Zoonoses

W. Ian Lipkin

Zoonoses, derived from the Greek words for animal, zoo, and the suffix modification indicating a state or condition, sis, are infectious diseases of humans that originate in animals. Infectious diseases that originate in humans and move into other animals are commonly described as reverse zoonoses. The majority of emerging viral diseases, up to 70%, represent zoonoses, with such prominent examples as human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), influenza, West Nile virus encephalitis, Nipah virus disease, Hendra virus disease, severe acute respiratory syndrome (SARS), Ebola virus disease, Marburg virus disease, hantavirus pulmonary syndrome (Sin Nombre virus), and rabies. Common examples of nonviral zoonoses include Lyme disease (Borrelia burgdorferi in North America, Borrelia afzelii and Borrelia garinii in Europe), cat-scratch disease (Bartonella henselae), new-variant Creutzfeldt-Jakob disease, salmonellosis, and toxoplasmosis. Although secondary microbial contamination of agricultural products can cause significant disease, the term zoonosis does not apply unless there is direct transmission to humans from an infected animal.

Many zoonotic diseases can be attributed to anthropogenic changes. Loss of wildlife habitat to development and consumption of bushmeat, necessitated by poverty or resulting from cultural preference, increases opportunities for cross-species jumps. Global warming may also increase the geographic range of phlebotomous arthropod vectors, such as mosquitoes and ticks, that serve as reservoirs and vectors for infectious agents. Because there are more than 50,000 vertebrate species, for example, if we were to assume an average of 20 endemic viruses per vertebrate species, the potential reservoir of vertebrate viruses could be estimated at 1 million. Although it is unlikely that most of them can be transmitted to humans and cause disease, it is sobering to consider the challenge of detecting and responding even to 1% of them—10,000 novel viruses.

One Health Initiative

The connection between human and animal microbiology was originally recognized by Virchow and Osler in the 19th century. Nonetheless, the relationship has only recently been emphasized through the One Health Initiative, which promotes coequal collaborations between practitioners and researchers in human and comparative medicine, as well as surveillance programs in wildlife, domestic animals, and humans. An important catalytic event for the Initiative was the West Nile virus outbreak in New York City in 1999, where two independent lines of research investigation converged—one focused on high mortality in native corvids (including crows) and exotic birds in the Bronx Zoo that ultimately led to the culture and identification of the virus by the U.S. Department of Agriculture, and another focused on human encephalitis cases. These were initially attributed to St. Louis encephalitis virus but found to be West Nile virus when brain material of victims underwent DNA sequence analysis by a team composed of investigators at the University of California and the New York State Department of Health.¹ Retrospective analysis indicated that the cause of the human outbreak would have been ascertained earlier if the veterinary and medical practitioners had collaborated in sharing data and samples. A series of national and international meetings culminated in the One Health Resolution signed by the presidents of the American Medical Association and American Veterinary Medical Association, with endorsement by the Centers for Disease Control, the U.S. Department of Agriculture, and the European Union.

Mechanisms of Transmission

The mechanisms by which zoonotic agents are transmitted to humans vary widely. Many are linked to food collection, processing, or consumption. The most dramatic examples are diseases associated with the slaughter and consumption of wild animals, also known as bushmeat, such as infections caused by Ebola, Marburg, and monkeypox viruses, as well as SARS, and tularemia. However, less exotic meats are associated with transmission of Salmonella, highly pathogenic Escherichia coli, and prion diseases (e.g., new-variant Creutzfeldt-Jakob disease).

Phlebotomous (blood-sucking) arthropods, such as mosquitoes, ticks, and flies, may also serve as vectors for transmission of viruses and bacteria from birds and mammals to humans. Prominent examples include West Nile virus, St. Louis encephalitis virus, tick-borne encephalitis virus, and Borrelia spp. (Lyme disease). Direct transmission can occur through exposure to infected urine or feces, as in leptospirosis, toxoplasmosis, lymphocytic choriomeningitis virus infection, hantavirus pulmonary syndrome, or through wound inoculation as in Bartonella (cat-scratch fever), or rabies—the oldest recorded example of zoonotic disease and the most common one transmitted directly from infected animals to human by bite.

Factors in the Emergence of Zoonotic Diseases

Travel and trade are increasingly global, carrying pathogens as well as passengers and products to new locations. John F. Kennedy airport, for example, one of two international airports in the greater New York metropolitan area, receives nonstop flights from more than 100 international destinations and serves annually more than 12 million international passengers.² Similar traffic data apply in other major metropolitan areas. Given that an infected individual, mosquito, or other cargo can cross the world in less than 24 hours, clinicians and public health practitioners must be prepared to encounter known and novel agents in virtually any context.

The advent of global agribusiness and urbanization are also important factors in zoonotic diseases. The international food trade has burgeoned by more than 200% since 1975.³^,⁴ A hundred years ago, most fresh food was produced and consumed within a radius of a few kilometers. It is now not unusual for individuals to consume plants and animals harvested thousands of kilometers away.⁵ Contamination of meat by prions, influenza viruses, Salmonella, and Rift Valley fever virus has been documented in international trade of livestock.⁶ The centralization of food production and processing, particularly of ground meat or raw fruits and vegetables, has resulted in outbreaks of infectious diseases that may be distributed over large geographic areas.

Illegal trafficking in wildlife as pets or food is difficult to monitor. However, annual sales estimates in the United States alone exceed $10 billion for pets and $15 billion for bushmeat.⁷ Analysis of bushmeat from bats, rodents, and primates confiscated in major ports has revealed evidence of foamy viruses, herpesviruses, and pathogenic bacteria.⁸ Imported pets have been linked to outbreaks of human infection with poxviruses and Salmonella, as well other pathogens.⁸

Attention has also increasingly focused on the role of land use dynamics in infectious disease emergence.⁹ Deforestation and the expansion of agriculture and the extractive industries, particularly in tropical regions with high wildlife biodiversity, has led directly or indirectly to the emergence of Nipah virus and filoviruses.¹⁰^,¹¹ The growth of suburbs in areas that were once only sparsely populated, particularly in the northeastern United States, has been associated with an increase in the incidence of Lyme disease.

Global warming is already extending the geographic range of mosquitoes and ticks that harbor and transmit Plasmodium and arboviruses, resulting in outbreaks of malaria, and dengue and yellow fever in new locations.¹² Recent examples in North America include the appearance of dengue fever in Florida in 2010¹³^,¹⁴ and a surge in cases of West Nile encephalitis in Texas in 2012.¹⁵ Mass migration (resulting from war, natural disaster, poverty, and desertification) can lead to increases in the population density, not only of humans, but also of disease vectors, such as rodents and ectoparasites that carry pathogenic viruses and bacteria. In concert, these factors, malnutrition, lack of access to or refusal of vaccines, and exposure to contaminated food and water have enabled the emergence and transmission of zoonoses and other infectious diseases.¹⁶^,¹⁷

Prediction and Early Detection of Emerging and Reemerging Zoonotic Diseases

Rapid recognition and response are critical to reducing the mortality, morbidity, and economic and social costs of zoonotic outbreaks. An important factor in early outbreak detection has been the advent of tools for Internet-based infectious disease surveillance. The first of these was ProMED-mail (Programme for Monitoring Emerging Infectious Diseases), created in 1994, which provides continuous, free email updates on new or evolving outbreaks and epidemics¹⁸ in people, domestic animals, and wildlife. Reports submitted by readers are curated by a panel of experts who post submissions with commentary in several languages to a listserve of subscribers in nearly 200 countries. Another program, the fee-based service, GPHIN (Global Public Health Intelligence Network)¹⁹ scans news services worldwide in several languages for information concerning outbreaks.

HealthMap²⁰ integrates reports from news media, ProMED-mail, and official documents into a user-friendly map that displays real-time updates of disease emergence. HealthMap also allows public submission observations via its website or cellular phone applications.

An ideal surveillance system for zoonotic disease is one that allows identification of potential health threats before they move into the human population. By considering factors implicated as drivers in the emergence of zoonotic diseases, such as human demographics, agricultural production, land-use change, travel and trade patterns, climate and wildlife distribution, risk algorithms can be developed and used to focus surveillance on sites, populations, professions, and species of domestic animals and wildlife where there is an increased probability of known or novel high-threat pathogen emergence.

Zoonotic Diseases

A chapter concerned with infectious agents that share one feature—the capacity to jump host species from domestic animals or wildlife into humans—could be organized by agent, mechanism of transmission, or clinical presentation. I have tried to do all three. The following sections provide an overview of a representative set of zoonotic diseases associated with bats, rodents, and other wildlife as well as domesticated animals. It is illustrative; others might highlight different choices. Nonetheless, it provides a framework for thinking about the range of zoonotic diseases and the factors that contribute to their emergence and control. Table 322-1 indicates routes of transmission and associated syndromes, respectively.

TABLE 322-1

Important and Representative Zoonotic Pathogens of Humans

VECTOR		AGENT FAMILY	AGENT	DISEASE
Arthropod	Mosquito	Bunyaviridae	La Crosse encephalitis virus, California encephalitis virus	Encephalitis
		Bunyaviridae	Rift Valley fever virus	Hemorrhagic fever
		Flaviviridae	Japanese encephalitis virus, St. Louis encephalitis virus, West Nile virus	Encephalitis
		Flaviviridae	Dengue virus, yellow fever virus, Zika virus	Hemorrhagic fever
		Togaviridae	Eastern equine encephalitis virus, western equine encephalitis virus, Venezuelan equine encephalitis virus, chikungunya virus, o’nyong-nyong fever virus	Encephalitis
	Tick	Bunyaviridae	Crimean-Congo hemorrhagic fever virus	Hemorrhagic fever
		Flaviviridae	Tick-borne encephalitis virus, Powassan encephalitis virus	Encephalitis
		Flaviviridae	Omsk hemorrhagic fever virus, Kyasanur forest virus, Langat virus	Hemorrhagic fever
		Spirochaetaceae	Borrelia	Lyme disease
	Flea	Enterobacteriaceae	Yersinia pestis	Hemorrhagic fever (plague)
Mammal	Rodent	Arenaviridae	Lassa fever virus, Guanarito virus, Junin virus, Machupo virus, Sabia virus, Lujo virus	Hemorrhagic fever
		Arenaviridae	Lymphocytic choriomeningitis virus	Meningitis, encephalitis
		Bunyaviridae	Dobrava-Belgrade virus, Hantaan virus, Puumala virus, Seoul virus	Hemorrhagic fever
		Bunyaviridae	Sin Nombre virus	Pulmonary syndrome
		Spirochaetaceae	Leptospira	Leptospirosis
	Rabbit	Francisellaceae	Francisella tularensis	Tularemia
	Bat	Filoviridae	Ebola virus, Bundibugyo virus, Sudan virus, Tai Forest virus, Marburg virus	Hemorrhagic fever
		Rhabdoviridae	Rabies virus, Chandipura virus	Encephalitis
		Paramyxoviridae	Hendra virus, Nipah virus	Pulmonary, encephalitis
		Coronaviridae	Severe acute respiratory syndrome coronavirus, Middle Eastern coronavirus	Pulmonary
	Cattle	Prions	Bovine spongiform encephalopathy prion	Neurodegeneration
	Cat	Bartonellaceae	Bartonella	Cat-scratch disease
	Cat	Sarcocystidae	Toxoplasma	Toxoplasmosis
Avian	Bird	Orthomyxovirus	Influenza virus	Constitutional illness