WNV has three different effects on humans. The first is an asymptomatic[*3] infection; the second is a mild febrile[*4] syndrome termed West Nile Fever;[*5] the third is a neuroinvasive disease termed West Nile meningitis[*6] or encephalitis[*7] .[*8] In infected individuals the ratio between the three states is roughly 110:30:1.[*9]
The second, febrile stage has an incubation period of 3-8 days followed by fever, headache, chills, diaphoresis[*10] , weakness, lymphadenopathy[*11] , and drowsiness. Occasionally there is a short-lived truncal rash and some patients experience gastrointestinal symptoms including nausea, vomiting, loss of appetite, or diarrhea. All symptoms are resolved within 7-10 days, although fatigue can last for some weeks and lymphadenopathy can take up to two months to resolve.
The more dangerous encephalitis is characterized by similar early symptoms but also a decreased level of consciousness, sometimes approaching near-coma. Deep tendon reflexes are hyperactive at first, later diminished. There are also extrapyramidal disorders[*12] . Recovery is marked by a long convalescence with fatigue.
More recent outbreaks have resulted in a deeper study of the disease and other, rarer, outcomes have been identified.The spinal cord may be infected, marked by anterior myelitis[*13] with or without encephalitis.[*14] WNV-associated Guillain-Barré syndrome[*15] has been identified[*16] and other rare effects include multifocal chorioretinitis[*17] (which has 100% specificity for identifying WNV infection in patients with possible WNV encephalitis)[*18] hepatitis[*19] , myocarditis[*20] , nephritis[*21] , pancreatitis[*22] , and splenomegaly[*23] .[*24] [*25] [*26]
The virus is transmitted through mosquito vectors, which bite and infect birds. The birds are amplifying hosts, developing sufficient viral levels to transmit the infection to other biting mosquitoes which go on to infect other birds (in the Western hemisphere[*27] the American Robin[*28] and the American Crow[*29] are the most common carriers) and also humans. The infected mosquito species vary according to geographical area; in the US Culex pipiens (Eastern US), Culex tarsalis (Midwest and West), and Culex quinquefasciatus (Southeast) are the main sources.[*30]
In mammals the virus does not multiply as readily, and it is believed that mosquitoes biting infected mammals do not further transmit the virus,[*31] making mammals so-called dead-end infections.
A 2004 paper in Science found that Culex pipiens mosquitoes existed in two populations in Europe[*32] , one which bites birds and one which bites humans. In North America 40% of Culex pipiens were found to be hybrids of the two types which bite both birds and humans, providing a vector for West Nile virus. This is thought to provide an explanation of why the West Nile disease has spread more quickly in North America than Europe.
It was initially believed that direct human-to-human transmission was only caused by occupational exposure,[*33] or conjunctival exposure to infected blood.[*34] The US outbreak revealed novel transmission methods, through blood transfusion,[*35] organ transplant,[*36] intrauterine exposure,[*37] and breast feeding.[*38] Since 2003 blood banks in the US routinely screen for the virus amongst their donors.[*39] As a precautionary measure, the UK’s National Blood Service[*40] runs a test for this disease in donors who donate within 28 days of a visit to the United States or Canada[*41] .
The more severe outcomes of WNV infection are clearly associated with advancing age[*42] and a patient history of organ transplantation.[*43] A genetic factor also appears to increase susceptibility to West Nile disease. A mutation of the gene CCR5 gives some protection against HIV[*44] but leads to more serious complications of WNV infection. Carriers of two mutated copies of CCR5 made up 4 to 4.5% of a sample of West Nile disease sufferers while the incidence of the gene in the general population is only 1%.[*45] [*46]
There is no vaccine[*47] for humans. A vaccine for horses based on killed viruses exists; some zoos[*48] have given this vaccine to their birds, although its effectiveness there is unknown. Dogs and cats show few if any signs of infection. There have been no cases of direct canine-human or feline-human transmission, but these common pets may incubate the virus and pass it along through mosquitoes.[*49]
For humans to escape infection the avoidance of mosquito is key[*50] – remaining indoors at dawn and dusk, wearing light-colored clothing which protects arms and legs as well as trunk, using insect repellents on both skin and clothing (such as DEET[*51] , picaradin[*52] , or oil of lemon eucalyptus[*53] for skin and permethrin[*54] for clothes)[*55] Treatment is purely supportive: analgesia for the pain of neurologic diseases; rehydration for nausea, vomiting, or diarrhea; encephalitis may also require airway protection and seizure management.
On August 19[*56] , 2006[*57] , the LA Times[*58] reported that the expected incidence rate of West Nile was dropping as the local population becomes exposed to the virus. “In countries like Egypt and Uganda, where West Nile was first detected, people became fully immune to the virus by the time they reached adulthood, federal health officials said.” [*59] However days later the CDC said that West Nile cases could reach a 3-year high because hot temperatures had allowed a larger brood of mosquitoes. [*60] Reported cases in the U.S. in 2005 exceeded those in 2004 and cases in 2006 exceeded 2005s totals.