Zoonoses and Veterinary Public Health

1. Zoonoses and Veterinary Public Health DVM, PHD, OKAMOTO Karoku Prof. Veterinary Public Health, Dep. Veterinary Medicine, Fac. Agriculture, Kagoshima University Approximately 75% of recently emerging infectious diseases affecting humans are diseases of animal origin; approximately 60% of all human pathogens are zoonotic. Quoted from CDC, USA

2. Examples of emerging infectious disease (Pathogen, Year, Natural reservoir) SARS 2003 palm civet et.al HPAI H5N1 1997/2003 Water bird HPS 1993 Rodentia E. Coli O157 1982 Cow/Food BSE 1986/1993 Cow HPS: Hantavirus Pulmonary Syndrome SARS: Severe Acute Respiratory Syndrome West Nile 1999 Bird/Mosquito Ebola 1976 Monkey H1N1 Pandemic 2009 Swine/Bird Lassa 1969 Rodentia BzHF 1994 Rodentia Nipahvirus 1998 Megabat/Swine Hendravirus 1994 Megabat/Horse VzHF 1991 Rodentia Venezuelan & Brazilian Hemorrhagic Fever

3. International Health Regulations(2005): IHR 2005 Annex 2 Decision instrument for the assessment and notification of events Event detected by national surveillance system National IHR Focal Point ● Small pox ● Poliomyelitis(wild type) ●Influenza(new subtype) ●Severe acute respiratory syndrome (SARS) ● Cholera ●Plague ●Yellow fever ● Viral haemorrhagic fevers(Ebola, Lassa, Marburg) ● West Nile fever ● Others(Dengue fever, Rift Valley fever) Each State Party shall notify WHO within 24 hours of assessment. DOES THE EVENT MEET AT LEAST TWO OF THE FOLLOWING CRITERIA? I. Is the public health impact of the event serious? II. Is the event unusual or unexpected? III. Is there a significant risk of international spread? IV. Is there a significant risk of international travel or trade restrictions? Diseases in the red are zoonoses. Event shall be notified to WHO under the International Health Regulations

4. Many of zoonoses have the potential to spread through various means over long distances and to become global problems. Calvin W. Schwabe(1927 – 2006) Veterinary Epidemiology, UC Davis Classification of Zoonoses Dr. Schwabe provided the following classification system of zoonoses based on the type of life cycle of the pathogen. Direct zoonosesare transmitted from an infected vertebrate host to another host by direct contact, fomite or mechanical vector. The pathogen does not undergo developmental change or propagation during the transmission. Cyclozoonosisrequires more than one vertebrate host but no invertebrate host is needed. An example is echinococcosis. Metazoonoses does require an invertebrate host where the pathogen multiples or develops before it can infect a vertebrate host. Saprozoonosesare diseases transferred through a non-animal reservoir, such as a plant, or through the abiotic environment, such as through water or soil.

5. an vertebrate host Avian influenza, Rabies, Hantavirus, Psittacosis, Bovine tuberculosis, Brucellosis, E. coli O157, Anthrax more than one vertebrate host Echinococcosis, Cｙｓｔｉｃｅｒｃｏｓｉｓ, Toxoplasmosis, Tｒｉｃｈｉｎｉａｓｉｓ Direct zoonoses Cyclozoonosis non-animal reservoir Tetanus, Bｏｔｕｌｉｓｍ, Aｓｐｅｒｇｉｌｌｏｓｉｓ, Hｉｓｔｏｐｌａｓｍｏｓｉｓ,Tｏｘｏｃａｒｉａｓｉｓ, Fascioliasis, Anthrax an invertebrate host West Nile fever, Yｅｌｌｏｗｆｅｖｅｒ, Ｒｉｆｔ　Ｖａｌｌｅｙ　ｆｅｖｅｒ, Plague,Aｎｉｓａｋｉａｓｉｓ Metazoonoses Saprozoonoses

6. The World Health Organization Expert Committee on Zoonoses came up with the classification system of zoonosesprovided by Dr. Schwabe. Calvin Schwabe One Health Project A CENTER OF EXCELLENCE AT THE INTERSECTION OF HUMAN, ANIMAL, AND ENVIRONMENTAL HEALTH Our Mission To strengthen the UC Davis School of Veterinary Medicine's commitment to the One World-One Health movement by educating veterinarians of the future to integrate human, animal, and ecosystem protection into their professional lives. The Calvin Schwabe One Health Project fosters a diverse and sustainable planet, with the goal of encouraging a new generation of veterinary expertise in the integration of better health for humans, animals, and their environment. To that end, One Health expands career pathways for veterinary students in disciplines such as public practice, wildlife and ecosystem health, food safety, herd health, disaster preparedness, rural health, and zoonotic disease threats.

7. Human Equine Metazoonoses West Nile fever Life cycle of West Nile virus (WNV) １．WNV is spread by the bite of an infected mosquito (vector). ２．Mosquitoes become infected when they feed on infected birds(Reservoir). ３．WNV can cause most clinical cases in humans and horses that does generally not allow transmission to others(Dead-end host). Dead-end host Vector Mosquito Bird Reservoir host Other animals

8. Many of zoonoses have the potential to spread through various means over long distances and to become global problems. West Nile fever suddenly occurred in the New York in 1999 . A mosquito traveled by air? ★ Endemic area of Japanese encephalitis and West Nile fever

9. WNV Positive ratio ofdead birds WNV Positive mosquito Human case Newark Liberty International Airport Kennedy International Airport A mosquito arrived at this terminal. Spread of West Nile virus in New York City in 1999

10. fatality rate(%) No. of patients Initial high fatality rate may due to the following reasons. 1. Diagnostic and treatment system were not prepared. 2. The number of patients in mild was increased with the progression of surveillance. 3. Acquisition of immunity. 20 10000 WNV amplification between birds and mosquitoes took three years. 18 16 8000 14 12 6000 10 8 4000 6 4 2000 66 2 62 21 0 0 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 Progression of West Nile fever in USA(1)

11. No. of State affected No. of death Why the number of death in 2002 was more than in 2003 when the number of patients peaked. 300 60 250 50 200 40 150 30 100 20 WNF occurred in almost all Sates in 2002, and many people acquired immunity. 50 10 0 0 2003 2000 2001 2002 2004 2005 2006 2007 2008 1999 Progression of West Nile fever in USA(2)

12. Small pox Smallpox is an infectious disease unique to humans(not zoonosis), caused by Variolavirus. The fatality rate for flat-type is 90% or greater and nearly 100% is observed in cases of hemorrhagic smallpox. Smallpox is believed to have emerged in human populations about 10,000 BC. In the early 1950s an estimated 50 million cases of smallpox occurred in the world each year. To eradicate smallpox, each outbreak had to be stopped from spreading, by isolation of cases and vaccination of everyone who lived close by. This process is known as "ring vaccination". The global program on smallpox eradication initiated by WHO in 1958 and intensified since 1967. The global eradication of smallpox was certified by a commission of eminent scientists on December 1979. Hemorrhagic-type smallpox.

13. Virus families not assigned to an order(65 Families) Family: Poxviridae Orthopoxvirus is a genus of poxviruses that includes many species isolated from mammals. Although Variola virus infects only human, some Orthopoxviruses have the ability to infect non-host species, such as monkeypoxvirus. I now offer a few topics related with small pox eradication. Subfamily: Chordopoxvirinae Genus: Orthopoxvirus Camelpoxvirus Cowpox virus Ectromelia virus Monkeypox virus Raccoonpoxvirus Taterapoxvirus Vacciniavirus Variolavirus Volepoxvirus Genus: Parapoxvirus Bovine papular stomatitis virus Orf virus Parapoxvirus of red deer in New Zealand Pseudocowpox virus

14. Monkeypox was first found in 1958 in laboratory monkeys. African squirrels might be the common host for the disease. Rats, mice, and rabbits can get monkeypox, too. Direct zoonoses Monkeypox

15. Human monkeypox Seven years old girl in Republic of Zaire Monkeypox is an exotic infectious disease caused by the monkeypoxvirus, and is usually transmitted to humans from rodents, pets, and primates through contact with the animal's blood or through a bite. Human monkey pox can be difficult to distinguish clinically from smallpox. Case-fatality ratios in Africa have ranged from 1% to 10%. It is assumed that vaccination against smallpox would provide protection against human monkeypox infection. Since the eradication of smallpox in 1979, human case increase gradually. Six months later, she healed but many pockmark remained.

16. Endemic Human Monkeypox, Democratic Republic of Congo, 2001–2004 Emerg Infect Dis. 2007 Among 136 patients, 51 (37.5%) had laboratory-confirmed MPX infection, 61 (44.8%) had laboratory-confirmed chickenpox virus infection, and 1 (0.7%) had coinfection. Age and sex distribution of patients with monkeypox Age <4 5–14 15–24 25–34 >35 Total male 8/12 12/22 5/17 2/9 1/6 28/66 female 7/21 9/19 8/13 0/8 1/7 24/68 Monkeypox positive/No. cases investigated Distribution of 52 confirmed cases of human monkeypox.

17. Movement of imported African rodents to pet shops and distribution of prairie dogs from a pet shop associated with human cases of monkeypox, in 2003 USA. 762 rodents MMWR 2003 Rodents and prairie dogs contacted with each other. African rodents were resell to Japan, but 15 already dead before arrival and lived two rodents was not infected. All 35 human cases of monkeypox were associated with prairie dogs.

18. Cowpox and Pseudocowpoxvirus In 1796, Dr Edward Jenner used “cowpox virus” to inoculate a patient to prevent them from contracting smallpox. Discovery of virus is in 1892(tobacco mosaic disease), so it is not as clear what virus he used for vaccine 100 years ago. In fact, milker'snodule is usally caused by a parapox virus(Pseudocowpox), not by cowpox virus. Milker's nodules What is cowpox? Nowadays, cowpox is a rare disease. It mostly occurs in Great Britain and some European countries. Cows are no longer the main carrier of the virus; instead woodland rodents are the natural hosts of the virus who then pass it on to domestic cats. Feline cowpox virus infection

19. Cowpox Virus Transmission from Pet Rats to Humans Germany: Outbreak including 5 patients caused by infected pet rats from the same litter in 2009. Human cowpox infections seem to be increasing. One obvious reason for an increase might be the fading cross-protective immunity to cowpoxafter the cessation of small pox vaccination. Human cowpox is a disease of young people, with half of all cases occurring in individuals younger than 18 years, because of their not having been vaccinated for smallpox, which may confer some protection against cowpox. 16 years old boy

20. Original animal vaccine strein imported in 1887 Brazilian Vaccinia Viruses and Their Origins VACV species imported to Brazil in 1804, when human vaccine arrived at a port on the arms of slaves returning from Portugal. The species was maintained in this manner(arm to arm) and in 1887 the first animal vaccine was produced in calves. In 1963, Brazilian VACVs(Group 1, 2) was isolated from the blood of a rice rat captured near the edge of Amazon rain forest. Since then, those virus were naturally isolated from a wild rodent. In 1999, exanthematousoutbreaks affecting dairy cattle and their handlers were reported. Brazilian VACVs existed before the beginning of the WHO smallpox eradication vaccination campaigns. VARV: Variola virus CPXV: cowpox virus VACV: vacciniavirus

21. The virus that Dr. Edward Jenner used for vaccination derived from milker's nodule in 1796 may be Brazilian VACVs. Voyages of Christopher Columbus(1492-1504)

22. Echinococcosis (Hydatid Disease) Cyclozoonosis Skunk, liver. The inner surface of the cyst is lined by hydatid sand, and the cyst is surrounded by a thick capsule of fibrous connective tissue Human, liver. Multiple thin-walled hydatid cysts project from the capsular surface of the liver. Iowa Sate Univ.: CFSPH

23. WHO: Echinococcosis Humans are accidental intermediate hosts and are not able to transmit the disease. There are areas of high endemicity in southern South America, Mediterranean coast, southern part of Russia, Middle East, south-western Asia, northern Africa, Australia, Kenya, New Zealand and Uganda. Relate to wool industry Echinococcusgranulosus Oral intake

24. Echinococcusmultilocularis E. multilocularisis found primarily in the northern hemisphere. It is widely distributed in continental Europe, and also occurs in much of northern and central Eurasia eastward to Japan (where it is found only on the island of Hokkaido), and in North America, where it primarily occurs in Canada, Alaska and the north central U.S. from Montana to central Ohio. Definitive Host Fox Dog Cat ingesting eggs shed in the feces predatism CFSPH: Echinococcosis Intermediate Host Rodent

25. For the production of fur, red foxes were imported in Rebunisland in 1924. First patient with hydatid cyst was detected in 1937, after a lapse of 2 years reaching 129 patients. Hokkaido authorities gave instructions to destroy all foxes and stray dogs. Although the outbreak resolved, a hydatid patient was detected in east area of Hokkaido in 1965, and infection of Ezo red foxes were confirmed diffusely. Rebunisland in 1965 Since then, about 10 patients each year continues to suffer the disease. Several monkeys, gorillas and orangutans died by hydatiddesease in 2 zoological gardens in 1992 and 1994. By this circumstance, the Zoo were forced to shut. Since 1999, anthelmintic pellet including Praziquantel(Biltricide: effective against flatworms) were put in place widely where foxes are ranging. Before 1989-98 199 5,157 313 6.1 After 2000-05 148 3,840 18 0.5 キツネの駆虫に関するガイドライン 参考資料 Nuber of points captured Nuber of foxes captured Nuber of positive foxes Positive rate(%)

26. No. of foxescaptured: 25,358 No. of hydatidfoxes: 5,174 Positive rate: 20.4% No. of stray dogs : 9,945 No. of hydatiddogs: 99 Positive rate: 1.0% 8 7 北海道におけるエキノコックス症対策の経緯 6 Fox 5 4 3 2 Dog 1 0 Progression of prevalence of Echinococcosis in the foxes and dogs at Hokkaido through 1966-2008.

27. 北海道におけるエキノコックス症対策の経緯 Number of pigs slaughtered: 27,321,373 Number of hydatidpigs: 31,253 Positive rate: 0.11% Echinococcus specific PCR using Cox1 primer Progression of prevalence of Echinococcosis in the pig slaughtered at Hokkaido through 1983-2008.

28. Saprozoonoses Anthrax In May 1881 Louis Pasteur performed a public experiment to demonstrate his concept of vaccination. The trial was held under the supervision of two graziers and three government officials at Junee Junction in Australia during September and October 1888. The trial was undertaken on 39 sheep and 6 cattle. It was a complete success: all vaccinated animals remained in very good health, whereas all 19 unprotected sheep and one of the two non-vaccinated cows died within a few days. Pasteur's Vaccine of Anthrax in Australia: as a preventative against Cumberland Disease in sheep, cattle and horses.

29. When conditions are not conducive to growth and multiplication of the vegetative bacilli, B. anthracistends to form spores. These spores are extremely resistant to inactivation by heat or chemicals, and can survive in the environment for decades. Capsulated B. anthracisin the blood of an animal that has died of anthrax. Rain and other agents can disperse the spores to other locations. Heavy rains, alternating with dry periods, may concentrate the spores and result in outbreaks among grazing animals. Spores and vegetative cells of B. anthracis

30. Virtually all mammals and some birds can contract anthrax, but susceptibility varies widely and most clinical cases occur in wild and domesticated herbivores. Cattle, sheep, and goats are considered to be highly susceptible; horses somewhat less so. Pigs, other omnivores, and carnivores are more resistant to disease, but they may become ill if the dose is high. Birds are highly resistant. Bloody discharges from the nose, mouth, and anus Enlarged spleenhas a ‘blackberry jam’ consistency.

31. Louisiana State Univ.: World Anthrax Site 20,000-100,000 cases estimated globally/year Human case rates for anthrax are highest in Africa and central and southern Asia. Where the disease is infrequent or rare in livestock, it is rarely seen in humans.

32. It was revealed that the application of bone meal was very effective to crop growth in Kagoshima Prefecture consisting of volcanic ash soils in the middle of Edo period. 300 Cow 250 Number of cases 200 The bone meals imported from Chinaand Korea in Meiji period were contaminated with Anthrax spores. 150 Equine 100 50 Human 0 1908 1910 1912 1914 1916 1918 1920 1922 1924 1926 1928 1930 1932 Occurrence of Anthrax in Kagoshima prefecture through 1908-1932

33. In Japan, only one animal-Anthrax case in several years was reported recently. The spores still may be distributed in the soil, the number of them do not reach the onset dose. 60 50 Number of cases By the oral route, minimum infectious dose for sheep was 3.5 x 10 4spores and that the dose needed to ensure lethal infection in sheep, horses and cattle was 5 x 108spores. 40 30 WHO: Anthrax in humans and animals 20 10 0 1996 2000 1972 1976 1980 1984 1988 1992 1960 1964 1968 Numer of cattles with Anthrax in Japan, 1960-2000

34. During the first documented outbreak of anthrax, in the summer of 1962, 281 bison died in the eastern Slave River Lowlands. 400 Outbreaks soon became widespread, extending during the course of the next few years to as far south as bison herds in the Sweet Grass area. 350 Number of deaths 300 Number of Bisons in National Park 250 Wood Buffalo National Park Slave River Lowlands Mackenzie Bison Liard River Valley (Nahanni) 4500 1800 1555 400 200 No cases of human anthrax have been diagnosed in the last two decades in Canada. 150 100 50 Wood bison is designated as the Status of Endangered Wildlife in Canada Wood Bison in the NWT 0 1962 1963 1965 1967 1968 1971 1978 1991 1993 2000 2001 Number of bisons died of anthrax in Canada

35. Anthrax in U.S. • Cutaneous anthrax • Early 1900s: 200 cases annually • Late 1900s: 6 cases annually • Inhalational anthrax • 20th century: 18 cases/16 fatal Outbreaks of anthrax in wild animals including bison were a public health threat in United States, formerly. CDC: Epizootiologyand Ecology of Anthrax Distribution by decade of 75 cases of anthrax in humans in Texas, 1935 to 2001.

36. 2001 Anthrax Letters

37. 2001 anthrax attacks The second letter dated at 9 November Who did it for what purpose? The truth has not been revealed until now. • 22 cases • 11 cutaneous • 11 inhalational • 5 deaths (all inhalational) • Index case in Florida • 2 postal workers in Maryland • Hospital supply worker in New York City • Elderly farm woman in Connecticut

38. AumShinrikyo • Japanese religious cult • 1993 • Unsuccessful attempts at biological terrorism • Released anthrax from office building • Vaccine strain used – not toxic • No human injuries • Successful attempt in 1995 • Sarin gas release in Tokyo subway • 1,000 injured – 12 deaths A group behaving fanatically would exist in any country. It is an unavoidable phenomenon resulting from the mentally suffering society. Guru in the cult

39. The International Health Regulations (2005) provide not only the ability of the world community to cope with public health emergencies affecting more than one country, but they have important implications for biosecurity, including the response to transborder incidents involving the accidental or deliberate release of biological or chemical agents or radiological materials.