Human asymptomatic Ebola infection and strong inflammatory response

Background Ebola virus is one of the most virulent pathogens, killing a ver y high proportion of patients within 5-7 days. Two outbreaks of fulminating haemorrhagic fever occurred in northern Gabon in 1996, with a 70% case-fat ality rate. During both outbreaks we identified some individuals in direct contact with sick patients who never developed symptoms. We aimed to determ ine whether these individuals were indeed infected with Ebola virus, and ho w they maintained asymptomatic status. Methods Blood was collected from 24 close contacts of symptomatic patients. These asymptomatic individuals were sampled 2, 3, or 4 times during a 1-mo nth period after the first exposure to symptomatic patients. Serum samples were analysed for the presence of Ebola antigens, virus-specific IgM and Ig G (by ELISA and western blot), and different cytokines and chemokines. RNA was extracted from peripheral blood mononuclear cells, and reverse-transcri ptase-PCR assays were done to amplify RNA of Ebola virus. PCR products were then sequenced. Findings 11 of 24 asymptomatic individuals developed both IgM and IgG respo nses to Ebola antigens, indicating viral infection. Western-blot analysis s howed that IgG responses were directed to nucleoprotein and viral protein o f 40 kDa. The glycoprotein and viral protein of 24 kDa genes showed no nucl eotide differences between symptomatic and asymptomatic individuals. Asympt omatic individuals had a strong inflammatory response characterised by high circulating concentrations of cytokines and chemokines. Interpretation This study showed that asymptomatic, replicative Ebola infec tion can and does occur in human beings. The lack of genetic differences be tween symptomatic and asymptomatic individuals suggest that asymptomatic Eb ola infection did not result from viral mutations. Elucidation of the facto rs related to the genesis of the strong inflammatory response occurring ear ly during the infectious process in these asymptomatic individuals could in crease our understanding of the disease.