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The cyanobacterial lectin, microvirin-N, enhances the specificity and sensitivity of lipoarabinomannan-based TB diagnostic tests.

ABSTRACT: Tuberculosis (TB) is one of the top ten causes of death globally, despite being treatable. The eradication of TB disease requires, amongst others, diagnostic tests with high specificity and sensitivity that will work at the point of care (POC) in low-resource settings. The TB surface glycolipid antigen, mannose-capped lipoarabinomannan (ManLAM) currently serves as the only POC molecular diagnostic biomarker suitable for use in low cost immunoassays. Here, we demonstrate the high affinity and exceptional specificity of microvirin-N (MVN), a 14.3 kDa cyanobacterial lectin, toward H37Rv TB ManLAM and utilize it to develop a novel on-bead ELISA. MVN binds to ManLAM with sub-picomolar binding affinity, but does not bind to other variants of LAM expressed by non-pathogenic mycobacteria - a level of binding specificity and affinity that current commercially available anti-LAM antibodies cannot achieve. An on-bead ELISA was subsequently developed using MVN-functionalized magnetic beads which allows for the specific capture of ManLAM from human urine with a limit of detection (LOD) of 1.14 ng mL^-1 and no cross-reactivity when tested with PILAM, a variant of LAM found on non-pathogenic mycobacteria.

SUBMITTER: van der Horst M

PROVIDER: S-EPMC8374243 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundLassa fever virus has been enlisted as a priority pathogen of epidemic potential by the World Health organization Research and Development (WHO R & D) Blueprint. Diagnostics play a crucial role in epidemic preparedness. This systematic review was conducted to determine the sensitivity and specificity of Lassa fever diagnostic tests for humans.MethodsWe searched OVID Medline, OVID Embase, Scopus and Web of Science for laboratory based and field studies that reported the performance of diagnostic tests for Lassa fever in humans from 1 January 1990 to 25 January 2019. Two reviewers independently screened all the studies and included only studies that involved the evaluation of a Lassa fever diagnostic test and provided data on the sensitivity and specificity. The quality of the studies was assessed using the QUADAS-2 criteria. Data on the study location, study design, type of sample, index test, reference tests and diagnostic performance were extracted from the studies.ResultsOut of a total of 1947 records identified, 1245 non-duplicate citations were obtained. Twenty-six (26) full-text articles examined which identified 08 studies meeting pre-defined criteria. Only one study was a field evaluation study. The sensitivity and specificity of the point of care (RDT) against the Nikisins qPCR were 91.2%(95% CI:75.2-97.7) and 86%(95% CI: 71.4-94.2) at temperatures 18-30 °C, while the sensitivity and specificity of the single IgM ELISA assay against standard RT-PCR were 31.1%(95%CI: 25.6-37) and 95.7%(95%CI:92.8-97.7). The sensitivity of the combined ELISA Antigen/IgM assay(against virus isolation), the recombinant IgM/IgG ELISA(against standard RT-PCR), and the IgM/IgG immunoblot(against IFA) were 88%(95%CI:77-95), 25.9%(95%CI:20.8-31.6), and 90.7%(95%CI:84.13-97.27) respectively. The specificity of the combined ELISA Antigen/IgM assay(against virus isolation), the recombinant IgM/IgG ELISA(against standard RT-PCR), and the IgM/IgG immunoblot(against IFA) were 90%(95%CI:88-91), 100%(95%CI:98.2-100), and 96.3%(95%CI:92.2-100) respectively.ConclusionLassa fever has assays for antigenaemia, IgM, IgG and PCR detection. The RDT reportedly performed well but more data are needed from other countries and at temperatures above 30 °C. Most combined immunoassays perform better than the single IgM. Multiplex and pan-Lassa assays are needed. More well conducted field studies are needed.Trial registrationProspero registration number: CRD42018091585 .

Project description:BACKGROUND:Schistosomiasis remains one of the most prevalent parasitic infections in the world and has significant economic and public health consequences, particularly in poor communities. Reliable and accurate diagnosis plays a key role in surveillance, prevention and control of schistosomiasis. Currently, the microscopic Kato Katz (KK) stool thick smear technique is the most commonly used method to diagnose Schistosoma mansoni infections in epidemiological surveys. It is well-known that the sensitivity of this parasitological method decreases when infection intensities are moderate to low, however. The urine-based Point-of Care Circulating Cathodic Antigen (POC-CCA) test has been extensively evaluated as a further diagnostic tool. Several studies have shown that the POC-CCA test is more sensitive but less specific than the KK method. However, to clarify the meaning of inconsistent results between KK and POC-CCA tests in clinical routine, this study compares the accuracy of microscopy and POC-CCA versus real-time polymerase chain reaction (real-time PCR) results of urine and faecal samples from African school children participants. METHODOLOGY:This was a school-based cross-sectional study conducted in 2015 among 305 school children aged 7-16 years from two primary schools located in Ilemela and Magu Districts, north-western Tanzania. Single stool and urine samples were collected from each participant and examined for the presence of Schistosoma mansoni eggs, parasite antigen, and parasite DNA using KK thick smears, POC-CCA tests, and real-time PCR, respectively. PRINCIPAL FINDINGS:The prevalence of S. mansoni infection, calculated by KK was 85.2%, by real-time PCR 92.9% and by POC-CCA 94.9%. In comparison to KK, the POC-CCA and real-time PCR tests had sensitivities of 89.7% and 99.5% and specificities of 22.73% and 29.55%, respectively. However, due to the known limitations of the KK assay, we also used latent class analysis (LCA) that included POC-CCA, KK, and schistosome-specific real-time PCR results to determine their sensitivities and specificities. The POC-CCA test had the highest sensitivity (99.5%) and a specificity of 63.4% by LCA and the real-time PCR test had a sensitivity of 98.7% and the highest specificity (81.2%). CONCLUSION:In moderate and high prevalence areas, the POC-CCA cassette test is more sensitive than the KK method and can be used for screening and geographical mapping of S. mansoni infections. Real-time PCR is highly sensitive and also shows the highest specificity among the 3 investigated diagnostic procedures. It can offer added value in diagnosing schistosomiasis.

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The cyanobacterial lectin, microvirin-N, enhances the specificity and sensitivity of lipoarabinomannan-based TB diagnostic tests.

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