C-reactive Protein-based Screening of People with Tuberculosis Symptoms: A Diagnostic Accuracy Study.

: C-reactive protein (CRP)-based tuberculosis (TB) screening is recommended for people with HIV (PWH). However, its performance among people without HIV and in diverse settings is unknown. : In a multi-country study, we aimed to determine whether CRP meets the minimum accuracy targets (sensitivity ≥90%, specificity ≥70%) for an effective TB screening test.

C-reactive protein-based tuberculosis triage testing: a multi-country diagnostic accuracy study.

Rationale: C-reactive protein (CRP)-based tuberculosis (TB) screening is recommended for people with HIV (PWH). However, its performance among people without HIV and in diverse settings is unknown.

Objectives: In a multi-country study, we aimed to determine whether CRP meets the minimum accuracy targets (sensitivity ≥90%, specificity ≥70%) for an effective TB triage test.

Point-of-care C-reactive protein and Xpert MTB/RIF Ultra for tuberculosis screening and diagnosis in unselected antiretroviral therapy initiators: a prospective, cross-sectional, diagnostic accuracy study.

Background: Tuberculosis, a major cause of death in people living with HIV, remains challenging to diagnose. Diagnostic accuracy data are scarce for promising triage and confirmatory tests such as C-reactive protein (CRP), sputum and urine Xpert MTB/RIF Ultra (Xpert Ultra), and urine Determine TB LAM Ag (a lateral flow lipoarabinomannan [LF-LAM] test), without symptom selection. We evaluated novel triage and confirmatory tests in ambulatory people with HIV initiating antiretroviral therapy (ART).

Point-of-care C-reactive protein and Xpert MTB/RIF Ultra for tuberculosis screening and diagnosis in unselected antiretroviral therapy initiators: a prospective diagnostic accuracy study.

Background: Tuberculosis (TB), a major cause of death in people living with HIV (PLHIV), remains challenging to diagnose. Diagnostic accuracy data are lacking for promising triage tests, such as C-reactive protein (CRP), and confirmatory tests, such as sputum and urine Xpert MTB/RIF Ultra (Ultra), and urine LAM, without prior symptom selection.

Methods: 897 PLHIV initiating antiretroviral therapy were consecutively recruited in settings with high TB incidence, irrespective of symptoms.

Clinical utility of WHO-recommended screening tools and development and validation of novel clinical prediction models for pulmonary tuberculosis screening among outpatients living with HIV: an individual participant data meta-analysis.

Background: The World Health Organization (WHO) recommends that outpatient people living with HIV (PLHIV) undergo tuberculosis screening with the WHO four-symptom screen (W4SS) or C-reactive protein (CRP) (5 mg·L cut-off) followed by confirmatory testing if screen positive. We conducted an individual participant data meta-analysis to determine the performance of WHO-recommended screening tools and two newly developed clinical prediction models (CPMs).

Methods: Following a systematic review, we identified studies that recruited adult outpatient PLHIV irrespective of tuberculosis signs and symptoms or with a positive W4SS, evaluated CRP and collected sputum for culture.

Viral suppression among adults with HIV receiving routine dolutegravir-based antiretroviral therapy and 3 months weekly isoniazid-rifapentine.

Objective: We aimed to evaluate safety of 3 months weekly isoniazid-rifapentine (3HP) for tuberculosis (TB) prevention when co-administered with dolutegravir-based antiretroviral therapy (TLD), and compare viral suppression among those initiating TLD + 3HP vs. TLD alone.

Design/methods: We analyzed data from an ongoing Phase 3 randomized trial comparing TB screening strategies among adults with CD4 + ≤350 cells/μl initiating routine antiretroviral therapy (ART) in Kampala, Uganda.

Tuberculosis screening improves preventive therapy uptake (TB SCRIPT) trial among people living with HIV in Uganda: a study protocol of an individual randomized controlled trial.

Background: People living with HIV (PLHIV) have an increased risk of developing active tuberculosis (TB). To reduce the burden of TB among PLHIV, the World Health Organization (WHO) recommends systematic TB screening followed by (1) confirmatory TB testing for all who screen positive and (2) TB preventive therapy (TPT) for all TPT-eligible PLHIV who screen negative. Symptom-based screening remains the standard of care in most high TB burden settings, including Uganda.

The Role of C-Reactive Protein as a Triage Tool for Pulmonary Tuberculosis in Children.

Background: C-reactive protein (CRP) has shown promise as a triage tool for pulmonary tuberculosis (TB) in adults living with the human immunodeficiency virus. We performed the first assessment of CRP for TB triage in children.

Methods: Symptomatic children less than 15 years old were prospectively enrolled in Kampala, Uganda.

Impact of hematocrit on point-of-care C-reactive protein-based tuberculosis screening among people living with HIV initiating antiretroviral therapy in Uganda.

Point-of-care C-reactive protein (POC CRP) testing is a potential tuberculosis (TB) screening tool for people living with HIV (PLHIV). Unlike lab-based assays, POC assays do not routinely adjust CRP levels for hematocrit, potentially resulting in TB screening status misclassification. We compared the diagnostic accuracy of unadjusted and hematocrit-adjusted POC CRP for culture-confirmed TB among PLHIV with CD4 cell-count ≤350 cells/uL initiating antiretroviral therapy (ART) in Uganda.

C-Reactive Protein Testing for Active Tuberculosis among Inpatients without HIV in Uganda: a Diagnostic Accuracy Study.

The objective of this prospective cross-sectional study, conducted at a national referral hospital in Kampala, Uganda, was to determine diagnostic performance of serum C-reactive protein (CRP) as a triage test for tuberculosis (TB) among HIV-seronegative inpatients. We calculated the sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values to determine the diagnostic performance of a CRP enzyme-linked immunosorbent assay (ELISA) (Eurolyser) in comparison to that of a reference standard of culture on two sputum samples. We constructed receiver operating curves and reported performance in reference to the manufacturer's cutoff and also to a threshold chosen to achieve sensitivity of >90%, in accordance with the WHO's target-product profile for a triage test.

Management and Outcomes of Critically-III Patients with COVID-19 Pneumonia at a Safety-net Hospital in San Francisco, a Region with Early Public Health Interventions: A Case Series.

Background: Following early implementation of public health measures, San Francisco has experienced a slow rise and a low peak level of coronavirus disease 2019 (COVID-19) cases and deaths.

Methods And Findings: We included all patients with COVID-19 pneumonia admitted to the intensive care unit (ICU) at the safety net hospital for San Francisco through April 8, 2020. Each patient had ≥15 days of follow-up.

Evaluation of multi-antigen serological screening for active tuberculosis among people living with HIV.

Better triage tests for screening tuberculosis (TB) disease are needed for people living with HIV (PLHIV). We performed the first evaluation of a previously-validated 8-antigen serological panel to screen PLHIV for pulmonary TB in Kampala, Uganda. We selected a random 1:1 sample with and without TB (defined by sputum culture) from a cohort of PLHIV initiating antiretroviral therapy.

Brief Report: Yield and Efficiency of Intensified Tuberculosis Case-Finding Algorithms in 2 High-Risk HIV Subgroups in Uganda.

Background: Tuberculosis (TB) risk varies among different HIV subgroups, potentially impacting intensified case finding (ICF) performance. We evaluated the performance of the current ICF algorithm [symptom screening, followed by Xpert MTB/RIF (Xpert) testing] in 2 HIV subgroups and evaluated whether ICF performance could be improved if TB screening was based on C-reactive protein (CRP) concentrations.

Methods: We enrolled consecutive adults with CD4 counts ≤350 cells/µL initiating antiretroviral therapy and performed symptom screening, CRP testing using a low-cost point-of-care (POC) assay, and collected sputum for Xpert testing.

Guidance for Studies Evaluating the Accuracy of Tuberculosis Triage Tests.

Approximately 3.6 million cases of active tuberculosis (TB) go potentially undiagnosed annually, partly due to limited access to confirmatory diagnostic tests, such as molecular assays or mycobacterial culture, in community and primary healthcare settings. This article provides guidance for TB triage test evaluations.

Point-of-care C-reactive protein and risk of early mortality among adults initiating antiretroviral therapy.

Objectives: In resource-limited settings, mortality in the initial months following antiretroviral therapy (ART) initiation remains unacceptably high. Novel tools to identify patients at highest risk of poor outcomes are needed. We evaluated whether elevated C-reactive protein (CRP) concentrations predict poor outcomes among people living with HIV (PLWH) initiating ART.

A Novel, 5-Transcript, Whole-blood Gene-expression Signature for Tuberculosis Screening Among People Living With Human Immunodeficiency Virus.

Background: Gene-expression profiles have been reported to distinguish between patients with and without active tuberculosis (TB), but no prior study has been conducted in the context of TB screening.

Methods: We included all the patients (n = 40) with culture-confirmed TB and time-matched controls (n = 80) enrolled between July 2013 and April 2015 in a TB screening study among people living with human immunodeficiency virus (PLHIV) in Kampala, Uganda. We randomly split the patients into training (n = 80) and test (n = 40) datasets.

Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV.

Background: Approaches to screening for active tuberculosis (TB) among people living with HIV are inadequate, leading to missed diagnoses and poor implementation of preventive therapy.

Methods: Consecutive HIV-infected adults hospitalized at Mulago Hospital (Kampala, Uganda) between June 2011 and July 2013 with a cough ≥ 2 weeks were enrolled. Patients underwent extensive evaluation for pulmonary TB.

Yield and Efficiency of Novel Intensified Tuberculosis Case-Finding Algorithms for People Living with HIV.

Rationale: The recommended tuberculosis (TB) intensified case finding (ICF) algorithm for people living with HIV (symptom-based screening followed by Xpert MTB/RIF [Xpert] testing) is insufficiently sensitive and results in unnecessary Xpert testing.

Objectives: To evaluate whether novel ICF algorithms combining C-reactive protein (CRP)-based screening with urine Determine TB-LAM (TB-LAM), sputum Xpert, and/or sputum culture could improve ICF yield and efficiency.

Methods: We compared the yield and efficiency of novel ICF algorithms inclusive of point-of-care CRP-based TB screening and confirmatory testing with urine TB-LAM (if CD4 count ≤100 cells/μl), sputum Xpert, and/or a single sputum culture among consecutive people living with HIV with CD4 counts less than or equal to 350 cells/μl initiating antiretroviral therapy in Uganda.

Point-of-care C-reactive protein-based tuberculosis screening for people living with HIV: a diagnostic accuracy study.

Background: Symptom-based screening for tuberculosis is recommended for all people living with HIV. This recommendation results in unnecessary Xpert MTB/RIF testing in many individuals living in tuberculosis-endemic areas and thus poor implementation of intensified case finding and tuberculosis preventive therapy. Novel approaches to tuberculosis screening are needed to help achieve global targets for tuberculosis elimination.