Alexander the Great and West Nile virus encephalitis.Alexander the Great died in Babylon in 323 BC. His death at age 32 followed a 2-week febrile febrile /feb·rile/ (feb´ril) pertaining to or characterized by fever.
Of, relating to, or characterized by fever; feverish. illness. Speculated causes of death have included poisoning, assassination, and a number of infectious diseases. One incident, mentioned by Plutarch but not considered by previous investigators, may shed light on the cause of Alexander's death. The incident, which occurred as he entered Babylon, involved a flock of ravens exhibiting unusual behavior and subsequently dying at his feet. The inexplicable behavior of ravens is reminiscent of avian illness and death weeks before the first human cases of West Nile virus West Nile virus, microorganism and the infection resulting from it, which typically produces no symptoms or a flulike condition. The virus is a flavivirus and is related to a number of viruses that cause encephalitis. infection were identified in the United States. We posit that Alexander may have died of West Nile virus encephalitis encephalitis (ĕnsĕf'əlī`təs), general term used to describe a diffuse inflammation of the brain and spinal cord, usually of viral origin, often transmitted by mosquitoes, in contrast to a bacterial infection of the meninges .
Alexanderthe Great died in the ancient Mesopotamian city of Babylon, on June 10, of 323 BC (Figure). His death after a 2-week febrile illness (Table) has fascinated ancient scholars and contemporary medical investigators (1), who have posited various diagnoses based on sparse clinical information--a few recorded signs and symptoms. Retrodiagnoses have included poisoning and infectious as well as noninfectious diseases (1-6). After reviewing ancient accounts and modern theories, we have concluded that Alexander may have died of West Nile virus encephalitis.
Few poisons induce fever, and few of these were available in Alexander's time--except plant salicylates Salicylates
A group of drugs that includes aspirin and related compounds. Salicylates are used to relieve pain, reduce inflammation, and lower fever. , which disturb temperature regulation; alkaloids alkaloids,
n alkaline phytochemicals that contain nitrogen in a heterocyclic ring structure. They can have powerful pharmacological effects and are more often used in traditional medicine than in herbal treatments. , which interfere with perspiration; and ergot ergot (ûr`gət), disease of rye and other cereals caused by the fungus Claviceps purpurea. The cottony, matlike body, or mycelium, of the fungus develops in the ovaries of the host plant; it eventually turns into a hard pink or purple mycotoxins, which produce a subjective sensation of heat. Plutarch mentions that Aristotle (Alexander's tutor) procured arsenic to poison Alexander (7). But plants, mycotoxins, and arsenic are not the likely causes of death since none would have caused the reported high, sustained lever.
Alexander's death occurred in late spring, upon his return to Babylon from the Indian subcontinent. Environmental conditions were unremarkable (8). Babylon, located on the Euphrates River (90 km south of present-day Baghdad), was bordered on the east by a swamp. Animals, including birds, were abundant (9), and arthropeds were also likely present (available from: URL URL
in full Uniform Resource Locator
Address of a resource on the Internet. The resource can be any type of file stored on a server, such as a Web page, a text file, a graphics file, or an application program. : http://www.ac.wwu.edu/~stephan/Animation/alexander.ht ml). Diseases endemic to the area (present-day Iraq) (leishmaniasis leishmaniasis (lēsh'mənī`əsĭs), any of a group of tropical diseases caused by parasitic protozoans of the genus Leishmania. , bubonic plague, hemorrhagic fevers) were not mentioned by chroniclers of Alexander's death. Also not reported was illness among his troops, mainly Macedonians and local recruits. Descriptions of Alexander's illness do not include common disease signs (e.g., rash, icterus icterus /ic·ter·us/ (ik´ter-us) [L.] jaundice.icter´ic
icterus neonato´rum jaundice in newborn children.
See jaundice. , "thin blood," vomiting, diarrhea or dysentery dysentery (dĭs`əntĕr'ē), inflammation of the intestine characterized by the frequent passage of feces, usually with blood and mucus. , hematuria hematuria
Blood in the urine. It usually indicates injury or disease of the kidney or another structure of the urinary system or possibly, in males, the reproductive system. It may result from infection, inflammation, tumours, kidney stones, or other disorders. , seizures).
Malaria, a diagnosis postulated by previous authors (1-3), occurred in Mesopotamia (10,11), and is common in today's Middle East (12). Some of Alexander's symptoms are compatible with malaria: continuous fever, chills, diaphoresis diaphoresis /di·a·pho·re·sis/ (-fah-re´sis) sweating, especially of a profuse type.
Perspiration, especially when copious and medically induced. , prostration prostration /pros·tra·tion/ (pros-tra´shun) extreme exhaustion or lack of energy or power.
heat prostration see under exhaustion.
n. , myalgia myalgia /my·al·gia/ (mi-al´jah) muscular pain.myal´gic
epidemic myalgia see under pleurodynia.
n. , progressive weakness, stupor stupor /stu·por/ (stoo´per) [L.]
1. a lowered level of consciousness.
2. in psychiatry, a disorder marked by reduced responsiveness.stu´porous
n. , diminished sensorium sensorium /sen·so·ri·um/ (sen-sor´e-um)
1. a sensory nerve center.
2. the state of an individual as regards consciousness or mental awareness.
n. pl. , delirium delirium
Condition of disorientation, confused thinking, and rapid alternation between mental states. The patient is restless, cannot concentrate, and undergoes emotional changes (e.g., anxiety, apathy, euphoria), sometimes with hallucinations. ; however, dark urine, so called "black water fever," or intermittent fevers were not reported. Today, most malaria in Iraq is due to Plasmodium vivax (13). Given Alexander's travel history, had his illness been malaria, it would have been due to P. falciparum; however, absence of P. falciparum's dramatic signature fever curve diminishes the possibility of malaria as a probable cause.
Typhoid fever and its complications also have been thoroughly considered (1). Alexander had a 2-week febrile illness culminating in terminal encephalopathy. As do encephalitis, endocarditis endocarditis (ĕn'dōkärdī`tĭs), bacterial or fungal infection of the endocardium (inner lining of the heart) that can be either acute or subacute. , pneumococcal pneumonia, psittacosis psittacosis (sĭtəkō`sĭs) or parrot fever, infectious disease caused by the species of Chlamydia psittaci and transmitted to people by birds, particularly parrots, parakeets, and lovebirds. , rickettsial disease, and tularemia tularemia (tlərē`mēə) or rabbit fever, acute, infectious disease caused by Francisella tularensis (Pasteurella tularensis). , typhoid causes sustained or continuous fever (14). The typical course of typhoid fever lasts one month. In fatal cases, death usually occurs at the end of week 2. Typhoid's neurologic manifestations, which also include delirium and expressionless demeanor, are seen in week 3. Other signs include cough, diarrhea, "rose spots," epistaxis epistaxis /ep·i·stax·is/ (-stak´sis) nosebleed; hemorrhage from the nose, usually due to rupture of small vessels overlying the anterior part of the cartilaginous nasal septum.
n. , and bloody stool (15). None of these signs or other illnesses similar to Alexander's were documented by Plutarch. Most other enteric infections have no neurologic sequelae sequelae Clinical medicine The consequences of a particular condition or therapeutic intervention and are generally self-limited. Vibrio vulnificus infection, which may cause fatal sepsis in heavy drinkers (as was Alexander), causes rapid death, accompanied by skin and muscle lesions and bleeding.
Other suggested diagnoses include Schistosoma haematobium infection (4), which causes painless hematuria; however, ectopic ectopic /ec·top·ic/ (ek-top´ik)
1. pertaining to ectopia.
2. located away from normal position.
3. arising from an abnormal site or tissue.
adj. egg deposition may occur at any time, causing transverse myelitis, paralysis, and death (16). Exposure to cercariae Cercariae
The free-living form of the schistosome worm that has a tail, swims, and has suckers on its head for penetration into a host.
Mentioned in: Schistosomiasis produces pruritus pruritus /pru·ri·tus/ (proo-ri´tus) itching.prurit´ic
pruritus a´ni intense chronic itching in the anal region.
pruritus hiema´lis xerotic eczema. and Katayama fever induces serum sickness (4), but symptoms include low grade fever and pruritic swellings, which were not reported in Alexander's case. Some leptospirosis leptospirosis (lĕp'təspīrō`sĭs), febrile disease caused by bacteria of the genus Leptospirae. The disease occurs in dogs, cattle, pigs, sheep, goats, and horses and is transmissible to humans. symptoms are consistent with Alexander's illness; however, other classic leptospirosis signs (biphasic bi·pha·sic
Having two distinct phases: a biphasic waveform; a biphasic response to a stimulus. fever, calf or thigh pain, jaundice, hemorrhage, pulmonic pulmonic /pul·mon·ic/ (pul-mon´ik) pulmonary.
Of or relating to the lungs; pulmonary.
pulmonary. involvement) were not reported. Acanthamoeba Acanthamoeba /Acan·tha·moe·ba/ (ah-kan?thah-me´bah) a genus of free-living ameboid protozoa (order Amoebida) found usually in fresh water or moist soil. Certain species, such as A. astronyxis, A. castellanii, A. culbertsoni, A. spp. (pathogenic free-living amoebae) and Naegleria spp. cause meningoencephalitis meningoencephalitis /me·nin·go·en·ceph·a·li·tis/ (me-ning?go-en-sef?ah-li´tis) inflammation of the brain and meninges.
toxoplasmic meningoencephalitis , which is acquired during bathing, an activity in which Alexander reportedly participated with compulsion. Acanthamoebae are cosmopolitan but prefer compromised hosts. Moreover, death from naegleriasis usually occurs within a week of onset, and encephalitis caused by acanthamoebae causes death only after a prolonged period of symptoms.
When Alexander's clinical symptoms were listed on GIDEON (Global Infectious Diseases and EpidemiOlogy Network (13), influenza ranked highest (41.2% probability) on the list of differential diagnoses. While influenza could have killed Alexander, reports did not mention others becoming ill with similar symptoms. Lymphocytic choriomeningitis, an influenzalike illness followed by meningoencephalitis, is rare. Poliomyelitis poliomyelitis (pō'lēōmī'əlī`tĭs), polio, or infantile paralysis, acute viral infection, mainly of children but also affecting older persons. can occur as an isolated case or as an epidemic; its characteristics include fever, vomiting, severe myalgia, and prostration, as well as the early complication of flaccid paralysis, which has been postulated as another late sign in Alexander's illness (1). This interpretation narrows the differential diagnosis to include poliomyelitis (see above), Guillain-Barre syndrome, and the encephalitides. (A list of the many other infectious diseases others have considered as well as additional, less likely candidates is available from the authors.)
West Nile Fever West Nile fever West Nile meningoencephalitis Infectious disease An acute, mosquito-borne flaviviral infection endemic–rarely, epidemic–in the Near East, Africa, former Soviet Union, India Clinical After a 3-6 day incubation, children present with a and Encephalitis
West Nile fever was not considered by previous authors as cause of Alexander's death, possibly because it has only recently emerged globally. West Nile virus (family Flaviviridae, genus Flavivirus), first isolated from a febrile patient in Uganda in 1937 (17), is one of many viruses causing encephalitis. Infection is marked by fever, encephalitis, or meningoencephalitis. Until the early 1990s, the virus was largely confined to Africa, Europe, and Asia. In 1941, an outbreak occurred in Tel Aviv, with no deaths reported. Over the next 60 years, seven outbreaks occurred in Israel and its environs (18). In 1957, during an outbreak in an army camp, a single case of encephalitis was recognized in a group of 300 soldiers (19). By 2000, a countrywide outbreak occurred, with a case-fatality rate of 8.4% (20). In 1999, West Nile virus was introduced to the United States, and 4,156 laboratory-confirmed human cases of infection (earliest onset of illness, June 10) occurred in 2002 (21). Median age in fatal cases was 72 years, although neurologic disease occurred in persons of all ages. Also recognized in both fatal and nonfatal cases was flaccid paralysis in patients with encephalitis.
West Nile virus infections in vertebrates may have been occurring in the Middle East for centuries. Now the virus has spread to new areas of the world and to new populations and causes infection characterized by new signs and symptoms. In the 2000 epidemic in Israel, encephalitis occurred in nearly 59% of 417 human cases. Of 233 hospitalized patients (case-fatality rate 14%), >98% had fever, 46% cognitive changes, and 17% abdominal pain or myalgias. Nearly 18% became comatose co·ma·tose
1. Of, relating to, or affected with coma.
2. Marked by lethargy; torpid.
comatose (kō´m (22). Acute flaccid paralysis was noted, as in the United States in 1999 and later (23).
When West Nile virus-infected Culex Culex /Cu·lex/ (ku´leks) a genus of mosquitoes found throughout the world, many species of which are vectors of disease-producing organisms.
n. spp. mosquitoes take a blood meal from a susceptible vertebrate, the virus may be incidentally transmitted. Birds serve as amplifying hosts, the degree of amplification depending on avian species, environmental conditions, and other factors. Birds with viremia viremia /vi·re·mia/ (vi-re´me-ah) the presence of viruses in the blood.
The presence of viruses in the bloodstream. provide mosquitoes blood meals; these mosquitoes subsequently serve to bridge West Nile virus infection to humans. Responses to recent epizootics and epidemics have improved our understanding of the disease. New, competent mosquito vectors are recognized, new human and mammalian symptoms are identified, and new bird species are determined as poor, intermediate, or excellent amplifiers of the virus.
Ludwig et al. examined 437 birds at the Bronx Zoo and Wildlife Conservation Park during the 1999 West Nile virus epizootic ep·i·zo·ot·ic
Affecting a large number of animals at the same time within a particular region or geographic area. Used of a disease.
ep and epidemic in New York City New York City: see New York, city.
New York City
City (pop., 2000: 8,008,278), southeastern New York, at the mouth of the Hudson River. The largest city in the U.S. (24), where virus activity was first recognized in wild and captive birds in the United States. Avian deaths were observed weeks before the first human West Nile virus encephalitis cases. Even though 42% of birds tested were New World birds, 14 (82%) of 17 deaths were in New World birds and 3 (5%) of 57 were in Old World birds, which suggests that birds in the latter group might have had innate immunity by virtue of their ancestral, coevolutionary history with the virus. Diseased birds manifested various symptoms, including abnormal head and neck posture, ataxia ataxia (ətăk`sēə), lack of coordination of the voluntary muscles resulting in irregular movements of the body. Ataxia can be brought on by an injury, infection, or degenerative disease of the central nervous system, e.g. , tremors, circling, disorientation, and impaired vision. Most birds with symptoms died.
In Iraq, several mosquito species, including Culex tritaeniorhynchus, Cx. theileri, and Aedes caspius (25) have been implicated in West Nile virus transmission. Although mosquitoes in Iraq have not been completely catalogued, it is likely that, as in the United States, other mosquitoes there also serve as vectors of West Nile virus. Mosquitoes are found throughout Iraq, from March to December, and have various larval larval
1. pertaining to larvae.
see cutaneous and visceral larva migrans. habitats. Annual spring flooding of the Tigris and Euphrates Tigris and Euphrates is a German strategy board game designed by Reiner Knizia and first published in 1997 by Hans im Glück in German (as Euphrat und Tigris). rivers provides ideal breeding grounds for Culex spp. Mosquito species that may have occurred in Babylon are unknown; however, breeding habits must be ancient, and mosquitoes are well known for their proclivity pro·cliv·i·ty
n. pl. pro·cliv·i·ties
A natural propensity or inclination; predisposition. See Synonyms at predilection.
[Latin pr to breed in swamps.
Still, the possibility that West Nile virus killed Alexander is mitigated by the fact that he fell ill in May. Although the virus may have occurred there at that time, most recent human cases in Israel occurred in July to September, with only a few cases occurring in June. In temperate areas, West Nile virus infection in humans is seasonal. Amplification occurs in mosquitoes and birds several months before the virus spills over into dead-end hosts. Experimentally infected indigenous mosquitoes showed an intrinsic incubation period of 7 to 14 days at 28[degrees]C (26). Others have shown that when Cx. pipiens mosquitoes were allowed to feed on viremic chicks infected with West Nile virus and incubated at 30[degrees]C virus could be detected 4 days later (27). This suggests that maximum virus amplification may not be reached until mid-summer. Iraq's mean high spring temperature is 29[degrees]C (28), somewhat higher than Tel Aviv's (24[degrees]C).
Israel has had West Nile virus activity and human cases during the last 3 years, with most human cases not detected until August. Israel is at the same latitude as Iraq and has similar climate. If Iraq also had slightly higher temperatures 2,000 years ago (we will never know this with certainty), onset of disease in humans and birds, including inexplicable avian die-offs, could have occurred earlier in the summer. We reread Plutarch and saw the following passage about Alexander's entrance into Babylon: "... when he arrived before the walls of the city he saw a large number of ravens flying about and pecking one another, and some of them fell dead in front of him." (29)
Bird observers (dagil issuri) were common in Asia Minor at the time. These diviners considered birds as oracles. Greek Kulturkreis and Babylonian Alalakh tablets mention auguries based on the behavior of birds, particularly fighting birds, to predict the future (30). Plutarch presumably pre·sum·a·ble
That can be presumed or taken for granted; reasonable as a supposition: presumable causes of the disaster. thought it sufficiently noteworthy to record angry or disoriented dis·o·ri·ent
tr.v. dis·o·ri·ent·ed, dis·o·ri·ent·ing, dis·o·ri·ents
To cause (a person, for example) to experience disorientation.
Adj. 1. ravens, although it is impossible to determine whether this event was added later as a necessary metaphoric foreboding of Alexander's death.
Current geographic distribution of corvids indicates that these likely were ravens (Corvus corax) and not crows (Corvus corone sardonius or other crow species). No ravens were at the Bronx Zoo in 1999 (T. MacNamara, Wildlife Conservation Society, and pers. comm., 2003). However, in the United States today, New World crows (American crow, C. brachyrhynchos and fish crow, C. ossifragus) are among the birds most susceptible to fatal West Nile virus infections. One wonders if an influx of migratory birds might have served as reservoirs of West Nile virus and directly or indirectly (through mosquitoes) infected ravens in Babylon, causing a massive die-off.
Pathogenicity of West Nile virus for corvids was established 50 years ago. Work et al., assigned by the Rockefeller Foundation to study arbovirnses in Egypt, isolated 23 West Nile virus strains from blood samples of febrile children in the Sindbis area and found that the virus caused illness in more children and young adults than in older adults. In addition, and particularly germane to our hypothesis, they isolated West Nile virus from a hooded crow (Corvus corone sardonius) for the first time, demonstrating experimental infection of birds with viremia as high as [10.sup.9], and death rates of 100% (31,32). During winter, 80% of these crows were seropositive seropositive /se·ro·pos·i·tive/ (-poz´i-tiv) showing positive results on serological examination; showing a high level of antibody.
adj. , and the investigators assumed that during transmission season, crow death rates were high. The experimental studies showed that mosquitoes could be infected by feeding on hooded crows with viremia levels as low as [10.sup.3.5] and could subsequently serve as West Nile virus vectors to humans of any age. This early epidemiologic work provided an early clue in New York City in 1999, when both exotic and domestic birds signaled the introduction of West Nile virus disease to the New World (33). Before 1998, the virus was not recognized as an important cause of death in wild birds; therefore, it was surprising to find that the Israeli 1998 strain was the same as that which infected birds at the Bronx Zoo. Ravens dropping dead from the skies likely were also a surprise to Alexander.
Alexander the Great died in late spring in the semi-tropical, urban area of present-day Baghdad. Explanations for his death have included poisoning, enteric and parasitic diseases, influenza, and poliomyelitis. Our diagnosis, as well as previous alternative diagnoses, may be subject to author bias, errors in translation, and a paucity of clinical information. We assumed that he died in late spring in Babylon after a 2-week illness that included fever and signs suggestive of encephalitis. We presumed that diseases now endemic to Iraq were also present in ancient Mesopotamia. Recent scholarly thought has been ingenious and rigorous, given the sparseness of available information. Nonetheless, earlier diagnoses did not include West Nile virus encephalitis. Previous considerations omitted an event that was carefully recorded by Plutarch and which, before 1999, might have been considered irrelevant: the erratic behavior and observable deaths of numerous ravens outside the walls of Babylon. This observation might now be construed as an important clue. If this observation is included as part of the description of Alexander's illness, West Nile virus encephalitis complicated by flaccid paralysis becomes an alternative diagnosis. It is possible that, in the 3rd century BC, disease caused by West Nile virus arrived in Mesopotamia for the first time in recorded history, killing indigenous birds and an occasional human and causing only incidental febrile illnesses in many others. Over subsequent centuries the virus may have devolved, becoming less pathogenic for indigenous birds, while retaining its potential as a dangerous human pathogen. This is speculative, but in 1999, a "natural experiment" did occur when an Old World epizootic strain was introduced into the United States. What has been observed in the ongoing North American epizootic and epidemic might be similar to what happened in Babylon many years ago. We now know that unexplained bird die-offs can presage human cases of disease caused by West Nile virus. In 323 BC, a similar event might have been considered an omen of Alexander the Great's death. In this instance, the oracles would have been correct.
Table. Medical history and physical examination of Alexander the Great Patient characteristics Medical history Clinical symptoms Male Ten years before Escalating fever death, traveled widely associated with chills (Mediterranean, North Africa, and Middle East) Born in Macedonia Unexplained fever Excessive thirst, 5 years previously diaphoresis 32 years of age Penetrating right Acute abdominal pain chest wound one year before final illness Soldier Onset of final illness Single episode of back May 29, 323 BC pain at onset of fever Heavy drinking Death June 10, 323 BC Increased weakness leading to prostration with intermittent periods of energy Frequent bathing Delirium Married to many wives Aphonia One son Terminal flaccid paralysis
We thank many friends and colleagues, including Grayson B. Miller, David N. Gaines, John T. Cathey, and Gregory D. Ebel for their contributions; Robert Arnott for providing pertinent sections of Plutarch; and anonymous reviewers for their comments and suggestions, which greatly improved the final product.
(1.) Oldach DW, Richard RE, Borza EN, Benitz RM. A mysterious death. N Engl J Med 1998;338:1764-69.
(2.) Borza RN. Malaria in Alexander's army. Ancient History Bulletin 1987;1:36-8.
(3.) Moulopoulos SD. A mysterious death. N Engl J Med 1998;339:1248.
(4.) Behrman AJ, Wilson RB. A mysterious death. N Engl J Med 1998;339:1249.
(5.) Schnorf H. A mysterious death. N Engl J Med 1998;339:1249.
(6.) Sbarounis CN. Did Alexander the Great die of acute pancreatitis? J Clin Gastroenterol 1999;28:279-80.
(7.) Scott-Kilvert I (transl). Plutarch--the age of Alexander. London: Penguin Classics; 1973. p. 333.
(8.) Oppenheim AL. Ancient Mesopotamia: portrait of a dead civilization.. In: Reiner E, editor. Introduction: Assyriology--why and how. Revised edition. London: University of Chicago Press The University of Chicago Press is the largest university press in the United States. It is operated by the University of Chicago and publishes a wide variety of academic titles, including The Chicago Manual of Style, dozens of academic journals, including ; 1977. p. 38-44.
(9.) Oppenheim AL. Ancient Mesopotamia: portrait of a dead civilization. In: Reiner E, editor. Introduction: Assyriology--why and how. Revised edition. London: University of Chicago Press; 1977. p. 45-8.
(10.) Bruce-Chwatt LJ. Paleogenesis and paleo-epidemiology of primate malaria. Bull World Health Organ 1965;32:363-87.
(11.) Borza EN. Some observations on malaria and the ecology of central Macedonia in antiquity. American Journal of Ancient History 1979;4:102-24.
(12.) Ossi GT. Report on malaria eradication in Iraq presented at the twenty first meeting of the Inter-country Malaria Eradication Coordination Board between Iraq, Jordan, Lebanon, Syria and Turkey (eleventh plenary meeting), Amman, Nov 21-23, 1972. Bull Endem Dis (Baghdad) 1974;15:7-33.
(13.) Gideon Informatics, San Francisco, CA.
(14.) Cluff LE, Johnson JE. Clinical concepts of infectious diseases. Baltimore (MD): Williams and Wilkins; 1972. p. 112-21.
(15.) Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ. Medical progress: typhoid fever. N Engl J Med 2002;22:1770-82.
(16.) Scrimgeour EM, Gajdusek DC. involvement of the central nervous system in Schistosoma mansoni and S. haematobium infection. Brain 1985; 108:1023-38.
(17.) Smithburn JS, Hughes TP, Burke AW, Paul JH. A neurotropic neurotropic
pertaining to or emanating from neurotrophy, e.g. neurotropic osteopathy. virus isolated from the blood of a native of Uganda. Am J Trop Med Hyg 1940;20:471-92.
(18.) Leffkowitz M. On the frequent appearance of an unclear infectious disease. Harefuah 1942;22:3-4.
(19.) Goldblum N, Sterk VV, Paderski B. West Nile fever. The clinical features of the disease and the isolation of West Nile virus from the blood of nine human cases. Am J Hyg 1954;59:89-103.
(20.) Weinberger M, Pitlik SD, Gandacu D, Lang R, Nassar F, Ben David D, et al. West Nile fever outbreak, Israel, 2000: epidemiologic aspects. Emerg Infect Dis 2001;7:686-91.
(21.) Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center. . Provisional surveillance summary of the West Nile virus epidemic--United States, January-November, 2002. MMWR MMWR Morbidity & Mortality Weekly Report Epidemiology A news bulletin published by the CDC, which provides epidemiologic data–eg, statistics on the incidence of AIDS, rabies, rubella, STDs and other communicable diseases, causes of mortality–eg, Morb Mortal Wkly Rep 2002;51:1129-33.
(22.) Chowers MY, Lang R, Nassar F, Ben-David D, Giladi M, Rubinstein E, et al. Clinical characteristics of the West Nile fever outbreak, Israel, 2000. Emerg Infect Dis 2001;7:675-8.
(23.) Sejvar JJ, Leis AA, Stockic DS, Van Gerpen JA, Martin AA, Webb R, et al. Acute flaccid paralysis and West Nile virus infection. Emerg Infect Dis 2003;9:788-93.
(24.) Ludwig GV, Calle PP, Mangiafico JA, Raphael BL, Danner DK, Hile JA, et al. An outbreak of West Nile virus in a New York City captive wildlife population. Am J Trop Med Hyg 2002;67:67-75.
(25.) Abul-Hab J. Larvae Larvae, in Roman religion
Larvae: see lemures. of culicine culicine /cu·li·cine/ (ku´li-sin) (ku´li-sin)
1. a member of the genus Culex or related genera.
2. mosquitoes in North Iraq. Bull Entomol Res 1967;57:279-84.
(26.) Goddard LB, Roth AE, Reisen WK, Scott TW. Vector competence of California mosquitoes for West Nile virus. Emerg Infect Dis 2002;8:1385-91.
(27.) Dohm DJ, O'Guinn ML, Turell MJ. Effect of environmental temperature on the ability of Culex pipiens (Diptera: Culicidae) to transmit West Nile virus. J Med Entomol 2002;39:221-5.
(28.) USA TODAY Guide to month-to month climates. Available from: URL: http://www.usatoday.com/weather/forecast/international /middle-east-temps-index.him
(29.) The age of Alexander: nine Greek lives. Plutarchus, I. Scott-Kilvert, designer, Plutarch, G.T. Griffith, designer. New York: Viking Press; 1995. p. 330.
(30.) Oppenheim AL. Ancient Mesopotamia: portrait of a dead civilization. Reiner E, editor. The arts of the diviner. Revised edition. London: University of Chicago Press; 1977. p. 206-27.
(31.) Work TH, Hurlbut HS, Taylor RM. Isolation of West Nile virus thorn hooded crows and rock pigeons in the Nile Delta. Proc Soc Exp Biol Med 1953;84:719-2.
(32.) Work TH, Hurlbut HS, Taylor RM. Indigenous wild birds in the Nile Delta as potential West Nile circulating reservoirs. Am J Trop Med Hyg 1958;4:872-88.
(33.) Calisher CH. West Nile virus, humans and birds-Egypt 1950s. ProMED. October 7, 1999. Accessed at: http://www.promedmail.org, archive number: 19991007.1792 Available from: URL: http://www.healthnet.org/programs/promed.html
John S. Marr * and Charles H. Calisher ([dagger])
* Virginia Department of Health, Richmond, Virginia, USA; and ([dagger]) Colorado State University Colorado State University, at Fort Collins; land-grant with state and federal support; chartered 1870, opened 1879 as an agricultural college, assumed present name in 1957. There is a veterinary teaching hospital, an agricultural campus, and a research campus. , Fort Collins, Colorado The City of Fort Collins, a home rule municipality situated on the Cache la Poudre River along the Colorado Front Range, is the county seat and most populous city in Larimer County, Colorado. , USA
Dr. Marr is director of the Office of Epidemiology in the Virginia Department of Health. His research interests include medical history. He has written articles on possible causes of the 10 plagues of Egypt plagues of Egypt, in the Bible, the plagues and other troubles brought on Egypt by God through the hands of Moses, because Pharaoh would not let the people of Israel go out of Egypt. , the Mexican huey cocolitzlti epidemic of 1596, and the mysterious epidemic preceding the death of the last Incan emperor, Hayna Capac.
Dr. Calisher is professor of microbiology at the Arthropod-borne and Infectious Diseases Laboratory, Colorado State University. His research interests include disease epidemiology, virus evolution, everything about arborviruses, and the epidemiology of rodent-borne viruses.
Address for correspondence; Charles H. Calisher, Department of Microbiology, immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA; fax: 970-491-8323; email: email@example.com