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Emerging Infectious Diseases: a ‐ Zika Emerging Infectious Diseases: A ‐ Zika 2017 SIDP Programing at Microbe New Orleans, June 1, 2017 Scott K. Fridkin, MD Professor of Medicine Division of Infectious Diseases, Department of Medicine and Department of Epidemiology, Rollins School of Public Health, Emory University Director of Antimicrobial Stewardship Research, Emory Healthcare Antbiotics.emory.edu Disclosures • Centers for Disease Control and Prevention • Emerging Infections Program Cooperative Agreement • Co‐investigator • Sponsored Research ‐ Pfizer Inc. and Emory University • S. aureus surveillance in Fulton County, GA. • Vaccines and Related Biological Products Advisory Committee (VRBPAC) Strategic Advisory Board Meeting (Pfizer) Opinions expressed not those of Emory University or Emory Healthcare Antbiotics.emory.edu 1 By Jeff Stahler, The Cincinnati Post, for USA TODAY, June 11 Antbiotics.emory.edu Historical Epidemiologic Transitions –1st Transition •Paleolithic Age • 2.5 million years ago • Hunters and gatherers • Nomadic, Small groups • Parasitic infections •10,000 years ago • New social order due to agriculture • Zoonoses through animal domestication • Increases in infectious diseases • Epidemics in non‐immune populations Antbiotics.emory.edu 2 Historical Epidemiologic Transitions –2nd Transition • Coincided with mid‐19th century80 Industrial Revolution • Decreases in infectious 72 64 disease mortality 56 • Increasing life expectancy 48 Estimated life 40 expectancy 32 • Improved nutrition 24 • Antibiotics 16 Typhoid Rate 8 (per 100,000) 0 • “Diseases of Civilization” – 1900 1910 1920 1930 1940 1950 1960 • cancer, diabetes, cardiovascular diseases • Environmental problems • Chronic diseases Antbiotics.emory.edu Cholera –ecosystems and behavior (urbanization) • London, 1800s –first major vertical urbanization • The Ghost Map • describes the most intense outbreak of cholera in Victorian London • “1854 Broad Street cholera outbreak –Broad Street Pump” • Dr. John Snow, who created a map of the cholera cases and Reverend Henry Whitehead, whose extensive knowledge of the local community helped determine the initial cause of the outbreak • Water –not “Miasma” • The cholera outbreak from 1848‐49 killed approximately 54,000‐62,000 in London, and the outbreak from 1853‐54 killed an estimated 31,000 in London • Extensive rapid spread from point source, crossed social lines Antbiotics.emory.edu 3 Historical Epidemiologic Transitions –3rd Transition • Last 25 years • Emerging infectious diseases globally • New diseases and increases in mortality; first since 19th century • Antimicrobial resistance • 75 percent of diseases are zoonotic • Anthropogenic factors of emergence; the microbial “perfect storm” Antbiotics.emory.edu Examples of Emerging and Re‐emerging Infectious Diseases Antbiotics.emory.edu 4 Speed of Global Travel in Relation to World Population Growth 400 6 350 5 300 igate (250 ) 4 v e 200 3 150 the Glob 2 100 1 Days to Circumna 50 0 0 World Population in billions ( ) 1850 1900 1950 2000 Year Antbiotics.emory.edu Convergence Model Genetic and Physical and Biological Environmental Factors Factors Pathogen E I D Humans Environment /Animals Social, Political, Ecological and Economic Factors Factors Antbiotics.emory.edu 5 Convergence Model Genetic and Physical and Biological Environmental Factors Factors Pathogen E I D Humans Environment /Animals Social, Political, Ecological and Economic Factors Factors Antbiotics.emory.edu No. 1 CLUE: The monstrous Swamp Thing can control every iota of plant life on this planet, from the fungus on stale bread to forests of towering oaks. 6 Candida auris The monstrous Swamp Thing can control every iota of plant life on this planet, from the fungus on stale bread to forests of towering oaks. Candidemia is one of the most common HAIs in the U.S. • Bloodstream infection caused by Candida spp. • #1 organism in hospital‐associated bloodstream infections in recent study • Incidence is approximately 10‐14 per 100,000; varies by geographic location and patient population • Mortality 30‐50% Magill et al. “Multistate Point‐Prevalence of Health Care‐Associated Infections” NEJM, 2014. Pfaller et al. “Epidemiolog of invasive candidiasis: a persistent public health problem” Clin Microbiol Rev, 2007. Antbiotics.emory.edu 7 Very modest emergence of resistance Antbiotics.emory.edu A new Candida species: First report of C. auris from Japan in 2009 • Discovered during the course of a study to analyze antifungal yeast diversity in humans Satoh K et al. Microbiol Immunol, 2009 Antbiotics.emory.edu 8 C. auris is concerning • Multi‐drug resistant • Exhibits almost always resistance to fluconazole • Variable susceptibility to other azoles, amphotericin B, and echinocandins • Causing outbreaks/spread within healthcare facilities in India, UK • Challenging to identify • Can be misidentified as C. haemulonii, other Candida spp, or Saccharomyces with routine biochemical methods • Need MALDI‐TOF or sequencing to identify C. auris S. Africa Pakistan Kenya Venezuela Kuwait Israel Japan Korea India 2009 20102011 2012 2013 2014 2015 2016 Some hospitals reported 40% of candidemia was from C. auris Antbiotics.emory.edu C. auris WGS of 47 isolates from 4 world regions B11209 India 2013 SRR1664627 India 2013 B11218 India 2014 B11217 India 2014 Strains were: B11216 India 2014 B11215 India 2014 B11214 India 2014 B11213 India 2014 • Very different across regions B11212 India 2014 B11210 India 2013 B11096 Pakistan 2014 • Highly related within regions B11101 Pakistan 2014 B11118 Pakistan 2015 B11113 Pakistan 2015 • 93% resistant to fluconazole B11114 Pakistan 2015 250 B11097 Pakistan 2014 • 54% resistant to voriconazole B11117 Pakistan 2015 B11104 Pakistan 2015 India/Pakistan B11105 Pakistan 2015 • 35% resistant to amphotericin B B11098 Pakistan 2014 <60 SNPs B11116 Pakistan 2015 • 7% resistant to echinocandins B11115 Pakistan 2015 B11103 Pakistan 2015 11226 B11099 Pakistan 2014 • 41% MDR isolates B11200 India 2012 ERR899743 India • 4% resistant to all three major antifungal classes B11205 India 2013 B11201 India 2012 B11207 India 2013 8110 B11208 India 2013 B11206 India 2013 110 B11112 Pakistan 265 B8441 Pakistan 2010 B11230 South Africa 2014 B11224 South Africa 2013 B11228 South Africa 2014 27366 11975 B11226 South Africa 2014 B11221 South Africa B11222 South Africa 2012 B11223 South Africa 2013 South Africa 40,000‐140,000 B11225 South Africa 2014 B11227 South Africa 2014 <70 SNPs B11229 South Africa 2014 19688 SNPs across regions B11220 Japan 2009 B11247 Venezuela 2012 Japan B11244 Venezuela 2012 B11245 Venezuela 2012 47473 B11243 Venezuela 2013 B11246 Venezuela 2012 Venezuela <16 SNPs Antbiotics.emory.edu 9 CDC issued a clinical alert to healthcare facilities – June 2016 –“be on the lookout” • First description in U.S. ‐ As of August 31, CDC aware of 7 cases • All retrospectively found except for 1 • Most from New York, includes positive surveillance cultures, likely more to come • In the US, most isolates resistant to fluconazole, some resistant to amphotericin B, no echinocandin resistance • Continued need for reference testing of all • C. haemulonii, Saccharomyces, or C. auris –with pre‐emptive infection control Antbiotics.emory.edu No. 2 Clue The Hulk has explosive strength, creating chaos and havoc when loose, destroying most of that he comes in contact with…” Antbiotics.emory.edu 10 Ebola (VIRAL HEMORRHAGIC FEVERS) • Acute infection: fever, myalgia, malaise; often progression to prostration • Small vessel involvement: increased permeability, cellular damage • Multisystem compromise (varies with pathogen) • Hemorrhage often small in volume (indicates small vessel involvement, thrombocytopenia) • Poor prognosis associated with shock, dehydration, encephalopathy, extensive hemorrhage Antbiotics.emory.edu VHF: POPULATION AT RISK • Not everybody is equal • Africa includes several countries • Urban vs rural • All zoonosis • Travelers vs visitors • Healthcare workers, humanitarians • Ecologists, field workers Antbiotics.emory.edu 11 Ebola outbreaks in Africa Most burn out quickly Occasionally peripheral to cities Most < or = 300 cases Antbiotics.emory.edu 2016 Ebola outbreaks in Africa SENEGAL SIERRA LEONE Case 1 Cases 14,123 Death 0 Deaths 3,956 HCW 0 HCWs 221/307 MALI Cases 8 TOTAL Death 6 Cases 28,616 sHCWs 2/2 Deaths 11,310 HCWs 520/894 GUINEA Cases 3,814 Deaths 2,544 HCWs 100/196 NIGERIA Cases 20 LIBERIA Death 8 Cases 10,678 s HCWs 5/11 Deaths 4,810 HCWs 192/378 WHO May 19, 2016 12 26 Ebola cases outside West Africa 26 via air travel: From Guinea: 1; from Sierra Leone: 16; from Liberia: 9 (+1 Nigeria) Was there anything different ? •Virus ‐ no •Clinical manifestations ‐ no •Transmission mechanisms ‐ no •New countries involvement ‐ yes •People and behavior –yes •Difficult to break the transmission chain • Locally dense population/cultural obstables • Little experience in U.S. Antbiotics.emory.edu 13 Ebola therapeutics 2014 • Nothing for approved for human use before 2014 • Convalescent plasma • Valuable option for resource poor settings if overcome blood bank obstacles, experience since 1995 • Phase 2/3 100 person in Guinea – inconclusive • Phase 2/3 Liberia and Sierra Leone interrupted (low enrollment) • ZMAPP (humanized monoclonal antibiody cocktail) • Reversed symptoms in non human primates • Compassionate use now – • Phase 2 study in West Africa, Phase 1 study in UK/Italy planned • Favipiravir – influenza • Non-random open label phase 2 in Guinea – some effect if low viral load to start • Vaccine – two trials concluding – 100% effective, just approved
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