Dengue and dengue haemorrhagic fever: implications of host genetics

Abstract

Little is known of the role of human leucocyte antigen (HLA) alleles or non-HLA alleles in determining resistance, susceptibility or the severity of acute viral infections. Dengue fever (DF) and dengue haemorrhagic fever (DHF) are suitable models for immunogenetic studies, yet only superficial efforts have been made to study dengue disease to date. DF and DHF can be caused by both primary and secondary infection by any of the four serotypes of the dengue virus. Differences in host susceptibility to infectious disease and disease severity cannot be attributed solely to the virus virulence. Variations in immune response, often associated with polymorphism in the human genome, can now be detected. Data on the influence of human genes in DF and DHF are discussed here in relation to (1) associations between HLA polymorphism and dengue disease susceptibility or resistance, (2) protective alleles influencing progression to severe disease, (3) alleles restricting CD4(+) and CD8(+) T lymphocytes, and (4) non-HLA genetic factors that may contribute to DHF evolution. Recent discoveries regarding genetic associations in other viral infections may provide clues to understanding the development of end-stage complications in dengue disease. The scanty positive data presented here indicate a need for detailed genetic studies in different ethnic groups in different countries during the acute phase of DF and DHF on a larger number of patients.

Serologic Imprint of Dengue Virus in Urban Haiti: Characterization of Humoral Immunity to Dengue in Infants and Young Children

“…21 In particular, severe dengue illness appears to occur less frequently in people of African descent. 10,22 Possibly, Haitians are genetically or in some way protected from severe disease.…”

Clinical profile of dengue fever infection in King Abdul Aziz University Hospital Saudi Arabia

“…All the patients survived during 2005, but 4.55%, 25%, and 2.7% of patients died during 2006-2008. Therefore, the highest mortality rate (25%) occurred during 2007, when 25% of patients had Hb levels < 5g/dL, and 50% had severe thrombocytopenia (11)(12)(13)(14)(15)(16)(17)(18)(19)(20),000 platelets/μL). Consequently, 25% of patients required blood and platelet transfusions.…”

“…Host immune response variations have been associated with polymorphism in the human genome, which may help explain why some patients develop end-stage complications in dengue disease and others only experience a mild form of the disease [17]. In another study of children with DENV infection, host genetic differences were shown to affect the immune response and consequently, influence disease outcome [18].…”

Elevated levels of soluble ST2 protein in dengue virus infected patients

“…It infects humans and produces a disease with a broad spectrum of clinical manifestations that ranges from an acute self-limiting febrile illness (Dengue Fever, DF) to various grades of a severe disease (Dengue Hemorrhagic Fever, DHF) that could result in a life-threatening syndrome (Dengue Shock Syndrome, DSS) [1]. Symptoms include high fever, headache, myalgias, skin rash, thrombocytopenia, coagulation alterations, hepatic inflammation and hemorrhagic manifestations.…”