Emerging Infectious Diseases

Kevin Kain MD FRCPCDirector, Global Health

McLaughlin Centre for Molecular MedicineProfessor of Medicine University of Toronto

Who are we? Where are we going? What should we do?

Travel and Emerging Infectious Diseases

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Speed of Global Travel in Relation toWorld Population Growth

From: Murphy and Nathanson. Semin. Virol. 5, 87

Main migration movements

Wars and famines

Humans as Vectors of Disease Chen et al Med Clin NA 2008;92:1409

• 2007 ~898 million cross international borders by air

• 35-fold increase since 1950 (vs 2.6-fold increase in world population)

• > 50 million developing world• > 50 million refugees ~500M• > 280 million visitors to USA/yr (> 34M are

foreign born)WTO 2008

“There is no where in the world from which we are remote and no

one from whom we are disconnected”

IOM Microbial threats to Health in the USA

Global distribution of newly emerging and re-emerging infectious diseases

Nature 430: 242

Leprosy in Toronto Boggild A,. Kain KC. CMAJ 2004

• N = 184 cases at the TDU (66% male)• 80% arrived within the last 20 years• Indian subC 32%• Philippines 27%• Vietnam 20%• 33% had nerve dysfunction at

presentation• Lag time to Dx: 1.5-4.7 yrs

Babesiosis in Canada dos Santos and Kain CMAJ 2000

• 59 male editor TO paper• to TGH extremely ill• fever, toxic, DIC Dx “leukemia”• malaria smear “P falciparum 4%”• TDU Babesia microti (PCR +)• Lyme + IgM; Ehrlichia neg (PCR)

Babesiosis: Blood Supply Kain et al CMAJ 2001

• 53 female GI bleed Hb 70 g/L• transfused 5U Oct 98 and Feb 99• re-admitted 7 d. 40C, chills, N&V• smear Dx “P falciparum” at 2.5%• TDU Babesia microti• 5 donors 40 male smear, PCR+

Leishmaniasis MMWR 2004;53:264. Otero AJTMH 2000;62:128

• N = 500,000 troops in Iraq, Afghanistan and Kuwait

• N = >2000 confirmed cases of CL (L. major)• N = 2 cases of VL (L. infantum)• Delay of 14 months until onset• Brazil: 24% of sero+ blood donors = + PCR• ~15 cases of TTL pRBCs and plts• I.P. = 2-12 months

Chagas’ in North America Kirchhoff NEJM 1993. Herwaldt JID 2000.

Leiby et al. Transfusion 2002;42:549

• ~5x106 Latin immigrants to USA• 50,000-100,000+ infected

~20% symptomatic• Up to 5% of Latin American immigrants in

Washington DC are sero+• 0.01-1.1% of blood donors in LA sero+• Risk of infection is 13-23%/unit• ~100 USA pts infected by transfusion/yr

Clinical Chagas’ in USA Leiby et al. Circulation 2000;102:2978.

• n = 11430 cardiac surgery pts tested • N = 6 sero + by both EIA and RIPA• 2 were heart transplants & hearts PCR + • For Hispanic pts 2.7% were sero +• BUT none had been suspected for Chagas• Chagas is under Dx as a cause of cardiac

disease/CHF

T. cruzi in the USA Reisenman C et al. EID March 2010

• Collected triatomines around Tucson, AZ• 41.5% (n = 164) were + for T cruzi by PCR• 63% of collection sites were +• 7 autochthonous cases of Chagas’ in USA• Reservoirs: mice, rats, raccoons, opossums, dogs

Triatoma rubida

Emerging Infectious Diseases

• Where are we?• Where are we going?• What should we do?

Cruise Ships Chen et al. Med Clin NA 2008;92:1409

• 11.5 million took cruises in 2005• Passengers and crew risk EID

– Converge from many countries– Brief visits multiple countries– Many are elderly with underlying disease– Widely disperse before IP transmit

• Norovirus 2006 43 outbreaks• Legionella >200 cases (spas)• Influenza Alaska 1998 >33,000 cases• Salmonella, V cholera, diptheriae, rubella

Immunosuppression and Travel: Boggild…Kain JTM 2004 Boggild…Kain CMAJ 2005

• >25,000 transplants performed in NA/yr• >$2.5 billion in 1st year or treatment• N= 267 renal, heart, liver transplants• 99% were on > 2 immunosuppressives• ~2/3s were VFRs• <10% were adequately protected against

vector borne disease

A day in the life of Infectious Diseases Tuesday, January 6 2010

• PRO/AH/EDR> Avian influenza, human (01): China• PRO/AH/EDR> Avian influenza (02): India (WB)• PRO/EDR> Influenza oseltamivir resistance (10): CDC• PRO/EDR> Dengue update Rio, Australia(01)

PRO/EDR> Chikungunya and P. knowlesi - Singapore• PRO/AH/EDR> Angiostrongylus meningitis - US: [HI]• PRO/EDR> Poliomyelitis - Worldwide, updates• PRO/AH> Antibiotic contamination, food supply USA• PRO/AH/EDR> Ebola hemorrhagic fever - Congo DR• PRO/AH/EDR> Ebola, Zimbabwean soldiers DRC.

World migration of chicken wings and legs 5 million tons/year

•March 4, 2010:

• 486 cases and 287 deaths

• CFR = 60%

de Jong, M. D. et al. N Engl J Med 2005;353:2667-2672

Influenza A (H5N1) Viral RNA Load in Throat Swabs from Eight Patients

213 countries >16,455 deaths

Dengue/dengue hemorrhagic fever: annual number of cases reported to

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Aedes aegypti Distribution in the Americas

19701930's 2003

The Emergence of Dengue Hemorrhagic Fever in the Americas

Prior to 1981 1981-2003

DHF: Americas1970: 01990s: >60,000Texas 1980-99: 64Hawaii 2001: 122Florida 2009: 20

1900 cases/85000 inhabitants = 2.2% attack rate!!

Mosquitoes and the economy EID Nov 2008; 14:1747

• Mossies take advantage of tough times

• Sharp rise in WNV in California• Aerial survey 17% of pools were

“green” Culex +• Mortgage foreclosures houses

abandoned

• >1,500,000 cases

• attack rate 35%

Angiostrongyliasis Rat lung worm

• Angiostrongylus cantonensis` eosinophilic meningoencephalitis• Spreading in the Pacific Rim including

Hawaii rats in ships/containers• Transmitted to SEA slug also imported• Infected by eating slugs or more

commonly 1-2 mm. larvae on fresh produce

Rameriz-Avila et al CID 2009;48:322

Angiostrongyliasis Rameriz-Avila et al CID 2009;48:322

Clinical: I.P. 1-4 wks. Presents H/A, paiful migrating parasthesias, peripheral and CSF eosinophilia (occ. Ocular and cranial nerves)

Epidem: Asia, Australia, South Pacific, Hawaii, Caribbean (rats LA)

Diagnosis: clinical + serology (Mahidol)• CT and MRI usually normalTreatment: albendazole + steroids x 14 d esp. if

progressive

• Nigerian outbreak of polio 2003-2008 spread to 20 countries and required >$500M

• Still <40% of Nigerian children are fully immunized

Vaccine preventable Illness in Travellers ISTM 2009

• Analysis of 37,542 returned travellers in Geosentinel database 2009

• 580 Vaccine preventable illness (VPI)– Enteric fever = 276– HAV and HBV = 148– Influenza = 70

• 55% admitted to hospital• 3 deaths

Vaccines - USA Nature Medicine Jan 1998

Disease Max. cases/yr PresentMeasles 894,000 500Diptheria 207,000 1Pertussis 265,000 6400Mumps 152,000 600Rubella 58,000 210

Anti-vaccine Movements Measles- Netherlands

• Measles epidemic2,961 cases (97% no vaccine)3 died and 5 enceph (1/300)63 hospitalized (2.1%)439 complications (15%) pneu., OM

• Exported 2 outbreaks in CanadaMMWR April 14, 2000

Vaccines do NOT cause autism Offit PA et al CID 2009;48:456

• Rates of autism in vaccinated and unvaccinated children are the same

• 20 studies no association MMR with autism

• 7 studies no ass. of thimerosal with autism • The “Right to catch and transmit potentially

fatal infections”. Now Yes No??• Clusters of measles and Hib in unvaccinated

children

January 28, 2007Virulent TB in South Africa May Imperil

Millions Johannesburg, Jan. 27 — More than a year after a

virulent strain of tuberculosis killed 52 of 53 infected patients in a rural South African hospital, experts here and abroad say the disease has most likely spread to neighboring countries, and some say urgent action is essential to halt its advance.

XDR TB

Extensively-resistant TB USA JAMA Nov 2008;300:2153. EID 2008;14:1715

• 1993-2007 XDR TB Resistant INH, RMP, quino, 2nd line IM agent

• 3400 R to IHN, RMP• 83 XDR• 54% unemployed USA born• More like to be Hispanic and in jail• 400/6000 refugees to USA active TB• 24 had MDR TB

Antibiotics USA• > 50 yrs antibiotics used as growth

promoters (USA 25 million tons/yr)• ~70% of all antibiotics in USA• Linked to development of antibiotic

resistant bacteria in meat and milk transmitted to humans

• ~90% end up in urine and manure• Now concerns picked up by fresh

produce including organic farms

Ebola and Primates Bermejo M et al Science 2006;314:1564

• Ebola outbreak killed 5000 gorillas

• Gabon 3 outbreaks chimps • N = 110 CFR 59-75%• Cooked chimp CFR 0%

Bushmeat, animal trade & exotic food

• Serious threat to global wildlife 3.4 M tons/yr

• 40,000 primates, 4M birds, 650K reptiles, 350M fish traded/yr

• ~USD $6B/yr

• Animals source of >70% of emerging infectious diseases

Massive human disruption of animal habitat

Bushmeat and animal trade

Growth in ecotourism

Fatal Case of MHF in Dutch Tourist Visiting Python Cave

She was reportedly exposed to fruit bats during a visit to the “python cave” in the Maramagambo Forest between Queen Elisabeth Park and Kabale.

• 529 reported cases 116 hospitalized

8 deaths

• 40,000 Salmonella lab-confirmed cases reported USA/yr

• Only 3% of cases are confirmed and reported

• 1 case 40 other cases >20,000

• USA 76 million cases 350,000 hospitalized $7B health care costs

Maki DG NEJM Feb 11 2009

Food Factories Processing for Dollars!

• Single BSE-infected cow116 tons of “minced meat product”infect 400,000 people

National CJD Surveillance Unit, UK 2000

Ebola in Pigs?! Ebola-Reston Philippines Jan 23 2009

• 2 pig farms: pigs + for Ebola• 50 workers exposed • Evidence of infection in 4

farm workers

Emerging pathogens Factors promoting emergence• Global interdependence• International travel and trade• Environmental disruption• Health care alteration• Microbial changes• Breakdown in public health• Changes in human behaviour and

demographics

Pandemic Influenza Economic Impact USA

Meltzer M et al. EID 2001

• 1918, 1957, 1968 pandemics • Next pandemic:

estimated 90,000 to 207,000 deaths315,000 to 734,000 hospitalizationsCost USD $71 to 166.5 billion

Future of EID• Emerging infections have a human hand • Future of EID = future of human behavior = past• Increased resistance all micro-organisms• Increased food and water-borne illness• Global flu pandemic • Increased recognition of role of pathogens in

chronic disease, e.g. H. pylori, HPV• Expect “the unexpected”

largely human induced environmental, biothreat (synthetic)

• Global control will require improved molecular Dx and surveillance