Diagnostic accuracy of WHO screening criteria to guide lateral-flow lipoarabinomannan testing among HIV-positive inpatients: A systematic review and individual participant data meta-analysis.

BACKGROUND: WHO recommends urine lateral-flow lipoarabinomannan (LF-LAM) testing with AlereLAM in HIV-positive inpatients only if screening criteria are met. We assessed the performance of WHO screening criteria and alternative screening tests/strategies to guide LF-LAM testing and compared diagnostic accuracy of the WHO AlereLAM algorithm (WHO screening criteria followed by AlereLAM if screen positive) with AlereLAM and FujiLAM (a novel LF-LAM test) testing in all HIV-positive inpatients. METHODS: We searched MEDLINE, Embase, and Cochrane Library from Jan 1, 2011 to March 1, 2020 for studies among adult/adolescent HIV-positive inpatients regardless of tuberculosis signs and symptoms. The reference standards were (1) AlereLAM or FujiLAM for screening tests/strategies and (2) culture or Xpert for AlereLAM/FujiLAM. We determined proportion of inpatients eligible for AlereLAM using WHO screening criteria; assessed accuracy of WHO criteria and alternative screening tests/strategies to guide LF-LAM testing; compared accuracy of WHO AlereLAM algorithm with AlereLAM/FujiLAM testing in all; and determined diagnostic yield of AlereLAM, FujiLAM, and Xpert MTB/RIF (Xpert). We estimated pooled proportions with a random-effects model, assessed diagnostic accuracy using random-effects bivariate models, and assessed diagnostic yield descriptively. FINDINGS: We obtained data from all 5 identified studies (n = 3,504). The pooled proportion of inpatients eligible for AlereLAM using WHO criteria was 93% (95%CI 91, 95). Among screening tests/strategies to guide LF-LAM testing, WHO criteria, C-reactive protein (≥5 mg/L), and CD4 count (<200 cells/µL) had high sensitivities but low specificities; cough (≥2 weeks), hemoglobin (<8 g/dL), body mass index (<18.5 kg/m2), lymphadenopathy, and WHO-defined danger signs had higher specificities but suboptimal sensitivities. AlereLAM in all had the same sensitivity (62%) and specificity (88%) as WHO AlereLAM algorithm. Sensitivity of FujiLAM and AlereLAM was 69% and 48%, while specificity was 88% and 96%, respectively. In 2 studies that collected sputum and non-sputum samples for Xpert and/or culture, diagnostic yield of sputum Xpert was 40-41%, AlereLAM was 39-76%, and urine Xpert was 35-62%. In one study, FujiLAM diagnosed 80% of tuberculosis cases (vs 39% for AlereLAM), and sputum Xpert combined with AlereLAM, urine Xpert, or FujiLAM diagnosed 61%, 81%, and 92% of all cases, respectively. INTERPRETATION: WHO criteria and alternative screening tests/strategies have limited utility in guiding LF-LAM testing, suggesting that AlereLAM testing in all HIV-positive medical inpatients be implemented. Routine FujiLAM may improve tuberculosis diagnosis. FUNDING: None.

Tuberculosis screening among HIV-positive inpatients: a systematic review and individual participant data meta-analysis.

BACKGROUND: Since 2011, WHO has recommended that HIV-positive inpatients be routinely screened for tuberculosis with the WHO four-symptom screen (W4SS) and, if screened positive, receive a molecular WHO-recommended rapid diagnostic test (eg, Xpert MTB/RIF [Xpert] assay). To inform updated WHO tuberculosis screening guidelines, we conducted a systematic review and individual participant data meta-analysis to assess the performance of W4SS and alternative screening tests to guide Xpert testing and compare the diagnostic accuracy of the WHO Xpert algorithm (ie, W4SS followed by Xpert) with Xpert for all HIV-positive inpatients. METHODS: We searched MEDLINE, Embase, and Cochrane Library from Jan 1, 2011, to March 1, 2020, for studies of adult and adolescent HIV-positive inpatients enrolled regardless of tuberculosis signs and symptoms. The separate reference standards were culture and Xpert. Xpert was selected since it is most likely to be the confirmatory test used in practice. We assessed the proportion of inpatients eligible for Xpert testing using the WHO algorithm; assessed the accuracy of W4SS and alternative screening tests or strategies to guide diagnostic testing; and compared the accuracy of the WHO Xpert algorithm (W4SS followed by Xpert) with Xpert for all. We obtained pooled proportion estimates with a random-effects model, assessed diagnostic accuracy by fitting random-effects bivariate models, and assessed diagnostic yield descriptively. This systematic review has been registered on PROSPERO (CRD42020155895). FINDINGS: Of 6162 potentially eligible publications, six were eligible and we obtained data for all of the six publications (n=3660 participants). The pooled proportion of inpatients eligible for an Xpert was 90% (95% CI 89-91; n=3658). Among screening tests to guide diagnostic testing, W4SS and C-reactive protein (≥5 mg/L) had highest sensitivities (≥96%) but low specificities (≤12%); cough (≥2 weeks), haemoglobin concentration (<8 g/dL), body-mass index (<18·5 kg/m2), and lymphadenopathy had higher specificities (61-90%) but suboptimal sensitivities (12-57%). The WHO Xpert algorithm (W4SS followed by Xpert) had a sensitivity of 76% (95% CI 67-84) and specificity of 93% (88-96; n=637). Xpert for all had similar accuracy to the WHO Xpert algorithm: sensitivity was 78% (95% CI 69-85) and specificity was 93% (87-96; n=639). In two cohorts that had sputum and non-sputum samples collected for culture or Xpert, diagnostic yield of sputum Xpert was 41-70% and 61-64% for urine Xpert. INTERPRETATION: The W4SS and other potential screening tests to guide Xpert testing have suboptimal accuracy in HIV-positive inpatients. On the basis of these findings, WHO now strongly recommends molecular rapid diagnostic testing in all medical HIV-positive inpatients in settings where tuberculosis prevalence is higher than 10%. FUNDING: World Health Organization.

From chaos to control - experiences of healthcare workers during the early phase of the COVID-19 pandemic: a focus group study.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic has caused overwhelming challenges to healthcare systems worldwide. Healthcare workers (HCWs) have faced particular challenges: being exposed to the coronavirus SARS-CoV-2 and caring for patients having a new and potentially life-threatening disease. The aim of this study was to explore how HCWs in the Swedish healthcare system perceived their work situation during the first phase of the COVID-19 pandemic in 2020. METHODS: Focus group discussions and interviews with HCWs were performed from June to October 2020 in one Swedish healthcare region. A purposeful sampling approach was used to select a variety of professions (physicians, nurses, nurse aides and cleaners) and workplaces (hospital inpatient wards, emergency department, nursing home and home care service). Qualitative content analysis was used for data analysis. RESULTS: In total, 51 HCWs participated in eight focus group discussions and one HCW participated in an individual interview. The content analysis identified two main categories: 'Concerns about the risk of infection and transmission of infection to others', and 'Transition from chaos to managing in a new and challenging work situation'. The findings revealed how HCWs perceived working conditions, including experiences of fear for personal health, confusion and uncertainty regarding personal protective equipment and infection prevention and control (PPE/IPC), and fear of infecting others. Both fearful and appreciating attitudes were achieved from the surrounding community. Helpful strategies for transition from chaos to control were lifted i.e. present and supportive leadership, and finding comfort and strength in the working team. Both helplessness and meaningfulness were described when caring for COVID-19 patients. CONCLUSIONS: This study provides unique insights into HCWs experiences of an extremely challenging work situation during the first phase of the COVID-19 pandemic, including feelings of stress and insecurity in a chaotic and hazardous working environment. But there is also mitigation of these challenges and even positive experiences including feelings of safety and meaningfulness. To enhance safety among HCWs in healthcare crises such as the COVID-19 pandemic, the findings highlight the importance of avoiding confusion about PPE/IPC, having a supportive healthcare leadership and ensuring accurate information provision about virus transmission to the public.

Should Urine-LAM Tests Be Used in TB Symptomatic HIV-Positive Patients When No CD4 Count Is Available? A Prospective Observational Cohort Study From Malawi.

BACKGROUND: Current eligibility criteria for urine lateral-flow lipoarabinomannan assay (LF-LAM) in ambulatory, HIV-positive patients rely on the CD4 count. We investigated the diagnostic yield of LF-LAM and the 6-month mortality in ambulatory, TB symptomatic, HIV-positive patients regardless of their CD4 count. METHODS: We conducted a prospective, observational study that included all ambulatory, ≥15-year-old, TB symptomatic (cough, weight loss, fever, or night sweats) HIV-positive patients presenting at 4 health facilities in Malawi. Patients received a clinical examination and were requested urine LF-LAM, sputum microscopy, and Xpert MTB/RIF. TB was defined as bacteriologically confirmed if Xpert was positive. RESULTS: Of 485 patients included, 171 (35.3%) had a CD4 <200 and 32 (7.2%) were seriously ill. Median CD4 count was 341 cells/µL (interquartile range: 129-546). LAM was positive in 24.9% patients with CD4 < 200 (50% LAM grades 2-4) and 12.5% with CD4 ≥ 200 (12.8% LAM grades 2-4). Xpert was positive in 14.1% (44/312). Among Xpert-positive patients, LAM positivity was 56.7% (CD4 < 200) and 42.9% (CD4 ≥ 200), P = 0.393. Of the patients without an Xpert result, 13.4% (23/172) were LAM positive (ie, potentially missed patients). Overall, mortality was 9.2% (44/478). More pronounced LAM-positive patients had higher mortality than LAM-negative (grades 2-4: 36.0%; grade 1: 9.1%; negative: 7.4%; P < 0.001). LAM-positive patients with CD4 <200 cells/µL had higher risk of mortality than LAM negatives (adjusted hazard ratio: 3.2, 95% confidence interval: 1.4 to 7.2, P = 0.006), particularly those with LAM grades 2-4 (adjusted hazard ratio: 4.9, 95% confidence interval: 1.8 to 13.3, P = 0.002). CONCLUSIONS: Urine-LAM testing can be useful for TB diagnosis in HIV-positive TB-symptomatic patients with no CD4 cell count. LAM grade can identify patients at higher risk of death in this situation.