Natural History of Aerosol Induced Lassa Fever in Non‑Human Primates

Viruses

CharlesB. Larcom¹  HeatherL. Esham²  KyleA. Everson²  DavidL. Saunders²  WilliamD. Pratt²  Xiankun Zeng²  JoshuaC. Johnson²  IsaacL. Downs²  Franco Rossi²  MelissaK. Gregory²  JohnC. Trefry²  Lisa Hensley²  ArthurC. Okwesili²  KathleenA. Cashman²  CarlI. Shaia²  Anna Honko²  AnthonyP. Cardile² 

[1] Madigan Army Medical Center, Joint Base Lewis‑McChord, WA 98431, USA;US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA;

关键词: LASV;    Lassa;    Josiah;    VHF;    telemetry;    aerosol;   

DOI  :  10.3390/v12060593

来源: DOAJ

【 摘 要 】

Lassa virus (LASV), an arenavirus causing Lassa fever, is endemic to West Africa with up to 300,000 cases and between 5000 and 10,000 deaths per year. Rarely seen in the United States, Lassa virus is a CDC category A biological agent inasmuch deliberate aerosol exposure can have high mortality rates compared to naturally acquired infection. With the need for an animal model, specific countermeasures remain elusive as there is no FDA-approved vaccine. This natural history of aerosolized Lassa virus exposure in Macaca fascicularis was studied under continuous telemetric surveillance. The macaque response to challenge was largely analogous to severe human disease with fever, tachycardia, hypotension, and tachypnea. During initial observations, an increase trend of activated monocytes positive for viral glycoprotein was accompanied by lymphocytopenia. Disease uniformly progressed to high viremia followed by low anion gap, alkalosis, anemia, and thrombocytopenia. Hypoproteinemia occurred late in infection followed by increased levels of white blood cells, cytokines, chemokines, and biochemical markers of liver injury. Viral nucleic acids were detected in tissues of three non‑survivors at endpoint, but not in the lone survivor. This study provides useful details to benchmark a pivotal model of Lassa fever in support of medical countermeasure development for both endemic disease and traditional biodefense purposes.

【 授权许可】

Unknown