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Tracking Epidemics by Sequencing: West Nile Virus Spread to the Western Hemisphere

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It took a full century to determine the cause of the Philadelphia epidemic, but technological advances have greatly accelerated our ability to understand the natural histories of some modern-day outbreaks. While the sudden appearance of West Nile virus in the Western Hemisphere in 1999 fortunately did not result in massive loss of life, this epidemic is notable for the role that viral genome sequencing played in defining its origin in the Middle East.

Prior to the summer of 1999, West Nile virus infections were restricted to Africa and the Mediterranean basin. Upon introduction to the United States, West Nile virus spread with remarkable speed; in 3 years, the incidence of infection expanded from eight cases in Queens, New York City, to virtually all of the United States and much of Canada, where it is now endemic (Fig. 1.5).

The eight cases first identified in Queens held the key for major epidemiologic efforts to identify the source of this new infection. All victims had been healthy, and many had engaged in outdoor activities soon before showing signs of sickness. At about the same time, a high proportion of dead birds was found in and around New York City, including exotic birds within the Bronx Zoo, prompting epidemiologists to consider the possibility that the same virus had infected both hosts. PCR and genome sequencing were used to confirm that West Nile virus was the cause of both the bird deaths and the human illnesses. Subsequently, it was discovered that the virus was rapidly disseminated among avian and mammalian populations, and that mosquitos (again) were the vector that transmitted the virus to mammals, including humans. Fortunately, the consequences of infection are far less severe than for yellow fever: in 2009, 720 cases were diagnosed, but epidemiologists believe the true number to be >54,000; the discrepancy is likely due to the mild symptoms that the infection causes in most healthy individuals. Most deaths occur in the immunocompromised and the elderly.

How West Nile virus arrived in North America will never be known conclusively, but many think that the culprit was an infected mosquito (the natural reservoir) that arrived as a stowaway on a flight from Israel to New York. This scenario was deduced from the remarkable identity between genome sequences of the virus isolated in New York and an isolate obtained from a dead goose in Israel. It is sobering to contemplate that a virus that can now be found in virtually all states and provinces of North America may have begun with a single infected human, or perhaps a mosquito trapped in a suitcase or purse, an invisible passenger on a trans-Atlantic flight.

Figure 1.5 Spread of West Nile virus in the United States. The maps show the spread of West Nile virus from Queens, New York, throughout the country in four years (1999 to 2003). States highlighted in red indicate confirmed human infections (with numbers of confirmed cases). Data from Centers for Disease Control and Prevention.

Principles of Virology, Volume 2

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