Rift valley fever viral load correlates with the human inflammatory response and coagulation pathway abnormalities in humans with hemorrhagic manifestations.

• Type of Material: Article
• Authors: Annabelle de St Maurice, Viral Special Pathogens Branch, US CDC; Jessica Harmon, Viral Special Pathogens Branch, US CDC; Luke Nyakarahuka, Uganda Virus Research Institute; Stephen Balinandi, Viral Special Pathogens Branch, US CDC; Alex Tumusiime, Viral Special Pathogens Branch, US CDC; Jackson Kyondo, Uganda Virus Research Institute; Sophia Mulei, Uganda Virus Research Institute; Annemarion Namutebi, Kabale Regional Referral Hospital; Barbara Knust, Viral Special Pathogens Branch, US CDC; Trevor Shoemaker, Viral Special Pathogens Branch, US CDC; Stuart T. Nichol, Viral Special Pathogens Branch, US CDC; Anita Katherine McElroy, Emory University; Christina F. Spiropoulou, Viral Special Pathogens Branch, US CDC
• Language: English
• Date: 2018-05-04
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
• License: Creative Commons Creative Commons CC0 1.0 Universal
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pntd.0006460
• Title of Journal or Parent Work: PLoS Neglected Tropical Diseases
• ISSN: 1935-2727
• Volume: 12
• Issue: 5
• Start Page: e0006460
• End Page: e0006460
• Grant/Funding Information: This work was also supported by Children's Healthcare of Atlanta Pediatric Research Trust Startup Funds to AKM.; AKM is supported by an NIH K08 AI119448, and a Burroughs Wellcome Career Award for Medical Scientists #1013362.01.
• Keywords: Humans; Viral Load; Adolescent; Male; Rift Valley fever virus; Cytokines; P-Selectin; ADAMTS13 Protein; Blood Coagulation; Biomarkers; Middle Aged; Hemorrhage; Young Adult; Rift Valley Fever
• Research Categories: Health Sciences, Pathology; Health Sciences, Medicine and Surgery

Abstract

Rift Valley fever virus is an arbovirus that affects both livestock and humans throughout Africa and in the Middle East. Despite its endemicity throughout Africa, it is a rare event to identify an infected individual during the acute phase of the disease and an even rarer event to collect serial blood samples from the affected patient. Severely affected patients can present with hemorrhagic manifestations of disease. In this study we identified three Ugandan men with RVFV disease that was accompanied by hemorrhagic manifestations. Serial blood samples from these men were analyzed for a series of biomarkers specific for various aspects of human pathophysiology including inflammation, endothelial function and coagulopathy. There were significant differences between biomarker levels in controls and cases both early during the illness and after clearance of viremia. Positive correlation of viral load with markers of inflammation (IP-10, CRP, Eotaxin, MCP-2 and Granzyme B), markers of fibrinolysis (tPA and D-dimer), and markers of endothelial function (sICAM-1) were all noted. However, and perhaps most interesting given the fact that these individuals exhibited hemorrhagic manifestations of disease, was the finding of a negative correlation between viral load and P-selectin, ADAMTS13, and fibrinogen all of which are associated with coagulation pathways occurring on the endothelial surface.