: Of 431 recruited children, 392 completed the study. We diagnosed 48 (12.2%) cases of prevalent TB disease, 105 (26.8%) with TB infection, and 239 (60.9%) without TB infection or disease. Eighteen children aged 2 years and above had a positive TST but persistently negative IGRA. None received TB infection treatment and none developed TB disease. Ninety (26.1%) children qualified for TB infection treatment according to 2006 NICE guidelines. In contrast, 147 (42.7%) children would have qualified under revised NICE guidance, issued in 2016. Conclusions: In this low‐prevalence setting we saw no incident cases of TB disease in children who were TST‐positive but IGRA‐negative and did not receive treatment for TB infection. Following the latest NICE guidance, significantly more children will require medication.

Two Cases of BCG Osteomyelitis Diagnosed Through Polymerase Chain Reaction/Electrospray Ionization-Mass Spectrometry Technology

4. Tung E, Thomas A, Eichner A, Shalit P. Feasibility of a pharmacist-run HIV PrEP clinic in a community pharmacy setting. Presented at: Conference on Retroviruses and Opportunistic Infections; February 2017; Seattle, WA; abstract 961. 5. Project WERK: Network Support to Engage and Retain Younger Black MSM in PrEP Care R34MH11139201 (NIMH); PI: Bouris, Schneider. 08/01/16-07/30/19. Available at: https://project reporter.nih.gov/project_info_description. cfm?aid=9519034&icde=40899379&ddparam=&ddvalue=&ddsub=&cr=1&csb=default&cs=ASC&pball= 6. Bouris A, Jaffe K, Eavou R, et al. Project nGage: results of a randomized controlled trial of a dyadic network support intervention to retain young black men who have sex with men in HIV care. AIDS Behav 2017; 21:3618–29.

Imported dengue fever in East London: a 6-year retrospective observational study

Background Dengue fever (DF) is a frequently imported arthropod-borne infection in the United Kingdom but its broad range of clinical presentations makes it potentially unrecognized by clinicians. Methods We conducted a 6-year retrospective case note review of laboratory confirmed DF patients in East London in the period from 1 January 2010 through 31 December 2015. Epidemiological, clinical and laboratory features of imported DF were described. Risk factors associated with viraemic DF presentations were assessed. Results Forty-four patients (4 from primary care clinics and 40 from three acute hospitals) were confirmed to have DF through RNA and/or IgM detection. In total, 86.4% (38/44) had primary infection compared to 13.6% (6/44) with secondary infection. Viraemic DF presentations accounted for 59.1% (26/44) of cases. The median age was 34 years (IQR 25-43). Most patients were males (68.2%, 30/44) and of non-white ethnicity (81.8%, 36/44). South Asia was the most frequent travel destination (52.3%, 23/44) followed by Southeast Asia (20.5%, 9/44). July-September was the peak season of presentation (43.2%, 19/44). The median interval between arrival in the UK and laboratory testing was 7 days (IQR 4-13). Arriving from abroad ≤ 7 days before molecular testing (age-adjusted odds ratios [OR] 16.98, 95% CI 2.43-118.75, P  =   0.004) and travel to South or Southeast Asia regions (age-adjusted OR 4.41, 95% CI 1.07-18.21, P  =   0.040) were associated with detectable viraemia at presentation. Only one DF patient met the WHO severity criteria. HIV serostatus was determined in 61.4% (27/44) of cases. Conclusion Clinicians need to improve DF recognition as well as rates of HIV testing in tropical travellers. Region of travel and time since arrival from DF endemic settings may help clinicians optimize requests for molecular testing. Further research on the clinical and public health aspects of imported DF is needed.