HIV-Associated Tuberculosis in Children and Adolescents: Evolving Epidemiology, Screening, Prevention and Management Strategies

Children and adolescents living with HIV continue to be impacted disproportionately by tuberculosis as compared to peers without HIV. HIV can impact TB screening and diagnosis by altering screening and diagnostic test performance and can complicate prevention and treatment strategies due to drug–drug interactions. Post-tuberculosis lung disease is an underappreciated phenomenon in children and adolescents, but is more commonly observed in children and adolescents with HIV-associated tuberculosis. This review presents new data related to HIV-associated TB in children and adolescents. Data on the epidemiology of HIV-associated TB suggests that an elevated risk of TB in children and adolescents with HIV persists even with broad implementation of ART. Recent guidance also indicates the need for new screening strategies for HIV-associated TB. There have been major advances in the availability of new antiretroviral medications and also TB prevention options for children, but these advances have come with additional questions surrounding drug–drug interactions and dosing in younger age groups. Finally, we review new approaches to manage post-TB lung disease in children living with HIV. Collectively, we present data on the rapidly evolving field of HIV-associated child tuberculosis. This evolution offers new management opportunities for children and adolescents living with HIV while also generating new questions for additional research.

Modeling Plasmodium falciparum Diagnostic Test Sensitivity Using Machine Learning With Histidine-Rich Protein 2 Variants

Malaria, predominantly caused by Plasmodium falciparum, poses one of largest and most durable health threats in the world. Previously, simplistic regression-based models have been created to characterize malaria rapid diagnostic test performance, though these models often only include a couple genetic factors. Specifically, the Baker et al., 2005 model uses two types of particular repeats in histidine-rich protein 2 (PfHRP2) to describe a P. falciparum infection, though the efficacy of this model has waned over recent years due to genetic mutations in the parasite. In this work, we use a dataset of 100 P. falciparum PfHRP2 genetic sequences collected in Ethiopia and derived a larger set of motif repeat matches for use in generating a series of diagnostic machine learning models. Here we show that the usage of additional and different motif repeats in more sophisticated machine learning methods proves effective in characterizing PfHRP2 diversity. Furthermore, we use machine learning model explainability methods to highlight which of the repeat types are most important with regards to rapid diagnostic test sensitivity, thereby showcasing a novel methodology for identifying potential targets for future versions of rapid diagnostic tests.

92 Reshaping the Diagnostic Pathways for Investigation of Haematuria During and After The COVID-19 Pandemic: Diagnostic Accuracy of Strategies for Detection of Bladder Cancer from The IDENTIFY Cohort Study

Introduction Diagnostic haematuria services have been reduced due to the COVID-19 pandemic, compromising patient care, and necessitating a more pragmatic pathway. Method The IDENTIFY study was an international, prospective, multicentre cohort study of over 11,000 patients referred to secondary care for investigation of haematuria. Using this data, we developed strategies using combinations of imaging and cytology as triage tests to maximise cancer detection within a pragmatic pathway. Results 8112 patients (74·4%) received an ultrasound or a CT urogram, with or without cytology. 5737 (70·7%) patients had visible haematuria (VH) and 2375 (29·3%) had non-visible haematuria (NVH). Diagnostic test performance was used to determine optimal age cut-offs for four proposed strategies. We recommended proceeding directly to transurethral resection of bladder tumour for patients of any age with positive triage tests for cancer. Patients with negative triage tests under 35-years-old with VH, or under 50-years-old with NVH can safely be discharged without undergoing flexible cystoscopy. The remaining patients may undergo flexible cystoscopy, with a greater priority for older patients to capture high risk bladder cancer. Conclusions We suggest diagnostic strategies in patients with haematuria, which focus on detection of bladder cancer, whilst reducing the burden to healthcare services in a resource-limited setting.

Detection of SARS-CoV-2 variants by Abbott molecular, antigen, and serological tests

Background: Viral diversity presents an ongoing challenge for diagnostic tests, which need to accurately detect all circulating variants. The Abbott Global Surveillance program monitors severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants and their impact on diagnostic test performance. Objectives: To evaluate the capacity of Abbott molecular, antigen, and serologic assays to detect the SARS-CoV-2 B.1.1.7, B.1.351 and the P.1 variants. Study design: Virus variant culture stock dilutions (B.1.1.7, BEI NR-54011; B.1.351, BEI NR-54008 and 54009; P.1, BEI NR-54982) and clinical samples from patients with confirmed B.1.1.7 variant infection were run on the Abbott ID NOW COVID-19, m2000 RealTime SARS-CoV-2, Alinity m SARS-CoV-2, and Alinity m Resp-4-Plex molecular assays; the BinaxNOW COVID-19 Ag Card and Panbio COVID-19 Ag Rapid Test Device; and the ARCHITECT/Alinity i SARS-CoV-2 IgG and AdviseDx IgM assays, Panbio COVID-19 IgG assay, and ARCHITECT/Alinity i AdviseDx SARS-CoV-2 IgG II assay. Results: Cultured virus stocks and B.1.1.7 clinical samples were detected with molecular, antigen, and serologic assays in the expected ranges, confirming in silico predictions. The ratio between genome equivalents (GE) and calculated median tissue culture infectious dose (TCID50) were 31- to 83-fold higher for B.1.1.7 cultures compared to B.1.351 and P.1 cultures, demonstrating that GE are more consistent units between cultures than TCID50. Conclusions: Abbott molecular and antigen assays effectively detect B.1.1.7, B.1.351, and P.1 variant infections and Abbott serologic assays detect B.1.1.7 antibodies in patient sera. Future studies with SARS-CoV-2 virus cultures should use quantitative viral load values to compare detection of variants.

Major impact of left auricular cardiopathy when associated to supraventricular ectopy?

Funding Acknowledgements Type of funding sources: None. INTRODUCTION Left atrial cardiopathy (LAC) is an independent predictor of atrial fibrillation (FA) and embolic stroke. It is more frequent in patients with embolic stroke of undetermined source (ESUS) than in non-embolic strokes. The current definition doesn’t include supraventricular ectopy. AIM The aim of this work was to describe the importance of LAC in ESUS and to study the impact of adding the number of atrial premature complexes per hour (APC/h) to LAC criteria. METHODS Retrospective analysis of 123 ESUS patients (pts) admitted to Neurology service from 2014 to 2019. LAC was defined according to two criteria (LAC2: severe left atrial enlargement or p-wave terminal force in lead V1 [PTFV1] >5000 µV*ms) or 3 criteria (LAC3: additionally, >30 APC/h). Survival analysis for the occurrence of AF, stroke recurrence and death according to LAC2 and LAC3. Diagnostic test performance analysis for each criterion with ROC curves. RESULTS 43 (35%) of the ESUS pts had LAC2. Pts with LAC2 (35.0%) were older (p = 0.007), more frequently had hypertension (p = 0.004) and lower total cholesterol levels (p = 0.044) than patients without LAC2. The incidence of AF (median follow-up 21 months, IQR = 9-35) was higher both in LAC2 (p = 0.038) and LAC3 (p = 0.001). There were no differences in stroke recurrence or death between patients with or without LAC2 or 3. Among the 3 atrial dysfunction criteria included in LAC3 definition, the number of APC/h was associated with a higher area under the curve for the occurrence of AF (AUC = 0.822). Cox regression revealed that PTFV1 > 5000 µV·ms (HR = 5.12, IC95%=1.28-20.56, p = 0.021) and >30 APC/h (HR = 13.02, IC95%=3.57-47.56) were independent predictors of AF. In addition, the single predictor of the composite endpoint (occurrence of AF, stroke recurrence and death) was >30 APC/h (HR = 5.2, p < 0,001). CONCLUSION In ESUS pts, the subgroup with LAC2 had different clinical characteristics and a higher AF incidence. APC/h were also independently associated with AF incidence and had better diagnostic test performance than the other criteria. In sum, APC/h inclusion as a diagnostic criterion for LAC should be considered and may help in a better therapeutic approach.

Longitudinal assessment of diagnostic test performance over the course of acute SARS-CoV-2 infection

What is already known about this topic? Diagnostic tests and sample types for SARS-CoV-2 vary in sensitivity across the infection period. What is added by this report? We show that both RTqPCR (from nasal swab and saliva) and the Quidel SARS Sofia FIA rapid antigen tests peak in sensitivity during the period in which live virus can be detected in nasal swabs, but that the sensitivity of RTqPCR tests rises more rapidly in the pre-infectious period. We also use empirical data to estimate the sensitivities of RTqPCR and antigen tests as a function of testing frequency. What are the implications for public health practice? RTqPCR tests will be more effective than rapid antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (provided results reporting is timely). All modalities, including rapid antigen tests, showed >94% sensitivity to detect infection if used at least twice per week. Regular surveillance/screening using rapid antigen tests 2-3 times per week can be an effective strategy to achieve high sensitivity (>95%) for identifying infected individuals.