Overview of Arbovirus, Arenavirus, and Filovirus Infections
Arbovirus (arthropod-borne virus) applies to any virus that is transmitted to humans and/or other vertebrates by certain species of blood-feeding arthropods, chiefly insects (flies and mosquitoes) and arachnids (ticks). Arbovirus is not part of the current viral classification system, which is based on the nature and structure of the viral genome.
Families in the current classification system that have some arbovirus members include
Most viruses associated with hemorrhagic fevers are classified in the families Arenaviridae and Filoviridae. However, some flaviviruses (yellow fever, dengue viruses) and some Bunyaviridae (Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus, severe fever with thrombocytopenia virus, the hantaviruses) may be associated with hemorrhagic symptoms.
Arbovirus species number > 250 and are distributed worldwide; at least 80 cause human disease. Birds are often reservoirs for arboviruses, which are transmitted by mosquitoes to horses, other domestic animals, and humans. Other reservoirs for arboviruses include arthropods and vertebrates (often rodents, monkeys, and humans). These viruses may spread to humans directly from nonhuman reservoirs, but human-to-human transmission may also occur by blood transfusion, organ transplantation, sexual contact, and from mother to child during birth depending on the specific virus involved. Human-to-human transmission of most arboviruses through casual, everyday contact has not been documented. Most arboviral diseases are not transmissible by humans, perhaps because the typical viremia is inadequate to infect the arthropod vector; exceptions include dengue, yellow fever, Zika virus infection, and chikungunya disease, which can be transmitted from person to person via mosquitoes. Also, Zika virus can be transmitted during sexual activity from infected symptomatic or asymptomatic men to their sex partners (male or female) or from infected women to their sex partner.
Some infections (eg, West Nile virus infection, Colorado tick fever, dengue, Zika virus) have been spread by blood transfusion or organ donation.
The Arenaviridae includes lymphocytic choriomeningitis virus, Lassa fever virus, Mopeia virus, Tacaribe virus, Junin virus, Lujo virus, and Machupo virus; all are transmitted by rodents and thus are not arboviruses. Lassa fever virus can be transmitted from person to person.
The Filoviridae consists of 2 genera: Ebolavirus (consisting of 5 species) and Marburgvirus (consisting of 2 species). The specific vectors of these viruses have not been confirmed, but fruit bats are the prime candidates; thus, Filoviridae are not arboviruses. Human-to-human transmission of Ebola virus and Marburg virus occurs readily.
Many of these infections are asymptomatic. When symptomatic, they generally begin with a minor nonspecific flu-like illness that may evolve to one of a few syndromes (see table Arbovirus, Arenavirus, and Filovirus Diseases). These syndromes include lymphadenopathy, rashes, aseptic meningitis, encephalitis, arthralgias, arthritis, and noncardiogenic pulmonary edema. Many cause fever and bleeding tendencies (hemorrhagic fever). Decreased synthesis of vitamin K–dependent coagulation factors, disseminated intravascular coagulation, and altered platelet function contribute to bleeding.
Laboratory diagnosis often involves viral cultures, polymerase chain reaction, electron microscopy, and antigen and antibody detection methods where available.
Arbovirus, Arenavirus, and Filovirus Diseases
Distinguishing Symptoms |
Viral Agent or Disease |
Family |
Vector |
Major Distribution* |
Fever, malaise, headaches, myalgias |
||||
|
Additional features: none |
Colorado tick fever |
Reoviridae (Coltivirus) |
Ticks Dermacentor species |
Western US, western Canada |
|
Phlebotomus fever |
Bunyaviridae (Phlebovirus) |
Sand flies Phlebotomus species |
Mediterranean basin, Balkans, Middle East, Pakistan, India, China, eastern Africa, Panama, Brazil |
|
|
Venezuelan equine encephalitis |
Togaviridae (Alphavirus) |
Mosquitoes Culex species |
Argentina, Brazil, northern South America, Panama, Mexico, Florida |
|
|
Heartland virus |
Bunyaviridae (Phlebovirus) |
Tick Amblyomma americanum |
US |
|
|
Bunyaviridae (Phlebovirus) |
Mosquitoes Several species |
South Africa, eastern Africa, Egypt, Yemen, Saudi Arabia |
||
|
Oropouche virus |
Bunyaviridae (Simbu virus) |
Biting midge Culicoides paraensis |
South and Central America, Caribbean |
|
|
Rash |
Dengue fever |
Flaviviridae |
Mosquitoes Aedes species |
Southeast Asia, South Asia, West and East Africa, Oceania, Australia, South and Central America, Mexico, Caribbean, US |
|
Usutu |
Flaviviridae |
Mosquitoes |
Africa, Europe |
|
|
Flaviviridae |
Mosquitoes Aedes species |
Central and South America, Mexico, Caribbean, US, Africa, Pacific Islands, Asia |
||
|
Flaviviridae |
Mosquitoes Culex species |
Africa, Middle East, southern Europe, Russia, India, Indonesia, US, southern Canada, Mexico, South America, Caribbean Islands. |
||
|
Arthralgia, rash |
Togaviridae (Alphavirus) |
Mosquitoes Aedes species |
Africa, India, Pakistan, Guam, Southeast Asia, Reunion Island, New Guinea, limited areas of Europe, South and Central America, Mexico, US |
|
|
Bourbon virus |
Orthomyxoviridae (Thogotovirus) |
Tick Amblyomma americanum |
US |
|
|
Togaviridae (Alphavirus) |
Mosquitoes Haemagogus species |
Brazil, Bolivia, Trinidad |
||
|
Ross River virus |
Togaviridae (Alphavirus) |
Mosquitoes Aedes species, Culex species |
Australia, New Guinea, Solomon Islands, Samoa, Cook Islands |
|
|
Barmah Forest virus |
Togaviridae (Alphavirus) |
Mosquitoes Aedes species, Culex species |
Australia |
|
|
Sindbis virus disease (Ockelbo disease, Karelian fever) |
Togaviridae (Alphavirus) |
Mosquitoes Culex species |
Africa, Australia, Asia, former Soviet Union, Europe (including Finland and Sweden), Oceania |
|
|
Hemorrhagic signs§ |
Flaviviridae |
Mosquitoes Aedes species |
Panama, South America, Africa |
|
|
Flaviviridae |
Mosquitoes Aedes species |
Southeast Asia, South Asia, West and East Africa, Oceania, Caribbean, South and Central America, Mexico, US |
||
|
Flaviviridae |
Ticks Haemaphysalis species |
India |
||
|
Flaviviridae |
Ticks Dermacentor species |
Russia |
||
|
Crimean-Congo hemorrhagic fever |
Bunyaviridae (Nairovirus) |
Ticks Hyalomma species |
Africa, southern and eastern Europe, India, Pakistan China, Turkey, Middle East, former Soviet Union |
|
|
Bunyaviridae (Hantavirus) |
Rodent |
Korea, Japan, China, Far Eastern Russia, the Balkans |
||
|
Seoul virus |
Bunyaviridae (Hantavirus) |
Rodent |
Nearly worldwide, including Korea, Japan, the Americas and Europe |
|
|
Puumala virus (nephropathia epidemica) |
Bunyaviridae (Hantavirus) |
Rodent |
Scandinavia, Russia, the Balkans |
|
|
Dobrava-Belgrade virus |
Bunyaviridae (Hantavirus) |
Rodent |
The Balkans, Slovakia, Czech Republic, Turkey |
|
|
Machupo virus |
Arenaviridae |
Rodent |
Bolivia |
|
|
Junin virus |
Arenaviridae |
Rodent |
Argentina |
|
|
Guanarito virus |
Arenaviridae |
Rodent |
Venezuela |
|
|
Arenaviridae |
Rodent Mastomys species |
West Africa, including Nigeria |
||
|
Lujo virus |
Arenaviridae |
Unknown |
Zambia |
|
|
Filoviridae |
Human to human Monkey Bat |
Zimbabwe, Kenya, Uganda, Democratic Republic of Congo, South Africa |
||
|
Filoviridae |
Human to human Monkey Bat |
Zaire, Sudan Guinea, Liberia, Sierra Leone, Democratic Republic of Congo, Republic of the Congo, Gabon, Côte d'Ivoire, Uganda |
||
|
Severe fever with thrombocytopenia syndrome virus |
Bunyaviridae |
Ticks Haemaphysalis longicornis |
China, Korea, Japan |
|
|
Noncardiogenic pulmonary edema |
Hantavirus: Sin Nombre, Black Creek Canal, Bayou, Leguna Negra, Andes, Andes-like viruses Hu39694, Lechiguanas, Oran, Bermejo, Choclo |
Bunyaviridae (Hantavirus) |
Rodents |
US, Canada, Brazil, Bolivia, Paraguay, Argentina, Chile, Panama |
Fever and central nervous system involvement |
||||
|
|
Eastern equine encephalitis |
Togaviridae (Alphavirus) |
Mosquitoes Culex species, Culiseta melanura |
Atlantic and Gulf coasts of US, Caribbean, upper New York, Connecticut, western Michigan, Wisconsin |
|
Western equine encephalitis |
Togaviridae (Alphavirus) |
Mosquito Culex species |
US, Canada, Central and South America |
|
|
Flaviviridae |
Mosquitoes Culex species |
Africa, Middle East, southern Europe, former Soviet Union, India, Indonesia, US, southern Canada, Mexico, South America, Caribbean Islands |
||
|
St. Louis encephalitis |
Flaviviridae |
Mosquitoes Culex species |
US, Caribbean, South America |
|
|
Usutu |
Flaviviridae |
Mosquitoes |
Africa, Europe |
|
|
Venezuelan equine encephalitis |
Togaviridae (Alphavirus) |
Mosquitoes Culex species |
Argentina, Brazil, northern South America, Panama, Mexico, Florida |
|
|
La Crosse encephalitis |
Bunyaviridae |
Mosquitoes Aedes species |
North Central States, New York, Appalachian states |
|
|
Jamestown Canyon virus |
Bunyaviridae |
Mosquitoes Aedes species |
US from the Rocky Mountains to the East Coast, southeastern Canada |
|
|
Japanese encephalitis |
Flaviviridae |
Mosquitoes Culex species |
Japan, Korea, China, India, Nepal, Philippines, Southeast Asia, Russia |
|
|
Flaviviridae |
Tick Ixodes species |
Eastern Canada, New York, New England states, Wisconsin |
||
|
Murray Valley encephalitis |
Flaviviridae |
Mosquitoes Culex species |
Australia, New Guinea |
|
|
Flaviviridae |
Ticks Haemaphysalis spinigera |
India |
||
|
Flaviviridae |
Ticks Ixodes species Haemaphysalis species |
Europe, Balkans, Russia |
||
|
|
Lymphocytic choriomeningitis virus |
Arenaviridae |
Rodents |
Americas, Europe, Australia, Japan |
|
* Changes in climatic conditions can affect the geographic range of arboviruses by extending or contracting the habitats of their vectors. |
||||
|
† Rift Valley fever also causes hemorrhage, meningoencephalitis, and ocular disorders. |
||||
|
‡ West Nile virus also causes encephalitis. |
||||
|
§ The Seoul, Puumala, Dobrava, and Hantaan hantaviruses cause hemorrhagic fever with renal syndrome. |
||||
Treatment
Treatment for most of these infections is supportive.
In hemorrhagic fevers, bleeding may require phytonadione (vitamin K1). Transfusion of packed red blood cells or fresh frozen plasma may also be necessary. Aspirin and other NSAIDs (nonsteroidal anti-inflammatory drugs) are contraindicated because of antiplatelet activity. For advanced cases of hantavirus cardiopulmonary syndrome, extracorporeal membrane oxygenation (ECMO) may be needed.
The following is recommended for hemorrhagic fever caused by arenaviruses or bunyaviruses including Lassa fever, Rift Valley fever, and Crimean-Congo hemorrhagic fever:
Treatment of hemorrhagic fever with renal syndrome is with IV ribavirin: loading dose 33 mg/kg (maximum, 2.64 g), followed by 16 mg/kg every 6 hours (maximum, 1.28 g every 6 hours) for 4 days, then 8 mg/kg every 8 hours (maximum, 0.64 g every 8 hours) for 3 days.
Antiviral treatment for other syndromes has not been adequately studied. Ribavirin has not been effective in animal models of filovirus and flavivirus infections. However, the monoclonal antibody cocktail REGN-EB3 and the single monoclonal antibody mAb 114 reduced deaths in a field trial in the Ebola outbreak in the Democratic Republic of the Congo.
Prevention
The abundance and diversity of arboviruses means that it is often easier and cheaper to control arbovirus infections by destroying their arthropod vectors, preventing bites, and eliminating their breeding habitats than by developing specific vaccines or drug treatments.
Vector control and bite prevention
Diseases transmitted by mosquitoes or ticks can often be prevented by the following:
-
Wearing clothing that covers as much of the body as possible
-
Using insect repellants (eg, DEET [diethyltoluamide])
-
Minimizing the likelihood of exposure to the insect or tick (eg, for mosquitoes, limiting time outdoors in wet areas; for ticks, see sidebar Tick Bite Prevention)
-
There has been recent progress in reducing populations of Aedes aegypti through the release of sterile males or genetically modified males. Also, field trials are underway with introduction into the wild of Aedes aegypti mosquitoes that have been infected with Wolbachia bacteria. These bacteria do not reduce mosquito populations. Instead, they block infection of the mosquitoes by dengue, chikungunya, and Zika viruses, thus reducing transmission of disease. The Wolbachia are transmitted to the infected mosquito's offspring, thus multiplying the effectiveness of the technique.
Diseases transmitted by rodent excreta can be prevented by the following:
-
Before cleaning, ventilate for ≥ 15 minutes closed spaces where mice have been.
-
Wet down surfaces with a 10% bleach solution before sweeping or cleaning.
-
Avoid stirring up dust.
-
Seal sites of potential rodent entry into homes and nearby buildings.
-
Prevent rodent access to food.
-
Eliminate potential nesting sites in and around the home.
Guidelines for cleaning up after rodents and working in areas with potential rodent excreta are available from the Centers for Disease Control and Prevention (CDC).
Because transmission of the filoviruses Ebola virus and Marburg virus is predominantly from person to person, prevention of spread requires strict quarantine and isolation measures.
Vaccination
At present, in the US there are effective vaccines only for Ebola virus, yellow fever virus and Japanese encephalitis virus. Vaccines for tick-borne encephalitis are available in Europe, Russia and China. A vaccine for dengue is approved in several countries outside the US, but efficacy is only moderate and varies by dengue immune status, serotype, and patient age; studies are ongoing.
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
phytonadione |
MEPHYTON |
ribavirin |
VIRAZOLE |
Aspirin |
No US brand name |
