Zoonotic diseases Meral Sönmezoğlu, Assoc Prof Infectious Diseases Department Yeditepe University Hospital
Zoonoses From the Greek: Zoon: Animal Noson: Disease Diseases and infections which are naturally transmitted between vertebrate animals and humans - WHO 1959
Learningobjects 1. Know the general terminology and main organisms 2. Know epidemiology and clinical symptoms of main zoonotic diseases 3. Understand the importance of the diseases
Definition • Zoonosis are diseases of vertebrate animals that can be transmitted to man: either directly or indirectly through an insect vector. • Zoonosisare a complexgroup of diseasescausedby a remarkablediversity of pathogenicmicroorganismsthatordinarilyresideandcauseillness in thenonhumananimalworld
Definingcriteria introduction to the zoonosis include the following: • a vertebrate reservoir exclusive of humans; • transmission of the agent directly to people or from products derived from the host animal or through an arthropod intermediate; • and a recognized infectious disease syndrome in susceptible individuals
Zoonosis: Importance • In addition to their natural occurrence many of these microorganisms are prime candidates as biological weapons
Animal Health ZOONOSIS Zoonosis (Zoonotic Diseases) - all diseases naturally transmissible from animals to man
Zoonoses • Does NOT include • Fish and reptile toxins • Allergies to vertebrates • Diseases in which animal-derived food serves as a vehicle (e.g. hepatitis A contaminated deli meat) • Experimentally transmitted diseases
Zoonoses • > 250 zoonotic diseases • Multiple pets in the home • Human-animal bond • Exotic species as pets
Zoonoses: Common Diseases Frequency – (CDC, 2003) Salmonella 39,919 Lyme disease 18,991 West Nile (CNS) 2,862 Trichinosis 4
Zoonoses • Zoonotic diseases can be severe, life threatening, and contagious • and can even warn of an emerging epidemic or • a possible bioterror act
Zoonoses Spectrum of Disease Severity Death = rabies Severe illness = plague Chronic illness = Q-fever Mild illness = psittacosis
Zoonoses: Importance • Economics • Zoonotic disease are expensive • Rabies post-exposure prophylaxis • GI illness due to Salmonella or Campylobacter – lost productivity, medical costs • Import/Export • BSE – restriction on cattle • Avian Influenza – restriction on chicken • Travel/Globalization • Decreased transit time - SARS • Remote area accessibility
Zoonoses: Etiologic Classification • Viral • Bacterial • Parasitic • Mycotic
Zoonoses: Mycotic Examples Aspergillosis Blastomycosis Cryptococcosis Dermatophytosis Histoplasmosis Sporotrichosis
Zoonoses: Animal Species • Dogs & Cats • Rabies • Roundworm • Ringworm • Lyme Disease (dogs only) • Cat Scratch Disease (cats only) • Food Animals • Salmonella • E.coli • Brucellosis
Zoonoses: Animal Species • Birds: • Psittacosis • West Nile • Cryptococcus • Reptiles, Fish, & Amphibians • Salmonella • Mycobacterium • Wild Animals • Hantavirus • Plague • Tularemia
Routes of Transmission • Direct • Droplet or Aerosol • Oral • Contact • Indirect • Foodborne • Water-borne • Fomite • Vector-borne • Environmental
Routes of Transmission • direct contact, • ingestion, • inhalation, • arthropod intermediates, • animal bites.
Zoonoses - Life Cycle ORTHOZOONOSES • May be perpetuated in nature by a single vertebrate species • E.g. rabies, brucellosis, anthrax
Zoonosis: Rabies Life Cycle Virus inoculation (bite) Salivary gland excretion
Zoonoses - Maintenance Cycle CYCLOZOONOSES • Requires more than one vertebrate species but no invertebrate host • Most are cestodiases (tapeworm diseases) • Taenia saginata and T. solium require man to be one of vertebrate hosts • Others, such as hydatidosis, man is accidentally involved
Zoonoses - Life Cycle METAZOONOSES • Require both vertebrates and invertebrates to complete transmission • All arboviral infections • West Nile virus, Saint Louis encephalitis • Some bacterial diseases • Plague, many rickettsia • Some parasitic diseases • Leishmaniasis, schistosomiasis
Zoonoses: Metazoonoses • Invertebrate Host: Mosquitoes • Vertebrate Host: Birds • Incidental Hosts: • HUMANS, horses, amphibians, other mammals
Risk Factors • Companion Animal • Dogs & roundworm • Rats & Rat Bite Fever • Occupational • Animal control workers & rabies • Wildlife biologists & hantavirus • Foodborne • Raw meat & E.coli • Unpasteurized dairy & Listeria
Risk Factors • Recreational Activities • Camping & Lyme disease • Farm Settings • Sheep & Q-fever • Cattle & Cryptosporidium • Travel • Malaysia & Nipha • Australia & Hendra
Reportable Diseases of Animals • By veterinarian or other individual • Reported to Health Services • Plague • Rabies • Reportable to Dept Food and Agriculture • Anthrax • Brucellosis • Glanders • Listeriosis • Rabies in livestock • Venezuelan equine encephalomyelitis • West Nile • And more…
Rabies Virus • member of the Lyssavirus of the Rhabdoviridae. • ssRNA enveloped virus, characteristic bullet-shaped appearance with 6-7 nm spike projections. • virion 130-240nm * 80nm • -ve stranded RNA codes for 5 proteins; G, M, N, L, S • Exceedingly wide range of hosts. • There are 5 other members of Lyssavirus : Mokola, Lagosbat, Duvenhage, EBL-1, and EBL-2. • Duvenhage and EBL-2 have been associated with human rabies.
Rabies Virus Structure of rabies virus (Source: CDC) Rabies virus particles
DEFINITION • Rabies is an acute, progressive encephalomyelitis • The case to fatality rate is the highest of any infectious disease • One of the oldest described diseases • The leading viral zoonosis as regards global public health significance
Epidemiology Rabies is a zoonosis which is prevalent in wildlife. The main animals involved differs from continent to continent. Europe fox, bats Middle East wolf, dog Asia dog Africa dog, mongoose, antelope N America foxes, skunks, raccoons, insectivorous bats S America dog, vampire bats
DISTRIBUTION • Rabies is distributed on all continents (with the exception of Antarctica) • Several areas are considered ‘free’ of the disease, including many islands in Pacific Oceania • Globalization may threaten the disease-free status of many localities, due to the introduction of rabid animals
BURDEN • More than ~55,000 human rabies deaths per year • Most occur in developing countries • Millions of human exposures per year • The domestic dog is the single most important animal reservoir (>99%) • Wildlife important, especially in developed countries
RABIES PATHOGENESIS • Virus is transmitted via bite • Agents are highly neurotropic • Enter peripheral nerves • Centripetal travel by retrograde flow in axoplasm of nerves to CNS • Replicate in brain • Centrifugal flow to innervated organs, including the portal of exit, the salivary glands • Viral excretion in saliva
Pathogenesis • The commonest mode of transmission in man is by the bite of a rabid animal, usually a dog. Rabies is an acute infection of the CNS which is almost invariably fatal. • Following inoculation, the virus replicates in the striated or connective tissue at the site of inoculation and enters the peripheral nerves through the neuromuscular junction. • It then spreads to the CNS in the endoneurium of the Schwann cells. • Terminally, there is widespread CNS involvement but few neurons infected with the virus show structural abnormalities. The nature of the profound disorder is still not understood.
CLINICAL STAGES • Incubation Period (range = ~<7 days to >6 years; average is ~4-6 weeks) • Prodromal Phase (Non-specific signs) • Acute Neurological Phase • Coma • Death (recovery from rabies?)
RABIES RECOVERY? • Five historical human case recoveries, after vaccination, but before illness onset • Only one documented unvaccinated human survivor after clinical presentation
RABIES DIAGNOSIS • Based upon history of animal exposure and typical neurological clinical signs • Postmortem demonstration of viral antigen in CNS is gold standard • In humans, antemortem detection of virus or viral amplicons, antibodies, or antigens (sera, csf, saliva, nuchal biopsy)
Laboratory Diagnosis • Histopathology - Negri bodies are pathognomonic of rabies. However, Negri bodies are only present in 71% of cases. • Rapid virus antigen detection - in recent years, virus antigen detection by IF had become widely used. Corneal impressions or neck skin biopsy are taken. The Direct Fluorescent Antibody test (DFA) is commonly used. • Virus cultivation - The most definitive means of diagnosis is by virus cultivation from saliva and infected tissue. Cell cultures may be used or more commonly, the specimen is inoculated intracerebrally into infant mice. Because of the difficulties involved, this is rarely offered by diagnostic laboratories. • Serology - circulating antibodies appear slowly in the course of infection but they are usually present by the time of onset of clinical symptoms.
Diagnosis of Rabies Negri Body in neuron cell (source: CDC) Positive DFA test (Source: CDC
PROPHYLAXIS • Pre-exposure Vaccination • Postexposure Prophylaxis (PEP)
Management and Prevention • Pre-exposure prophylaxis - Inactivated rabies vaccine may be administered to persons at increased risk of being exposed to rabies e.g. vets, animal handlers, laboratory workers etc. • Post-exposure prophylaxis - In cases of animal bites, dogs and cats in a rabies endemic area should be held for 10 days for observation. If signs develop, they should be killed and their tissue. • Wild animals are not observed but if captured, the animal should be killed and examined. The essential components of postexposure prophylaxis are the local treatment of wounds and active and passive immunization. • Once rabies is established, there is nothing much that could be done except intensive supportive care. To date, only 2 persons with proven rabies have survived.
Postexposure Prophylaxis • Wound treatment - surgical debridement should be carried out. Experimentally, the incidence of rabies in animals can be reduced by local treatment alone. • Passive immunization - human rabies immunoglobulin around the area of the wound; to be supplemented with an i.m. dose to confer short term protection. • Active immunization - the human diploid cell vaccine is the best preparation available. The vaccine is usually administered into the deltoid region, and 5 doses are usually given. • There is convincing evidence that combined treatment with rabies immunoglobulin and active immunization is much more effective than active immunization alone. Equine rabies immunoglobulin (ERIG) is available in many countries and is considerably cheaper than HRIG.