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Article for: “Undercover Medicine” Author: David Crowe Deadline: January 15, 2003 Wordcount: 1200 Subject: West Nile Virus West Nile Virus (WNV) has been the cause of increasing concern since it emerged in the United States in the New York City area in August, 1999 associated with a small cluster of encephalitis and meningitis. It has justified the widespread aerial spraying of insecticides and an army of sentinel chickens whose only job is to get bitten by mosquitoes believed to be carrying the virus. A worried citizenry has been draining standing pools, staying inside or covering up and applying DEET more religiously than ever before. The panic is hard to understand because, for more than 99% of people who test positive for WNV antibodies, the virus will bring them less than a bad headache or a fever, and most whose deaths are blamed on the virus are at least in their late 70’s [MMWR, 2002a]. A household survey in 1999 in the New York area found that, although there were only 7 deaths blamed on the virus that year [MMWR, 2001b], fully 2.6% of the people surveyed tested positive, The researchers estimated that there had been 8200 infections in New York City that year, about 1700 of which were associated with a fever. [Mostashari, 2001] However, they also noted that about one-third of this rate of fevers occurred in the non-WNV-positive population. A serosurvey the following year estimated that only about 1/157 people in Staten Island who had evidence of a recent infection had 'serious neurologic illness'. [MMWR, 2001a] There has been some opposition to the spray campaigns – mainly through questioning whether they are the best way to reduce transmission of the virus [Toxics, 2001] or whether the health and environmental damage caused by insecticides outweighs the benefits [NoSpray, 2002], but almost none based on questioning the viral causation theory, and very little discussion of alternative causes for the observed illnesses. The CDC, before making their October, 1999 pronouncement, performed antibody tests on the cerebrospinal fluid and serum of six people with encephalitis from northern Queens. They all tested positive for St. Louis encephalitis (SLE). Polymerase Chain Reaction (PCR) testing found a close match with the presumed genome of West Nile virus. Because the antibodies and antigens of SLE and WNV are believed to be very similar, and because genetic information is considered more direct evidence, a diagnosis of WNV was made [MMWR, 1999a]. The CDC's diagnosis was bolstered by positive PCR tests on mosquitoes and birds, mostly American crows. [MMWR, 1999b] Jim West was angered by the malathion spraying in his city by trucks and airplanes. He was suspicious that the deaths of a handful of elderly people at a hot, dry time of the year, with pollution indexes peaking, pointed more towards an environmental cause than an infectious disease. [West, 2003] He noted that the bird deaths started occurring weeks before human illness was first detected. The first theory was that the deaths were due to pesticide poisoning, but lab tests did not offer support. Air pollution was dismissed as a possibility by Ward Stone, a New York State Department of Environmental Conservation (NYSDEC) wildlife pathologist, even though he agreed that there was a correlation with high ozone levels, considered an important indicator of air pollution levels. West noted that the New York City area was the only place where reformulated gasoline with 11% MTBE (methyl ether butyl ether) was mandated from March through October and with 15% MTBE from November through February. This additive is intended to make gasoline burn cleaner, and reduce air pollution in the most polluted counties, but there are concerns about the toxicity of this product [Joseph, 1999; Joseph, 2000] and its use is being phased out in many areas. In the New York City area in 1999, ozone levels exceeded EPA limits more severely than in decades. The 17 counties with this high level of MTBE in gasoline had 117 of the WNV-positive birds in the NYSDEC database. Other counties in New York contributed a large number of dead birds to the database, but only 2 were found to be WNV positive. West found similar correlations in 2000 and 2001, although the number of dead birds and the severity of human disease was lower. An increase in bird deaths had been noted since 1995, when MTBE was first mandated, but was blamed on a variety of pesticides or an 'unknown' pathogen. A British scientist, Dr. Denis Summers-Smith, has blamed declines in sparrow populations in UK cities on the use of MTBE, and the higher concentration of automobile exhaust in urban areas. [McCarthy, 2000] Ontario and Quebec data on bird deaths also shows a much higher fraction of positive WNV tests in dead birds collected in urban areas, than in rural areas. [CCWHC, 2002]. 2002 found a dramatic increase in both the number and geographical spread of cases in the United States, with the first Canadian deaths also blamed on the virus. But does this represent a true increase in disease, or just an illusion caused by more widespread testing and the consequent reclassification of disease that would previously have been blamed on something else? According to the CDC, diagnosis of WNV disease requires compatible symptoms. However, the symptoms alone are 'usually indistinguishable from similar syndromes caused by other viruses' [CDC, 2002]. Other mandatory components of a diagnosis are positive serologic tests and the expectation that a pool of virus is present in the mosquito population (‘a period when arboviral transmission is likely'). The presence of antibodies in concert with disease usually leads to the conclusion that the virus is the cause of the illness. Inconsistent symptoms with a positive antibody test have led some doctors to suggest that polio-like symptoms should be added to the case definition, based on this logic [Glass, 2002; Leis, 2002]. Tests for a virus should be grounded in experiments that have shown a very high correlation with the actual presence of the virus. This is true for indirect tests, such as antibody tests, and also for more direct tests, such as PCR tests. Since PCR requires a portion of the genome to be used as the primer, it can only be relied on if this reagent is obtained from pure virus. In the case of West Nile Virus the standards for purification of the virus have been reduced to such a low level that isolation of the virus can be claimed when there is no proof that a virus is present. A paper in the prestigious journal Science shortly after the epidemic was announced claimed to have isolated the virus from mosquitoes and birds near New York City [Anderson, 1999]. However, a close reading of the paper shows that isolation, in the sense of separation of the virus from other organic materials, was most distinctly not achieved. The experiments consisted of passing ground up crow brains or entire mosquitoes through a filter with pores many times larger than the putative virus, checking some of the resulting material for antibodies and also adding some to a cell culture. ‘Isolation’ of West Nile Virus was claimed when cell-killing occurred. New infectious epidemics are claimed regularly by the CDC and similar organizations. Most fade away, but the West Nile Virus scare is one that has captured the public imagination. It is not clear why people want so much to believe this story, as the health risk to the average healthy person is negligible. But the belief in the story by people who count – the media, politicians, doctors and public health officials – is so strong that none seem to want to question the basic science. Surprisingly quickly, a small cluster of diseases in elderly people living in a hot, polluted city became a story of another African virus invading America. References [Anderson, 1999] Anderson JF et al. Isolation of West Nile Virus from Mosquitoes, Crows and a Cooper’s Hawk in Connecticut. Science. 1999 Dec 17; 286: 2331-3. Supplemented by personal correspondence in 2000. [CCWHC, 2002] Maps of Dead Birds Submitted for West Nile Virus Diagnosis by Health Region in Canada. http://wildlife.usask.ca/WestNileAlertHTML/WestNIleAlert2001ENG.htm. 2002 Nov [accessed]. [CDC, 2002] Encephalitis or Meningitis, Arboviral (includes California serogroup, eastern equine, St. Louis, western equine, West Nile, Powassan): 2001 Case Definition. CDC. 2002 Sep 6. http://www.cdc.gov/epo/dphsi/casedef/encephalitis_arboviral_current.htm [Glass, 2002] Glass JD et al. Poliomyelitis Due to West Nile Virus. NEJM. 2002 Oct 17. http://content.nejm.org/cgi/content/abstract/NEJMc026043v1 [Joseph, 1999] Joseph PM. Long story of MTBE's health hazard. http://www.lewisvillelakepark.com/id73.htm. 1999 Jun 24. [Joseph, 2000] Joseph PM. Health effects from MTBE in gasoline. http://www.garynull.com/Documents/MTBE/HealthEffects.htm. 2000 Nov 15. [Leis, 2002] Leis AA et al. A poliomyelitis-like syndrome from West Nile Virus infection. NEJM. 2002 Oct 17. http://content.nejm.org/cgi/content/abstract/NEJMc021587v1 [McCarthy, 2000] McCarthy M. Lead-free petrol may be villain in mystery of demise of the world's most famous bird. The Independent. 2000 Sep 11. [Mostashari, 2001] Mostashari F et al. Epidemic West Nile encephalitis, New York, 1999: results of a houshold-based seroepidemiological survey. Lancet. 2001 Jul 28; 358(9278): 261-4. [MMWR, 1999a] Outbreak of West Nile-like viral encephalitis - New York, 1999. MMWR. 1999 Oct 1; 48(38): 845-9. [MMWR, 1999b] Update: West Nile virus encephalitis - New York, 1999. MMWR. 1999 Oct 22; 48(41): 944-6, 955. [MMWR, 2001a] Serosurveys for West Nile Virus Infection --- New York and Connecticut Counties, 2000. MMWR. 2001 Jan 26; 50(3): 37-9. [MMWR, 2001b] Human West Nile Virus Surveillance --- Connecticut, New Jersey, and New York, 2000. MMWR. 2001 Apr 13; 50(14): 265-8. [MMWR, 2002a] West Nile Virus Activity --- United States, November 7--13, 2002. MMWR. 2002 Nov 15; 51(45): 1026-7. [NAFTA, 2002] Decision of NAFTA Tribunal (Methanex vs. USA]. 2002. [NoSpray, 2003] http://www.nospray.org. Accessed 2003 Jan. [Stone, 1999-2000] Personal communication between Ward Stone and Jim West. 1999-2000. [Toxics, 2001] Overkill: why pesticide spraying for West Nile virus may cause more harm than good. Toxics Action Center and Maine Environmental Policy Institute. 2001 Aug. [West, 2003] www.geocities.com/noxot/wnvDBcty.htm. Accessed 2003 Jan.