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    Samuel Lugovi
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  1. 1. Zoonosis D-r Mitova MU-Sofia
  2. 2. Modes of Disease Transmission
  3. 3. Zoonoses From the Greek: Zoon: Animal Noson: Disease Diseases and infections which are naturally transmitted between vertebrate animals and humans - WHO 1959
  4. 4. Zoonoses <ul><li>> 250 zoonotic diseases </li></ul>
  5. 5. Zoonoses: Common Diseases <ul><li>Frequency – (CDC, 2003) </li></ul><ul><ul><li>Salmonella 39,919 </li></ul></ul><ul><ul><li>Lyme disease 18,991 </li></ul></ul><ul><ul><li>West Nile (CNS) 2,862 </li></ul></ul><ul><ul><li>Trichinosis 4 </li></ul></ul>
  6. 6. Zoonoses <ul><li>Spectrum of Disease Severity </li></ul><ul><ul><li>Death = rabies </li></ul></ul><ul><ul><li>Severe illness = plague </li></ul></ul><ul><ul><li>Chronic illness = Q-fever </li></ul></ul><ul><ul><li>Mild illness = psittacosis </li></ul></ul>
  7. 7. Zoonoses: Importance <ul><li>Economics </li></ul><ul><ul><li>Zoonotic disease are expensive </li></ul></ul><ul><ul><ul><li>Rabies post-exposure prophylaxis </li></ul></ul></ul><ul><ul><ul><li>GI illness due to Salmonella or Campylobacter – lost productivity, medical costs </li></ul></ul></ul><ul><ul><li>Import/Export </li></ul></ul><ul><ul><ul><li>BSE – restriction on cattle </li></ul></ul></ul><ul><ul><ul><li>Avian Influenza – restriction on chicken </li></ul></ul></ul><ul><li>Travel/Globalization </li></ul><ul><ul><ul><li>Decreased transit time - SARS </li></ul></ul></ul>
  8. 8. Zoonoses: Etiologic Classification <ul><li>Viral </li></ul><ul><li>Bacterial </li></ul><ul><li>Parasitic </li></ul><ul><li>Mycotic </li></ul>
  9. 9. Zoonoses: Viral Examples Yellow fever Influenza West Nile virus* Herpesvirus B Rift Valley fever Hendra* Rabies* Hantaviruses Nipah* Equine encephalitides (WEE, EEE, VEE) Monkeypox* Ebola Japanese encephalitis Colorado tick fever
  10. 10. Zoonoses: Bacterial Examples Yersiniosis Lyme disease* Tularemia* Listeriosis* Salmonellosis* Leptospirosis* Relapsing fevers Cat-scratch disease* Q fever* Campylobacteriosis* Psittacosis* Brucellosis* Plague* Anthrax*
  11. 11. Zoonoses: Animal Species <ul><li>Dogs & Cats </li></ul><ul><ul><li>Rabies </li></ul></ul><ul><ul><li>Lyme Disease (dogs only) </li></ul></ul><ul><li>Food Animals </li></ul><ul><ul><li>Salmonella </li></ul></ul><ul><ul><li>E.coli </li></ul></ul><ul><ul><li>Brucellosis </li></ul></ul>
  12. 12. Zoonoses: Animal Species <ul><li>Birds: </li></ul><ul><ul><li>Psittacosis </li></ul></ul><ul><ul><li>West Nile </li></ul></ul><ul><li>Wild Animals </li></ul><ul><ul><li>Hantavirus </li></ul></ul><ul><ul><li>Plague </li></ul></ul><ul><ul><li>Tularemia </li></ul></ul>
  13. 13. <ul><li>The Rat </li></ul><ul><li>The best-known rat species are the Black Rat Rattus rattus and the Brown Rat R. norvegicus . The group is generally known as the Old World rats or true rats, and originated in Asia. Rats are bigger than most of their relatives, the Old World mice, but seldom weigh over 500 grams (1 lb) in the wild. The common term &quot;rat&quot; is also used in the names of other small mammals which are not true rats. Examples include the North American pack rats, a number of species loosely called kangaroo rats, and a number of others. Other rats such as the Bandicoot rat Bandicota bengalensis are murine rodents related to the true rats, but are not members of the genus Rattus. </li></ul>
  14. 14. <ul><li>Roof Rat </li></ul><ul><li>Order Rodentia : Family Muridae : Rattus rattus (Linnaeus) </li></ul><ul><li>Description. A blackish (or brownish), medium-sized, slender rat with long, naked, scaly tail; tail usually longer than head and body but not always so. External measurements average: total length, 370 mm; tail, 190 mm; hind foot, 36 mm. Weight, up to 200 g. </li></ul>
  15. 15. <ul><li>Norway Rat </li></ul><ul><li>Order Rodentia : Family Muridae : Rattus norvegicus (Berkenhout) </li></ul><ul><li>Description. Similar to the roof rat but larger and chunkier; tail shorter than length of head and body. External measurements average: total length, 440 mm; tail, 205 mm; hind foot, 46 mm. Weight, 400-500 g. </li></ul>
  16. 17. Routes of Transmission <ul><li>Direct </li></ul><ul><ul><li>Droplet or Aerosol </li></ul></ul><ul><ul><li>Oral </li></ul></ul><ul><ul><li>Contact </li></ul></ul><ul><li>Indirect </li></ul><ul><ul><li>Foodborne </li></ul></ul><ul><ul><li>Water-borne </li></ul></ul><ul><ul><li>Fomite </li></ul></ul><ul><ul><li>Vector-borne </li></ul></ul><ul><ul><li>Environmental </li></ul></ul>
  17. 18. Risk Factors <ul><li>Companion Animal </li></ul><ul><ul><li>Dogs & roundworm </li></ul></ul><ul><ul><li>Rats & Rat Bite Fever </li></ul></ul><ul><li>Occupational </li></ul><ul><ul><li>Animal control workers & rabies </li></ul></ul><ul><ul><li>Wildlife biologists & hantavirus </li></ul></ul><ul><li>Foodborne </li></ul><ul><ul><li>E.coli </li></ul></ul>
  18. 19. Risk Factors <ul><li>Recreational Activities </li></ul><ul><ul><li>Camping & Lyme disease </li></ul></ul><ul><li>Farm Settings </li></ul><ul><ul><li>Sheep & Q-fever </li></ul></ul><ul><li>Travel </li></ul><ul><ul><li>Maylasia & Nipha </li></ul></ul><ul><ul><li>Australia & Hendra </li></ul></ul>
  19. 20. Yersinia pestis <ul><li>Family Enterobacteriaceae </li></ul><ul><li>Gram negative coccobacillus (pleomorphic) </li></ul><ul><li>Aerobic, Facultatively anaerobic </li></ul><ul><li>Facultative intracellular pathogen </li></ul><ul><li>Survival </li></ul><ul><ul><li>Briefly in soil </li></ul></ul><ul><ul><li>Soft tissue ~1 week </li></ul></ul><ul><ul><li>Frozen - years </li></ul></ul>
  20. 21. History <ul><li>Outbreaks </li></ul><ul><ul><li>Justinian’s pandemic: 540-590 </li></ul></ul><ul><ul><li>Black Death pandemic: 1346~1400 </li></ul></ul><ul><ul><li>Great Plague of London: 1665 </li></ul></ul><ul><li>Hawaii, 1899 </li></ul><ul><li>San Francisco, 1900 </li></ul>
  21. 22. Black Death Pandemic <ul><li>Sudden appearance in Europe 1347 </li></ul><ul><ul><li>Rattus rattus and Xenopsylla cheopis </li></ul></ul><ul><li>Quarantine </li></ul><ul><li>Sporadic outbreaks throughout 14th century </li></ul><ul><li>17-55 million perished (1/3 of population) </li></ul>
  22. 23. Transmission to Humans <ul><li>Flea bite ~78% </li></ul><ul><ul><li>Especially those associated with ground squirrels </li></ul></ul><ul><li>Direct animal contact ~20% </li></ul><ul><ul><li>Tissues, body fluids, scratches, bites </li></ul></ul><ul><ul><ul><li>Y. pestis enters through break in skin </li></ul></ul></ul><ul><li>Aerosol (ie, cough) ~2% </li></ul><ul><ul><li>Cats </li></ul></ul><ul><li>Human cases, April-November </li></ul>
  23. 24. Flea Vectors <ul><li>Can live off host for months </li></ul><ul><li>Many species can transmit </li></ul>
  24. 28. Plague Epidemiology in Nature <ul><li>Sylvatic (wild) </li></ul><ul><li>Urban (domestic) </li></ul><ul><li>Reservoirs </li></ul><ul><ul><li>Rock squirrels </li></ul></ul><ul><ul><li>Ground squirrels </li></ul></ul><ul><ul><li>Prairie dogs </li></ul></ul><ul><ul><li>Mice </li></ul></ul><ul><ul><li>Voles </li></ul></ul><ul><ul><li>Others </li></ul></ul>
  25. 29. Sylvatic Plague <ul><li>Enzootic </li></ul><ul><ul><li>Plague maintained at steady level in rodent populations </li></ul></ul><ul><ul><li>Low death rates </li></ul></ul><ul><ul><li>Mice, voles </li></ul></ul>
  26. 30. Sylvatic Plague <ul><li>Epizootic </li></ul><ul><ul><li>Large die-offs, fleas change hosts </li></ul></ul><ul><ul><li>Amplifying hosts: prairie dogs, ground squirrels, rock squirrels, woodrats, chipmunks </li></ul></ul><ul><ul><li>Expansion into human occupied areas </li></ul></ul><ul><ul><li>Greatest threat to humans </li></ul></ul>
  27. 31. Robert B. Crave. Plague. Infectious Diseases, 5 th ed. J.B. Lippincott Co. 1994.
  28. 32. Urban Plague <ul><li>Infected fleas or rodents move to urban area </li></ul><ul><li>Interface areas around homes </li></ul><ul><li>Commensal (domestic) rodents </li></ul><ul><ul><li>Roof rat, Norway rat </li></ul></ul><ul><li>Rat fleas may feed on humans </li></ul><ul><ul><li>Poverty, filth, homelessness </li></ul></ul>
  29. 33. Human Disease <ul><li>Bubonic: </li></ul><ul><ul><li>Cutaneous infection </li></ul></ul><ul><ul><li>Swollen, tender lymph glands (buboes) </li></ul></ul><ul><ul><li>Fever, chills, headache, exhaustion </li></ul></ul><ul><li>Septicemic </li></ul><ul><ul><li>Multiplication in bloodstream </li></ul></ul><ul><ul><li>Fever, chills, prostration, </li></ul></ul><ul><ul><li>abdominal pain, shock, </li></ul></ul><ul><ul><li>bleeding into skin </li></ul></ul>
  30. 34. Human Disease <ul><li>Pneumonic: </li></ul><ul><ul><li>1 – 4 day incubation period </li></ul></ul><ul><ul><li>Infection of the lungs </li></ul></ul><ul><ul><li>High fever, chills, cough, difficulty breathing, bloody sputum </li></ul></ul><ul><ul><li>Most likely for BT (may also see gastrointestinal manifestations) </li></ul></ul><ul><ul><li>100% fatal if not treated early </li></ul></ul>
  31. 35. Laboratory Confirmation <ul><li>Acceptable specimens </li></ul><ul><ul><li>Material from infected bubo </li></ul></ul><ul><ul><li>Blood specimen (Series taken 10-30 minutes apart) </li></ul></ul><ul><ul><li>Bronchial or Tracheal Wash </li></ul></ul><ul><ul><li>Sputum (Not the best) </li></ul></ul>
  32. 36. Laboratory Diagnostic Tests PLAGUE Colonial Morphology on SBA at 72 hrs Gram Stain
  33. 37. Plague Treatment and Prophylaxis <ul><li>Without treatment: Death 2-6 days after exposure </li></ul><ul><li>Treatment is effective if begun early </li></ul><ul><li>Symptomatic Exposed (cough or fever) </li></ul><ul><ul><li>Streptomycin or Gentamicin </li></ul></ul><ul><ul><li>Doxycycline or Tetracycline </li></ul></ul><ul><ul><li>Ciprofloxacin </li></ul></ul><ul><li>Post-exposure Prophylaxis </li></ul><ul><ul><li>Doxycycline or Ciprofloxacin (7 days) </li></ul></ul><ul><li>Fever/Cough watch </li></ul>
  34. 38. <ul><li>Anthrax </li></ul><ul><li>Anthrax is primarily a disease of herbivorous mammals, although other mammals and some birds have been known to contract it. Until the introduction and widespread use of effective veterinary vaccines, it was a major cause of fatal disease in cattle, sheep, goats, camels, horses, and pigs throughout the world. </li></ul>
  35. 39. Anthrax <ul><li>Humans generally acquire the disease directly or indirectly from infected animals, or occupational exposure to infected or contaminated animal products. Control in livestock is therefore the key to reduced incidence. The disease is generally regarded as being non-contagious. Records of person-to-person spread exist, but are rare. </li></ul>
  36. 40. <ul><li>Leptospirosis </li></ul><ul><li>Leptospirosis is an infection in rodents and other wild and domesticated species. Rodents are implicated most often in human cases. The infection in man is contracted through skin abrasions and the mucosa of the nose, mouth and eyes. Exposure through water contaminated by urine from infected animals is the most common route of infection. Human-to-human transmission is rare. </li></ul>
  37. 41. Leptospirosis <ul><li>Outdoor and agricultural workers (rice-paddy and sugarcane workers for example) are particularly at risk but it is also a recreational hazard to those who swim or wade in contaminated waters. In endemic areas the number of leptospirosis cases may peak during the rainy season and even may reach epidemic proportions in case of flooding because the floods cause rodents to move into the city. </li></ul>
  38. 43. Q-fever <ul><li>Coxiella burnetii </li></ul><ul><ul><li>Rickettsial agent </li></ul></ul><ul><ul><li>Obligate intracellular parasite </li></ul></ul><ul><ul><li>Stable and resistant </li></ul></ul><ul><ul><li>Killed by pasteurization </li></ul></ul><ul><ul><li>Two antigenic phases </li></ul></ul><ul><ul><ul><li>Phase 1: virulent </li></ul></ul></ul><ul><ul><ul><li>Phase 2: less pathogenic </li></ul></ul></ul>
  39. 44. Transmission <ul><li>Aerosol </li></ul><ul><ul><li>Parturient fluids </li></ul></ul><ul><ul><ul><li>10 9 bacteria per gram of placenta </li></ul></ul></ul><ul><ul><li>Urine, feces, milk </li></ul></ul><ul><li>Direct contact </li></ul><ul><li>Fomites </li></ul><ul><li>Ingestion </li></ul><ul><li>Arthropods (ticks) </li></ul>
  40. 45. Transmission <ul><li>Person-to-person (rare) </li></ul><ul><ul><li>Transplacental (congenital) </li></ul></ul><ul><ul><li>Blood transfusions </li></ul></ul><ul><ul><li>Intradermal inoculation </li></ul></ul><ul><ul><li>Bone marrow transplants </li></ul></ul><ul><ul><li>Possibly sexually transmitted </li></ul></ul>
  41. 46. Acute Infection <ul><li>Flu-like, self limiting </li></ul><ul><li>Atypical pneumonia (30-50%) </li></ul><ul><ul><li>Non-productive cough, chest pain </li></ul></ul><ul><ul><li>Acute respiratory distress possible </li></ul></ul><ul><li>Hepatitis </li></ul><ul><li>Skin rash (10%) </li></ul><ul><li>Other signs (< 1%) </li></ul><ul><ul><li>Myocarditis, pericarditis, meningoencephalitis </li></ul></ul><ul><li>Death: 1-2% </li></ul>
  42. 47. Prognosis <ul><li>Overall case-fatality rate <1 - 2.4% </li></ul><ul><li>50% cases self-limiting </li></ul><ul><li>Only 2% develop severe disease </li></ul><ul><li>Active chronic disease </li></ul><ul><ul><li>Usually fatal if left untreated </li></ul></ul><ul><ul><li>Fatality for endocarditis: 35-55% </li></ul></ul><ul><ul><li>50-60% need valve replacement </li></ul></ul>
  43. 48. Diagnosis <ul><li>Serology (rise in titer) </li></ul><ul><ul><li>IFA, CF, ELISA, microagglutination </li></ul></ul><ul><li>DNA detection methods </li></ul><ul><ul><li>PCR </li></ul></ul><ul><li>Isolation of organism </li></ul><ul><ul><li>Risk to laboratory personnel </li></ul></ul><ul><ul><li>Rarely done </li></ul></ul>
  44. 49. Treatment <ul><li>Treatment </li></ul><ul><ul><li>Doxycycline </li></ul></ul><ul><ul><li>Chronic disease – long course </li></ul></ul><ul><ul><ul><li>2-3 years of medication </li></ul></ul></ul><ul><li>Immunity </li></ul><ul><ul><li>Long lasting (possibly lifelong) </li></ul></ul>
  45. 50. Prevention and Control <ul><li>Pasteurization </li></ul><ul><li>Vaccination </li></ul><ul><ul><li>Human and animal </li></ul></ul><ul><li>Eradication not practical </li></ul><ul><ul><li>Too many reservoirs </li></ul></ul><ul><ul><li>Constant exposure </li></ul></ul><ul><ul><li>Stability of agent in environment </li></ul></ul>
  46. 51. Rabies Virus <ul><li>member of the Lyassavirus of the Rhabdoviridae. </li></ul><ul><li>ssRNA enveloped virus, characteristic bullet-shaped appearance with 6-7 nm spike projections. </li></ul><ul><li>virion 130-240nm * 80nm </li></ul><ul><li>5 proteins; G, M, N, L, S </li></ul><ul><li>Exceedingly wide range of hosts. </li></ul><ul><li>There are 5 other members of Lyassavirus : Mokola, Lagosbat, Duvenhage, EBL-1, and EBL-2. </li></ul><ul><li>Duvenhage and EBL-2 have been associated with human rabies. </li></ul>
  47. 52. Rabies Virus Structure of rabies virus (Source: CDC) Rabies virus particles
  48. 53. Epidemiology <ul><li>Rabies is a zoonosis which is prevalent in wildlife. The main animals involved differs from continent to continent. </li></ul><ul><li>  </li></ul><ul><ul><li>Europe fox, bats </li></ul></ul><ul><ul><li>Middle East wolf, dog </li></ul></ul><ul><ul><li>Asia dog </li></ul></ul><ul><ul><li>Africa dog, mongoose, antelope </li></ul></ul><ul><ul><li>N America foxes, skunks, raccoons, insectivorous bats </li></ul></ul><ul><ul><li>S America dog, vampire bats </li></ul></ul>
  49. 54. Pathogenesis <ul><li>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. </li></ul><ul><li>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. </li></ul><ul><li>It then spreads to the CNS in the endoneurium of the Schwann cells. </li></ul><ul><li>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. </li></ul>
  50. 55. Laboratory Diagnosis <ul><li>Histopathology - Negri bodies are pathognomonic of rabies. However, Negri bodies are only present in 71% of cases. </li></ul><ul><li>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. </li></ul><ul><li>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. </li></ul><ul><li>Serology - circulating antibodies appear slowly in the course of infection but they are usually present by the time of onset of clinical symptoms.   </li></ul>
  51. 56. Negri Body in neuron cell (source: CDC) Positive DFA test (Source: CDC Diagnosis of Rabies
  52. 57. Control of Rabies <ul><li>Urban - canine rabies accounts for more than 99% of all human rabies. Control measures against canine rabies include; </li></ul><ul><ul><li>stray dog control. </li></ul></ul><ul><ul><li>Vaccination of dogs </li></ul></ul><ul><ul><li>quarantine of imported animals </li></ul></ul><ul><li>Wildlife - this is much more difficult to control than canine rabies. However, there are on-going trials in Europe where bait containing rabies vaccine is given to foxes. Success had been reported in Switzerland. </li></ul>
  53. 58. Arenaviruses <ul><li>Enveloped ssRNA viruses </li></ul><ul><li>virions 80-150nm in diameter </li></ul><ul><li>genome consists of 2 pieces of ambisense ssRNA. </li></ul><ul><li>7-8 nm spikes protrude from the envelope. </li></ul><ul><li>host cell ribosomes are usually seen inside the outer membrane but play no part in replication. </li></ul><ul><li>Members of arenaviruses include Lassa fever, Junin and Macupo viruses. </li></ul>Lassa fever virus particles budding from the surface of an infected cell. (Source: CDC)
  54. 59. Lassa Fever <ul><li>Found predominantly in West Africa, in particular Nigeria, Sierra Leone and Liberia. </li></ul><ul><li>The natural reservoir is multimammate rat ( Mastomys ) </li></ul><ul><li>Man may get infected through contact with infected urine and faeces. </li></ul><ul><li>Man to man transmission can occur through infected bodily fluids and Lassa fever had caused well-documented nosocomial outbreaks. </li></ul>Mastomys
  55. 60. Clinical Manifestations <ul><li>Incubation period of 3-5 days. </li></ul><ul><li>Insidious onset of non-specific symptoms such as fever, malaise, myalgia and a sore throat. </li></ul><ul><li>Typical patchy or ulcerative pharyngeal lesions may be seen. </li></ul><ul><li>Severe cases may develop the following: </li></ul><ul><ul><li>Myocarditis </li></ul></ul><ul><ul><li>Pneumonia </li></ul></ul><ul><ul><li>Encephalopathy </li></ul></ul><ul><ul><li>Haemorrhagic manifestations </li></ul></ul><ul><ul><li>Shock </li></ul></ul><ul><li>The reported mortality rate for hospitalized cases of Lassa fever is 25%. It carries a higher mortality in pregnant women. </li></ul>
  56. 61. Laboratory Diagnosis <ul><li>Lassa fever virus is a Group 4 Pathogen. Laboratory diagnosis should only be carried out in specialized centers. </li></ul><ul><ul><li>Detection of Virus Antigen - the presence of viral antigen in sera can be detected by EIA. The presence of viral antigen precedes that of IgM. </li></ul></ul><ul><ul><li>Serology - IgM is detected by EIA. Using a combination of antigen and IgM antibody tests, it was shown that virtually all Lassa virus infections can be diagnosed early. </li></ul></ul><ul><ul><li>Virus Isolation - virus may be cultured from blood, urine and throat washings. Rarely carried out because of safety concerns. </li></ul></ul><ul><ul><li>RT-PCR - being used experimentally. </li></ul></ul>
  57. 62. Management and Prevention <ul><li>Good supportive care is essential. </li></ul><ul><li>Ribavirin - had been shown to be effective against Lassa fever with a 2 to 3 fold decrease in mortality in high risk Lassa fever patients. Must be given early in the illness. </li></ul><ul><li>Hyperimmune serum - the effects of hyperimmune serum is still uncertain although dramatic results have been reported in anecdotal case reports. </li></ul><ul><li>Postexposure Prophylaxis - There is no established safe prophylaxis. Various combinations of hyperimmune immunoglobulin and/or oral ribavirin may be used. </li></ul><ul><li>There is no vaccine available, prevention of the disease depends on rodent control. </li></ul>
  58. 63. Hantaviruses <ul><li>Forms a separate genus in the Bunyavirus family. </li></ul><ul><li>Unlike under bunyaviridae, its transmission does not involve an arthropod vector. </li></ul><ul><li>Enveloped RNA virus. </li></ul><ul><li>Virions 98nm in diameter with a characteristic square grid-like structure. </li></ul><ul><li>Genome consists of three RNA segments: L, M, and S. </li></ul>
  59. 64. History <ul><li>Haemorrhagic Fever with Renal Syndrome (HFRS: later renamed hantavirus disease) first came to the attention of the West during the Korean war when over 3000 UN troops were afflicted. </li></ul><ul><li>It transpired that the disease was not new and had been described by the Chinese 1000 years earlier. </li></ul><ul><li>In 1974, the causative was isolated from the Korean Stripped field mice and was called Hantaan virus. </li></ul><ul><li>In 1995, a new disease entity called hantavirus pulmonary syndrome was described in the “four corners” region of the U.S. </li></ul>
  60. 65. Some Subtypes of hantaviruses associated with human disease <ul><li>Hantaan, Porrogia and related viruses - This group is found in China, Eastern USSR, and some parts of S. Europe. It is responsible for the severe classical type of hantavirus disease. It is carried by stripped field mice. ( Apodemus agrarius) </li></ul><ul><li>Seoul type - associated with moderate hantavirus disease. It is carried by rats and have a worldwide distribution. It has been identified in China, Japan, Western USSR, USA and S.America. </li></ul><ul><li>Puumala type - mainly found in Scandinavian countries, France, UK and the Western USSR. It is carried by bank voles ( Clethrionomys glareolus) and causes mild hantavirus disease (nephropathia epidemica). </li></ul><ul><li>Sin Nombre - found in many parts of the US, Canada and Mexico. Carried by the Deer Mouse ( Peromyscus maniculatus ) and causes hantavirus pulmonary syndrome. </li></ul>
  61. 66. Rodent Carriers of Hantaviruses Stripped field mouse ( Apodemus agrarius ) Bank vole ( Clethrionomys glareolus ) Deer Mouse ( Peromyscus maniculatus ) Rat (Rattus)
  62. 67. Clinical Features of Hantavirus Disease <ul><li>The multisystem pathology of HVD is characterized by damage to capillaries and small vessel walls, resulting in vasodilation and congestion with hemorrhages. </li></ul><ul><li>Classically, hantavirus disease consists of 5 distinct phases. These phases may be blurred in moderate or mild cases. </li></ul><ul><ul><li>Febrile phase - abrupt onset of a severe flu-like illness with a erythematous rash after an incubation period of 2-3 days. </li></ul></ul><ul><ul><li>Hypotensive phase - begins at day 5 of illness </li></ul></ul><ul><ul><li>Oliguric phase - begins at day 9 of illness. The patient may develop acute renal failure and shock. Haemorrhages are usually confined to petechiae. The majority of deaths occur during the hypotensive and oliguric phases </li></ul></ul><ul><ul><li>Diuretic phase - this occurs between days 12-14 . </li></ul></ul><ul><ul><li>Convalescent phase - this may require up to 4 months. </li></ul></ul>
  63. 68. Comparative Clinical Features of Recognized Hantavirus Disease (HVD)
  64. 69. Hantavirus Pulmonary Syndrome (HPS) <ul><li>More than 250 cases of HPS have been reported throughout North and South America with a mortality rate of 50% </li></ul><ul><li>In common with classical HVD, HPS has a similar febrile phase. </li></ul><ul><li>However, the damage to the capillaries occur predominantly in the lungs rather than the kidney. </li></ul><ul><li>Shock and cardiac complications may lead to death. </li></ul><ul><li>The majority of HPS cases are caused by the Sin Nombre virus. The other cases are associated with a variety of other hantaviruses e.g. New York and Black Creek Canal viruses. </li></ul>
  65. 70. Diagnosis <ul><li>Serological diagnosis - a variety of tests including IF, HAI, SRH, ELISAs have been developed for the diagnosis of HVD and HPS. </li></ul><ul><li>Direct detection of antigen - this appears to be more sensitive than serology tests in the early diagnosis of the disease. The virus antigen can be demonstrated in the blood or urine. </li></ul><ul><li>RT-PCR - found to of great use in diagnosing hantavirus pulmonary syndrome. </li></ul><ul><li>Virus isolation - isolation of the virus from urine is successful early in hantavirus disease. Isolation of the virus from the blood is less consistent. Sin Nombre virus has never been isolated from patients with HPS. </li></ul><ul><li>Immunohistochemistry - useful in diagnosing HPS. </li></ul>
  66. 71. Treatment and Prevention <ul><li>Treatment of HVD and HPS depends mainly on supportive measures. </li></ul><ul><li>Ribavirin - reported to be useful if given early in the course of hantavirus disease. Its efficacy is uncertain in hantavirus pulmonary syndrome. </li></ul><ul><li>Vaccination - an inactivated vaccine is being tried out in China. Other candidate vaccines are being prepared. </li></ul><ul><li>Rodent Control - control measures should be aimed at reducing contact between humans and rodents. </li></ul>
  67. 72. Rodenticides
  68. 73. Rodenticides may be classified in several ways but the most medically useful of classifying them is by toxicity. <ul><li>Highly toxic rodenticides </li></ul><ul><li>Highly toxic rodenticides are those substances with a single dose LD50 of less than 50mg/kg body weight. This group includes thallium, sodium monofluoroacetate, strychnine, zinc phosphide, yellow phosphorus and arsenic. Some of these compounds have largely been abandoned because of serious human toxicity. </li></ul>
  69. 74.  Thallium Thallium is an odourless; tasteless compound that can be absorbed through unbroken skin and can cause death secondarily. There is no known effectiveness antidote for thallium. In sublethal doses, thallium can cause complete loss of hair, paresthesias, nausea, vomiting and abdominal pain, pulmonary oedema and bronchopneumonia. Rodenticides
  70. 75.  Sodium monofluoroacetate Sodium monofluoroacetate is a white, odourless, tasteless, water-soluble salt that looks like flour or baking soda. Unlike thallium, sodium monofluoroacetate cannot be absorbed through unbroken skin. However, it is toxic when ingested, inhaled in dust or absorbed through open wounds. Toxic effects in humans, extrapolated from observed effects in rhesus monkeys, might be nausea and apprehension followed by cardiac arrhythmias, seizures and coma. Death may result from ventricular tachycardia and fibrillation or respiratory failure secondary to pulmonary oedema or bronchopneumonia. · Strychnine Strychnine is a central nervous system stimulant that causes painful recurrent motor seizures. It is rapidly absorbed from the gastrointesstinal tract and nasal mucosa but not from the skin. Symptoms include nausea and vomiting, diaphoresis, blurred vision and severe symmetric extensor muscle spasms during which patients are conscious. Rodenticides
  71. 76.  Zinc phosphide Zinc phosphide is another highly toxic rodenticide in which its colour, &quot;rotten fish&quot; odour and taste make it unattractive to other animals but attractive to other animals but attractive to rats. Usually mixed with a tartar emetic, it nevertheless is highly toxic because it releases phosphine gas on contact with water or weak acids. Poisoned patients manifest hypotension, dyspnea, pulmonary oedema, circulatory collapse, vomiting, cardiac arrhythmias, convulsions and coma, renal damage, leukopenia and death in four days to two weeks. Rodenticides
  72. 77.  Yellow phosphorus Yellow phosphorus is highly poisonous compares with the relatively non- toxic red phosphorus. When used as a rodenticide, yellow phosphorus is usually mixed with molasses or peanut butter and spread on bread as bait for rodents or roaches. For obvious reasons, it is occasionally ingested by children. Yellow phosphorus is most toxic to the gastrointestinal tract and liver. Ingestion is usually followed by vomiting which is said to be luminescent and have a garlicky odour. Delirium, coma and death from cardiovascular collapse may ensue. · Arsenic Arsenic is a white, crystalline powder that causes dysphagia, muscle cramps, convulsions, vomiting and bloody diarrhoea. Death can occur due to circulatory failure. Rodenticides
  73. 78. Low toxicity rodenticides <ul><li>Low toxicity rodenticides are those with LD50 between 500 and 5,000 mg/kg body weight and include red squill, norbomide and anticoagulant, warfarin-type rodenticides, which are the most commonly used rodenticides today. </li></ul><ul><li>· Red squill </li></ul><ul><li>Red squill contains several compounds with chemical and pharmacological properties similar to those of digitalis glycosides. Because of its emetic properties, poor gastrointestinal absorption and decreased potency (compared to that of digitalis), red squill has seldom been associated with human toxicity. </li></ul><ul><li>· Norbomide </li></ul><ul><li>Norbomide is an irreversible smooth muscle constrictor. It causes widespread ischaemic necrosis and death in rats but does not appear to affect other animals or humans, presumably due to the presence of a specific smooth muscle norbomide receptor found only in rats. </li></ul>
  74. 79.  Anticoagulant Anticoagulant rodenticides belong to a group that exerts a blood-thinning effect. It has been used for many decades and are readily available as over- the counter preparations. Technically, these may be divided into two types: hydroxiycoumarin compounds are made up of warfarin, difenacoum, bromadiolone and brodifacoum while the indandiones cover a wide range of chemicals including diphacinone, pindone and chlorphacinone. Aside from warfarin, the others are said to be longer-acting. They produce a more potent and prolonged anticoagulant effect and they are often referred to as superwarfarins Rodenticides
  75. 80. Haemorrhage is the most frequent encountered complication from anticoagulant poisoning. The effect seen in cases of acute ingestion, however, depends very much on whether warfarin or superwarfarin rodenticides have been ingested. A one-time ingestion of warfarin usually does not lead to any bleeding problems. Otherwise, ingestion of warfarin rodenticides has to be done repeatedly over a periods of days before bleeding can occur. Rodenticides
  76. 81. Warfarin poisoning can cause spontaneous bleeding, usually from the nose, gums as well as the gastrointestinal and urinary tracts. Haemorrhage into the skin and brain can also occur, throuh this is less common. Ingestion of superwarfarin, on the other hand, can produce a prolonged coagulopathy in humans even with a single ingestion. This is thought to be associated with the firmer binding capability of superwarfarins to the lipophilic sites of the liver Rodenticides