ARBOVIRUSES The members of the Togaviridae and Flaviviridae families are enveloped, positive, ssRNA viruses Most are

are transmitted by arthropods and are therefore arboviruses (arthropod borne) The Togaviruses can be classified into three major genera 1. Alphavirus 2. Rubivirus (Rubella virus) 3. Arterivirus The Flaviviridae include: 1. flaviviruses 2. Pestivirus 3. hepatitis C and G Alphaviruses and Flaviviruses are discussed together because of similarities in the disease they cause and their epidemiology

MODES OF CONTROL

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Mosquito breeding sites and mosquitoes should be eliminated Live attenuated vaccines are available for yellow fever virus and Japanese encephalitis virus.

ALPHAVIRUSES AND FLAVIVIRUSES Historically classified as arboviruses, because they are usually spread by arthropod vectors: arthropod-borne Host: vertebrates & invertebrates Hepatitis C: recently classified as a Flavivirus
Patterns of alphavirus and flavivirus transmission. The cycle of arbovirus transmission maintains and amplifies the virus in the environment. Hostvector relationships that can provide this cycle are indicated by the double arrow. Dead-end infections with not transmission of the virus back to the vector are indicated by the single arrow. For St. Louis encephalitis, yellow fever, and dengue viruses, humans are not dead-end hosts and support an urban cycle. The Russian spring-summer encephalitis virus can be transmitted to humans by a tick bite and in milk form from infected goats.

ALPHAVIRUSES 1. 2. 3. 4. 5. 6. Venezuelan Equine Encephalitis Eastern Equine Encephalitis Western Equine Encephalitis Chikungunya Semliki Sindbis

FLAVIVIRUSES Epidemiology (of Togavirus and Flavivirus Infection)

Both alpha- and flaviviruses are prototypical arboviruses Most common vector: mosquito Others: ticks & sandflies Usual reservoir: birds & small mammals
DISEASE/VIRAL FACTORS o Enveloped virus must stay wet and can be o o

1. 2. 3. 4. 5. 6. 7.

Dengue Yellow Fever Japanese Encephalitis West Nile St. Louis Encephalitis Russian spring-summer encephalitis Powassan

Arboviruses (main characteristics) 1. 2. 3. Should infect both vertebrates & invertebrates Initiate a sufficient viremia in the vertebrate host to allow acquisition by the invertebrate vector Initiate a persistent infection of the salivary gland of the vector to provide virus for infecting other vertebrate hosts

inactivated by drying, soap, and detergents. Virus can infect mammals, birds, reptiles, and insects Asymptomatic or nonspecific (flulike fecer or chills), encephalitis, hemorrhagic fever, or arthritis. and flaviviruses: specific arthropods characteristic of each virus (zoonosis: arbovirus). who enter ecological arthropod: arboviruses niche of

TRANSMISSION o Togaviruses

Clinical Syndromes Infection with Alphaviruses o EEE,WEE,VEE: can progress to encephalitis in humans o S/S: chills, fever, rash, aches o Sindbis & Chikungunya: cause only systemic disease more of a problem to livestock than to humans Infection with Flaviviruses o relatively benign (although encephalitis or hemorrhagic disease can still occur) o encephalitis viruses: St. Louis, Japanese, Murray Valley, Russian spring-summer o hemorrhagic viruses: Dengue & Yellow Fever Usually mild & self-limited but when re-challenged with a related strain can cause severe hemorrhagic/shock

WHO IS AT RISK? o People

GEOGRAPHY/SEASON o Endemic regions

for each arbovirus are determined by habitat of mosquito or other vector Aedes mosquito, which causes dengue and yellow fever, is found in urband areas and in pools of water. Culex mosquito, which causes St. Louis encephalitis, is found in forest and urban areas. Disease is more common in summer

DENGUE

symptoms DHF/DSS: due to rupture of vasculature, internal bleeding, loss of plasma

Pathogenesis Lesions are in small blood vessels, with endothelial swelling, perivascular edema and mononuclear infiltrates

Viruses are good inducers of interferon, which can account for the influenza-like symptoms of infection. Viruses, except rubella and hepatitis C, are arboviruses Flaviviruses infect cells of the monocyte-macrophage lineage. Non-neutralizing antibody can enhance flavivirus infection via Fc receptors on the macrophage.
Influenzalike syndrome Encephalitis Hepatitis Hemorrhage Shock

DHF/DSS are altered manifestations of dengue, often in epidemic form Pathogenesis: not well understood, but seems to involve pre-existing dengue antibodies DHF: abrupt course & is assoc with hypoprotenemia, thrombocytopenia, prolonged BT, elevated PT DSS: characterized by shock & hemoconcentration

Dengue Yellow F. St. Louis E Venezuelan E Western equine E Eastern equine E Japanese E

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YELLOW FEVER Severe systemic disease with degeneration of liver, kidney, heart & hemorrhage of blood vessels Lesions are due to the localization & propagation of the virus in a particular organ Mortality: as high as 50%

ARENAVIRUSES Generalities Include lymphocytic choriomenigitis(LCM) & hemorrhagic fever viruses (Lassa fever, Junin, Machupo) Zoonoses (persistent infection of specific rodents) Virus becomes endemic in the habitat of the rodent

Laboratory Diagnosis Cell culture (both vertebrate & invertebrate cell line) Cytopathology, IF, hemadsorption of avian erythrocytes ELISA, HI, LPA

Tx, Prevn, Control Mainly supportive No specific treatment Vector elimination Avoidance of endemic places Vaccination: Yellow Fever, Jap enceph, EEE, WEE, Russian spring-summer Vaccine for VEE: only for domestic animals

Pathogenesis Infect macrophages, cause vascular damage and tissue destruction

Epidemiology Mainly found: tropical Africa & South America Infect specific rodents & are endemic to their habitat Infection of humans: aerosol, contamination of food or fomites Human-to-human: Lassa fever

Clinical Manifestations Lymphocytic Choriomenigitis o fever with myalgia occurs more often than meningitis o menigeal illness: subacute & persists for several months o brain & meninges: perivascular mononuclear infiltrates Lassa Fever, etc. o endemic: West Africa, Argentina (Junin), Bolivia (Machupo) o S/S: fever, coagulopathy, petechiae, occasional visceral hemorrhages, liver & spleen necrosis o others: pharingitis, diarrhea, vomiting o Dx: recent travel to endemic areas

Laboratory Diagnosis
Disease syndromes of alphaviruses and flaviviruses. Primary viremia may be associated with mild systemic disease. Most infections are limited to this. If sufficient virus is produced during the secondary viremia to escape immune protection and to reach critical target tissue, severe systemic disease or encephalitis may result. For dengue hemorrhagic fever (DHF), which can cause dengue shock syndrome (DSS) because of the loss of luids from the vasculature.

Serology (due to the danger of routine isolation)

Tx, Prevn, Control For Lassa fever: Ribavirin (although with limited activity) Supportive Limit contact with vectors

Disease Mechanisms of Togavirus and Flavivirus Viruses are cytolytic, except for rubella. Viruses establish systemic infection and viremia.