The pathogenesis of severe human
monkeypox, which causes systemic and fulminant
infections, is not clear. This study presents a case repot of fulminant
monkeypox with bacterial
sepsis after experimental
infection with monkeypox virus in a cynomolgus monkey (Macaca fascicularis). In our previous study (Saijo et al., 2009, J Gen Virol), two cynomolgus monkeys became moribund after experimental
infection with monkeypox virus Liberia strain, West African strain. One exhibited typical
monkeypox-related papulovesicular lesions. The other monkey presented fulminant clinical symptoms with a characteristic flat red
rash similar to that found in
smallpox, which is associated with extremely high fatality rates. In this study, we found that the monkey with flat red
rash had high levels of
viremia and
neutropenia, as well as high plasma levels of pro-inflammatory
cytokines and
chemokines compared with the other monkey. Monkeypox virus replicates in epithelial cells and macrophages in various organs.
Sepsis due to Gram-positive cocci was confirmed histopathologically in the monkey with flat red
rash. The lack of inflammatory response in the lesion suggested that the monkey with
sepsis experienced strong immune suppression during the
viral infection. The
neutropenia and excessive inflammatory
cytokine responses indicate that neutrophils play key roles in the pathogenesis of systemic and fulminant human monkeypox virus
infections with
sepsis.