Zoono tic diseases

1. Zoonotic diseases Meral Sönmezoğlu, Assoc Prof Infectious Diseases Department Yeditepe University Hospital

2. Zoonoses From the Greek: Zoon: Animal Noson: Disease Diseases and infections which are naturally transmitted between vertebrate animals and humans - WHO 1959

3. 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

4. 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

5. 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

6. Zoonosis: Importance • In addition to their natural occurrence many of these microorganisms are prime candidates as biological weapons

7. Animal Health ZOONOSIS Zoonosis (Zoonotic Diseases) - all diseases naturally transmissible from animals to man

8. 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

9. Zoonoses • > 250 zoonotic diseases • Multiple pets in the home • Human-animal bond • Exotic species as pets

10. Zoonoses: Common Diseases Frequency – (CDC, 2003) Salmonella 39,919 Lyme disease 18,991 West Nile (CNS) 2,862 Trichinosis 4

11. Zoonoses • Zoonotic diseases can be severe, life threatening, and contagious • and can even warn of an emerging epidemic or • a possible bioterror act

12. Zoonoses Spectrum of Disease Severity Death = rabies Severe illness = plague Chronic illness = Q-fever Mild illness = psittacosis

13. 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

14. Zoonoses: Etiologic Classification • Viral • Bacterial • Parasitic • Mycotic

15. Zoonoses: Viral Examples

16. Zoonoses: Bacterial Examples

17. Zoonoses: Parasitic Examples

18. Zoonoses: Mycotic Examples Aspergillosis Blastomycosis Cryptococcosis Dermatophytosis Histoplasmosis Sporotrichosis

19. Zoonoses: Animal Species • Dogs & Cats • Rabies • Roundworm • Ringworm • Lyme Disease (dogs only) • Cat Scratch Disease (cats only) • Food Animals • Salmonella • E.coli • Brucellosis

20. Zoonoses: Animal Species • Birds: • Psittacosis • West Nile • Cryptococcus • Reptiles, Fish, & Amphibians • Salmonella • Mycobacterium • Wild Animals • Hantavirus • Plague • Tularemia

21. Routes of Transmission • Direct • Droplet or Aerosol • Oral • Contact • Indirect • Foodborne • Water-borne • Fomite • Vector-borne • Environmental

22. Routes of Transmission • direct contact, • ingestion, • inhalation, • arthropod intermediates, • animal bites.

23. Zoonoses - Life Cycle ORTHOZOONOSES • May be perpetuated in nature by a single vertebrate species • E.g. rabies, brucellosis, anthrax

24. Zoonosis: Rabies Life Cycle Virus inoculation (bite) Salivary gland excretion

25. 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

26. Life Cycle:

27. 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

28. Zoonoses: Metazoonoses • Invertebrate Host: Mosquitoes • Vertebrate Host: Birds • Incidental Hosts: • HUMANS, horses, amphibians, other mammals

29. 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

30. Risk Factors • Recreational Activities • Camping & Lyme disease • Farm Settings • Sheep & Q-fever • Cattle & Cryptosporidium • Travel • Malaysia & Nipha • Australia & Hendra

31. 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…

32. RABIES

33. 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.

34. Rabies Virus Structure of rabies virus (Source: CDC) Rabies virus particles

35. 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

36. 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

37. 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

39. 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

40. 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

41. 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.

42. 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?)

43. RABIES RECOVERY? • Five historical human case recoveries, after vaccination, but before illness onset • Only one documented unvaccinated human survivor after clinical presentation

45. 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)

46. 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.  

47. Diagnosis of Rabies Negri Body in neuron cell (source: CDC) Positive DFA test (Source: CDC

48. PROPHYLAXIS • Pre-exposure Vaccination • Postexposure Prophylaxis (PEP)

49. 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.

50. 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.