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EMERGING INFECTIOUS DISEASES JOHN BEREZOWSKI DVM PHD VETERINARY PUBLIC HEALTH INSTITUTE UNIVERSITY OF BERN BERN SWITZERLAND FEB 05 2015 1 Learning Objectives Understand emerging infectious diseases, what they look like and how we find out about them Understand the process and stages of infectious disease emergence Learn about some of the determinants for infectious disease emergence Learn a little bit about the complex relationship between infectious disease and societal values 2 WHAT IS AN EMERGING INFECTIOUS DISEASE? Definition: emerging and re-emerging infectious diseases What does an emerging infectious disease look like? How do we find out about emerging infectious diseases? 3 Then… “We can look forward with confidence to a considerable degree of freedom from infectious diseases at a time not too far in the future. Indeed…it seems reasonable to anticipate that within some measureable time …all major infections will have disappeared” T. Aidan Cockburn: 1963 and Now 15 million (>25%) annual human deaths worldwide are caused by infectious diseases 61% of human pathogens are zoonotic At least 30 new diseases of humans have emerged in the last 20 years Morens. 2004. Nature, Vol 430, 242-249 One World, One Medicine, One Health 4 Chikungunya St Martin Dec 5 2013 RNA Virus A. Aegypti +Albopictus http://www.healthmap.org/en/ 5 http://www.healthmap.org/en/ http://www.healthmap.org/en/ 6 IDs emerge world wide Source: National Institutes of Health 7 IDs also emerge into animal populations! Pathogen Porcine Epidemic Diarrhea Virus (PEDv) Porcine Respiratory Reproductive (PRRS) Porcine Circovirus (PCV) Schmallenberg virus: Bovine Spongiform Encephalopathy Canine Parvovirus Influenza viruses West Nile virus in North America: Monkey Pox in the USA Canine Distemper Virus Chronic wasting disease Lyme disease Feline Immunodeficiency Virus Nipah virus Hendra virus Devil facial tumor disease White Nose Syndrome Species Pigs Pigs Pigs Cattle, sheep, goats Cattle, people Dogs Birds, pigs, dogs, equids Birds, horses, people, others Prairie dogs, people Seals, others Deer, elk Dogs Cats Bats Pigs people Bats Horses people Tazmanian devils Bats 8 Definitions Emerging: 1. PREVIOUSLY UNKNOWN disease that suddenly appears (emerges) in a population • Diseases that have never been seen before • First appear as diagnostic dilemmas 2. KNOWN disease that suddenly appears (emerges) in a new population • A different age, production type • A different part of the world • Foreign animal diseases (also called transboundary diseases) Re-Emerging: 1. KNOWN disease, previously on the decline, that is becoming more common and will likely continue to do so 9 What Does An Emerging Dz Look Like? Emerging, re-emerging dz are recognized as increases in the burden of disease Quantity • Increased amount (incidence) of new, endemic or transboundary (foreign) dzes Quality • Change in the way a pathogen affects the host • Increased severity of dz: increased morbidity, mortality • Reduced productivity, reproductive performance Diagnostic dilemmas • New previously unrecognized dz..usually as a syndrome • Changed clinical presentation of endemic dz 10 Porcine Epidemic Diarhea http://www.aphis.usda.gov/ http://www.aphis.usda.gov/ 11 Known Disease Emergence 2001 Foot And Mouth Disease UK MS-NBC BBC http://www.pbs.org/newshour/bb/health/jan-june01/footmouth_3-30.html# 12 Known Dz re-emerging Monkeypox in Central Africa Eradication of Small Pox Cessation of Small Pox Vaccination Increased Susceptible People Increased Monkeypox Disease http://www.environment.ucla.edu/ctr/news/article.asp?parentid=11358 13 How are they recognized? 1. Known Diseases – We know what to look for – Well developed structured processes are in place – Surveillance: mostly based on disease reporting 2. Unknown Diseases (previously unseen) – Don’t know what to look for – Not well developed, unstructured, informal – Surveillance: for what? 14 How are they recognized? Detection Investigation Response Public Farmer Health care worker Veterinarian Pathologist Epidemiologist Academic Weirdness Champion National, Provincial, International agencies, industries Identifies something abnormal, weird, unusual dx dilemma Promotes Communicates Dz Importance Attracts resources Implement Dz control, mangement eradication, mitigation 15 Member of public finds sick pigeon Takes to Vet Vet Sends Pigeon to Dx Lab Pathologist IDs new parasite Sarcocystitis calchasi Published in Journals/Media http://blogs.scientificamerican.com/guest-blog/2012/01/31/a-wildlife-vet-a-pigeon-a-groundbreaking-discovery/ 16 PROCESS OF INFECTIOUS DISEASE EMERGENCE Chain of infection How do infectious diseases emerge? Stages of infectious disease emergence 17 “Chain” of Infection Accesstocontinuingeducation.com 18 Reservoir Population Pathogen Exposure Susceptible Population Introduction of a new agent into a susceptible population Exposure is caused by movement of infectious agents Pathogen Transmission Dz +/Epidemic 19 Reservoir Population Pathogen Exposure Susceptible Population Pathogen Adoption, establishment, and dissemination in the susceptible population Transmission Requires a pathogen that can adapt to, and transmit Dz +/between, these hosts Epidemic 20 Stages of Cross-Species Disease Emergence Old Host 1. 2. 3. 4. 5. Pathogen exclusive to an animal reservoir Animal reservoir transmits to humans/other animals, but no transmission among them Animal reservoir transmits to humans/other animals with a few cycles of transmission among them Animal reservoir transmits to humans/other animals with sustained transmission among them Pathogen exclusive to humans/new animal reservoir New Host Reservoir -- Reservoir Accidental & Dead-end Reservoir Accidental (not always dead-end) Reservoir Also a Reservoir -- Reservoir Wolfe ND et al. Nature May 2007 Vol 447: 279-283 21 Stage 1: Pathogen exclusive to a single species Host that dz Number of Pathogens with Many pathogens have multiple host species occurs in Pathogens Multiple Hosts Humans 1415 61.6% Livestock 616 77.3% 374 90.9% 1922 62.7% Overall, only 37.3% of pathogens have Dogs + Cats one known host Total Are they really one-host pathogens? Or do we not know the other hosts they infect? Livestock = cattle sheep, goats, pigs and horses S. Cleaveland, et al. Phil.Trans.R.Soc.Lond.B (2001) Vol. 356, pp. 991-999 22 Stage 2. Animal reservoir transmits to humans/other animals, but no transmission among them (dead end hosts) Rabies – Reservoirs are carnivores and chiroptera (bats) – Cattle and horses and people are dead end hosts WNV, EEEV, WEEV – Reservoir: Birds – Humans, horses, and dogs are dead end hosts Influenza H5N1 – Reservoir: waterfowl and poultry – Humans are dead end hosts 23 1997 – Present H5N1 Avian Influenza First outbreak: 1997, Hong Kong – A few human respiratory cases – Acquired directly from chickens – 1.2 million chickens culled Southeast Asia, 2004... – Widespread outbreak; not controlled, in spite of massive culling of domestic poultry – Spread by wild birds? poultry smuggling? use of poultry vaccine that was partially protective? Jan 23, 2015 – Outbreaks continue to occur in chickens – 718 human cases have been reported since 2003, with a case fatality rate of 57.5% (413 deaths) WHO/GIP, data in HQ as of 23 January 2015 24 Malignant Catarrhal Fever Viruses 25 Stage 3. Animal reservoir transmits to humans/other animals with a few cycles of transmission among them Mycobacterium bovis – Reservoir: cattle, bison, elk – Transmitted to people via respiratory route – Poor human to human transmission Nipah Virus – Reservoir: fruit bats – Human to human transmission is poor – Pig to pig transmission is also relatively poor 26 1998-1999 Nipah Virus Suddenly emerged in Malaysia – Outbreak Sept 1998 – April 1999 – A fruit bat origin paramyxovirus that had been “smoldering” in pigs (in retrospect) since ~1996 Sick pigs – Respiratory, rapid spread – 1.1 million were culled to prevent spread (out of a national herd of 2.4 million!) Sick people (n=265) – Encephalitis in many cases – Cases had 40% fatality rate (n=105) – Survivors often have neurologic sequelae 27 Nipah Virus Bangladesh Risk: Drinking Raw Date Sap Fruit Bats drink (saliva) urinate, defecate in collecting jars No Tx 157 of 208 Infected have died From 2001 to 2012 http://www.bdnews24.com/details.php?id=217759&cid=2 28 Stage 4. Animal reservoir transmits to humans/other animals with sustained transmission among them SARS: Severe Acute Respiratory Syndrome – Reservoir: fruit bats – Efficient transmission in humans Schmallenberg virus – Reservoir species: ? – Efficient transmission in sheep, goats and cattle 2009 Influenza H1N1 “Swine Influenza” – Reservoir: swine – Very efficient transmission in humans 29 2009: Swine Influenza H1N1, “swine flu”, “Mexican flu”… A recombinant strain – The segments in the current strain have been “together”, as a pig virus in North America, since 1998 – Some segments were originally avian, one was via humans First human cases recognized in April, 2009, from Mexico – Global spread within a few weeks – June 11: officially declared pandemic by the WHO First swine cases were recognized in Canada in late April, 2009 – Why not in Mexico? 30 Stage 5. Pathogen exclusive to new reservoir species Human examples – HIV/AIDs Origin: non-human primates – Measles Origin: cattle – Smallpox Origin: likely camels (camelpox) – Falciparum malaria Origin: Birds – Rota virus Origin: domestic herbivores or mammals 31 WHAT MAKES A DISEASE LIKELY TO EMERGE? Determinants of disease emergence: • Pathogen type, adaptation and change • Reservoir determinants • Host population determinants • Enhancing transmission 32 Determinants of emergence Pathogen Type of agent Mutation/Change Host Susceptibility Reservoir Phylogenetic distance Transmission Reservoir size Pathogen prevalence Contact frequency Accesstocontinuingeducation.com 33 1.Pathogen: Type of Agent Of the >1400 species of pathogen known to infect humans, 61% are zoonotic 75% of emerging diseases of humans are zoonotic Zoonotic pathogens are twice as likely to be associated with emerging diseases Which taxonomic groups of pathogens are most likely to emerge? Category Relative Risk Zoonotic Status Not zoonotic 0.52 Zoonotic 1.93 Taxonomic Division Viruses 4.33 Bacteria 0.71 Fungi 0.33 Protozoa 2.49 Helminths 0.24 Adapted from Table 1, from: Taylor, Latham, and Woodhouse. 2001. Phil. Trans. R. Soc. Lond. B. 356:983-989. 34 Increased antibiotic resistance Increased virulence (E. coli O157:H7) Mutations that enhance transmissibility within or between species Evasion of host immunity % of Isolates 1. Pathogen: Adaptation and Change 40 35 30 25 20 15 10 5 0 Salmonella Resistant to ≥4 Antibiotic Classes Chicken breast Ground turkey Data from NARMS Retail Meat Report, 2010. FDA. Released 1 March 2012. 35 2. Reservoir Phylogenetic distance between reservoir and new host – Best transmission: within a species – Pathogens are more likely to cross between closely related species than distant ones • Close relatives: cattle sheep – Pathogens that somehow cross between distantly related species often cause very different, often more severe, disease • Consider Nipah virus, bats pigs OR people 36 3. New Host Species New host: susceptibility!!! – Applies to all diseases, even those that emerge into new populations of the same species – Intensive agriculture: a lot of genetically similar hosts, managed under the same conditions, will have the same susceptibility – More people with weakened immune systems: elderly, HIV/AIDS, cancer patients and survivors, organ transplant recipients – Countries that are free of FADs do not vaccinate, because the lack of disease in susceptible animals proves they are “disease free” 37 Host Susceptibility: How it works Susceptible + Infected + Recovered 38 Host Susceptibility: How it works Susceptible + Infected + Recovered Or Dead Because the entire population is susceptible the consequences can be catastrophic 39 Susceptibles Fuel the Outbreak Life…Stranger than fiction! Photo Credit: Google Images Photo Credit : Wikipedia 40 Susceptibles Fuel the Outbreak Photo Credit: OPB.org 41 Resistance slows/stops the outbreak H3N2v A variant of H3N2 Influenza with the Matrix (M) Gene of pH1N1 US Only Summer and Fall Fairs 2011, 12, 13 Mostly Young Children Photo Credit: http://www.maniacworld.com/kissing-a-pig.html http://www.cdc.gov/flu/swineflu/h3n2v-cases.htm 42 4. Factors Increasing Transmission The probability of transmission from a reservoir to a new host increases with: Increasing abundance of the reservoir Increasing pathogen prevalence in the reservoir Increasing contact between the reservoir and the new host Epidemiologists define “contact” as whatever it takes to transmit the disease in question 43 Increased Transmission: Livestock Production Chickens in Maryland Increasing Production – World meat production will double from 2010 to 2020, mostly in developing countries – Fewer, larger livestock holdings – Production/output per animal is increasing – Results in uniform genetics, production, susceptibility Rushton,J., Upton, M : Res Vet Sci 2006: 25 (1), 375-388 Small holdings will be a conduit between intensive production systems and wildlife – The 80:20 rule - even in developing countries – Biosecurity may not be enough! A new disease emerges in farmed swine every two years, on average Weiss RA, McMichael AJ 2004 Nature Med Supp;10:S70 44 Small Production will not go away Industrialization: Change from diversity to uniformity – Genetics, production practices, max productivity, susceptibility Will Biosecurity be effective? – John Iverson and the pail of milk Will new pathogens emerge – Foodborne? Weiss RA, McMichael AJ Social and environmental risk factors in the emergence of infectious disease. 2004 Nature Med Supp;10:S70 45 Not Restricted to Developing Countries http://www.thebostonchannel.com/health/29481961/detail.ht ml Urban Agriculture Will companion animal general practitioners need to be able to service urban livestock operations? http://www.amherstma.gov/DocumentView.aspx?DID=4635 46 Increased Transmission: Animal Trade 40,000 ships on the world’s oceans at any time are carrying animals or animal products Examples: Live animal markets Exotic pet “swap meets” International transport 47 Monkey Pox : 2003 762 African Rodents West Africa Texas Gambian giant pouched rat 71 cases 18 hospitalized No fatalities Illinois via Iowa Illinois Indiana Kansas Missouri Wisconsin 48 Increased Transmission: Development & Changing Ecosystems Urbanization increases density of susceptible human populations Changing land use and climate influence waterborne and vectorborne disease transmission (e.g. dams, deforestation) 2006 Outbreak of Bluetongue in Europe) Change in Bluetongue vector range following a 1°C temperature increase http://europa.eu/rapid/press-release_IP-061113_en.htm?locale=en 49 6 Persons infected with an exotic disease anywhere in the world can be in a major US city within hours Days to Circumnavigate ( the Globe 350 ) 400 5 300 4 250 200 3 150 2 100 50 1 0 0 1850 1900 Year 1950 2000 Animal-based tourism increases contact with both domestic and wildlife species Koh Chang, Thailand North Georgia State Fair 50 World Population in billions ( ) Increased Transmission: Travel and Tourism 2004 to 2006 11 million pounds of bush meat entered the US http://news.discovery.com/animals/bushmeat-diseases-entering-new-york.html http://www.google.com/imgres?hl=en&sa=X&biw=1707&bih=1171&tbm=isch& prmd=imvns&tbnid=EOkMEirmOFMPTM:&imgrefurl=http://www.ensnewswire.com/ens/may2001/2001-05-2206.asp&docid=k4nAKsv7qwoyUM&imgurl=http://www.ensnewswire.com/ens/pics12/bushmeat1.jpg&w=287&h=258&ei=CncxT7CcMsjf0Q H0nKDbBw&zoom=1&iact=hc&vpx=1429&vpy=451&dur=1394&hovh=206&hovw =229&tx=187&ty=104&sig=111577599839487095308&page=2&tbnh=132&tbnw =144&start=67&ndsp=67&ved=1t:429,r:25,s:67 51 Last but not Least: Transmission from Intentional Release Surprisingly Few Examples Siege of Kaffa 1347 French Indian War Salmonella in a salad bar in Oregon 1984 Anthrax In Mail in US 2001 52 Social Disobedience New Zealand Rabbit Calicivirus Fiasco 1997 53 54 54 DZ AND SOCIETAL VALUES Some examples 55 Change in economic conditions Everyone must exit the population India Largest cattle population in the world 287 Million 56 Cows Vs Badgers Badgers are a reservoir for bovine tuberculosis 26,000 cattle culled last year 40,000 badgers to be culled in the next 4 years Badger Trust VS Farmers Union http://www.thisiscornwall.co.uk/Badger-cull-aheadsoon-possible/story-16880569-detail/story.html 57 Cows Vs Badgers UK Gov’t Postponed Cull For One Year http://blogs.nature.com/news/2012/10/badger-cull-update.html 58 Squirrel Wars 59 Chytridiomycosis Policy Development Batrachochytrium dendrobatidis • Devastated amphibian populations around the world • Bullfrogs are non-clinical carriers Issues: Commerce, Culture, Risk • Commerce in bullfrogs: food, pets, dissection • Asian culture • Risk to California amphibians Societal values are not unified • Culture and Commerce Vs • Environmental groups Policy: Ban import of bullfrogs • Fish and Game Commission Voted to ban imports • Dept. of Fish and Game Chose not to implement ban http://www.latimes.com/news/local/la-me-frog-legs-20111121,0,7997537.story 60 Range Wars Sheep Have an MCF Virus Bison are very susceptible Who’s fault is it? Are sheep producers responsible if their sheep kill the neighbor’s bison? Bison producers exit the industry Municipal governments have been petitioned Ban sheep production Ban new sheep producers Require a buffer zone between sheep and bison 61 61 62 http://www.telegraph.co.uk/news/worldnews/ebola/11363433/Ebola-has-killed-athird-of-the-worlds-chimpanzees-and-gorillas.html 63 http://conservationmagazine.org/2014/05/ebola-vaccine-trial-in-chimps-could-savewild-apes/ 64 Questions 65