Prospective Validation of a Rapid Host Gene Expression Test to Discriminate Bacterial From Viral Respiratory Infection

Importance: Bacterial and viral causes of acute respiratory illness (ARI) are difficult to clinically distinguish, resulting in the inappropriate use of antibacterial therapy. The use of a host gene expression-based test that is able to discriminate bacterial from viral infection in less than 1 hour may improve care and antimicrobial stewardship. Objective: To validate the host response bacterial/viral (HR-B/V) test and assess its ability to accurately differentiate bacterial from viral infection among patients with ARI. Design, Setting, and Participants: This prospective multicenter diagnostic study enrolled 755 children and adults with febrile ARI of 7 or fewer days\u27 duration from 10 US emergency departments. Participants were enrolled from October 3, 2014, to September 1, 2019, followed by additional enrollment of patients with COVID-19 from March 20 to December 3, 2020. Clinical adjudication of enrolled participants identified 616 individuals as having bacterial or viral infection. The primary analysis cohort included 334 participants with high-confidence reference adjudications (based on adjudicator concordance and the presence of an identified pathogen confirmed by microbiological testing). A secondary analysis of the entire cohort of 616 participants included cases with low-confidence reference adjudications (based on adjudicator discordance or the absence of an identified pathogen in microbiological testing). Thirty-three participants with COVID-19 were included post hoc. Interventions: The HR-B/V test quantified the expression of 45 host messenger RNAs in approximately 45 minutes to derive a probability of bacterial infection. Main Outcomes and Measures: Performance characteristics for the HR-B/V test compared with clinical adjudication were reported as either bacterial or viral infection or categorized into 4 likelihood groups (viral very likely [probability score \u3c0.19], viral likely [probability score of 0.19-0.40], bacterial likely [probability score of 0.41-0.73], and bacterial very likely [probability score \u3e0.73]) and compared with procalcitonin measurement. Results: Among 755 enrolled participants, the median age was 26 years (IQR, 16-52 years); 360 participants (47.7%) were female, and 395 (52.3%) were male. A total of 13 participants (1.7%) were American Indian, 13 (1.7%) were Asian, 368 (48.7%) were Black, 131 (17.4%) were Hispanic, 3 (0.4%) were Native Hawaiian or Pacific Islander, 297 (39.3%) were White, and 60 (7.9%) were of unspecified race and/or ethnicity. In the primary analysis involving 334 participants, the HR-B/V test had sensitivity of 89.8% (95% CI, 77.8%-96.2%), specificity of 82.1% (95% CI, 77.4%-86.6%), and a negative predictive value (NPV) of 97.9% (95% CI, 95.3%-99.1%) for bacterial infection. In comparison, the sensitivity of procalcitonin measurement was 28.6% (95% CI, 16.2%-40.9%; P \u3c .001), the specificity was 87.0% (95% CI, 82.7%-90.7%; P = .006), and the NPV was 87.6% (95% CI, 85.5%-89.5%; P \u3c .001). When stratified into likelihood groups, the HR-B/V test had an NPV of 98.9% (95% CI, 96.1%-100%) for bacterial infection in the viral very likely group and a positive predictive value of 63.4% (95% CI, 47.2%-77.9%) for bacterial infection in the bacterial very likely group. The HR-B/V test correctly identified 30 of 33 participants (90.9%) with acute COVID-19 as having a viral infection. Conclusions and Relevance: In this study, the HR-B/V test accurately discriminated bacterial from viral infection among patients with febrile ARI and was superior to procalcitonin measurement. The findings suggest that an accurate point-of-need host response test with high NPV may offer an opportunity to improve antibiotic stewardship and patient outcomes

Barriers and facilitators to HIV testing among young men who have sex with men and transgender women in Kingston, Jamaica: a qualitative study

Introduction: Young men who have sex with men (MSM) in Jamaica have the highest HIV prevalence in the Caribbean. There is little information about HIV among transgender women in Jamaica, who are also overrepresented in the Caribbean epidemic. HIV-related stigma is a barrier to HIV testing among Jamaica’s general population, yet little is known of MSM and transgender women’s HIV testing experiences in Jamaica. We explored perceived barriers and facilitators to HIV testing among young MSM and transgender women in Kingston, Jamaica. Methods: We implemented a community-based research project in collaboration with HIV and lesbian, gay, bisexual and transgender (LGBT) agencies in Kingston. We held two focus groups, one with young (aged 18–30 years) transgender women (n = 8) and one with young MSM (n = 10). We conducted 53 in-depth individual semi-structured interviews focused on HIV testing experiences with young MSM (n = 20), transgender women (n = 20), and community-based key informants (n = 13). We conducted thematic analysis to identify, analyze, and report themes. Results: Participant narratives revealed social-ecological barriers and facilitators to HIV testing. Barriers included healthcare provider mistreatment, confidentiality breaches, and HIV-related stigma: these spanned interpersonal, community and structural levels. Healthcare provider discrimination and judgment in HIV testing provision presented barriers to accessing HIV services (e.g. treatment), and resulted in participants hiding their sexual orientation and/or gender identity. Confidentiality concerns included: clinic physical arrangements that segregated HIV testing from other health services, fear that healthcare providers would publicly disclose their status, and concerns at LGBT-friendly clinics that peers would discover they were getting tested. HIV-related stigma contributed to fear of testing HIV-positive; this intersected with the stigma of HIV as a “gay” disease. Participants also anticipated healthcare provider mistreatment if they tested HIV positive. Participants identified individual (belief in benefits of knowing one’s HIV status), social (social support) and structural (accessible testing) factors that can increase HIV testing uptake. Conclusions: Findings suggest the need for policy and practice changes to enhance confidentiality and reduce discrimination in Jamaica. Interventions to challenge HIV-related and LGBT stigma in community and healthcare settings can enhance access to the HIV prevention cascade among MSM and transgender youth in Jamaica