Endotheliopathy and Platelet Dysfunction as Hallmarks of Fatal Lassa Fever

This is the authors' abstract. We don't add key points for this paper.

L assa fever (LF) is an acute viral hemorrhagic fever endemic to West Africa, where ≈300,000-500,000 cases/year occur and mortality rates are high (1).Humans primarily are infected from exposure to excreta from the rodent host, Natal multimammate mouse (Mastomys natalensis).Pregnant women especially are susceptible to severe disease; infection during pregnancy usually leads to spontaneous abortion (2).The high rates illness and death, lack of vaccines or approved treatments, and potential to cause a public health emergency led to the US Centers for Disease Control and Prevention to classify LF as a category A bioterrorism agent (https://emergency.cdc.gov/agent/agentlist-category.asp) and the World Health Organization to classify LF as a priority disease (https://www.who.int/dg/priorities).Early clinical manifestations and symptoms of LF often are nonspecific and easily confused with other diseases prevalent in the endemic region, such as malaria and typhoid fever.Consequently, patients often are not admitted for LF treatment until symptoms are severe and they have failed other therapies.Bleeding at mucous membranes and edema generally are seen in the most severe cases (3,4), but bleeding diathesis reportedly was common during a recent outbreak in Nigeria (4).Overt hemorrhage is rare, mostly limited to the mucosal surfaces, and not severe enough to cause shock.Pathologic changes seen on autopsy lack major cell and tissue injury but include signs of pleural effusion, pulmonary edema, ascites, and gastrointestinal mucosa bleeding (5,6), all indications of systemic vascular leakage.Severely ill LF patients often have mild to moderate thrombocytopenia, but rarely have platelet counts <100,000/μL (7).Thrombocytopenia is a common feature of hemorrhagic fevers and vascular permeability disorders (8), but the decrease in platelet counts in acute LF is not low enough to cause spontaneous hemorrhage.LF could be characterized as a disease of enhanced vascular permeability but the underlying Endotheliopathy and Platelet Dysfunction as Hallmarks of Fatal Lassa Fever