Immunity and immune response, pathology and pathologic changes: progress and challenges in the immunopathology of yellow fever

Abstract

Yellow fever is a viral hemorrhagic fever, which affects people living in Africa and South America and is caused by the yellow fever virus, the prototype species in the Flavivirus genus (Flaviviridae family). Yellow fever virus infection can produce a wide spectrum of symptoms, ranging from asymptomatic infection or oligosymptomatic illness to severe disease with a high fatality rate. In this review, we focus in the mechanisms associated with the physiopathology of yellow fever in humans and animal models. It has been demonstrated that several factors play a role in the pathological outcome of the severe form of the disease including direct viral cytopathic effect, necrosis and apoptosis of hepatocyte cells in the midzone, and a minimal inflammatory response as well as low-flow hypoxia and cytokine overproduction. New information has filled several gaps in the understanding of yellow fever pathogenesis and helped comprehend the course of illness. Finally, we discuss prospects for an immune therapy in the light of new immunologic, viral, and pathologic tools.

Frequency of histopathological changes in Howler monkeys ( Alouatta sp.) naturally infected with yellow fever virus in Brazil

“…YFV virulence is considered highly dependent on the virus strain and host species susceptibility (4) . Differences in liver histological patterns during naturally acquired YFV infection have been observed elsewhere (4) (8) .…”

“…These pathological changes are usually intense and occur in combination with midzonal necrosis. The infl ammatory response is generally quite mild or absent and does not correspond to the extent and severity of hepatic injury and this may be in conjunction with over expression of tumor necrosis factor beta (TNF-β), even with the presence of hepatocyte necrosis (6) (8) . However, a considerable number of YFV-infected Brazilian Howler monkeys presented hepatic infl ammatory mononuclear cell infi ltration and hemorrhage during epizootics in Brazil.…”

“…Histopathological diagnosis is based on characteristic injury patterns such as midzonal necrosis and liver steatosis, the presence of Councilman bodies, and the paucity of hepatic infl ammation and hemorrhage (5) (6) (7) (8) .…”

“…These animal models led to the validation of YF histopathological diagnosis patterns that are observed in almost all human cases (4) (5) (8) .…”

The Yellow Fever Outbreak in Global Perspective is Serious and of Great Concern

“…Although, a small proportion of infections are asymptomatic and after three and six days of infection victims develops influenza-like symptoms (fever, joint pains, and headache), and after three or four days appearance of these symptoms may disappear, and in most cases, the period of recovery begins [30,31]. In other cases, febrile symptoms accompanied by nausea, vomiting, epigastric pain, renal failure, jaundice and hemorrhaging [2,32]. In some cases within 10-14 days, half of the patients at this stage die, while some may be recovered without any significant organ damage.…”