Epidemiology and Control of Zoonotic Infections

1. Epidemiology and Control of Zoonotic Infections Emerging Infections: Monkeypox, Nipah virus, Avian influenza Jason Stull, CDHS, Veterinary Public Health Jstull@dhs.ca.gov 916-552-9740 Pictures of DaVinci horses from www2.truman.edu/ ~capter/jins343/vinc.htm Wing picture taken from www.geocities.com/ CollegePark/8265/gall4.htm Pictures of DaVinci horses from www2.truman.edu/ ~capter/jins343/vinc.htm Wing picture taken from www.geocities.com/ CollegePark/8265/gall4.htm

2. Overview � Emerging Zoonoses Background Examples Monkeypox Nipah virus Avian Influenza

11. Monkeypox

12. Monkeypox - Background Rare zoonosis found in Western and Central Africa 1st identified in1958 in primates Documented in numerous animal species 1st human infection 1970 > 400 documented human cases may infect rodents; African squirrel � host? Human - Congo may infect rodents; African squirrel � host? Human - Congo

13. Monkeypox Virus Orthopoxvirus Double stranded DNA Similar but distinct from Smallpox and Vaccinia Same group of virus � vaccinia (smallpox vaccine) Explain what similar and distinct Same group of virus � vaccinia (smallpox vaccine) Explain what similar and distinct

14. Clinical Features - Animals Fever Cough Ocular discharge Lymphadenopathy Dermal rash Decreased appetite Death possible

15. Clinical Features - Humans Transmission - bite or contact, respiratory droplets Incubation: 10-14 days Clinical signs � Fever, headache, muscle aches, swollen lymph nodes Papular rash, lesions in the same stage, milder than smallpox, illness lasts 2-4 weeks before lesions crusted Rarely fatal; no specific treatment Smallpox vaccine is protective Contact lesion, blood, bedding, long periods of face-face contactContact lesion, blood, bedding, long periods of face-face contact

16. Child: Primary inoculation site. 14 days after prairie dog bites, 11 days after febrile illness, hospital day 5. 5/11, Mothers� Day, Two prairie dogs given to Mother in Dorchester, WI. 5/13 Prairie dog bites 3 1/2 year old daughter 5/15 Prairie dog seen by veterinarian due to skin lesions and discharge from nose and eyes. Prairie bites veterinarian technician. 5/16 Child get fevers, wounds are red. 5/20 Child seen by primary care physician. Child has URI-like symptoms. Prairie dog dies. Head sent by veterinarian for rabies check, negative. Enlarged submandibular lymph gland harvested and sent for cultures. 5/22 Child hospitalized because of festering wounds, fevers, sweats, right eye discharge, new skin lesions, including scalp, perineum and extremities. 5/25 Dermatology consult obtained because of persistent fevers and new skin lesions. Primary inoculation sites on right index finger and dorsal left hand have central hemorrhagic crusts 5/27 28 year old mother gets vesiculation around cat scratch on dorsal right hand. Biopsies taken for viral culture, electron microscopy, and histology. Swab sent for aerobic culture. Mother has had drenching sweats, malaise, sore throat and does not feel well. 5/28 Mother has disseminated skin lesions. 5/29 Mother�s primary lesion is re-biopsied. Disseminated lesion on right forearm biopsied. 5/30 Orthopox virus seen on mothers initial biopsy. Valacyclovir stopped. Orthopox virus cultured from skin. 5/31-6/1 38 year old father gets sweats, malaise and develops multiple skin lesions. 6/2 Primary care physician reports 12-15 disseminated skin lesions on all extremities, trunk and head. Father now feeling well but kept out of work. 6/5 Family seen in clinic. All feeling well. Primary lesions are crusted ulcerations. Mother�s tonsils are smaller and she has no adenopathy. Father has at least two lesions that are still vesiculated and some axillary adenopathy. Acute serum and viral cultures obtain from father. Mother and Father told to stay out of work. Orthopox virus cultured from prairie dog lymph node. 5/11, Mothers� Day, Two prairie dogs given to Mother in Dorchester, WI. 5/13 Prairie dog bites 3 1/2 year old daughter 5/15 Prairie dog seen by veterinarian due to skin lesions and discharge from nose and eyes. Prairie bites veterinarian technician. 5/16 Child get fevers, wounds are red. 5/20 Child seen by primary care physician. Child has URI-like symptoms. Prairie dog dies. Head sent by veterinarian for rabies check, negative. Enlarged submandibular lymph gland harvested and sent for cultures. 5/22 Child hospitalized because of festering wounds, fevers, sweats, right eye discharge, new skin lesions, including scalp, perineum and extremities. 5/25 Dermatology consult obtained because of persistent fevers and new skin lesions. Primary inoculation sites on right index finger and dorsal left hand have central hemorrhagic crusts 5/27 28 year old mother gets vesiculation around cat scratch on dorsal right hand. Biopsies taken for viral culture, electron microscopy, and histology. Swab sent for aerobic culture. Mother has had drenching sweats, malaise, sore throat and does not feel well. 5/28 Mother has disseminated skin lesions. 5/29 Mother�s primary lesion is re-biopsied. Disseminated lesion on right forearm biopsied. 5/30 Orthopox virus seen on mothers initial biopsy. Valacyclovir stopped. Orthopox virus cultured from skin. 5/31-6/1 38 year old father gets sweats, malaise and develops multiple skin lesions. 6/2 Primary care physician reports 12-15 disseminated skin lesions on all extremities, trunk and head. Father now feeling well but kept out of work. 6/5 Family seen in clinic. All feeling well. Primary lesions are crusted ulcerations. Mother�s tonsils are smaller and she has no adenopathy. Father has at least two lesions that are still vesiculated and some axillary adenopathy. Acute serum and viral cultures obtain from father. Mother and Father told to stay out of work. Orthopox virus cultured from prairie dog lymph node.

17. Child: Secondary lesions, adjacent to primary inoculation site on left hand.

18. Child and mother, crusted primary inoculation sites.

19. Monkeypox outbreak - 2003 April 9, 2003 � 762 African rodents imported to Texas ? Midwest

20. Redistribution leads to prairie dogs infected at pet stores Monkeypox outbreak - 2003

21. Infected prairie dogs infect buyers Monkeypox outbreak - 2003

22. Monkeypox outbreak - 2003 71 cases 35 lab-confirmed Several states Median age = 28 y.o. 26% hospitalized, no deaths 30 get smallpox vaccination

24. California�s Response Alerted animal-related professionals Conducted onsite inspections of the 13 facilities possessing prairie dogs CDFG permit required to possess most wildlife No cases identified, illegal importation? CDC and FDA issue embargo on importation of rodents from AfricaCDC and FDA issue embargo on importation of rodents from Africa

25. NIPAH VIRUS

26. Nipah Virus - Background First identified in 1999 in Malaysia Paramyxoviridae Single stranded RNA virus Natural host = Fruit Bats (�Flying Fox�)

27. Nipah Virus � Malaysia and Singapore Outbreak Sept 1998-April 1999 265 human cases 105 Deaths 93% Pig farm/abattoir workers >900,000 pigs culled Exposure from bats in orchards; Imported to Singapore via live pigs Exposure from bats in orchards; Imported to Singapore via live pigs

28. Nipah Virus � Epidemic Curve

29. Nipah Virus - Transmission Flying Foxes

30. Nipah Virus - Animal Disease Natural Reservoir - Fruit bats Asymptomatic Virus in urine Pigs Other animals Cats Dogs Horses

31. Nipah Virus - Human Disease Incubation 3 to 14 days Symptomatic cases Onset �influenza-like� illness Progresses to encephalitis 40% fatal if symptomatic Treatment Supportive care Ribavirin (efficacy?) Fever and headacheFever and headache

32. Nipah Virus - Human Disease Live virus found in human respiratory secretions and urine No known human-to-human transmission during outbreak Relapse encephalitis (12 cases) Late-onset encephalitis (10 cases) Mean time for complications 8.4 months

33. Nipah Virus - Diagnostic Tests Serology Immunohistochemistry MRI Histopathology Vasculitis Endothelial damage Characteristic viral inclusions MRI - Multiple discrete small high-signal-intensity lesions FLAIR-fluid attenuated inversion recovery sequences improve imaging MRI - Multiple discrete small high-signal-intensity lesions FLAIR-fluid attenuated inversion recovery sequences improve imaging

34. Swine control Slaughter Transportation bans Education Protective equipment Surveillance to detect swine and human cases Nipah Virus � Control & Prevention

35. Nipah Virus � Continues� Outbreaks in 2001 and 2003 in Bangladesh 25 cases No obvious zoonotic source Transmission: Close contact with other patients? Exposure to common source?

36. Avian Influenza

37. Influenza - Background Orthomyxoviridae family Gene segments can re-assort Infected species include: birds, pigs, humans, horses and sea mammals.

38. Surface proteins Hemagglutinin (HA) Site of attachment to host cells Antibody to HA is protective Neuraminadase (NA) Helps to release virions from cells Antibody to NA can help modify disease severity

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40. Genetic Changes Drift � constant small genetic changes caused by natural selection when antibodies to virus are made Partial antibody protection May result in epidemic Shift- abrupt, major genetic change creating new hemagglutinin and/or neuraminidase proteins Little or no antibody protection May result in pandemic Drift � seasonal epidemics Shift - Drift � seasonal epidemics Shift -

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46. The Ultimate Mixing Vessel?

47. Virus Classification - Birds Low Pathogenic (LPAI) Most AI virus strains Cause little or no clinical disease Can mutate to HPAI Highly Pathogenic (HPAI) Highly infectious to chickens Can inflect flocks without warning Spreads rapidly in flocks and flock to flock Morbidity and mortality can approach 100% Death within 12 days of onset Most AI virus strains are classified as LPAI; they cause little or no clinical signs of disease in infected birds. However, some LPAI virus strains can mutate to HPAI given right field conditions. Morbidity and mortality often approach 100% within 2 to 12 days after the first signs of illness. Any survivors are usually in poor condition and do not begin laying again for several weeks. HPAI extremely infectious and fatal to chickens; Can infect without warning in flocks; spreads rapidly in flocks and flock to flock. USDA APHIS works to keep HPAI from establishing within the US poultry population.Most AI virus strains are classified as LPAI; they cause little or no clinical signs of disease in infected birds. However, some LPAI virus strains can mutate to HPAI given right field conditions. Morbidity and mortality often approach 100% within 2 to 12 days after the first signs of illness. Any survivors are usually in poor condition and do not begin laying again for several weeks. HPAI extremely infectious and fatal to chickens; Can infect without warning in flocks; spreads rapidly in flocks and flock to flock. USDA APHIS works to keep HPAI from establishing within the US poultry population.

49. Influenza - Birds Clinical signs: Decline egg production Mild respiratory disorder Chronic respiratory infection Death Diagnosis � serology, egg inoculation Control Management is best prevention (Biosecurity) De-population Vaccinate?

50. Influenza A - Birds Outbreaks occur throughout the world Low pathogenic avian influenza Limited to poultry Sporadic Recently in U.S.: Texas (2004) � H5N2 Maryland (2004) � H7N2 Pennsylvania (2004) � H2N2 Delaware & New Jersey (2004) � H7N2

51. Influenza - Animal Transmission Migratory waterfowl � natural reservoir Initial source of infection Poultry, migratory waterfowl, domestic pigs, pet birds Shed by feces, nasal secretions, saliva Aerosol Shared drinking water Fomites Migratory waterfowl are widely considered to be the reservoirs of avian influenza virus. Feces and respiratory secretions contain large amounts of virus, which can infect a new host through the conjunctiva or respiratory tract. Avian influenza virus can spread by aerosols when birds are in close proximity, and might also be transmitted through shared drinking water. The virus appears to be present in eggs laid by infected hens, but they are unlikely to survive and hatch. Fomites and infected birds can transmit the disease between flocks. In one outbreak in Pennsylvania, the virus may have been spread by garbage flies. Airborne dissemination may be possible as well as movement of infected poultry. In experimental studies AI viruses can be excreted in the feces and maintained in the environment and can re-emerge after a significantly stressful event. Once a flock is infected, it should be considered a potential source of virus for life. Fecal-oralMigratory waterfowl are widely considered to be the reservoirs of avian influenza virus. Feces and respiratory secretions contain large amounts of virus, which can infect a new host through the conjunctiva or respiratory tract. Avian influenza virus can spread by aerosols when birds are in close proximity, and might also be transmitted through shared drinking water. The virus appears to be present in eggs laid by infected hens, but they are unlikely to survive and hatch. Fomites and infected birds can transmit the disease between flocks. In one outbreak in Pennsylvania, the virus may have been spread by garbage flies. Airborne dissemination may be possible as well as movement of infected poultry. In experimental studies AI viruses can be excreted in the feces and maintained in the environment and can re-emerge after a significantly stressful event. Once a flock is infected, it should be considered a potential source of virus for life. Fecal-oral

52. Influenza - Humans Transmission: Droplets/aerosol, contact Incubation: 1-4 days Shedding: day before onset to 5 days after Acute febrile respiratory illness Symptoms may differ by age Types A and B viruses cause substantial illness and death among humans

54. Impact of Influenza - Humans Seasonal epidemics in temperate regions U.S., Canada, Europe, Russia, China, Japan, Australia, Brazil, Argentina Year-round activity in tropical climates Equatorial Africa, Southeast Asia U.S. impact Average of >200,000 influenza-related hospitalizations/year Average of >36,000 influenza-related deaths/year 3 global pandemics in the 20th century

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57. Confirmed human infections associated with poultry outbreaks: H5N1 (severe respiratory disease) 1997 Hong Kong (18 cases, 6 deaths) 2003 Hong Kong (2 cases, 1 death) H7N7 (mild illness, conjunctivitis) 2003 Netherlands (89 cases, 1 death) H7N3 (mild illness, conjunctivitis) 2004 Canada (2 cases, 0 deaths) H7N3 (British Columbia, Canada, Feb. - April 2004) Highly pathogenic H7N3 detected in chicken farms 2 persons involved in H7N3 poultry outbreak culling activities (mild illness and conjunctivitis; conjunctivitis and headache) H7N3 isolated One worker was not wearing eye protection One worker was wearing glasses Oseltamivir treatment given, full recovery low pathogenic avian influenza A viruses: H9N2 (uncomplicated influenza-like illness) 1998 China (6 cases, no deaths) 1999 Hong Kong (2 cases, no deaths) 2003 Hong Kong (1 case, no death) H7N2 2002, 2003 U.S. (2 cases, no deaths) H7N3 (British Columbia, Canada, Feb. - April 2004) Highly pathogenic H7N3 detected in chicken farms 2 persons involved in H7N3 poultry outbreak culling activities (mild illness and conjunctivitis; conjunctivitis and headache) H7N3 isolated One worker was not wearing eye protection One worker was wearing glasses Oseltamivir treatment given, full recovery low pathogenic avian influenza A viruses: H9N2 (uncomplicated influenza-like illness) 1998 China (6 cases, no deaths) 1999 Hong Kong (2 cases, no deaths) 2003 Hong Kong (1 case, no death) H7N2 2002, 2003 U.S. (2 cases, no deaths)

58. H5N1 in Asia, 2003-05 Unprecedented highly pathogenic avian influenza A (H5N1) outbreak among poultry Farms, backyard flocks affected Millions of chickens, ducks died; >100 million culled

59. H5N1 in Asia, 2003-05

60. Cumulative # of confirmed cases (Jan. 2004 � Feb. 2, 2005): Cambodia � 1 case (1 death) Thailand � 17 cases (12 deaths) Vietnam � 37 cases (29 deaths) Total = 55 cases (42 deaths) Most cases had contact with sick or dead poultry Majority of cases: children, young adults Viruses resistant to antiviral drugs amantadine, rimantadine (susceptible to oseltamivir) No evidence of sustained human-to-human transmission H5N1 in Asia - Human cases

61. Additional H5N1 Issues Can infect cats domestic tigers, leopards (Thailand) Can infect pigs Ducks may be infected without illness

63. Testing for avian influenza (H5N1) should be considered for hospitalized or ambulatory patients with: a.�� Documented temperature of >38�C (>100.4�F), AND b.�� One or more of the following: cough, sore throat, shortness of breath, AND c.�� History of contact with poultry (e.g., visited a poultry farm, a household raising poultry, or a bird market) or a known or suspected human case of influenza A (H5N1) in an H5N1-affected country within 10 days of symptom onset. U.S. Surveillance for H5N1

64. Avian Influenza - Public Health Can spread from poultry to humans Genetic re-assortment ? virus more easily transmitted among people Infection is uncommon, but preventive measures are critical If sustained human-human transmission�

65. Worldwide Influenza Surveillance Systems Group on Influenza Pandemic Preparedness and Emergency Response (GrIPPE) On-farm biosecurity and containment measures Vaccination U.S. bird ban Avian Influenza - Public Health Bird ban � all birds from specific Asian countriesBird ban � all birds from specific Asian countries

66. Prediction & Prevention of Emerging Zoonoses Enhanced communications across disciplinary and agency boundaries Assessment/development of surveillance tools Examination of link between animal-human health outcomes Cross-disciplinary training and research Prediction & prevention of new diseases before resulting in health effects or will we be forced to react after human health is impactedPrediction & prevention of new diseases before resulting in health effects or will we be forced to react after human health is impacted

67. Acknowledgements Dr. Ben Sun Dr. Jim Glover Dr. Gundula Dunne Dr. Janice Louie Dr. Dennis Spann