Chapter 25: Dengue, Yellow Fever, Chikungunya, Lassa Fever, and Crimean-Congo Hemorrhagic Fever

INTRODUCTION

Families of RNA viruses such as Flaviviridae (Dengue and Yellow Fever), Togaviridae (Chikungunya), Arenaviridae (Lassa Fever) and Bunyaviridae (Crimean-Congo Hemorrhagic Virus) can lead to hemorrhagic fevers with limited treatment options.

DENGUE

Dengue virus is transmitted by the arthropod Aedes aegypti (Figure 25-1) to humans at an increasingly rapid rate, with cases found mostly in warm tropical climates. Reports in the past several years have indicated that this viral infection is no longer being contained to tropical areas and have been reported in the southern border of the United States in Texas and in Hawaii also.^1,2 Data from the World Health Organization (WHO) has identified 796 cases of dengue in the United States during the period of 2001–2007.² Dengue virus has caused high morbidity throughout the world. Symptomatic disease has been estimated in as high as 96 million cases of annually reported worldwide infections and overall as high as 390 million dengue viral infections have been reported yearly.¹

Pathogenesis

Dengue virus is a single stranded RNA genome consisting of seven nonstructural proteins (NS1, NS2A, NS2 B, NS3, NS4A, NS4B, and NS5), structural envelope, membrane, and capsid viral structural proteins³ (Figure 25-2). The envelope protein plays a key role in the viral pathogenicity with receptor binding, activation of immunological responses, and antibodies as well as agglutination of red cells.³ NS1 increases vascular permeability through its various interactions with the vascular endothelium, activates of the complement cascade, and the amount of NS1 and Sc5b-9 in serum may be related to severity.^3–5

Dengue virus has four serotypes (DENV-1, DENV-2, DENV-3, and DENV-4). DENV-2 is associated with Dengue Shock Syndrome.^6–9 Infection from one of the four serotypes does not prevent infection from the other serotypes, but provides immunity from re-infection from the original serotype.^10,11

Susceptibility to severe infection includes obese persons, females, children and obese persons, females, children, human major-histocompatibility complex class I related sequence B, and phospholipase C epsilon1 genes.^4,11

Clinical Manifestations

Dengue virus infection becomes symptomatic after 5–7 days of incubation. The clinical state is divided into three phases. The first phase is biphasic febrile illness, which is associated with constitutional symptoms, such as vomiting, malaise, severe headache, pharyngitis, retro-orbital pain, and conjunctivitis with associated flushing, and it lasts for 2–7 days.^4,11 Petechiae, Ecchymosis, and palpable liver can also often be found.^4,11 Most patients improve after fevers resolve.^4,11