Animal Zoonotic Related Diseases

Mina Said; Ekta Tirthani; Emil Lesho

Animal Zoonotic Related Diseases

Author: Mina S. Said Author: Ekta Tirthani Editor: Emil Lesho Updated: 4/10/2023 2:54:54 PM

Introduction

Animals play a valuable role in our lives as food, livestock, hunting, travel, sports, zoo, fairs, research, pets, and guide-pets.[1][2] Zoonotic diseases encompass more than 200 diseases that are transmitted to humans from an animal origin, where humans are usually accidental hosts. They were first recognized by Rudolf Virchow and Osler in the 1800s. The word “zoonosis” consists of 2 parts; “Zoo” means an animal, and “nosis” means sickness.

Etiology

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Etiology

One important reason for the spread of zoonoses is anthropogenic changes in animal biodiversity, leading to the predominance of bats and rodents in the environment. Other important factors include the rapid increase in the human population, the intersection with animal habitats, deforestation practices, suburbs formation, bushmeat industry (worth $15 billion annually in the U.S.), effects of global warming, free travel and open trade, adoption of exotic pets, consumption of edible insects, genetic mutations, asymptomatic animal carriers especially poultry, and the spill-over effect, i.e., the transmission of a pathogen from one host species to another new one, crossing the biological barriers, due to the high infection prevalence in the former.[3][4][5][6][7][8][9][10][11]

Children below 5 years of age, the elderly above 65, immunocompromised persons, and pregnant women are all vulnerable populations at the highest risk for zoonotic diseases.[12][13] Those with specific occupations like veterinarians, butchers, hunters, etc., are by nature at a higher risk of acquiring zoonotic diseases. It is interesting to note that new and young pets carry a higher risk of transmitting zoonotic disease than old adult ones.[14]

More than 2200 species of rodents exist, making them the most abundant zoonotic hosts. Almost 1100 species of bats act as a reservoir for many serious zoonoses like Nipah, Hendra, Menangle, Corona, Ebola, and Marburg viruses.[15][16] Carnivores make up the greatest fraction of carrier zoonotic hosts, especially for bacteria and viruses.[17]

Classification of zoonotic diseases can be done according to pathogen type, transmission, animal source, affected human organ system, or ecosystem.

Table 1. List of the most common pathogens causing zoonoses[18][19][20][21][22][23][24][25][26]

Bacteria (42%)	Viruses (22%)	Fungi (5%)	Parasites (29%)	Prion (2%)
Listeria	B-virus	Dermatophytes	Fasciolae	vCJD
Clostridium botulinum	Cowpox	Sporothrix	Echinococcus granulosus
Bacillus anthracis	Monkeypox	Aspergillus	Dipylidium caninum
Rhodococcus equi	Orf	Cryptococcus	Toxocara canis / cati
Mycobacterium bovis	SARS/MERS/SARS-CoV-2	Histoplasma	Ancylostoma caninum/ braziliense
Mycobacterium marinum	Influenza A*	Blastomyces	Trichinella spiralis
Mycobacterium leprae	Nipah	Coccidioides	Capillariae
Erysepilothrix	Hendra		Dirofilaria immitis
E.coli O157:H7	Rabies		Giardia lamblia
Salmonella	Dengue		Leishmania
Yersinia pestis	Yellow Fever		Trypanosoma cruzi
Yersinia enterocolitica	WNV		Trypanosoma brucei
Vibrio parahaemolyticus	St Louis		Babesia microti
Vibrio vulnificus	Tick-borne encephalitis		Toxoplasma gondii
Campylobacter jejuni	Powassan		Cryptosporidium parvum
Brucella	Zika		Pentastomida
Bordetella bronchiseptica	Chikungunya		Sarcoptes scabiei
Pasteurella multocida	EEE, WEE, VEE		Cheyletiella
Bartonella henselae	Rift Valley Fever
Francisella tularensis	CCHF
Streptobacillus moniliformis, Spirillum minus	Hanta
Capnocytophaga	Lassa
Burkholderia mallei	LCMV
Borrelia burgdorferi	Ebola
Leptospira	Marburg
Coxiella burnetii	HIV
Rickettsia prowazekii	Noro
Rickettsia rickettsii	Hepatitis E
Ehrlichia
Anaplasma
Chlamydia psittaci

(*: Avian: H5N1, H7N9, H9N2. Swine: H1N1, H1N2, H3N2, H7N2. Spanish Flu is H1N1 from bats)

(SARS: Severe Acute Respiratory Syndrome, MERS: Middle East respiratory syndrome, WNV: West Nile virus, EEE: Eastern Equine encephalitis, WEE: Western Equine encephalitis, VEE: Venezuela Equine encephalitis, LCMV: Lymphocytic Chorio-Meningitis virus, HIV: human immunodeficiency virus, vCJD: Variant Creutzfeldt-Jakob disease)

Epidemiology

In the U.S., 68% of households have pets. There are 45 million dog owners and 77 million cat owners.

Zoonoses constitute 61% of infectious diseases, 75% of emerging infectious diseases, and 80% potential bioterrorism pathogens.[27][28]

Per the last report by the Centers for Disease Control and Prevention (CDC), Department of the Interior, and U.S. Department of Agriculture, the eight most important zoonoses in the U.S., based on their pandemic potential, severity, economic impact, local potential, and bioterrorism risk, are influenza, salmonella, West Nile virus, plague, coronaviruses, rabies, brucella, and Lyme disease.

Important statistics about each zoonotic disease:

Influenza has caused several outbreaks in different countries in the last few decades, especially H1N1 swine flu in 2009 & H5N1 avian flu since 2003.[29]

Salmonella is the most common cause of zoonotic outbreaks in the USA in the last decade, per the CDC.

WNV is the most common mosquito-borne zoonosis in the USA. It is estimated that there are 70 unreported cases for each reported case of the disease.

Plague is endemic in western states - California, Arizona, Colorado, and New Mexico. The incidence rate is 1-17 cases/year.

Coronaviruses: SARS caused >8000 infections in 2003 in Southeast Asia. MERS has infected >2000 people since 2012.[30] SARS-CoV-2 has infected around 120 million people since 2019.

Rabies: There are around 40,000 exposures reported per year in the U.S., which costs the health system $225 million to $500 million for post-exposure prophylaxis alone. There were only nine established rabies in humans from 2008 to 2019 due to stray animal control, rabies vaccine, and oral rabies vaccine baiting programs.[31]

Brucella: Almost all cases in the U.S. are related to immigrants, imported animals, or unpasteurized milk. There are around 100 reported cases annually.

Lyme disease is the most common vector-borne disease in the U.S., with 20,000 cases/year; 95% of the cases belong to 12 states in the Northeast & Mid-Atlantic U.S.

Leptospira is the most common zoonotic disease worldwide. Most cases in the U.S. are seen in Hawaii in farmers, veterinarians, and surfers.

RMSF is the most common rickettsial disease in the U.S., with 600 to 1200 cases/year, mainly in the Southeastern and South Central U.S., especially North Carolina and Arkansas.

Hanta: The Sin Nombre & Seoul strains are found in the U.S., mainly Utah, Colorado, Arizona, and New Mexico.

Babesiosis: B.microti is seen in the Northeastern states, and B.divergens is seen in Europe.

Toxoplasma: 30% of the US population are asymptomatic carriers.[32]

Giardia is one of the most common gastrointestinal parasites in the U.S.

Pathophysiology

Modes of Transmission:

Direct Contact (touch, scratch, licking)
Indirect Contact (fomites, soil, water)
Animal Bites cause >4.7 million cases, 0.3 million ED visits, 10,000 hospitalizations, and 20 deaths in the U.S. per year, most commonly from dogs (80-90%) and cats (5% to 15%).[33][34]
Vector-borne (ticks, mosquitoes, lice, fleas, mites)
Inhalation (droplet, aerosols from products of animal conception and feces)
Ingestion (vegetables, meats, eggs, milk, water)

According to ND Wolfe’s paper in Nature 2007, pathogens go through five stages to transmit infections from animals to man:[35]

Stage 1: pathogens existing among animals only
Stage 2: limited infections from animals to some humans
Stage 3: limited outbreak level
Stage 4: long outbreak level where human to human transmission can occur
Stage 5: the pathogen can become an exclusively human pathogen with free transmission potential

Table 2. Mode of transmission and animal source of important zoonotic diseases[36][37][38][39][40][41][42][43]

Organism	Mode of Transmission	Animal Source
Influenza	Droplet, Aerosol, Contact	Poultry, Swine, Bats, Dogs, Cats, Horses.
Salmonellae	Ingestion, Contact	Reptiles, Hedgehogs, Poultry, Cats, Pigs, Horses.
WNV	Culex Mosquito Bites	Birds, Horses.
Yersinia pestis	Flea bites, Scratches, Droplet	Rodents, Cats, Dogs.
Coronaviruses	Droplet, Aerosol, Contact	Bats, Camels, Rodents.
Rabies	Animal Bites, Inhalation (rare)	Bats, Raccoons, Skunks, Foxes, Dogs.
Brucella	Ingestion, Inhalation, Contact	Bison, Elk, Cattle, Sheep, Dogs, Horses.
Borrelia burgdorferi	Tick Bites	White-footed mice, Chipmunks, Squirrels, Rats.*
Campylobacter	Ingestion, Contact	Poultry, Swine, Cattle, Sheep, Cats, Dogs.
Bartonella henselae	Scratches, Animal bites, Flea Bites	Cats.
Coxiella	Inhalation, Ingestion of Milk	Cattle, Goats, Sheep, Cats, Dogs.
Pasteurella	Bites, Scratches, Licking	Cats, Dogs, Horses, Pigs.
Capnocytophaga	Bites	Dogs, Cats.
B. bronchiseptica	Inhalation, Contact	Dogs, Cats, Rodents, Rabbits, Swine.
Francisella tularensis	Tick Bites, Animal Bites, Scratches, Contact, Inhalation, Ingestion	Rabbits, Rodents.
Rhodococcus equi	Contact with soil manure, Inhalation, Ingestion	Horses.
Erysipelothrix	Contact	Fish, Swine, Cattle, Sheep, Cats, Birds.
Burkholderia	Contact, Inhalation	Horses, Donkeys, Dogs, Cats.
Chlamydia psittaci	Inhalation of dry feces	Birds, especially parrots (psittacines).
Ehrlichia	Tick Bites	White-footed mice, Deer.
Leptospira	Contact, Ingestion (rare)	Rats, Dogs, Cats, Cattle.
Dermatophytes	Contact	Rodents, Cats, Dogs.
Sporothrix	Contact	Cats.
Cryptococcus	Inhalation	Bird Droppings.
Histoplasma	Inhalation	Bird Droppings, Bat Guano.
Cowpox	Contact	Cats, Cattle.
Monkeypox	Contact, Animal Bites	Prairie Dogs.
B-virus	Bites, Scratches, Contact	Macaque Monkeys.
Orf	Direct or Indirect Contact	Cattle, Sheep, Goats, Camels.
Strep Moniliformis, and Spirillum Minus	Animal Bites, Scratches, Ingestion	Rats, Mice, Squirrels.
Hanta	Contact, Inhalation	Mice.
LCMV	Contact, Inhalation	Mice, Dogs.
Ebola	Contact	Bats, Primates.
Dipylidium caninum	Ingestion of fleas	Dogs.
Giardia	Ingestion	Dogs, Cats, Horses.
Cryptosporidium	Ingestion	Lizards, Cats, Horses, Rabbits.
T. cruzi	Reduviid bite with feces inoculation	Dogs, Cats, Rodents.
Dirofilaria immitis	Mosquito Bites	Dogs, Cats, Raccoons, Rabbits.
Toxoplasma gondii	Ingestion	Cats.

(*Deer only act as an alternative reservoir for the Ixodes scapularis itself; hence the name “deer tick.”)

History and Physical

A detailed history must be obtained from patients with special attention to travel history, location of residence, occupation, vaccination status, hobbies, pets, other animal exposure, and diet. Immunosuppressed patients have more aggressive diseases than the general population.

Table 3. The clinical picture of important zoonotic diseases classified by affected organ systems[44][45][13]

Infection	Clinical Picture
Respiratory
Influenza	fever, headache, myalgia, cough, sore throat
COVID-19	asymptomatic, fever, headache, malaise, sore throat, cough, dyspnea, loss of taste/smell, nausea, vomiting, diarrhea
Psittacosis	asymptomatic, fever, headache, myalgia, sore throat, cough, dyspnea, diarrhea, confusion
Rhodococcus equi	fever, fatigue, cough, hemoptysis, chest pain, skin/brain abscesses
Dirofilaria immitis	asymptomatic, cough, chest pain
Neurological
West Nile Fever	asymptomatic, fever, headache, myalgia, muscle weakness, rigidity
Rabies	fever, headache, myalgia, sore throat, pharyngeal spasms, hydrophobia, weakness, numbness, agitation
Herpes B	skin vesicles, fever, headache, myalgia, abdominal pain, vomiting, paraesthesia, weakness, dysphagia, confusion
vCJD	depression, apathy, agitation, numbness, ataxia, dementia
Gastrointestinal
Salmonella	asymptomatic, fever, abdominal pain, diarrhea, nausea, vomiting
Campylobacter	abdominal pain, fever, diarrhea, hematochezia, nausea
Giardia	asymptomatic, abdominal pain, diarrhea, steatorrhea, flatulence, malaise, nausea, vomiting
Musculoskeletal
Trichinella	asymptomatic, fever, vomiting, diarrhea, myalgia, splinter hemorrhages, periorbital swelling
Dermatological
Capnocytophaga	fever, rash, cellulitis, sepsis or septic shock, meningitis, confusion
Bartonella	fever, lymphadenopathy, bacillary angiomatosis, endocarditis, peliosis hepatis
Pasteurella	soft tissue infection, arthritis, osteomyelitis, sepsis, meningitis, endocarditis
Cowpox	painful hemorrhagic pustules or black eschars
Dermatophytes	patches of itchy scaly ringworm skin lesions, hair loss, nail infections
Sporothrix	skin nodules, ulcers, nodular lymphangitic spread
CLM	pruritic papules, serpiginous lesions
Blood
Babesiosis	fever, headache, fatigue, jaundice
Systemic
Plague	Bubonic: painful lymphadenopathy Septicemic: fever, fatigue Pneumonic: dyspnea, cough, hemoptysis
Lyme disease	Stage 1: target lesion Stage 2: carditis and neuropathy Stage 3: meningitis, encephalitis, and arthritis
Anthrax	Cutaneous: ulcer with black eschar Gastrointestinal: abdominal pain, nausea, vomiting, oropharyngeal ulcers Pulmonary: dyspnea, hemoptysis, respiratory failure
Rift Valley Fever	fever, headache, malaise, arthralgia, bleeding tendency
Q fever	fever, fatigue, pneumonia, hepatitis, carditis, meningitis, rash
Ebola	fever, malaise, diarrhea, vomiting, rash, hemorrhages, confusion
RMSF	fever, headache, malaise, nausea, rash
Brucella	fever, night sweats, headache, abdominal pain, hepatosplenomegaly, arthralgia
Leptospirosis	asymptomatic, conjunctival suffusion, jaundice, bleeding, respiratory distress, aseptic meningitis
Nipah	fever, myalgia, confusion, seizures, neurological symptoms
Toxocara	fever, malaise, hepatitis, pneumonitis, meningoencephalitis

(WNV: West Nile Virus, vCJD: Variant Creutzfeldt-Jakob Disease, CLM: Cutaneous larva migrans, RMSF: Rocky Mountain spotted fever)

Evaluation

It is important to have public health data available at both national and local levels as a valuable reference while considering a possible zoonotic infection.

CBC: lymphocytosis is seen in influenza and brucellosis, lymphopenia is seen with COVID-19, thrombocytopenia in babesiosis, Coxiella, RMSF and leptospirosis, eosinophilia in trichinellosis.
Peripheral blood smear: maltese cross appearance is seen in babesiosis
Kidney function tests, liver function tests
Imaging as a chest x-ray
CSF testing: to look for WNV, vCJD, rabies
EEG: to look for waveform abnormalities as seen with WNV and vCJD
Cultures (blood, sputum, tissue): to detect plague, anthrax, salmonella, and Capnocytophaga
Serology: to detect Lyme disease, WNV, psittacosis, Bartonella.
PCR / RT-PCR: to detect influenza, COVID-19, WNV, psittacosis
Matrix-assisted laser desorption/ionization (MALDI-TOF): as in anthrax
Animal autopsy: for rabies

Treatment / Management

Treatment varies with the pathogen.

Influenza is usually self-limited. Otherwise, treatment regimens include Oseltamivir or Baloxavir.

Salmonella is usually managed supportively. Quinolones, azithromycin, trimethoprim-sulfamethoxazole, and ceftriaxone are all available options.

Plague is classically managed with aminoglycosides, tetracyclines, and quinolones as a last resort.

A combination treats brucella of doxycycline and an aminoglycoside or rifampicin in non-pregnant adults.

COVID-19 is currently managed per the latest guidelines on remdesivir, dexamethasone, and supportive measures.

Lyme disease is treated by doxycycline or a beta-lactam depending on the stage and presentation.

RMSF is managed by doxycycline as the drug of choice.

Psittacosis is recommended to be treated by tetracyclines, with azithromycin as an alternative.

Coxiella is managed with doxycycline, with the addition of hydroxychloroquine in vascular complications.

A combination lately treats anthrax of quinolones, carbapenems, linezolid, and immunoglobulin for systemic infections. Quinolones or doxycycline are utilized for limited cutaneous infections.

Dermatophytes: Topical or systemic antifungals in addition to animal treatment as well.

WNV, Rabies, and Rift Valley Fever are managed through supportive treatment only.

Ebola is suggested to be managed with the new agents atoltivimab, maftivimab, odesivimab (REGN-EB3), and ansuvimab.

Government strategies to decrease zoonoses include ensuring safe food products of animal origin, scaling back economic development in the wild, the shift from reactionary to pre-emptive approach on zoonoses, and availability of travel medicine guidelines.[46]

The ‘One Health 2006 Initiative’ focuses on the collaboration between human (physicians, nurses, and public health practitioners), animal (veterinarians), plants (agricultural workers), and environmental (ecologists, and wildlife experts) sectors to achieve optimal health since they are all interconnected.[47] This was started after the 1999 WNV outbreak in New York City, where one-sided prevention was shown to be inefficient. One Health Zoonotic Diseases Prioritization (OHZDP) workshops aim to prioritize zoonoses, develop action plans, maintain equative collaborative sectors’ input, and appropriately focus resources.[48](B2)

Differential Diagnosis

Zoonotic diseases must not be confused with other groups of diseases, including:[49]

Zooanthroponosis (reverse-zoonosis), which are infections transmitted from humans to animals, such as tuberculosis

Amphixenosis, which are infections transmitted in both directions from animals to humans and vice versa, such as staphylococcal infections

Euzoonosis, where humans act as an obligatory host in the pathogen’s life cycle, such as Taenia solium and Taenia saginata

Zoonoses also have to be differentiated from other common infections of similar presentations, and one should not be completely misled by a certain animal exposure in the context. Similarly, contact with animals, insects, and the wilderness, can cause other non-infectious pathologies like allergic reactions, which have to be considered in the differential diagnosis.

Prognosis

Prognosis varies with the pathogen:

Influenza: Case fatality is up to 60% in Avian flu and less than 1% in Swine flu.

WNV: Case fatality is 6%.

Plague: Case fatality is 13% with treatment and more than 80% without treatment.

The fatality of SARS is 9.6%, MERS is 35%, and SARS-CoV-2 is 3% to 6%, resulting in more than 2.5 million deaths.[50]

Rabies: Globally causes more deaths than any other zoonosis at 30,000 to 70,000 annually.[51][52]

Brucella: Case fatality is 2% to 5% if untreated.

Anthrax: Case fatality is more than 80% from inhalation anthrax.

Coxiella: Case fatality is 2% in acute and 20% in chronic disease.

Ebola: Case fatality is around 50%.

RMSF: Case fatality is 22% without treatment and 6% with treatment.[53]

Low mortality zoonoses (less than 1%) include salmonellosis, Lyme disease, rift valley fever, and psittacosis.

Complications

Known complications of the important zoonotic diseases are as follows:[54]

Influenza: Secondary pneumonia, myositis, myocarditis, encephalitis, and Guillain-Barre syndrome

Salmonella: Bacteremia, osteomyelitis, endocarditis, and mycotic aneurysms

WNV: Meningitis, encephalitis, chorioretinitis, fatal hemorrhagic fever, hepatitis, and myocarditis

Plague: Meningitis, shock, DIC, and multiorgan failure

COVID-19: Respiratory failure, arrhythmias, acute coronary syndrome, shock, thromboembolic manifestations, acute kidney injury, and systemic inflammation

Rabies: Seizures, coma, respiratory failure, arrhythmias, and myocarditis

Brucella: Arthritis, meningitis, pneumonia, orchitis, abortion, uveitis, and endocarditis

Lyme: Bannwarth syndrome, facial palsy, meningitis, atrioventricular blocks, acrodermatitis chronica atrophica, and post-Lyme syndrome

The economic impact of zoonotic diseases is a major concern, mostly due to its notorious effect on international travel, tourism, and trade, especially about animals and animal products. For example, the avian flu 2015 outbreak has caused a $3.3 billion loss to the U.S. economy.

Many zoonotic diseases also have the potential for causing severe complex diseases in transplant patients and other immunocompromised individuals. Also, many of them can be utilized as bioterrorism weapons.

Deterrence and Patient Education

Veterinarian visits should be scheduled regularly and for any pet illness. Catclaw clipping is recommended to avoid scratches. Owners should avoid feeding their pets any raw meat or eggs.[12] Reptile pets are strongly recommended to be kept away from children less than 5 years old and away from kitchens.

Proper tetanus immunization with or without immunoglobulins for bites is to be followed per guidelines. Animal vaccination for rabies, leptospira, and brucella, is also an essential practice. WNV vaccination is essential for horses. New vaccines are in process for several zoonoses, such as the new influenza A strains and plague.

Tick and flea control can be done by advising the public to wear light-colored clothes, long sleeves, tucking-in pants, using DEET spray, conducting body checks for early removal of ticks, and inspecting pets for ticks after going into wooded areas. Leaf debris removal and importation of fire ants to eat tick eggs can be done by environmental authorities to control the breeding of ticks and fleas.[55] Measures should be taken to avoid mosquito bites.

Public awareness programs to encourage handwashing is important. Awareness should be raised among healthcare workers about emerging infectious diseases and the available resources for the same. Continuous surveillance, disease reporting, and mapping programs for zoonotic diseases are ongoing in humans and animals.

Enhancing Healthcare Team Outcomes

Medical providers, including physicians, nurse practitioners, and physician assistants, must keep in mind the possibility of certain zoonotic diseases, depending on the geographical location, travel history, and exposure to certain animals.[56] The COVID-19 pandemic typifies the importance of the human-animal interface and the One World One Health paradigm. Appreciation of the effect of human behavior as a coordinated interprofessional team, and the potential disruption of natural barriers to species jumping infections can help prevent a pathogenic emergency, which may lead to epidemics or pandemics.

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