Evaluation of four lassa virus IgM immunoassays for early detection and seroprevalence studies in West Africa
Year: 2025
Type: article
Abstract: Introduction Immunoglobulin M (IgM) antibodies are the earliest serologic markers of acute Lassa virus (LASV) infection, making LASV-specific IgM assays essential for early diagnosis, particularly when combined with clinical suspicion. In clinical research, IgM assays may be used to assess immune responses to natural infection or vaccination. For reliable utility in such settings, assays should demonstrate high sensitivity (>90%) and specificity (>95%). However, performance data on available LASV IgM assays remain limited. This study evaluates the diagnostic performance of four commercial LASV IgM assays to determine their applicability in seroprevalence assessments and vaccine trials within Lassa-endemic regions. Methods This retrospective, multicenter diagnostic evaluation was conducted at three Lassa-endemic sites: Irrua Specialist Teaching Hospital (Nigeria), Kenema Government Hospital (Sierra Leone), and Phebe Hospital (Liberia). Four LASV-specific IgM immunoassays were assessed using archived frozen sera from RT-PCR-confirmed acute Lassa fever cases in Nigeria and Liberia, and LASV antigen-positive cases from Sierra Leone. All samples were collected within 12 weeks of diagnosis. LASV-negative sera were obtained from Gabon (non-endemic), and the U.S. CDC LASV IgM ELISA was used as the reference standard. Results In pooled analysis, the ReLASV nucleoprotein (NP) assay demonstrated the highest sensitivity (95.3%, 95% CI: 81.0–99.0), while the BLACKBOX IgM assay showed the highest specificity (91.4%, 95% CI: 85.7–94.9). The ReLASV prefusion glycoprotein (pfGP) assay showed consistently poor sensitivity. Specificity varied by country, with reduced values observed in Sierra Leone. IgM sensitivity versus RT-PCR ranged from 18.5% to 62.3%, and specificity from 80.7% to 99.0%. Conclusion Although none of the four assays met ideal diagnostic thresholds, the BLACKBOX IgM assay demonstrates sufficient specificity for use in high-prevalence settings and may be suitable for IgM seroprevalence studies at the evaluated sites.
Authors: Ephraim Ogbaini-Emovon, Hanesh Chi, Mambu Momoh, Emmanuel Kerkula, Rachael Omiunu, Yemisi Ighodalo, Oluwasola Babatunde, John Sandi, Fritz Fonkeng, Berra Erkosar, Sylvanus Okogbenin, Cyril Erameh, Mckenzie Colt, David Wohl, William Fischer II, Ghyslain Mombo-Ngoma, Michael Ramharter, Nelson Adedosu, Joseph Okoguale, Goerge Akpede, Mojeed Rafiu, Reuben Eifediyi, Chiedozie Ojide, Stephan Guenther, Daniel Bausch, Aurelia Vessiere, Donald Grant, J. Sibley, Devy Emperador
Institutions: Irrua Specialist Teaching Hospital, FIND, Centre de Recherche Médicales de Lambaréné, Federal Medical Centre, Alex Ekwueme Federal University, Ndufu-Alike, University Medical Center Hamburg-Eppendorf, Bernhard Nocht Institute for Tropical Medicine, National University of Singapore, World Health Organization
Language: English
Topic: Viral Infections and Vectors
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4416144426