Infectious Diseases
Jamie M. Strampe, BS
PhD Candidate
Boston University
Somerville, Massachusetts, United States
Danny Asogun, MBBS
Irrua Specialist Teaching Hospital
Irrua, Edo, Nigeria
Emily Speranza, PhD
National Institutes of Health, National Institute of Allergy and Infectious Disease
Bethesda, Maryland, United States
Meike Pahlmann, PhD
Bernhard Nocht Institute for Tropical Medicine
Hamburg, Hamburg, Germany
Ali Soucy, MPH
National Emerging Infectious Diseases Laboratories
Boston, Massachusetts, United States
Sabrina Bockholt, MSc
Bernhard Nocht Institute for Tropical Medicine
Hamburg, Hamburg, Germany
Elisa Pallasch, BSc
Bernhard Nocht Institute for Tropical Medicine
Hamburg, Hamburg, Germany
Beate Becker-Ziaja, BSc
Bernhard Nocht Institute for Tropical Medicine
Hamburg, Hamburg, Germany
Sophie Duraffour, PhD
Bernhard Nocht Institute for Tropical Medicine
Hamburg, Hamburg, Germany
Nahid Bhadelia, M.D.
Boston University School of Medicine
Boston, Massachusetts, United States
Yemisi Ighodalo, BSc
Irrua Specialist Teaching Hospital
Irrua, Edo, Nigeria
Jennifer Oyakhilome, BSc
Irrua Specialist Teaching Hospital
Irrua, Edo, Nigeria
Emmanuel Omomoh, BCs
Irrua Specialist Teaching Hospital
Irrua, Edo, Nigeria
Thomas Olokor, BSc
Irrua Specialist Teaching Hospital
Irrua, Edo, Nigeria
Donatus Adomeh, PhD
Irrua Specialist Teaching Hospital
Irrua, Edo, Nigeria
Odia Ikponwonsa, MSc
Irrua Specialist Teaching Hospital
Irrua, Edo, Nigeria
Chris Aire, FMLSCN
Irrua Specialist Teaching Hospital
Irrua, Edo, Nigeria
Ekaete Tobin, MBBCh
Irrua Specialist Teaching Hospital
Irrua, Edo, Nigeria
Nosa Akpede, MBBS
Irrua Specialist Teaching Hospital
Irrua, Edo, Nigeria
Peter O. Okokhere, FWACP
Irrua Specialist Teaching Hospital
Irrua, Edo, Nigeria
Sylvanus A. Okogbenin, MBBS
Irrua Specialist Teaching Hospital
Irrua, Edo, Nigeria
George Akpede, FWACP
Irrua Specialist Teaching Hospital
Irrua, Edo, Nigeria
Cesar Muñoz-Fontela, PhD
Bernhard Nocht Institute for Tropical Medicine
Hamburg, Hamburg, Germany
Ephraim Ogbaini-Emovon, FMCPath
Irrua Specialist Teaching Hospital
Irrua, Edo, Nigeria
Stephan Günther, MD
Bernhard Nocht Institute for Tropical Medicine
Hamburg, Hamburg, Germany
John H. Connor, PhD
National Emerging Infectious Diseases Laboratories
Boston, Massachusetts, United States
Lisa Oestereich, PhD
Bernhard Nocht Institute for Tropical Medicine
Hamburg, Hamburg, Germany
Lassa virus (LASV) causes the acute disease Lassa fever (LF) in humans and is endemic throughout western Africa. Symptoms of LF include fever, body aches, hypovolemic shock, and multi-system organ failure, leading to high mortality in hospitalized patients. The progression of LF is not well understood, so it is difficult to predict which patients will most need critical care, or which types of care will best improve patient outcomes. We aimed to identify protein biomarkers in blood that could predict patient mortality over the course of hospitalization. Samples were collected longitudinally from 201 patients with LF in Nigeria and measured by Luminex assay for 62 serum cytokines and proteins associated with the immune response, inflammation, and hemostasis. Statistical analysis followed by logistic regression modeling revealed 18 host proteins significantly elevated at admission in patients that died, of which PAI-1 (ROC AUC=0.88), soluble thrombomodulin (AUC=0.84), and soluble TNFR1 (AUC=0.81) most consistently predicted fatal outcome. We then applied our statistical pipeline to later timepoints to further characterize the predictive ability of these biomarkers throughout the course of disease. At 2-3 days post admission, when many of the fatal cases were close to death, PAI-1, sTM, and TNFR1 remained highly predictive, and the chemokines fractalkine and MCP-1 became highly predictive of mortality (all five AUCs >0.87). Lastly, we tested whether pairs of these markers could improve predictive accuracy over single markers. All top predictive pairs at admission included PAI-1, with the best combination showing slight improvement over PAI-1 alone (PAI-1 + M-CSF, AUC=0.90).
