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West Nile virus: a primer for infection control professionals
West Nile virus: A primer for infection control professionals Angella M. Goetz, RN, MNEd, CIC, and Barbara A. Goldrick, MPH, PhD, RN, CIC Pittsburgh, Pennsylvania, and Chatham, Massachusetts
In 1999, an outbreak of human West Nile encephalitis occurred in New York City. During the outbreak, 62 cases of human West Nile virus (WNV) infection were diagnosed, with 7 deaths. This was the first time that human WNV infections were detected in the Western Hemisphere. By 2002, the total number of human cases of WNV that year alone reached 4156, with 284 fatalities. In addition, investigations have shown that WNV can be acquired through organ transplantation, blood transfusion, breast milk, transplacental transmission, and occupational exposure. This article provides an overview of the 2002 WNV epidemic in the United States and reviews the epidemiology of WNV, the clinical presentation of human WNV infection, and the prevention and control of this emerging pathogen. (Am J Infect Control 2004;32:101-5.)
BACKGROUND The various outbreaks of the West Nile virus (WNV) over the past decade demonstrate our vulnerability to emerging infectious diseases and the ease with which they move from continent to continent. WNV, a mosquito-borne human neuropathogen, was first isolated in the West Nile region of Uganda in 1937.1 Over the ensuing years, reports of WNV in humans were sporadic. However, intermittent outbreaks were reported between 1951 and 1974.1 In the 1990s, the epidemiology of WNV infection changed. The severity of human disease increased as well as higher avian death rates.1 In August 1999, an outbreak of West Nile encephalitis occurred in New York City. This was the first time that human WNV infections were detected in the Western Hemisphere.2 Although New York City had an aggressive mosquito control campaign in place during the 1999 outbreak, the epidemic was not controlled, leading investigators to suggest that migratory birds contributed to the spread of disease.3
EPIDEMIOLOGY OF WNV The outbreaks of the last decade have been linked to a new West Nile variant, which is genetically divided into 2 lineages, lineage 1 and 2. Only lineage 1 viruses were associated with human encephalitis. The United States cases appear to be related to the lineage 1 viruses isolated in Israel from 1997 to 2000. Lanciotti et al reported that complete genome sequencing of a flavovirus isolated from the brain of a Chilean flamingo and Reprint requests: Barbara A. Goldrick, PhD, PO Box 139, Chatham, MA 02633-0139. 0196-6553/$30.00 Copyright ª 2004 by the Association for Professionals in Infection Control and Epidemiology, Inc. doi:10.1016/j.ajic.2003.10.010
partial sequence analysis of envelope glycoprotein genes from other species, including mosquitoes and humans, showed that WNV was responsible for human disease. Antigenic mapping confirmed that these viruses were WN and were closely related to a WNV isolated in Israel.4 Interestingly, only Israel and the United States have reported disease and death by this variant.2 The 2002 epidemic of WNV peaked from June through October. The mosquito was the principal vector, transmitting the causative virus from infected to noninfected hosts, including birds, animals, and humans. However, other modes of WNV transmission, including blood transfusions, transplantation, transplacental transmission, and occupational exposure, were also reported during this time.5-7
Surveillance for WNV activity Avian surveillance. During the 1999 outbreak in New York City, thousands of American crows (Corvus brachyrhyncos) and exotic birds in local zoos died. This led investigators to theorize that the virus arrived in the United States by infected migrating birds or by imported birds.3 Consequently, an electronic surveillance system, which monitored dead or ill birds, was instituted in New York and Connecticut. More than half of 18,000 dead birds tested positive for WNV, one third of which were American crows.8 During the 2002 epidemic, the avian surveillance system identified 7719 dead crows and 6403 other dead birds with WNV infection from 42 states and the District of Columbia. In addition, 9157 WNV infections were reported in mammals from 38 states, with the majority (9144) occurring in equines. WNV antibodies also have been reported in 366 sentinel chicken flocks in 7 states.9 Mosquito surveillance. By 2000, the WNV was found in 14 mosquito species, including a high number of Culex salinarius. This species feeds on both birds and mammals and readily bites humans.3 In the 2002 101
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sample of the infant’s blood confirmed antibodies to the WNV, indicating that the infant had been infected. A sample of the mother’s breast milk also tested positive for WNV.16 A case of transplacental transmission of WNV following a blood transfusion7 and infection in laboratory workers through occupational exposure have also been reported.6
Control of vector transmission
Fig 1. West Nile virus activity, by state—United States, 1999-2002.9 epidemic, 4943 WNV-positive mosquito pools were reported from 37 states.8 In addition, several studies have documented natural vertical transmission of WNV among different species of mosquitoes.10 As a result, the Centers for Disease Control and Prevention (CDC) reports that it is unlikely that the WNV can be eliminated from the United States.11 Human surveillance. In the 1999 New York City epidemic, 62 cases of WNV were diagnosed, with 7 deaths.1 Between 1999 and 2001, 149 cases of human infections were reported in the United States, with 18 fatalities.12 The total number of human cases of WNV in 2002 alone reached 4156, with 284 fatalities.13 Most cases occurred in Illinois (884), Michigan (614), Ohio (441), Louisiana (329), and Indiana (293) (see Fig 1).9 The onset of human WNV infection occurred between June and November and more often in males (54%). The median age of the patients was 55 years (range, 1 month to 99 years); however, in fatality cases, the median age was 78 years (range, 24-99 years), and 61% were male.9 Nash et al.2 found that increased age ([65) and diabetes mellitus were significant predictors of mortality following WNV infection. Ongoing investigations have shown that WNV can also be transmitted through organ transplantation and blood transfusion.14-16 Intrauterine transmission has also been reported.7 In August 2002, the CDC reported 4 cases of WNV meningoencephalitis following organ transplantation from the same donor, who had received blood transfusions prior to her death.14 By October 2002, the CDC received reports of 25 patients who developed West Nile meningoencephalitis and 4 who developed other WNV-associated illnesses after receiving blood components within a month before the onset of illness.5 In 1 case, a 40-year-old woman who had received red blood cells postpartum was diagnosed with meningoencephalitis. Follow-up investigation confirmed WNV infection, and the patient recovered. Although the infant, who was breast-fed for 18 days prior to the mother’s diagnosis, remained healthy, a
In 1999, the CDC developed guidelines to control both sporadic cases and outbreaks of WNV.17 In the summer of 2003, the CDC released updated guidelines for surveillance, prevention, and control of WNV18; however, the case definitions for WNV and all cases of arboviral meningitis and encephalitis remain the same. The guidelines emphasize the necessity to focus on both surveillance of the host population and control of the mosquito vector.17 The guidelines stress year-round surveillance in southern states because of bird migration and in the early spring to autumn in the northern states. Surveillance includes monitoring the avian population, primarily the crows, for disease. Controlling mosquito infestation is the primary way to break the cycle of WNV transmission. Eliminating mosquitobreeding sites should be a year-round activity. This will reduce the number of adult mosquitoes that emerge in the spring and early summer. This is accomplished through surveillance of adult and larval mosquitoes and habitats, mosquito traps, biting counts, and public complaints.19 Pesticides, which are administered only by trained public health personnel in low doses so as not to become a hazard to other animal species, are available to control mosquitoes.19 Unfortunately, because of financial constraints, most public health departments use methods to kill only the adult mosquito.17 In addition, veterinarians are advised to report neurologic disease in animals, eg, in horses, birds, and dogs.17
PATHOGENESIS AND CLINICAL PRESENTATION OF WNV INFECTION CDC case definition of human WNV Infection The CDC has classified WNV infections into probable cases and confirmed cases.20 A ‘‘probable case’’ is defined as encephalitis or meningitis occurring during a period when arboviral transmission is likely and with supportive laboratory findings (Table 1).20 A ‘‘confirmed case’’ of WNV is defined as encephalitis or meningitis that is laboratory confirmed.20 Laboratory criteria for WNV diagnosis are outlined in Table 1.20 However, results of a single serum sample cannot accurately determine a new WNV infection. Interpretation of serologic WNV IgM-positive tests taken early in the WNV season should be made with caution because the presence of WNV-reactive IgM in serum alone is not
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necessarily diagnostic of an acute WNV infection. Roehrig et al21 reported WNV-specific IgM antibody present in blood at approximately 500 days after the onset of severe WNV illness.
Signs and symptoms of human WNV infection Because WNV and St. Louis encephalitis virus are closely related arboviruses, the latter should be ruled out in areas where both occur.20 The incubation period following WNV exposure is usually 3 to 14 days,22 and an estimated 20% of those who become infected will develop West Nile fever, characterized by flu-like symptoms: fever, headache, and body aches. A skin rash on the trunk of the body and swollen lymph glands also may occur.22 Through a household-based seroepidemiologic survey, Mostashari et al estimated that thousands of symptomatic and nonsymptomatic West Nile viral infections probably occurred during the 1999 West Nile virus outbreak in New York City, with fewer than 1% resulting in severe neurologic disease.23 Approximately 1 in 150 persons infected with the West Nile virus will develop a more severe form of disease.22 Human arboviral meningitis is characterized by fever, headache, stiff neck, and pleocytosis. Arboviral encephalitis is characterized by fever, headache, and altered mental status, ranging from confusion to coma with or without additional signs of brain dysfunction (eg, paresis or paralysis, cranial nerve palsies, sensory deficits, abnormal reflexes, generalized convulsions, and abnormal movements).24 Symptoms of severe disease may last several weeks; however, neurologic damage may be permanent.22 Severe neuroinvasive encephalitis and death have been associated with increased age.11 In a follow-up assessment of 16 confirmed WNV-seropositive patients with neurologic involvement (5 with meningitis, 8 with encephalitis, and 3 with acute flaccid paralysis), Sejvar et al found persistent neurological sequelae after eight months.25 In both the 1999 outbreak and the 2002 epidemic, some cases were associated with acute flaccid paralysis. Clinical symptoms demonstrated a peripheral demyelinating process (ie, Guillain-Barre´ Syndrome) or anterior myelitis.5 WNV-specific antibodies in the patients’ sera confirmed acute WNV infection in 6 of these cases.26 Some clinical findings also suggested pathologic involvement of the central nervous system similar to that found in acute poliomyelitis.27 Because the symptoms of acute WNV infection are similar to other illnesses, especially among those [50 years of age, health care providers should consider possible WNV in differential diagnoses, particularly during the summer and early fall in areas where WNV is prevalent. For example, in the 2002 epidemic, stroke was the preliminary diagnoses in 2 male patients,
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Table 1. Laboratory criteria to confirm WNV encephalitis/meningitis Probable cases A single elevated titer of WNVspecific serum antibodies. Serum IgM antibodies detected in blood. No confirmatory test for IgG antibodies in same or later specimen.
Confirmed cases A 4-fold or greater change in WVN antibodies. OR Specific WVN antigen found in tissue, CSF, or other body fluid. OR Genomic sequence in tissue, blood, CSF, or other body fluid. OR WNV-specific IgM antibodies found in CSF. OR WNV-specific IgM antibodies found in serum and confirmed by WNV-specific serum IgG antibodies in same or later specimen.
Source: CDC.20
based on findings of tremor and areflexic weakness in both arms and asymmetric weakness in both legs. Subsequent clinical findings and antibody tests confirmed acute WNV infection.26 Another case was a 46year-old male patient, with a history of coronary artery disease, who presented with fever, chills, fatigue, and plegic and areflexic right leg and mild left leg weakness. The patient was admitted with a diagnosis of Guillain-Barre´ Syndrome and was treated with immune globulin and antibiotics. Again, antibody tests confirmed an acute WNV infection.26
PATIENT CARE IMPLICATIONS Health care providers, particularly emergency room personnel, working in areas where WNV is prevalent, should evaluate patients presenting with acute, painless, asymmetric weakness, in the presence of an acute febrile illness for evidence of WNV infection, particularly in patients over age 50. Appropriate history and diagnostic tests should be conducted to differentiate Guillain-Barre´ Syndrome from other causes of acute flaccid paralysis before initiating therapy.26 Treatment for WNV illness is supportive, and, in severe cases, this often involves hospitalization, intravenous fluids, respiratory support, and prevention of secondary infections. Although there is currently no vaccine against WNV, researchers are predicting that a vaccine will be available by 2005.28 The CDC has established a mechanism through state and local health departments for reporting WNV infection occurring in individuals who have received blood component transfusions within 4 weeks prior to onset of illness.28 When assessing patients, nurses and other health care providers should report persons who develop illness within 2 weeks of donating blood.28 Prompt reporting is important so that withdrawal of
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mendations include using repellents on exposed skin, especially after dusk; wearing light-colored longsleeved tops and long trousers (dark colors attract mosquitoes); using window or door screens; mosquito netting used over beds when camping; and being aware that animals attract mosquitoes.31
Health care facility surveillance and prevention
Fig 2. Areas reporting West Nile virus (WNV) activity—United States, 2003 (as of 3 AM Mountain Daylight Time, September 24, 2003).32 infectious blood components can occur.28 In addition, the Food and Drug Administration (FDA), the CDC, and health departments monitor WNV cases related to blood transfusions. The FDA has implemented ‘‘Guidance to Industry’’ recommendations for assessing donor suitability and product safety for donors with proven WNV infections or with illnesses potentially caused by WNV.29 Between August 2002 and January 2003, the CDC identified 60 cases of possible transfusion-associated WNV infections in mostly asymptomatic patients; 23 of these have been confirmed. As of May 2003, a WNV-sensitive test has become available for screening donated blood.30 As many as 60% of persons with an acute WNV infection of the central nervous system could have persistent WNV-specific IgM antibody present in their blood up to 18 months after the onset of illness. Therefore, results of a single serum sample cannot accurately determine a new WNV infection, and the presence of WNV-reactive IgM in serum alone is not necessarily diagnostic of an acute WNV infection.21
Prevention of human WNV infection Since WNV has found its niche in North America, it is unlikely that diseases associated with it will be eliminated. Therefore, education of the public is of prime importance in the prevention of WNV infection. Health care providers can play an important role in educating the public about modes of WNV transmission and preventing or reducing the risk of mosquito bites. To prevent mosquito bites, repellents such as N, Ndiethylmetatoluamid (DEET) should be used; however, dependence on repellents is not the sole method to prevent exposure/transmission to WNV.17 The public also should be taught to eliminate potential breeding grounds for mosquitoes around their homes. Discarded tires can be a breeding ground for mosquitoes; thus, they should be sprayed or destroyed.31 Other recom-
Carol A. Pate, CIC, an infection control professional (ICP) in Mississippi, a state where some of the unusual cases of human WNV cases occurred, reported that, to be safe, her hospital probably erred on the side of overtesting for WNV. Her facility has been a sentinel hospital for several years, reporting any meningitis/ encephalitis cases at her hospital during the summer months, and has a system in place to assist the State Health Department in the surveillance and data collection for WNV infections. During the 2002 epidemic, Pate and the Infection Control Department coordinated efforts between the State Health Department and hospital physicians, case managers, staff nurses, and laboratories. She informed them that the State Health Department tests serum for arboviruses at no cost. Pamphlets with information on WNV and prevention of infection with mosquito repellents were distributed. The high number of WNV cases in Mississippi drew much media attention. Using the media as a teaching tool, the Health Department communicated to the public the prevention and control methods to contain the spread of the virus. Pate provided several community programs on WNV (personal communication, October 2002). Nosocomial transmission of WNV can be prevented by being aware of the potential risk of WNV infection following transfusion of blood products or organ transplantation. Health care providers also should use standard precautions when handling needles to prevent injury and exposures to all bloodborne pathogens in the health care setting. In addition, health care providers should consider WNV as a differential diagnosis, particularly among elderly adults during the summer months. Suspected cases should be reported to state or local health departments promptly. Health departments are excellent resources for obtaining WN testing information.
Authors’ note: 2003 WNV update The United States WNV epidemic continued in the spring-summer season of 2003. As of late September 2003, 4827 human cases of WNV infections and 93 deaths had been reported.32 Unlike 2002, the majority of cases shifted further west (Fig 2),32 with Colorado reporting the most cases (1542), followed by Nebraska (788), South Dakota (699), Texas (311), and Wyoming (302).32 Up to that date, the Pacific Coast states and
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Idaho had not reported any human cases of WNV.32 Using known demographic data, the CDC shows that the majority (53%) of the cases occurred among men; the median age was 47 years (range, 1 month to 99 years), and the dates of illness onset ranged from March 28 to September 17.32 Most of the 93 fatalities were in Colorado (27), Nebraska (13), South Dakota (8), Texas (7), Wyoming (7), and New Mexico (4).32 By midSeptember 2003, a total of 489 WNV-viremic blood donors had been reported. Based on data from 333 of these donors, the CDC shows that 35 developed WN fever, and 2 developed WN meningoenciphalitis; however, most (296, 89%) of the cases remained asymptomatic. The mean age was 45 years (range, 15-83 years); 181 (54%) were male.33 As of midSeptember, 2 cases of confirmed transfusion-associated WNV transmission had been identified, 1 each in Texas and Nebraska.33 In the animal population, 8406 dead birds with WNV infection were reported from 42 states and New York City by late September 2003.32 WNV infections had been reported in 2143 horses from 36 states, 12 WNV infections were reported in dogs, 5 infections were reported in squirrels, and 17 infections were reported in unidentified animal species.32 During that same period, WNV seroconversions had been reported in 603 sentinel chicken flocks from 13 states, and 11 seropositive sentinel horses had been reported from 4 states. By late September, a total of 4941 WNV-positive mosquito pools had been reported from 38 states and New York City.32 References 1. Peterson LR, Roehrig JT. West Nile virus: a reemerging global pathogen. Emerg Infect Dis 2001;7:611-4. 2. Nash D, Mostashari F, Fine A, Miller J, O’Leary D, Murray K, et al. The outbreak of West Nile virus infection in the New York City area in 1999. N Engl J Med 2001;344:1807-14. 3. Rappole JH, Derickson SR, Huba´lek Z. Migratory birds and spread of West Nile virus in the western hemisphere. Emerg Infect Dis 2000;6:319-28. 4. Lanciotti RS, Roehrig JT, Deubel V, Smith J, Parker M, Steele K, et al. Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States. Science 1999;286:2333-7. 5. Centers for Disease Control and Prevention (CDC). West Nile virus activity—United States, October 10-16, 2002, and update on West Nile virus infections in recipients of blood transfusion. MMWR 2002;51:929-31. 6. CDC. Laboratory-acquired West Nile virus infections—United States 2002. MMWR 2002;51:1133-5. 7. CDC. Intrauterine West Nile virus infection—New York, 2000. MMWR 2002;51:1135-6. 8. Eidson M, Komar N, Sorhage F, Nelson R, Talbot T, Mostashari F, et al. Crow deaths as a sentinel surveillance system for West Nile virus in the northeastern United States, 1999. Emerg Infect Dis 2001;7:615-20. 9. CDC. Provisional surveillance summary of West Nile virus epidemic—United States, January-November 2002. MMWR 2002;51:1129-33. 10. Reisen WK. Overwintering and vertical transmission: Fourth National Conference on West Nile Virus in the United States, New Orleans,
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28. 29.
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31.
32. 33.
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LA, February 9-11, 2003. Available at: http://www.cdc.gov/ncidod/ dvbid/westnile/conf/pdf/Reisen4th03.pdf. Accessed September 12, 2003. Rovner J. Federal officials say progress being made on control of West Nile virus. Reuters Medical News; 2002. Campbell GL, Marfin AA, Lanciotti RS, Gubler DJ. West Nile virus. Lancet Infect Dis 2002;2:519-29. CDC. West Nile virus 2002 case counts. Available at: http:// www.cdc.gov/ncidod/dvbid/westnile/surv&controlCaseCount02.htm. Accessed August 27, 2003. CDC. Public dispatch: West Nile virus infection in organ donor and transplantrecipients—Georgia and Florida, 2002. MMWR 2002;51:790. CDC. West Nile Virus activity—United States, September 26-October 2, 2002, and investigations of West Nile virus infections in recipients of blood transfusion and organ transplantation. MMWR 2002;51:884, 895. CDC. Update: investigation of West Nile virus infections in recipients of organ transplantation and blood transfusion—Michigan, 2002. MMWR 2002;51:879. CDC. Guidelines for surveillance, prevention, and control of West Nile virus infection—United States. MMWR 2000;49:25-8. CDC. Updated guidelines for surveillance, prevention, and control of West Nile virus. Available at: www.cdc.gov/ncidod/dvbid/westnile/ resources/wnv-guidelines-aug-2003.pdf. Accessed September 12, 2003. Rose RI. Pesticides and public health: integrated methods of mosquito management. Emerg Infect Dis 2001;7:17-23. CDC. 2001 West Nile virus case definition: encephalitis or meningitis, arboviral. Available at: www.cdc.gov/epo/dphsi/casedef/encephalitis_ arboviral_current.htm. Accessed August 27, 2003. Roehrig JT, Nash D, Maldin B, Labowitz A, Martin DA, Lanciotti RS, et al. Persistence of virus-reactive serum immunoglobulin M antibody in confirmed West Nile virus encephalitis cases. Emerg Infect Dis 2003;9:376-9. CDC. West Nile virus. Available at: www.cdc.gov/ncidod/dvbid/ westnile/qa/symptoms.htm. Accessed August 27, 2003. Mostashari F, Bunning ML, Kitsutani PT, Singer DA, Nash D, Cooper MJ. Epidemic West Nile encephalitis, New York, 1999: results of a household-based seroepidemiological survey. Lancet 2001;358:261-4. Tyler KL. West Nile virus encephalitis in America. N Engl J Med 2001;344:1858. Sejvar JJ, Haddad MB, Tierney BC, Campbell GL, Marfin AA, Van Gerpen J, et al. Neurologic manifestations and outcome of West Nile virus infection. JAMA 2003;290:511-5. CDC. Acute flaccid paralysis syndrome associated with West Nile virus infection—Mississippi and Louisiana, July-August 2002. MMWR 2002;51:825-8. Solomon T, Kneen R, Dung NM, Khanh VC, Thuy TT, Ha DQ, et al. Poliomyelitis-like illness due to Japanese encephalitis virus. Lancet 1998;351:1094-7. CDC. Update: investigations of West Nile virus infections in recipients of organ transplantation and blood transfusion. MMWR 2002;51:833-6. Food and Drug Administration. Recommendations for the assessment of donor suitability and blood and blood product safety in cases of known or suspected West Nile virus infection. U.S. Department of Health and Human Services Food and Drug Administration, Center for Biologics Evaluation and Research (CBER) October 2002. Available at: www.fda.gov/cber/gdlns/wnvguid.htm. Accessed September 9, 2003. Layton M. Lessons learned from the West Nile virus: implications for other unusual and exotic diseases. Presented at the Association for Professionals in Infection Control 30th Educational Conference, San Antonio, TX; June 2003. Chin J, editor. Control of communicable diseases manual, 7th ed. Washington, DC: American Public Health Association; 2000. p. 41-42, 315. CDC. West Nile virus activity—United States, September 18-24, 2003 MMWR 2003;52:919-20. CDC. Update: Detection of West Nile virus in blood donations— United States, 2003. MMWR 2003;52:916-9.
In 1999, an outbreak of human West Nile encephalitis occurred in New York City. During the outbreak, 62 cases of human West Nile virus (WNV) infection were diagnosed, with 7 deaths. This was the first time that human WNV infections were detected in the Western Hemisphere. By 2002, the total number of human cases of WNV that year alone reached 4156, with 284 fatalities. In addition, investigations have shown that WNV can be acquired through organ transplantation, blood transfusion, breast milk, transplacental transmission, and occupational exposure. This article provides an overview of the 2002 WNV epidemic in the United States and reviews the epidemiology of WNV, the clinical presentation of human WNV infection, and the prevention and control of this emerging pathogen. (Am J Infect Control 2004;32:101-5.)
BACKGROUND The various outbreaks of the West Nile virus (WNV) over the past decade demonstrate our vulnerability to emerging infectious diseases and the ease with which they move from continent to continent. WNV, a mosquito-borne human neuropathogen, was first isolated in the West Nile region of Uganda in 1937.1 Over the ensuing years, reports of WNV in humans were sporadic. However, intermittent outbreaks were reported between 1951 and 1974.1 In the 1990s, the epidemiology of WNV infection changed. The severity of human disease increased as well as higher avian death rates.1 In August 1999, an outbreak of West Nile encephalitis occurred in New York City. This was the first time that human WNV infections were detected in the Western Hemisphere.2 Although New York City had an aggressive mosquito control campaign in place during the 1999 outbreak, the epidemic was not controlled, leading investigators to suggest that migratory birds contributed to the spread of disease.3
EPIDEMIOLOGY OF WNV The outbreaks of the last decade have been linked to a new West Nile variant, which is genetically divided into 2 lineages, lineage 1 and 2. Only lineage 1 viruses were associated with human encephalitis. The United States cases appear to be related to the lineage 1 viruses isolated in Israel from 1997 to 2000. Lanciotti et al reported that complete genome sequencing of a flavovirus isolated from the brain of a Chilean flamingo and Reprint requests: Barbara A. Goldrick, PhD, PO Box 139, Chatham, MA 02633-0139. 0196-6553/$30.00 Copyright ª 2004 by the Association for Professionals in Infection Control and Epidemiology, Inc. doi:10.1016/j.ajic.2003.10.010
partial sequence analysis of envelope glycoprotein genes from other species, including mosquitoes and humans, showed that WNV was responsible for human disease. Antigenic mapping confirmed that these viruses were WN and were closely related to a WNV isolated in Israel.4 Interestingly, only Israel and the United States have reported disease and death by this variant.2 The 2002 epidemic of WNV peaked from June through October. The mosquito was the principal vector, transmitting the causative virus from infected to noninfected hosts, including birds, animals, and humans. However, other modes of WNV transmission, including blood transfusions, transplantation, transplacental transmission, and occupational exposure, were also reported during this time.5-7
Surveillance for WNV activity Avian surveillance. During the 1999 outbreak in New York City, thousands of American crows (Corvus brachyrhyncos) and exotic birds in local zoos died. This led investigators to theorize that the virus arrived in the United States by infected migrating birds or by imported birds.3 Consequently, an electronic surveillance system, which monitored dead or ill birds, was instituted in New York and Connecticut. More than half of 18,000 dead birds tested positive for WNV, one third of which were American crows.8 During the 2002 epidemic, the avian surveillance system identified 7719 dead crows and 6403 other dead birds with WNV infection from 42 states and the District of Columbia. In addition, 9157 WNV infections were reported in mammals from 38 states, with the majority (9144) occurring in equines. WNV antibodies also have been reported in 366 sentinel chicken flocks in 7 states.9 Mosquito surveillance. By 2000, the WNV was found in 14 mosquito species, including a high number of Culex salinarius. This species feeds on both birds and mammals and readily bites humans.3 In the 2002 101
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sample of the infant’s blood confirmed antibodies to the WNV, indicating that the infant had been infected. A sample of the mother’s breast milk also tested positive for WNV.16 A case of transplacental transmission of WNV following a blood transfusion7 and infection in laboratory workers through occupational exposure have also been reported.6
Control of vector transmission
Fig 1. West Nile virus activity, by state—United States, 1999-2002.9 epidemic, 4943 WNV-positive mosquito pools were reported from 37 states.8 In addition, several studies have documented natural vertical transmission of WNV among different species of mosquitoes.10 As a result, the Centers for Disease Control and Prevention (CDC) reports that it is unlikely that the WNV can be eliminated from the United States.11 Human surveillance. In the 1999 New York City epidemic, 62 cases of WNV were diagnosed, with 7 deaths.1 Between 1999 and 2001, 149 cases of human infections were reported in the United States, with 18 fatalities.12 The total number of human cases of WNV in 2002 alone reached 4156, with 284 fatalities.13 Most cases occurred in Illinois (884), Michigan (614), Ohio (441), Louisiana (329), and Indiana (293) (see Fig 1).9 The onset of human WNV infection occurred between June and November and more often in males (54%). The median age of the patients was 55 years (range, 1 month to 99 years); however, in fatality cases, the median age was 78 years (range, 24-99 years), and 61% were male.9 Nash et al.2 found that increased age ([65) and diabetes mellitus were significant predictors of mortality following WNV infection. Ongoing investigations have shown that WNV can also be transmitted through organ transplantation and blood transfusion.14-16 Intrauterine transmission has also been reported.7 In August 2002, the CDC reported 4 cases of WNV meningoencephalitis following organ transplantation from the same donor, who had received blood transfusions prior to her death.14 By October 2002, the CDC received reports of 25 patients who developed West Nile meningoencephalitis and 4 who developed other WNV-associated illnesses after receiving blood components within a month before the onset of illness.5 In 1 case, a 40-year-old woman who had received red blood cells postpartum was diagnosed with meningoencephalitis. Follow-up investigation confirmed WNV infection, and the patient recovered. Although the infant, who was breast-fed for 18 days prior to the mother’s diagnosis, remained healthy, a
In 1999, the CDC developed guidelines to control both sporadic cases and outbreaks of WNV.17 In the summer of 2003, the CDC released updated guidelines for surveillance, prevention, and control of WNV18; however, the case definitions for WNV and all cases of arboviral meningitis and encephalitis remain the same. The guidelines emphasize the necessity to focus on both surveillance of the host population and control of the mosquito vector.17 The guidelines stress year-round surveillance in southern states because of bird migration and in the early spring to autumn in the northern states. Surveillance includes monitoring the avian population, primarily the crows, for disease. Controlling mosquito infestation is the primary way to break the cycle of WNV transmission. Eliminating mosquitobreeding sites should be a year-round activity. This will reduce the number of adult mosquitoes that emerge in the spring and early summer. This is accomplished through surveillance of adult and larval mosquitoes and habitats, mosquito traps, biting counts, and public complaints.19 Pesticides, which are administered only by trained public health personnel in low doses so as not to become a hazard to other animal species, are available to control mosquitoes.19 Unfortunately, because of financial constraints, most public health departments use methods to kill only the adult mosquito.17 In addition, veterinarians are advised to report neurologic disease in animals, eg, in horses, birds, and dogs.17
PATHOGENESIS AND CLINICAL PRESENTATION OF WNV INFECTION CDC case definition of human WNV Infection The CDC has classified WNV infections into probable cases and confirmed cases.20 A ‘‘probable case’’ is defined as encephalitis or meningitis occurring during a period when arboviral transmission is likely and with supportive laboratory findings (Table 1).20 A ‘‘confirmed case’’ of WNV is defined as encephalitis or meningitis that is laboratory confirmed.20 Laboratory criteria for WNV diagnosis are outlined in Table 1.20 However, results of a single serum sample cannot accurately determine a new WNV infection. Interpretation of serologic WNV IgM-positive tests taken early in the WNV season should be made with caution because the presence of WNV-reactive IgM in serum alone is not
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necessarily diagnostic of an acute WNV infection. Roehrig et al21 reported WNV-specific IgM antibody present in blood at approximately 500 days after the onset of severe WNV illness.
Signs and symptoms of human WNV infection Because WNV and St. Louis encephalitis virus are closely related arboviruses, the latter should be ruled out in areas where both occur.20 The incubation period following WNV exposure is usually 3 to 14 days,22 and an estimated 20% of those who become infected will develop West Nile fever, characterized by flu-like symptoms: fever, headache, and body aches. A skin rash on the trunk of the body and swollen lymph glands also may occur.22 Through a household-based seroepidemiologic survey, Mostashari et al estimated that thousands of symptomatic and nonsymptomatic West Nile viral infections probably occurred during the 1999 West Nile virus outbreak in New York City, with fewer than 1% resulting in severe neurologic disease.23 Approximately 1 in 150 persons infected with the West Nile virus will develop a more severe form of disease.22 Human arboviral meningitis is characterized by fever, headache, stiff neck, and pleocytosis. Arboviral encephalitis is characterized by fever, headache, and altered mental status, ranging from confusion to coma with or without additional signs of brain dysfunction (eg, paresis or paralysis, cranial nerve palsies, sensory deficits, abnormal reflexes, generalized convulsions, and abnormal movements).24 Symptoms of severe disease may last several weeks; however, neurologic damage may be permanent.22 Severe neuroinvasive encephalitis and death have been associated with increased age.11 In a follow-up assessment of 16 confirmed WNV-seropositive patients with neurologic involvement (5 with meningitis, 8 with encephalitis, and 3 with acute flaccid paralysis), Sejvar et al found persistent neurological sequelae after eight months.25 In both the 1999 outbreak and the 2002 epidemic, some cases were associated with acute flaccid paralysis. Clinical symptoms demonstrated a peripheral demyelinating process (ie, Guillain-Barre´ Syndrome) or anterior myelitis.5 WNV-specific antibodies in the patients’ sera confirmed acute WNV infection in 6 of these cases.26 Some clinical findings also suggested pathologic involvement of the central nervous system similar to that found in acute poliomyelitis.27 Because the symptoms of acute WNV infection are similar to other illnesses, especially among those [50 years of age, health care providers should consider possible WNV in differential diagnoses, particularly during the summer and early fall in areas where WNV is prevalent. For example, in the 2002 epidemic, stroke was the preliminary diagnoses in 2 male patients,
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Table 1. Laboratory criteria to confirm WNV encephalitis/meningitis Probable cases A single elevated titer of WNVspecific serum antibodies. Serum IgM antibodies detected in blood. No confirmatory test for IgG antibodies in same or later specimen.
Confirmed cases A 4-fold or greater change in WVN antibodies. OR Specific WVN antigen found in tissue, CSF, or other body fluid. OR Genomic sequence in tissue, blood, CSF, or other body fluid. OR WNV-specific IgM antibodies found in CSF. OR WNV-specific IgM antibodies found in serum and confirmed by WNV-specific serum IgG antibodies in same or later specimen.
Source: CDC.20
based on findings of tremor and areflexic weakness in both arms and asymmetric weakness in both legs. Subsequent clinical findings and antibody tests confirmed acute WNV infection.26 Another case was a 46year-old male patient, with a history of coronary artery disease, who presented with fever, chills, fatigue, and plegic and areflexic right leg and mild left leg weakness. The patient was admitted with a diagnosis of Guillain-Barre´ Syndrome and was treated with immune globulin and antibiotics. Again, antibody tests confirmed an acute WNV infection.26
PATIENT CARE IMPLICATIONS Health care providers, particularly emergency room personnel, working in areas where WNV is prevalent, should evaluate patients presenting with acute, painless, asymmetric weakness, in the presence of an acute febrile illness for evidence of WNV infection, particularly in patients over age 50. Appropriate history and diagnostic tests should be conducted to differentiate Guillain-Barre´ Syndrome from other causes of acute flaccid paralysis before initiating therapy.26 Treatment for WNV illness is supportive, and, in severe cases, this often involves hospitalization, intravenous fluids, respiratory support, and prevention of secondary infections. Although there is currently no vaccine against WNV, researchers are predicting that a vaccine will be available by 2005.28 The CDC has established a mechanism through state and local health departments for reporting WNV infection occurring in individuals who have received blood component transfusions within 4 weeks prior to onset of illness.28 When assessing patients, nurses and other health care providers should report persons who develop illness within 2 weeks of donating blood.28 Prompt reporting is important so that withdrawal of
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mendations include using repellents on exposed skin, especially after dusk; wearing light-colored longsleeved tops and long trousers (dark colors attract mosquitoes); using window or door screens; mosquito netting used over beds when camping; and being aware that animals attract mosquitoes.31
Health care facility surveillance and prevention
Fig 2. Areas reporting West Nile virus (WNV) activity—United States, 2003 (as of 3 AM Mountain Daylight Time, September 24, 2003).32 infectious blood components can occur.28 In addition, the Food and Drug Administration (FDA), the CDC, and health departments monitor WNV cases related to blood transfusions. The FDA has implemented ‘‘Guidance to Industry’’ recommendations for assessing donor suitability and product safety for donors with proven WNV infections or with illnesses potentially caused by WNV.29 Between August 2002 and January 2003, the CDC identified 60 cases of possible transfusion-associated WNV infections in mostly asymptomatic patients; 23 of these have been confirmed. As of May 2003, a WNV-sensitive test has become available for screening donated blood.30 As many as 60% of persons with an acute WNV infection of the central nervous system could have persistent WNV-specific IgM antibody present in their blood up to 18 months after the onset of illness. Therefore, results of a single serum sample cannot accurately determine a new WNV infection, and the presence of WNV-reactive IgM in serum alone is not necessarily diagnostic of an acute WNV infection.21
Prevention of human WNV infection Since WNV has found its niche in North America, it is unlikely that diseases associated with it will be eliminated. Therefore, education of the public is of prime importance in the prevention of WNV infection. Health care providers can play an important role in educating the public about modes of WNV transmission and preventing or reducing the risk of mosquito bites. To prevent mosquito bites, repellents such as N, Ndiethylmetatoluamid (DEET) should be used; however, dependence on repellents is not the sole method to prevent exposure/transmission to WNV.17 The public also should be taught to eliminate potential breeding grounds for mosquitoes around their homes. Discarded tires can be a breeding ground for mosquitoes; thus, they should be sprayed or destroyed.31 Other recom-
Carol A. Pate, CIC, an infection control professional (ICP) in Mississippi, a state where some of the unusual cases of human WNV cases occurred, reported that, to be safe, her hospital probably erred on the side of overtesting for WNV. Her facility has been a sentinel hospital for several years, reporting any meningitis/ encephalitis cases at her hospital during the summer months, and has a system in place to assist the State Health Department in the surveillance and data collection for WNV infections. During the 2002 epidemic, Pate and the Infection Control Department coordinated efforts between the State Health Department and hospital physicians, case managers, staff nurses, and laboratories. She informed them that the State Health Department tests serum for arboviruses at no cost. Pamphlets with information on WNV and prevention of infection with mosquito repellents were distributed. The high number of WNV cases in Mississippi drew much media attention. Using the media as a teaching tool, the Health Department communicated to the public the prevention and control methods to contain the spread of the virus. Pate provided several community programs on WNV (personal communication, October 2002). Nosocomial transmission of WNV can be prevented by being aware of the potential risk of WNV infection following transfusion of blood products or organ transplantation. Health care providers also should use standard precautions when handling needles to prevent injury and exposures to all bloodborne pathogens in the health care setting. In addition, health care providers should consider WNV as a differential diagnosis, particularly among elderly adults during the summer months. Suspected cases should be reported to state or local health departments promptly. Health departments are excellent resources for obtaining WN testing information.
Authors’ note: 2003 WNV update The United States WNV epidemic continued in the spring-summer season of 2003. As of late September 2003, 4827 human cases of WNV infections and 93 deaths had been reported.32 Unlike 2002, the majority of cases shifted further west (Fig 2),32 with Colorado reporting the most cases (1542), followed by Nebraska (788), South Dakota (699), Texas (311), and Wyoming (302).32 Up to that date, the Pacific Coast states and
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Idaho had not reported any human cases of WNV.32 Using known demographic data, the CDC shows that the majority (53%) of the cases occurred among men; the median age was 47 years (range, 1 month to 99 years), and the dates of illness onset ranged from March 28 to September 17.32 Most of the 93 fatalities were in Colorado (27), Nebraska (13), South Dakota (8), Texas (7), Wyoming (7), and New Mexico (4).32 By midSeptember 2003, a total of 489 WNV-viremic blood donors had been reported. Based on data from 333 of these donors, the CDC shows that 35 developed WN fever, and 2 developed WN meningoenciphalitis; however, most (296, 89%) of the cases remained asymptomatic. The mean age was 45 years (range, 15-83 years); 181 (54%) were male.33 As of midSeptember, 2 cases of confirmed transfusion-associated WNV transmission had been identified, 1 each in Texas and Nebraska.33 In the animal population, 8406 dead birds with WNV infection were reported from 42 states and New York City by late September 2003.32 WNV infections had been reported in 2143 horses from 36 states, 12 WNV infections were reported in dogs, 5 infections were reported in squirrels, and 17 infections were reported in unidentified animal species.32 During that same period, WNV seroconversions had been reported in 603 sentinel chicken flocks from 13 states, and 11 seropositive sentinel horses had been reported from 4 states. By late September, a total of 4941 WNV-positive mosquito pools had been reported from 38 states and New York City.32 References 1. Peterson LR, Roehrig JT. West Nile virus: a reemerging global pathogen. Emerg Infect Dis 2001;7:611-4. 2. Nash D, Mostashari F, Fine A, Miller J, O’Leary D, Murray K, et al. The outbreak of West Nile virus infection in the New York City area in 1999. N Engl J Med 2001;344:1807-14. 3. Rappole JH, Derickson SR, Huba´lek Z. Migratory birds and spread of West Nile virus in the western hemisphere. Emerg Infect Dis 2000;6:319-28. 4. Lanciotti RS, Roehrig JT, Deubel V, Smith J, Parker M, Steele K, et al. Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States. Science 1999;286:2333-7. 5. Centers for Disease Control and Prevention (CDC). West Nile virus activity—United States, October 10-16, 2002, and update on West Nile virus infections in recipients of blood transfusion. MMWR 2002;51:929-31. 6. CDC. Laboratory-acquired West Nile virus infections—United States 2002. MMWR 2002;51:1133-5. 7. CDC. Intrauterine West Nile virus infection—New York, 2000. MMWR 2002;51:1135-6. 8. Eidson M, Komar N, Sorhage F, Nelson R, Talbot T, Mostashari F, et al. Crow deaths as a sentinel surveillance system for West Nile virus in the northeastern United States, 1999. Emerg Infect Dis 2001;7:615-20. 9. CDC. Provisional surveillance summary of West Nile virus epidemic—United States, January-November 2002. MMWR 2002;51:1129-33. 10. Reisen WK. Overwintering and vertical transmission: Fourth National Conference on West Nile Virus in the United States, New Orleans,
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