Real-world diagnostic accuracy of lipoarabinomannan in three non-sputum biospecimens for pulmonary tuberculosis disease.

BACKGROUND: Development of a non-sputum test using readily-obtainable biospecimens remains a global priority for tuberculosis (TB) control. We quantified lipoarabinomannan (LAM) concentrations, a pathogen biomarker for Mycobacterium tuberculosis, in urine, plasma and serum for real-world diagnostic accuracy of pulmonary TB among people living with and without HIV. METHODS: We conducted a prospective diagnostic study among adults with TB symptoms in South Africa. We measured LAM concentrations in time-matched urine, plasma and serum with an electrochemiluminescence immunoassay using two capture antibodies (FIND 28 and S4-20). From the completed cohort, we randomly selected 210 participants (2 cases: 1 control) based on sensitivity estimates, and we compared diagnostic accuracy of LAM measurements against the microbiological reference standard. FINDINGS: Urine and blood specimens from 210 of 684 adults enrolled were tested for LAM. Among 138 TB-positive adults (41% female), median urine LAM was 137 pg/mL and 52 pg/mL by FIND 28 and S4-20, respectively. Average LAM concentrations were highest in HIV-positive participants with CD4+ T cells <200 cells/mm3. Urine LAM by S4-20 achieved diagnostic sensitivity of 62% (95% CI: 53%-70%) and specificity of 99% (95% CI: 96%-100%). Plasma and serum LAM by FIND 28 showed similar sensitivity (70%, 95% CI: 62%-78%) and comparable specificities (90%, 95% CI: 82%-97%; 94%, 95% CI: 88%-99%). Diagnostic sensitivity of urine LAM by S4-20 was higher among participants without HIV (41%, 95% CI: 24%-61%) compared to HIV-positive participants with CD4 ≥200 cells/mm3 (20%, 95% CI: 8%-39%). INTERPRETATION: Detection of LAM was achievable in non-sputum specimens for pulmonary TB, but additional analyte concentration or signal amplification may be required to achieve diagnostic accuracy targets. FUNDING: Bill and Melinda Gates Foundation.

Impact of the Liberian National Community Health Assistant Program on childhood illness care in Grand Bassa County, Liberia.

Liberia launched its National Community Health Assistant Program in 2016, which seeks to ensure that all people living 5 kilometers or farther from a health facility have access to trained, supplied, supervised, and paid community health workers (CHWs). This study aims to evaluate the impact of the national program following implementation in Grand Bassa County in 2018 using data from population-based surveys that included information on 1291 illness episodes. We measured before-to-after changes in care for childhood illness by qualified providers in a portion of the county that implemented in a first phase compared to those which had not yet implemented. We also assessed changes in whether children received oral rehydration therapy for diarrhea and malaria rapid diagnostic tests if they had a fever by a qualified provider (facility based or CHW). For these analyses, we used a difference-in-differences approach and adjusted for potential confounding using inverse probability of treatment weighting. We also assessed changes in the source from which care was received and examined changes by key dimensions of equity (distance from health facilities, maternal education, and household wealth). We found that care of childhood illness by a qualified provider increased by 60.3 percentage points (95%CI 44.7-76.0) more in intervention than comparison areas. Difference-in-differences for oral rehydration therapy and malaria rapid diagnostic tests were 37.6 (95%CI 19.5-55.8) and 38.5 (95%CI 19.9-57.0) percentage points, respectively. In intervention areas, care by a CHW increased from 0 to 81.6% and care from unqualified providers dropped. Increases in care by a qualified provider did not vary significantly by household wealth, remoteness, or maternal education. This evaluation found evidence that the Liberian National Community Health Assistant Program has increased access to effective care in rural Grand Bassa County. Improvements were approximately equal across three measured dimensions of marginalization.

A Novel Malaria Lateral Flow Assay for Detecting Plasmodium falciparum Lactate Dehydrogenase in Busia, Uganda.

Rapid diagnostic tests (RDTs) for Plasmodium falciparum commonly detect histidine-rich protein 2 (HRP-2), but HRP-2 deletions are increasingly recognized. We evaluated a prototype test detecting parasite lactate dehydrogenase (pLDH) and compared it to commercially available RDTs at a health facility in Uganda, using quantitative polymerase chain reaction as a gold standard. The prototype pLDH test had a high sensitivity for infections with at least 100 parasites/µL (98%), comparable to HRP-2, and greater than an existing pLDH RDT (89%). Specificity for the prototype test was 99.5%, which is greater than the HRP-2 tests (93-95%). Therefore, the prototype pLDH test may be an attractive alternative malaria diagnostic.