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==History==
==History==
Arboviruses have existed throughout human history, but were not known to exist until fairly recently. The connection between arthropods and disease was not postulated until 1881 when Cuban doctor and scientist [[Carlos Finlay]] proposed that Yellow fever may be transmitted by mosquitoes instead of human contact,<ref>{{cite pmid|16435764|noedit}}</ref> a reality that was verified by Major [[Walter Reed]] in 1901.<ref>{{cite doi|10.2105/AJPH.24.1.1|noedit}}</ref> The primary vector, ''[[Aedes aegypti]]'', had spread globally from the 15th to the 19th centuries as a result of [[globalization]] and the [[slave trade]].<ref>{{cite pmid|22494122|noedit}}</ref> This geographic spreading caused Dengue fever epidemics throughout the 18th century,<ref>{{cite pmid|9665979|noedit}}</ref> and later, in 1906, transmission by the ''[[Aedes]]'' mosquitoes was confirmed, making Yellow fever and Dengue fever the first two diseases known to be caused by viruses.<ref>{{cite pmid|2224837|noedit}}</ref> The discovery of the West Nile virus came in 1937,<ref>{{cite journal|last1=Smithburn|first1=K. C.|last2=Hughes|first2=T. P.|last3=Burke|first3=A. W.|last4=Paul|first4=J. H.|year=1940|title=A Neurotropic Virus Isolated from the Blood of a Native of Uganda|journal=American Journal of Tropical Medicine|volume=20|issue=|pages=471-472|url=http://www.cabdirect.org/abstracts/19412700112.html;jsessionid=5D57DBBCD1A15AC5915B05558D9161E2}}</ref> and has since been found in ''[[Culex]]'' populations<ref>{{cite pmid|13084817|noedit}}</ref> and causing epidemics throughout Africa, the Middle East and Europe. In 1999, the virus was introduced into the [[Western Hemisphere]], sparking a series of epidemics.<ref>{{cite news|title=West Nile epidemic on track to be deadliest ever: CDC|author=Sun, L. H.|url=http://articles.washingtonpost.com/2012-09-13/national/35496169_1_west-nile-vector-borne-infectious-diseases-lyle-petersen|newspaper=The Washington Post|date=13 September 2012|accessdate=19 June 2013}}</ref>
Arboviruses have existed throughout human history, but were not known to exist until fairly recently. The connection between arthropods and disease was not postulated until 1881 when Cuban doctor and scientist [[Carlos Finlay]] proposed that Yellow fever may be transmitted by mosquitoes instead of human contact,<ref>{{cite pmid|16435764|noedit}}</ref> a reality that was verified by Major [[Walter Reed]] in 1901.<ref>{{cite doi|10.2105/AJPH.24.1.1|noedit}}</ref> The primary vector, ''[[Aedes aegypti]]'', had spread globally from the 15th to the 19th centuries as a result of [[globalization]] and the [[slave trade]].<ref>{{cite pmid|22494122|noedit}}</ref> This geographic spreading caused Dengue fever epidemics throughout the 18th century,<ref>{{cite pmid|9665979|noedit}}</ref> and later, in 1906, transmission by the ''[[Aedes]]'' mosquitoes was confirmed, making Yellow fever and Dengue fever the first two diseases known to be caused by viruses.<ref>{{cite pmid|2224837|noedit}}</ref> The discovery of the West Nile virus came in 1937,<ref>{{cite journal|last1=Smithburn|first1=K. C.|last2=Hughes|first2=T. P.|last3=Burke|first3=A. W.|last4=Paul|first4=J. H.|year=1940|title=A Neurotropic Virus Isolated from the Blood of a Native of Uganda|journal=American Journal of Tropical Medicine|volume=20|issue=|pages=471-472|url=http://www.cabdirect.org/abstracts/19412700112.html;jsessionid=5D57DBBCD1A15AC5915B05558D9161E2}}</ref> and has since been found in ''[[Culex]]'' populations<ref>{{cite pmid|13084817|noedit}}</ref> and causing epidemics throughout Africa, the Middle East and Europe. In 1999, the virus was introduced into the [[Western Hemisphere]], sparking a series of epidemics.<ref>{{cite news|title=West Nile epidemic on track to be deadliest ever: CDC|author=Sun, L. H.|url=http://articles.washingtonpost.com/2012-09-13/national/35496169_1_west-nile-vector-borne-infectious-diseases-lyle-petersen|newspaper=The Washington Post|date=13 September 2012|accessdate=19 June 2013}}</ref> During the latter half of the 20th century, Dengue fever reemerged as a global disease, with the virus spreading geographically due to [[urbanization]], [[population growth]], increased international travel and [[global warming]],<ref>{{cite pmid|20616106|noedit}}</ref> and continues to cause at least 50 million infections per year, making Dengue fever the most common arboviral disease.<ref>{{cite pmid|20372965|noedit}}</ref><ref>{{cite pmid|21079655|noedit}}</ref>


Yellow fever, alongside [[malaria]], was a major obstacle in the construction of the [[Panama Canal]]. French supervision of the project in the 1880s was unsucessful because of these diseases, forcing the abandonment of the project in 1889.<ref name=contagion >{{cite web|url=http://ocp.hul.harvard.edu/contagion/panamacanal.html|title=Tropical Diseases and the Construction of the Panama Canal, 1904–1914|last1=|first1=|date=|website=Contagion: Historical Views of Diseases and Epidemics|publisher=|accessdate=19 June 2013}}</ref> During the American effort to construct the canal in the early 1900s, [[William C. Gorgas]], the Chief Sanitary Officer of Havana, was tasked with overseeing the health of the workers. He had past success in eradicating the disease in [[Florida]] and [[Havana]] by reducing mosquito populations through draining nearby pools of water, cutting grass, applying oil to the edges of ponds and swamps to kill larvae, and capturing adult mosquitoes that remained indoors during the daytime.<ref>{{cite web|url=http://www.cdc.gov/malaria/about/history/panama_canal.html|title=Malaria: The Panama Canal|last1=|first1=|date=8 February 2010|website=Centers for Disease Control and Prevention (CDC)|publisher=|accessdate=19 June 2013}}</ref> Joseph Augustin LePrince, the Chief Sanitary Inspector of the [[Panama Canal Zone|Canal Zone]], invented the first commercial [[larvicide]], a mixture of [[carbolic acid]], [[resin]] and [[caustic soda]], to be used throughout the Canal Zone.<ref>{{cite pmid|12862098|noedit}}</ref> The combined implementation of these sanitation measures led to a dramatic decline in the number of workers dying and the eventual eradication of Yellow fever in the Canal Zone as well as the containment of malaria during the 10-year construction period. Because of the success of these methods at preventing disease, they were adopted and improved upon in other regions of the world.<ref name=contagion /><ref>{{cite web|url=http://www.pbs.org/wgbh/americanexperience/features/general-article/panama-fever/|title=Yellow Fever and Malaria in the Canal|last1=|first1=|date=|website=PBS|publisher=American Experience|accessdate=19 June 2013}}</ref>
Yellow fever, alongside [[malaria]], was a major obstacle in the construction of the [[Panama Canal]]. French supervision of the project in the 1880s was unsucessful because of these diseases, forcing the abandonment of the project in 1889.<ref name=contagion >{{cite web|url=http://ocp.hul.harvard.edu/contagion/panamacanal.html|title=Tropical Diseases and the Construction of the Panama Canal, 1904–1914|last1=|first1=|date=|website=Contagion: Historical Views of Diseases and Epidemics|publisher=|accessdate=19 June 2013}}</ref> During the American effort to construct the canal in the early 1900s, [[William C. Gorgas]], the Chief Sanitary Officer of Havana, was tasked with overseeing the health of the workers. He had past success in eradicating the disease in [[Florida]] and [[Havana]] by reducing mosquito populations through draining nearby pools of water, cutting grass, applying oil to the edges of ponds and swamps to kill larvae, and capturing adult mosquitoes that remained indoors during the daytime.<ref>{{cite web|url=http://www.cdc.gov/malaria/about/history/panama_canal.html|title=Malaria: The Panama Canal|last1=|first1=|date=8 February 2010|website=Centers for Disease Control and Prevention (CDC)|publisher=|accessdate=19 June 2013}}</ref> Joseph Augustin LePrince, the Chief Sanitary Inspector of the [[Panama Canal Zone|Canal Zone]], invented the first commercial [[larvicide]], a mixture of [[carbolic acid]], [[resin]] and [[caustic soda]], to be used throughout the Canal Zone.<ref>{{cite pmid|12862098|noedit}}</ref> The combined implementation of these sanitation measures led to a dramatic decline in the number of workers dying and the eventual eradication of Yellow fever in the Canal Zone as well as the containment of malaria during the 10-year construction period. Because of the success of these methods at preventing disease, they were adopted and improved upon in other regions of the world.<ref name=contagion /><ref>{{cite web|url=http://www.pbs.org/wgbh/americanexperience/features/general-article/panama-fever/|title=Yellow Fever and Malaria in the Canal|last1=|first1=|date=|website=PBS|publisher=American Experience|accessdate=19 June 2013}}</ref>

Revision as of 22:14, 24 June 2013

Arbovirus

Arbovirus is a term used to refer to a group of viruses that are transmitted by arthropod vectors. The word arbovirus is an acronym (ARthropod-BOrne virus).[1] The word tibovirus is sometimes used to describe viruses transmitted by ticks (TIck-BOrne virus).[2] Symptoms of arbovirus infection generally occur 3-15 days after exposure to the virus and last 3 or 4 days. The most common clinical features of infection are fever, headache and malaise, but encephalitis and hemorrhagic fever may also occur.[3]

History

Arboviruses have existed throughout human history, but were not known to exist until fairly recently. The connection between arthropods and disease was not postulated until 1881 when Cuban doctor and scientist Carlos Finlay proposed that Yellow fever may be transmitted by mosquitoes instead of human contact,[4] a reality that was verified by Major Walter Reed in 1901.[5] The primary vector, Aedes aegypti, had spread globally from the 15th to the 19th centuries as a result of globalization and the slave trade.[6] This geographic spreading caused Dengue fever epidemics throughout the 18th century,[7] and later, in 1906, transmission by the Aedes mosquitoes was confirmed, making Yellow fever and Dengue fever the first two diseases known to be caused by viruses.[8] The discovery of the West Nile virus came in 1937,[9] and has since been found in Culex populations[10] and causing epidemics throughout Africa, the Middle East and Europe. In 1999, the virus was introduced into the Western Hemisphere, sparking a series of epidemics.[11] During the latter half of the 20th century, Dengue fever reemerged as a global disease, with the virus spreading geographically due to urbanization, population growth, increased international travel and global warming,[12] and continues to cause at least 50 million infections per year, making Dengue fever the most common arboviral disease.[13][14]

Yellow fever, alongside malaria, was a major obstacle in the construction of the Panama Canal. French supervision of the project in the 1880s was unsucessful because of these diseases, forcing the abandonment of the project in 1889.[15] During the American effort to construct the canal in the early 1900s, William C. Gorgas, the Chief Sanitary Officer of Havana, was tasked with overseeing the health of the workers. He had past success in eradicating the disease in Florida and Havana by reducing mosquito populations through draining nearby pools of water, cutting grass, applying oil to the edges of ponds and swamps to kill larvae, and capturing adult mosquitoes that remained indoors during the daytime.[16] Joseph Augustin LePrince, the Chief Sanitary Inspector of the Canal Zone, invented the first commercial larvicide, a mixture of carbolic acid, resin and caustic soda, to be used throughout the Canal Zone.[17] The combined implementation of these sanitation measures led to a dramatic decline in the number of workers dying and the eventual eradication of Yellow fever in the Canal Zone as well as the containment of malaria during the 10-year construction period. Because of the success of these methods at preventing disease, they were adopted and improved upon in other regions of the world.[15][18]

Transmission

Many female mosquitoes, like those of Aedes albopictus, require a vertebrate blood meal in order for their eggs to develop.[19]

Arboviruses maintain themselves in nature by being transmitted between a vertebrate host and the vector. The viruses replicate in the vector but usually do not harm it. In the mosquito-borne diseases, the virus establishes a persistent infection in the salivary glands and there is sufficient virus in the saliva to infect another host during feeding. Upon biting, the virus enters the circulatory system, where intracellular self-replication of the virus can lead to viremia, a condition in which viruses are capable of travelling throughout the body through the bloodstream.[20] Once the host has become infected, other female mosquitoes may feed on its blood, becoming infected themselves and continuing the cycle.

Structure and genome

The majority of the arboviruses are spherical in shape although a few are rod-shaped. They are 17-150 nm in diameter and most have an RNA genome (the single exception is African swine fever virus, which has a DNA genome).

Classification

In the past, arboviruses were organized into one of four groups: A, B, C and D. Group A denoted members of the genus Alphavirus,[21][22] Group B were members of the genus Flavivirus,[23] and Group C remains as the Group C serogroup of the genus Orthobunyavirus.[24] Group D was renamed in the mid-1950s to the Guama group and is currently the Guama serogroup in the genus Orthobunyavirus.[25] This renaming of the group was because the number of groups would eventually exceed the length of the alphabet. Since then, the organization of arboviruses into these groups has fallen out of usage as the standard biological classification system became more preferred for classifying viruses.[25]

Signs and symptoms

Many arboviruses (such as African Swine Fever virus) do not normally infect humans or if so, cause either no symptoms or mild and transient infections characterized by fever, headache and rash. Others of this group however can cause epidemic disease and severe infections such as fulminant meningitis, encephalitis, meningoencephalitis, or viral hemorrhagic fever that can be fatal.

Immune response to infection

The immune system plays a crucial role in defense against infection. Arboviruses are generally good inducers of the production of interferons, which may partially explain why acute infection is often similar to influenza (fever, headache, fatigue, myalgia). Antibodies can be important in controlling viremia and limiting the severity of infection. Recovery typically involves the cell-mediated immune system.[20]

Diagnosis

Preliminary diagnosis of arbovirus infection is usually based on clinical presentations of symptoms, places and dates of travel, activities and epidemiological history of the location where infection occurred.[26] Definitive diagnosis is typically made in a laboratory by employing some combination of blood tests, particularly immunologic, serologic and/or virologic techniques such as ELISA,[26][27] complement fixation,[27] polymerase chain reaction,[27][28] neutralization test[29] and hemagglutination-inhibition test.[30]

Prevention

Vector control measures, especially mosquito control, are essential to reducing the transmission of disease by arboviruses. Habitat control involves draining swamps and removal of other pools of stagnant water (such as old tires, large outdoor potted plants, empty cans, etc.) that often serve as breeding grounds for mosquitoes. Insecticides can be applied in rural and urban areas, inside houses and other buildings or in outdoor environments. They are often quite effective for controlling arthropod populations, though use of some of these chemicals is controversial, and some organophosphates and organochlorides (such as DDT) have been banned in many countries. Infertile male mosquitoes have been introduced in some areas in order to reduce the breeding rate of relevant mosquito species. Larvicides are also used worldwide in mosquito abatement programs. Temefos is a common mosquito larvicide.[31]

Tent made of mosquito netting

People can also reduce the risk of getting bitten by arthropods by employing personal protective measures such as sleeping under mosquito nets, wearing protective clothing, applying insect repellents such as permethrin and DEET to clothing and exposed skin, and (where possible) avoiding areas known to harbor high arthropod populations. Arboviral encephalitis can be prevented in two major ways: personal protective measures and public health measures to reduce the population of infected mosquitoes. Personal measures include reducing time outdoors particularly in early evening hours, wearing long pants and long sleeved shirts and applying mosquito repellent to exposed skin areas. Public health measures often require spraying of insecticides to kill juvenile (larvae) and adult mosquitoes.[32]

Vaccination

Vaccines are available for the following arboviral diseases:

  • Japanese encephalitis[33]
  • Yellow fever[34]

Vaccines are in development for the following arboviral diseases:

  • Dengue fever[35]
  • Eastern Equine encephalitis[36]
  • West Nile[37]

Treatment

Because the arboviral encephalitides are viral diseases, antibiotics are not an effective form of treatment and no effective antiviral drugs have yet been discovered. Treatment is supportive, attempting to deal with problems such as swelling of the brain, loss of the automatic breathing activity of the brain and other treatable complications like bacterial pneumonia.[1]

Epidemiology

List of common arboviruses

Common arboviruses include:

Family Genera Species (of high economic/epidemiologic importance) Vectors Diseases caused
Asfarviridae Asfivirus African swine fever virus tick viral encephalitis, viral hemorrhagic fever
Bunyaviridae Nairovirus Crimean–Congo hemorrhagic fever virus tick viral hemorrhagic fever
Bunyaviridae Orthobunyavirus Anopheles A virus, Anopheles B virus, California encephalitis virus, La Crosse encephalitis virus mosquito viral encephalitis
Bunyaviridae Phlebovirus Rift Valley fever virus, Naples virus, Sicilian virus, Toscana virus mosquito (Aedes spp., Culex spp., Phlebotomus spp.) viral encephalitis, viral hemorrhagic fever
Bunyaviridae Uukuvirus Bakau virus, Kaisodi virus, Mapputta virus, Nairobi sheep disease virus, Turlock virus tick viral encephalitis, viral hemorrhagic fever
Flaviviridae Flavivirus Louping ill virus, Powassan virus, Tick-borne encephalitis virus tick (Ixodes spp.) viral encephalitis
Flaviviridae Flavivirus Dengue virus, Japanese encephalitis virus, Murray Valley encephalitis virus, St. Louis encephalitis virus, West Nile virus, Yellow fever virus mosquito viral encephalitis, viral hemorrhagic fever
Reoviridae Coltivirus Colorado tick fever virus tick viral hemorrhagic fever
Reoviridae Orbivirus African horse sickness virus, Bluetongue disease virus, Epizootic hemorrhagic disease virus mosquito (Culicoides spp.) viral encephalitis
Togaviridae Alphavirus Chikungunya virus, Eastern equine encephalitis virus, O'nyong'nyong virus, Ross River virus, Semliki Forest virus, Venezuelan equine encephalitis virus, Western equine encephalitis virus mosquito viral encephalitis, arthritis

See also

References

  1. ^ a b "CDC Information on Arboviral Encephalitides". Archived from the original on January 27, 2007. Retrieved 2007-02-07. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  2. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 22526290, please use {{cite journal}} with |pmid=22526290 instead.
  3. ^ "Arbovirus Infection Symptoms". freemd. Retrieved 22 June 2013.
  4. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 16435764, please use {{cite journal}} with |pmid=16435764 instead.
  5. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.2105/AJPH.24.1.1, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.2105/AJPH.24.1.1 instead.
  6. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 22494122, please use {{cite journal}} with |pmid=22494122 instead.
  7. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 9665979, please use {{cite journal}} with |pmid=9665979 instead.
  8. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 2224837, please use {{cite journal}} with |pmid=2224837 instead.
  9. ^ Smithburn, K. C.; Hughes, T. P.; Burke, A. W.; Paul, J. H. (1940). "A Neurotropic Virus Isolated from the Blood of a Native of Uganda". American Journal of Tropical Medicine. 20: 471–472.
  10. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 13084817, please use {{cite journal}} with |pmid=13084817 instead.
  11. ^ Sun, L. H. (13 September 2012). "West Nile epidemic on track to be deadliest ever: CDC". The Washington Post. Retrieved 19 June 2013.
  12. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 20616106, please use {{cite journal}} with |pmid=20616106 instead.
  13. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 20372965, please use {{cite journal}} with |pmid=20372965 instead.
  14. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 21079655, please use {{cite journal}} with |pmid=21079655 instead.
  15. ^ a b "Tropical Diseases and the Construction of the Panama Canal, 1904–1914". Contagion: Historical Views of Diseases and Epidemics. Retrieved 19 June 2013.
  16. ^ "Malaria: The Panama Canal". Centers for Disease Control and Prevention (CDC). 8 February 2010. Retrieved 19 June 2013.
  17. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 12862098, please use {{cite journal}} with |pmid=12862098 instead.
  18. ^ "Yellow Fever and Malaria in the Canal". PBS. American Experience. Retrieved 19 June 2013.
  19. ^ "Human blood contains the secret ingredient for mosquito eggs". May 4, 2011. Retrieved 6 April 2013.
  20. ^ a b Hunt, M. (April 9, 2010). Arboviruses (Report). University of South Carolina School of Medicine.
  21. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 4128825, please use {{cite journal}} with |pmid=4128825 instead.
  22. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 1155702, please use {{cite journal}} with |pmid=1155702 instead.
  23. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1007/BF01252762, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1007/BF01252762 instead.
  24. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1007/BF01317828, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1007/BF01317828 instead.
  25. ^ a b Shope, R. E.; Woodall, J. P.; da Rosa, A. T. (1988). Monath, T. P. (ed.). The Arboviruses: Epidemiology and Ecology (PDF). Vol. 3. CRC Press. p. 38. ISBN 0849343879. Retrieved 16 June 2013.
  26. ^ a b "Arboviral Diagnostic Testing". Centers for Disease Control and Prevention (CDC). Retrieved April 17, 2013.
  27. ^ a b c "Arbovirus Antibodies Test". Medical Health Tests. March 27, 2012. Retrieved April 17, 2013.
  28. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 11337046, please use {{cite journal}} with |pmid=11337046 instead.
  29. ^ Seawright, G. L.; Harding, G.; Thomas, F. C.; Hanson, R. P. (1974). "Microculture Plaque Neutralization Test for California Group Arboviruses". Applied Microbiology. 28 (5): 802–806. PMC 186828.
  30. ^ Mettler, N. E.; Clarke, D. H.; Casals, J. (1971). "Hemagglutination Inhibition with Arboviruses: Relationship Between Titers and Source of Erythrocytes". Applied Microbiology. 22 (3): 377–379. PMC 376317.
  31. ^ Walsh, J.A.; Warren, K.S. (1980). "Selective primary health care: an interim strategy for disease control in developing countries". Social Science & Medicine. Part C: Medical Economics. 14 (2): 145–163. doi:10.1016/0160-7995(80)90034-9. PMID 114830.
  32. ^ "Preventing Mosquito Bites". North Carolina Department of Health and Human Services.
  33. ^ "Japanese Encephalitis Vaccine, What You Need to Know" (PDF). Centers for Disease Control and Prevention (CDC). December 7, 2011. Retrieved 20 March 2013.
  34. ^ "Yellow Fever Vaccine, What You Need to Know" (PDF). Centers for Disease Control and Prevention (CDC). March 30, 2011. Retrieved 20 March 2013.
  35. ^ "Dengue fever vaccine program". Global Vaccines. Retrieved 20 March 2013.
  36. ^ Pandya J., Gorchakov R., Wang E., Leal G., Weaver S.C. (2012). "A vaccine candidate for eastern equine encephalitis virus based on IRES-mediated attenuation". doi:10.1016/j.vaccine.2011.12.121. PMID 22222869. {{cite journal}}: Cite journal requires |journal= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  37. ^ Young, S. (August 12, 2012). "Few Options in the West Nile Fight". MIT Technology Review. Retrieved 20 March 2013.

External links

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