At least 27 alphaviruses and 68 flaviviruses have been recognized, approximately 
one-third of which are medically important human pathogens. They vary widely in 
their basic ecology; each virus occupies a distinct ecologic niche, often with 
restricted geographic and biologic distribution. As shown in Tables 54-1 and 
54-2, alphaviruses and flaviviruses can cause various syndromes, ranging from 
benign febrile illnesses to severe systemic diseases with hemorrhagic 
manifestations or major organ involvement. The neurotropic alphaviruses and 
flaviviruses can produce severe destructive central nervous system disease with 
serious sequelae. Several alphaviruses (chikungunya, Mayaro, and Ross River) 
cause painful arthritis that persists for weeks or months after the initial 
febrile illness. Yellow fever virus has unique hepatotropic properties that 
cause a clinically and pathologically distinct form of hepatitis with a 
hemorrhagic diathesis. The dengue viruses, which cause more human illness than 
all other members of their family, may produce a serious, sometimes fatal, 
immunopathologic disease in which shock and hemorrhage occur. Hepatitis C virus 
(Chapter 70) may be a flavivirus. Alphavirus is one of the two genera in the 
family Togaviridae; the other genus (Rubivirus) has rubella virus (Chapter 55) 
as its only member. Flavivirus, once classified in the Togaviridae, now 
constitutes one of three genera in the family Flaviviridae; the other two genera 
are Pestivirus and “Hepatitis C-like viruses”. Pestivirus includes animal 
pathogens (bovine viral diarrhea and hog cholera viruses) that are of 
considerable economic importance, but contains no known human pathogens. 
Hepatitis C virus is described in Chapter 70. All alphaviruses and flaviviruses 
that cause disease in humans are arthropod-borne viruses (arboviruses). In the 
original classification scheme based on antigenic relationships, alphaviruses 
and flaviviruses were termed group A and group B arboviruses, respectively. Most 
alphaviruses and flaviviruses survive in nature by replicating alternately in a 
vertebrate host and a hematophagous arthropod (mosquitoes or, for some 
flaviviruses, ticks). Arthropod vectors acquire the viral infection by biting a 
viremic host, and after an extrinsic incubation period during which the virus 
replicates in the vector's tissues, they transmit virus through salivary 
secretions to another vertebrate host. Virus replicates in the vertebrate host, 
causing viremia and sometimes illness. The ability to infect and replicate in 
both vertebrate and arthropod cells is an essential quality of alphaviruses and 
flaviviruses. The principal vertebrate hosts for most are various species of 
wild mammals or birds. The natural zoonotic cycles that maintain the virus do 
not usually involve humans. However, a few viruses (yellow fever virus, dengue 
virus types 1, 2, 3 and 4 and chikungunya virus) can be transmitted in a 
human-mosquito-human cycle. As a result of being pathogenic for humans and 
capable of transmission in heavily populated areas, these viruses can cause 
widespread and serious epidemics. Because of their high transmission potential, 
these viruses are major public health problems in many tropical and subtropical 
regions of the world where appropriate mosquito vectors are present. Because 
some of these agents are dangerous human pathogens and are highly infectious, 
special containment and safety precautions in the laboratory are required.