physician, that black people were immune to infection.
Figure 1.4 Deaths caused by the yellow fever epidemic in Philadelphia, 1793. This map records the locations of deaths due to yellow fever, with red and orange streets marking those with highest mortality. Yellow fever was most deadly near the northern wharves, where poorer people lived, and where Hell Town was located (just blocks away from Independence Hall and the current home of the Liberty Bell). These areas furnished breeding places for Aedes aegypti, the species of mosquito that transmits the disease. Adapted from Paul Sivitz and Billy G. Smith, with permission.
Because Philadelphia was a major port city, it is likely that the agent, which we now know was the yellow fever virus, was transported by infected individuals on cargo ships, and that standing water in the city provided a hospitable breeding ground for local mosquitos and rapid expansion of the disease along the wharves. Credit goes to Rush, who noticed identical symptoms in many victims and who recommended that individuals either leave the city or quarantine themselves, practices that helped to curtail the epidemic. Rush’s belief that the scourge arose from a pile of rotting coffee beans left on a dock, and his treatment regimen of purging and bloodletting, are less worthy of praise.
The city of Philadelphia was transformed after the epidemic. The outbreak, believed by many to be due to contaminated water (which was, in part, true), spurred the local government to establish a municipal water system, the first major city in the world to do so. Infirmaries to tend to the sick and isolate them from the healthy were developed. Finally, the epidemic promoted a city-supported effort to keep streets free of trash, leading to the development of a sanitation program that would be a model for similar programs elsewhere. Although an effective vaccine now exists, yellow fever still kills 30,000 people every year, about 90% of them in Africa.
Tracking Epidemics by Sequencing: West Nile Virus Spread to the Western Hemisphere
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.
Zoonotic Infections and Epidemics Caused by “New” Viruses
Viral epidemics often appear unexpectedly, raising questions about their origins. Some viral epidemics begin with a zoonotic infection, discussed in detail in Chapters 10 and 11. Zoonoses are infections transmitted from other animals to humans. Many viruses that can infect multiple species establish a reservoir in a host in which the virus causes no disease or only nonlethal disease. When a new host is in proximity to an infected reservoir animal, a species jump may occur. While zoonotic transmission may cause disease in the new host, trans-species infection is usually a dead end for the virus. Consequently, zoonotic infections rarely spread from human to human, as is the case for rabies virus, West Nile virus, and avian influenza. Although relatively rare, zoonotic infections are a concern to epidemiologists, because the human host will not have immunity, and the disease that occurs in the new host may be different (often more severe) than that in the reservoir host. The trans-species spread of a human immunodeficiency virus-like ancestor from monkeys to humans is a prime example of zoonotic transmission (Chapter 12), as is the likely zoonosis of SARS-CoV-2 from bats to humans.
Over the past few decades, new, or at least newly discovered, zoonotic and vector-borne viral diseases have emerged, many originating in Southeast Asia and the Western Pacific. These include viruses with which most people have little familiarity, including Japanese encephalitis, Ross River, chikungunya, Nipah, and Hendra viruses. While the first three of these are transmitted by mosquitos, the natural reservoir of both Nipah and Hendra viruses is fruit bats, prevalent in Southeast Asia (Fig. 1.6). As increased contact between animals is the predominant risk factor for trans-species infection, one can envision how changes in the environment or ecosystems of some animals may increase the risk for contact among different species. These changes are of particular concern when humans invade wilderness areas. For example, it is thought that Nipah virus, a paramyxovirus, underwent species-to-species transmission in 1999 in Malaysia, when pig farming began in the habitat occupied by infected fruit bats. The infection spread from bats to pigs and ultimately to the farmers themselves. Hendra and Nipah pose a significant human health threat: in a 2004 outbreak in Bangladesh, Nipah virus killed 60% of the people it infected, and additional out breaks have occurred in almost every year since. Symptoms of infection vary widely: some people experience a transient fever and cough, although complications can include life-threatening inflammation of the brain, respiratory failure, and, following recovery, seizures. Because infection by the virus depends on direct contact with fruit bats or infected hosts, the number of cases is typically low. Nevertheless, as the geographic range of the fruit bat is large, including
