Zoonosis and Zoonotic Agents

The term "zoonosis" is derived from the Greek words "zoon" meaning "animal", and "nosos" meaning "illness". [1]

The term "zoonosis" or "zoonotic disease" is used to refer to the spread of a disease from one species of an animal to another through a vector. Zoonosis can also be referred to the spread of a disease from an animal to a human. [2]

The carrier animal acts as the host for the zoonotic agent, which spreads the disease to humans upon coming into contact with them. This spread of disease from an animal to a human takes place either directly or indirectly through vectors or zoonotic agents.

♦ Direct contact - Direct consumption of contaminated or infected animal products

♦ Indirect contact - Contact through animal blood, faeces, urine, etc. [3]

Zoonotic Agents are those agents which are responsible for causing zoonotic diseases. Some of the most commonly occurring zoonotic agents include bacteria, fungi, viruses, or any other communicable agent. [4]


Types of zoonotic diseases

Zoonotic diseases are classified according to the type of causative agent involved - [5]

Causative

Agent

Causative species of micro-organism/agent

Carrier

Animal

Zoonotic

Disease

Bacteria [6]

Bacteria

Brucella melitensis

Brucella abortus

Brucella suis

Brucella canis

Leptospira icterohaemorrhagiae

Leptospira canicola

Leptospira hardjo

Leptospira pomona

Listeria monocytogenes

Yersinia pestis

Mycobacterium bovis

Chlamydia psittaci

Salmonella spp.

Bacillus anthracis

Francisella tularensis

Bartonella henselae

Spirillum minus

Burkholderia mallei

Goats, sheep, camel

Cattle, camels

Pigs

Dogs

Rodents (Rats)

Dogs

Cattle

Pigs

Fish, birds, swine

Rats, squirrels, rabbits

Cattle

Birds

Infected animal products

Herbivores

Rodents, rabbits, etc.

Cats

Rats

Equine animals

Human brucellosis

Leptospirosis

Listeriosis

Plague

Zoonotic bovine tuberculosis

Psittacosis

Salmonellosis

Anthrax

Tularemia

Cat-scratch disease

Sodoku

Glanders

Viruses

Lyssavirus sp.

Orthopoxvirus sp.

Parapoxvirus sp.

Yatapoxvirus sp.

Molluscipoxvirus sp.

Influenza A virus

(H5N1, H7N9 [10] strains)

Influenza A virus (H3N8 strain)

Influenza A virus (H7N7, H3N8 strains)

Influenza C virus (SIV virus)

Influenza A virus (H1N1, H1N2, H2N1, H3N1, H3N2, H2N3 strains)

Dogs, foxes, bats

Camels, monkeys

Sheep, goats, cattle

Aquatic organisms molluscs

Birds

Dogs

Horses


Pigs

Rabies [7]

Camelpox, monkeypox, cowpox, sheeppox, tanapox, molluscipox [8]

Avian flu [9]

Canine flu [11]

Equine flu [12]

Swine flu [13]

Parasites

Cryptosporidium

Trichinella

Baylisascaris procyonis

Cows, pigs

Bear, boar, pigs, rats

Raccoons

Gastroenteritis [14]

Trichinosis [15]

Zoonotic neurological damage [16]

Fungi

Fungi imperfecti

(Deuteromycota)

Candida albicans

(Monilia)

Histoplasma capsulatum

Cryptococcus neoformans

Cryptococcus gattii

Aspergillus fumigatus

Pet animals

Skin, mucous membranes, gut flora of warm-blooded animals

Bat or bird droppings

Pigeon droppings

(dried)

Ubiquitous

Tinea infections (ringworm) [17]

Candidiasis moniliasis (yeast infection) [18]

Histoplasmosis [19]

Cryptococcosis [20]

Aspergillosis [21]

Protozoa

Giardia lamblia

Toxoplasma gondii

Beaver, waterfowl, muskrat

Domestic cat and wild animals

Giardiasis [22]

Toxoplasmosis [23]

Ticks

Borrelia burgdorferi

Rickettsia rickettsii

Ticks present in deer, mice, squirrels, weasels

Dermacentor ticks

Lyme Disease [24]

Rocky Mountain Spotted Fever [25]

Unconventional agents

Misfolded protein

(Prion) - transformation in structure of protein from alpha helix to beta-pleated sheet which gives rise to pathogenicity

Infected meat or body parts of cattle

Bovine Spongiform Encephalopathy (BSE) or Mad Cow Disease [26]


Zoonotic Disease Therapies
  • Therapies for bacterial zoonotic diseases -

Zoonotic Disease

Therapies

Human Brucellosis

Combined Antibiotic Therapy - Streptomycin, Gentamycin, Tetracycline, Doxycycline, and Rifampicin. These antibiotics need to be taken in combination with one another so as to prevent recurrence of illness.

The most effective combination of antibiotic therapy is a combined dosage of 1 g of Streptomycin (intramuscular injection) for 14 days, alongwith 100 mg Doxycycline (oral) for 45 days. Gentamycin can be substituted for Streptomycin.

Another combination of antibiotic therapy is Doxycycline alongwith Rifampicin to be taken orally twice a day, for a period of six weeks.

Brucellosis affecting the nervous tissue can be treated with a combination of Doxycycline, Rifampicin, and Co-trimoxazole. Doxycycline possesses the advantage of permeating through the blood-brain barrier. However, Rifampicin and Co-trimoxazole need to be administered so as to prevent a relapse of infection.

The most severe and fatal form of brucellosis - Brucella endocarditis - can be optimally treated only through surgery. [27] [28] [29] [30]

Leptospirosis

Antibiotic therapy such as Doxycycline or Penicillin administered for a period of seven days. Erythromycin offered as alternative.

Intravenous antibiotic therapy for severe infection.

Analgesics such as paracetamol or ibuprofen can be used to relieve symptoms such as aches and fever.

Supportive therapy in the form of detoxification, maintenance of electrolyte balance, external administration of blood and blood products, as well as organ transplantation may be required. [31] [32] [33] [34] [35]

Listeriosis

Bacteria usually remains in digestive tract, therefore, over-the-counter medication can help in treating symptoms such as muscle ache and fever.

If bacteria invade the bloodstream and the central nervous system, antimicrobials and hospitalization are essential.

Antibiotic therapy includes ampicillin, penicillin, and amoxicillin.

Non-pregnant patients do not usually require medication.

For pregnant patients, antibiotics such as Amoxicillin and Erythromycin are administered to prevent spread of infection to foetus. [36] [37] [38]

Plague

Illness needs to be treated within 24 hours of first appearance of symptoms.

Antibiotics such as streptomycin, gentamycin, tetracycline, and ciprofloxacin, are administered.

Patients should be isolated so as to avoid spread of infection.

In case of contact with infected persons, prophylactic antibiotics are administered.

In case of poor drug action, Chloramphenicol can be administered as an alternative.

Illness should be managed effectively so as to avoid organ failure and respiratory distress due to hypoxia.

Preventive measures include administration of live, attenuated, and formalin-induced vaccines. However, during plague outbreaks, vaccine has negligible effect on chances of developing immunity against illness. [39] [40] [41] [42]

Zoonotic bovine tuberculosis

A combination of Isoniazid and Rifampicin for a period of nine months.

Culling of cattle suffering from tuberculosis.

Drugs used for treating human tuberculosis are also effective against zoonotic bovine tuberculosis.

Full course of prescribed drugs should be taken as Mycobacterium bovis virus can develop resistance for drugs treating M. tuberculosis. [43] [44] [45]

Psittacosis

Antibiotic therapy with tetracycline, doxycycline, chloramphenicol, and other antibiotics (except Penicillin as the bacterium Chlamydia psittaci is resistant to Penicillin). Therapy to last for 2-3 weeks to prevent relapse.

Erythromycin is administered to pregnant women and young children who cannot tolerate tetracycline.

Supportive treatment mechanisms include administration of electrolytes, intravenous fluid, and life support systems. [46] [47] [48]

Salmonellosis

Electrolytes and rehydration to replenish fluid loss.

Antibiotic therapy such as Fluoroquinolones, Cephalosporins, and Ampicillin to be administered only for severe cases of illness. [49] [50]

Anthrax

Cutaneous anthrax - Administration of antibiotics such as doxycycline or ciprofloxacin for a period of 60 days.

Pulmonary anthrax - Hospitalization and intravenous therapy. May not respond to antibiotics in some cases. Monoclonal antibody such as Raximacumab may be administered.

Patients need to be isolated as anthrax spores can spread through contaminated clothing. Contaminated belongings should be disinfected. [51] [52] [53]

Tularemia

Antibiotic therapy such as streptomycin (intramuscular), gentamycin (intravenous), tetracycline (oral), etc. However, these drugs do not cross the blood-brain barrier, and therefore, cannot be administered for neural complications arising out of tularemia. These drugs need to be directly introduced in to the cerebrospinal fluid in order to treat neural complications. [54] [55]

Cat-scratch disease

Medical treatment usually not required.

Swollen lymph nodes may require fluid removal. Relief can be obtained from painful lymph nodes by painkillers such as Acetaminophen or Ibuprofen.

In severe cases, antibiotic therapy is recommended. [56] [57]

Sodoku

Antibiotic therapy such as Penicillin. In case of allergy, tetracycline or erythromycin can also be administered. [58]

Glanders

Human cases of glanders are rare. However, antibiotic therapy is administered.

The bacterium Burkholderia mallei has been found to be sensitive to antibiotics such as tetracyclines, ciprofloxacin, streptomycin, etc., and resistant towards chloramphenicol.

Sulfadiazine has been found to be an effective antibiotic in experimental animal models. [59] [60]

  • Therapies for viral zoonotic diseases -

Zoonotic Disease

Therapies

Rabies

Preventive vaccine given in 5 doses over a period of 28 days.

On the day of the bite, HRIG (Human Rabies Immunoglobulin) is administered as treatment.

Post-exposure prophylaxis - cleaning wound, administration of HRIG, and vaccination.

Three types of rabies vaccine -

Human Diploid Cell Vaccine (HDCV), synthesized from human cells;

Purified Chick Embryo Cell Rabies Vaccine (PCEC), synthesized from samples of chick embryos;

Nerve Tissue Vaccine, synthesized from neural tissue

As per WHO, only HDCV or PCEC can be administered as vaccines due to safety concerns over Nerve Tissue Vaccine. [61] [62] [63] [64]

Camelpox

Rare cases of humans being infected.

Supportive treatment of administration of Vitamin C and antibiotics (oxytetracycline) so as to increase immunity.

Administration of live or attenuated vaccine for a period of six to twelve months before expected outbreak season.

Antiviral medications such as Cidofovir are also administered, which acts by inhibiting the action of the viral DNA polymerase.

Camelpox virus is extremely sensitive to disinfectants, UV radiation, heat, etc. [65] [66]

Cowpox

Antibiotics to be administered only for secondary bacterial infection

Viral DNA polymerase inhibitor (Cidofovir) administered parenterally, topically, or in aerosol form for widespread cases

Severe cases may be treated by administration of antivaccinia gammaglobulin. [67] [68] [69]

Monkeypox

Analgesics may be administered to reduce symptoms of fever.

Smallpox vaccine may be effective to prevent monkeypox. This vaccine needs to be administered within 14 days of infection.

In severe cases, immunoglobulin or antiviral medication may be administered. [70] [71]

Sheeppox

Symptomatic treatment is carried out. Avoid contact with infected animals. [72]

Tanapox

No specific treatment for tanapox.

Smallpox vaccine may prove effective against subsequent infection. [73]

Molluscipox

Lesions are contagious, therefore, treatment is essential.

Anaesthesia is administered to avoid pain during treatment.

Treatments for removing lesions include salicylic acid, potassium hydroxide, and antiviral topical applications such as Imiquimod.

Surgical treatments include Scraping, Cryotherapy, and laser therapy. [74] [75]

Avian flu

Hospitalization and isolation of affected individuals.

Severity of illness decreases upon administration of Oseltamivir or Zanimivir within 48 hours of infection.

Virus is resistant to Amantadine and Rimantadine.

FDA and WHO approved Avian Flu vaccine to prevent spread of illness.

H7N9 strain needs to be studied further for developing strain-specific medications. [76] [77] [78]

Canine flu

No cases of canine flu reported in humans so far.

However, research is in progress to study H3N8 viral strain so as to observe its possible effects in humans. [79]

Equine flu

Humans do not get infected with equine flu.

However, horses can get infected due to presence of infection in surrounding areas. [80]

Swine flu

Vaccination is the best form of prevention and/or treatment of swine flu.

Approved drugs for reducing illness are Zanamivir, Peramivir, and Oseltamivir, to be administered only within 48 hours of first appearance of symptoms. [81] [82] [83]

  • Therapies for parasitic zoonotic diseases -

Zoonotic Disease

Therapies

Gastroenteritis

Fluid and electrolyte therapy [84]

Trichinosis

Aim of treatment is to stop larval growth. Within a period of 1 week, drugs such as albendazole, or mebendazole, or thiabendazole are administered.

Bed rest, antipyretics, analgesics are highly effective. [85] [86]

Zoonotic neurological damage

Antihelmintic drugs so as to kill adult worms, such as piperazine, fenbendazole, albendazole, organophosphates, etc.

Laser can kill larvae present in eye, but migration of larvae cannot be controlled. [87] [88]

  • Therapies for fungal zoonotic diseases -

Zoonotic Disease

Therapies

Ringworm

Anti-fungal topical applications are highly effective.

Oral anti-fungal therapy is also administered in case of severe and widespread infection. [89] [90]

Candidiasis

Oral candidiasis - Oral liquid medication or oral tablets, lozenges, or capsules.

Vaginal candidiasis - Antifungal cream or vaginal suppositories. If infection reoccurs after treatment is stopped, liquid antifungal medication is administered.

Oesophageal candidiasis - More difficult to treat as compared to oral and vaginal candidiasis. Drugs administered include Flucanozole, Itraconazole, and Ketaconazole.

Drug-resistant candidiasis - Above lines of treatment do not work. Amphotericin is administered intravenously. Administered only in severe cases of candidiasis. [91] [92] [93] [94]

Histoplasmosis

Antifungal drugs such as Amphotericin B, itraconazole, ketaconazole, etc.

In cases of acute illnesses, treatment period lasts for 6-12 weeks.

In severe cases, treatment continues for more than one year. [95] [96]

Cryptococcosis

People suffering from HIV-AIDS need much more extensive treatment. Flucytosine or flucanazole are recommended drugs in combination with Amphotericin B. [97] [98]

Aspergillosis

Anti-fungal medication such as Voriconazole is the first line of treatment for invasive aspergillosis.

In case of non-response to Voriconazole, other anti-fungal drugs such as itraconazole, caspofungin, micafungin, etc. are administered.

Bronchial artery embolization used for life-threatening hemoptysis.

Allergic bronchopulmonary aspergillosis is a hypersensitive reaction that is treated with oral corticosteroids.

In case of non-response to any kind of anti-fungal medication, surgery is the only option for treatment. [99] [100] [101] [102]

  • Therapies for protozoal zoonotic diseases -

Zoonotic Disease

Therapies

Giardiasis

Antibiotic therapy - Metronidazole for 5-10 days.

Fluid and electrolyte replenishment in case of large quantity of fluid loss.

Various factors such as medical history, immune system, nutritional status, etc. determine recovery time. [103] [104] [105]

Toxoplasmosis

In case of healthy individuals, generally no treatment required. However, a combination of drugs is administered - Pyrimethamine and Sulfadiazine. Treatment lasts for 3-6 weeks. [106] [107]

  • Therapies for tick-borne zoonotic diseases -

Zoonotic Disease

Therapies

Lyme Disease

Oral antibiotics (doxycycline or amoxicillin) or Intravenous antibiotics (Ceftriaxone or Penicillin G).

For symptom relief, pain killers such as Ibuprofen may also be administered. Painful swollen joints can be treated by fluid removal from joints through a process called arthrocentesis. [108] [109] [110]

Rocky Mountain Spotted Fever

First line of treatment is doxycycline which is to be administered within the first 5 days of symptoms appearing. [111]

  • Therapies for Bovine Spongiform Encephalopathy (BSE) -

♦ Currently, there is no treatment or cure or vaccine for BSE.

♦ The only way to prevent or control the spread of BSE is to avoid feeding infected animal feed to other cattle, and also avoid the consumption of infected animal products by humans.

♦ Culling is the best way to avoid spread of infection and disease to other animals or humans.

♦ The body parts of cattle which are the most susceptible to infection are the brain, spinal cord, eyes, intestines, tonsils, etc. Therefore, these body parts are classified as "specified risk materials", and should be disposed off carefully so as to avoid spread of infection.

♦ BSE is a prion disease. As prion diseases are slow-developing, scientists have managed to develop two drugs which can control the symptoms and eventual spread of disease, thus avoiding the need for culling infected cattle. These two drugs are Trimipramine and Fluphenazine.

♦ As prion diseases are slow-developing, treating prion diseases is much simpler as compared to bacterial or viral diseases. [112] [113] [114]





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