High false discovery rate of the Architect anti-HCV screening test in blood donors in Uganda and evaluation of an algorithm for confirmatory testing.

BACKGROUND AND OBJECTIVES: Adequate supplies of donor blood remain a major challenge in sub-Saharan Africa. This is exacerbated by a lack of confirmatory testing for transfusion-transmitted infections by blood transfusion services (BTS), leading to significant blood disposal owing to putatively high seroprevalence rates amongst Ugandan blood donors. We aimed to ascertain the false discovery rate of the Architect anti-hepatitis C virus (HCV) screening assay and categorize screen-reactive samples into three groups: presumed false positive, active and past infection, and develop an algorithm for confirmatory testing. MATERIALS AND METHODS: A total of 470 screen-reactive HCV blood donations were retested using the Architect anti-HCV assay, an alternative antibody test (SD Biosensor) and a core antigen (cAg) test. signal-to cut-off (S/CO) ratios and pre-analytical factors (centrifugation speed, haemolysis check, time between collection and testing) were recorded. Based on the S/CO ratio evaluation, we propose a testing algorithm to guide supplemental tests. RESULTS: The false discovery rate of the Architect anti-HCV assay was 0.84 as 395/470 (84%) screen-reactive samples had no evidence of HCV infection (SD Biosensor and cAg negative) (presumed false positive), 38/470 (8.1%) were antigenaemic, and 32/470 (6.8%) had evidence of past infection. The median S/CO ratios of the presumed false-positive and active infection samples were 1.8 and 17.3, respectively. The positive predictive value of HCV positivity in samples with ratios above 12 was 91.8%. On retesting, 104/470 (22.1%) samples became negative. CONCLUSION: The Architect anti-HCV assay has a very high false discovery rate in Ugandan BTSs, leading to excessive blood disposal. Pre-analytical factors likely contribute to this. An introduction of confirmatory testing using an algorithm based on S/CO ratio evaluation could limit unnecessary blood wastage and donor deferral.

Utility of EBUS-TBNA in diagnosing mediastinal tuberculous lymphadenitis in East London.

OBJECTIVES: To characterise and describe the diagnostic utility of Endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) in intrathoracic tuberculosis in a cohort of patients with mediastinal lymphadenopathy of unknown aetiology. METHODS: Consecutive patients with intrathoracic lymphadenopathy undergoing EBUS-TBNA between 2012 and 2016 were identified. Demographic data, biopsy cytopathology and mycobacteriology results, HIV and vitamin D status, susceptibility results and final diagnoses were recorded. Pre- and post-procedure probability scores were assigned to each case to reflect the probability of tuberculosis. RESULTS: 315 cases were identified; 54 (17.1%) had tuberculosis and 261 (82.9%) had a non-tuberculosis diagnosis. amongst TB cases, the sensitivity of EBUS-TBNA was 59.3% (95% CI 45.06-72.14), specificity 100% (95% CI 98.19-100) and the negative predictive value (NPV) was 92.23% (95% CI 88.31-94.95). 19/54 (35%) TB cases were confirmed by EBUS mycobacterial culture and 13/54 (24.1%) by cytopathology.  33 (61.1%) of the TB cases, had a low to medium pre-test probability score assigned prior to EBUS-TBNA. Amongst EBUS culture-confirmed cases, we found a resistance rate of 10.5% to one or more first line TB drugs, with one case of multi-drug resistant TB. CONCLUSIONS: We confirmed the utility of EBUS-TBNA in the diagnosis of intrathoracic tuberculosis in an undifferentiated cohort of patients with mediastinal lymphadenopathy of unknown aetiology and advocate sending samples for mycobacterial culture in all cases in high tuberculosis incidence areas.

Invasive Aggregatibacter infection: shedding light on a rare pathogen in a retrospective cohort analysis.

Introduction. Aggregatibacter are Gram-negative, facultatively anaerobic rods or coccobacilli that are infrequently encountered as pathogens causing infection.Hypothesis/Gap Statement. The range of invasive infection that Aggregatibacter cause is poorly described. The pathogenicity of species such as Aggregatibacter segnis is debated.Aim. To identify invasive infection due to Aggregatibacter species in a large healthcare organization and to characterize clinical syndromes, co-morbidities and risk factors.Methodology. All microbiological samples positive for Aggregatibacter species were identified by conventional culture or 16S rRNA PCR between October 2017 and March 2021. Electronic records for all patients with positive samples were reviewed and the infection syndrome classified for patients with invasive disease.Results. Twenty-seven patients with invasive infection were identified, with a statistically significant difference in species-specific patterns of invasive infection (P=0.02) and a statistically significant association with residence in the 30 % most deprived households in the UK by postcode (P<0.01). The three most common co-morbidities were periodontitis or recent dental work (29.6%), cardiovascular disease (25.9%) and diabetes (18.5 %).Conclusion. We describe a novel association of Aggregatibacter segnis with skin and soft tissue infection. The propensity of the Aggregatibacter species to cause invasive infection at different body sites and be associated with deprivation is reported. Aggregatibacter actinomycetemcomitans bacteraemia was associated with infective endocarditis, and Aggregatibacter aphrophilus was implicated in severe appendicitis and noted to cause brain abscess. Areas warranting future research include exploring the risk-factors required for invasive infection and those that may determine the species-specific differences in patterns of invasive disease.

The CINAMR (Clinical Information Network-Antimicrobial Resistance) Project: A pilot microbial surveillance using hospitals linked to regional laboratories in Kenya: Study Protocol.

Background: Antimicrobial resistance (AMR) is a global threat and is thought to be acute in low-and middle-income country (LMIC) settings, including in Kenya, but there is limited unbiased surveillance that can provide reliable estimates of its burden. Current efforts to build capacity for microbiology testing in Kenya are unlikely to result in systematic routine microbiological testing in the near term. Therefore, there is little prospect for microbiological support to inform clinical diagnoses nor for indicating the burden of AMR and for guiding empirical choice of antibiotics. Objective: We aim to build on an existing collaboration, the Clinical Information Network (CIN), to pilot microbiological surveillance using a 'hub-and-spoke' model where selected hospitals are linked to high quality microbiology research laboratories. Methods: Children admitted to paediatric wards of 12 participating hospitals will have a sample taken for blood culture at admission before antibiotics are started. Indication for blood culture will be a clinician's prescription of antibiotics. Samples will then be transported daily to the research laboratories for culture and antibiotic susceptibility testing and results relayed back to clinicians for patient management. The surveillance will take place for 6 months in each hospital. Separately, we shall conduct semi-structured interviews with frontline health workers to explore the feasibility and utility of this approach. We will also seek to understand how the availability of microbiology results might inform antibiotic stewardship, and as an interim step to the development of better national or regional laboratories linked to routine surveillance. Conclusions: If feasible, this approach is less costly and periodic 'hub-and-spoke' surveillance can be used to track AMR trends and to broadly guide empirical antibiotic guidance meaning it is likely to be more sustainable than establishing functional microbiological facilities in each hospital in a LMIC setting.

Reactivation of latent Histoplasma and disseminated cytomegalovirus in a returning traveller with ulcerative colitis.

INTRODUCTION: We describe a case of progressive disseminated histoplasmosis (PDH) and disseminated cytomegalovirus (CMV) with development of haemophagocytic lymphohistiocytosis in a 62-year-old man of Bangladeshi origin living in the UK. CASE PRESENTATION: The patient had a background of ulcerative colitis for which he took prednisolone and azathioprine. He presented with fever, lethargy, cough, weight loss and skin redness, and was initially treated for bacterial cellulitis and investigated for underlying malignancy. He developed multiple progressive erythematous skin lesions, sepsis and colitis requiring management on intensive care. A skin biopsy showed yeasts in the dermis and sub-cutaneous fat, which were confirmed as Histoplasma capsulatum by PCR. Disseminated CMV with evidence of end organ gastrointestinal disease was also diagnosed. Despite anti-viral and anti-fungal treatment, the patient deteriorated with evidence of bone marrow suppression and a diagnosis of haemophagocytic lymphohistiocytosis was made. CONCLUSION: PDH is classically seen in patients with significant immunosuppression, e.g. those with human immunodeficiency virus (HIV) or on anti-TNF therapy; however, we present a case of reactivation of Histoplasma in a non-HIV patient. We consider the importance of contemplating reactivation of endemic mycoses and CMV in critically unwell and deteriorating patients.

Impact of a training package for community birth attendants in Madagascar.

This brief report assesses the impact of community birth attendant training and explores barriers to safe delivery in rural Madagascar. We assessed the knowledge of 25 community birth attendants using interviewer-administered questionnaires and explored attitudes to delivery in 4 focus groups of 10 women of reproductive age and 1 focus group of 10 birth attendants. We found a mismatch between hygiene knowledge and reported practice. Clinical experience appears to reinforce training to achieve longer lasting change in practitioner knowledge (e.g. of labour complications). Focus groups helped to identify practical barriers to clean (delivery kits) and safe delivery (cost) despite this knowledge. We proposed that a facilitated women's group programme may complement such training.