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A Global Perspective on Emerging Mosquito-Borne Diseases

A Global Perspective on Emerging Mosquito-Borne Diseases. Laura D. Kramer Wadsworth Center New York State Dept Health. JV Irons / RR Parker Memorial Lecture. Ft. Worth, Texas June 3, 2009. Defined the concept of EID Identified factors contributing to disease emergence

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A Global Perspective on Emerging Mosquito-Borne Diseases

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  1. A Global Perspective on Emerging Mosquito-Borne Diseases Laura D. Kramer Wadsworth Center New York State Dept Health JV Irons / RR Parker Memorial Lecture Ft. Worth, Texas June 3, 2009

  2. Defined the concept of EID • Identified factors contributing • to disease emergence • Pointed to challenges posed • by infectious diseases Emerging Infections: Microbial Threats to Health in the United States. Joshua Lederberg, Robert E. Shope, and Stanley C.Oaks, Jr., Editors; Committee on Emerging Microbial Threats to Health, Institute of Medicine (1992)

  3. “…the United States has no comprehensive national system for detecting outbreaks of infectious disease. Outbreaks of any disease that is not on CDC's current list of notifiable illnesses may go undetected or may be detected only after an outbreak is well under way.” “Although many local and regional vector-control programs can effectively combat small and even medium-size outbreaks of vector-borne disease, they are not equipped to deal with outbreaks that are national in scope.” “The significance of zoonoses in the emergence of human infections cannot be overstated.” Emerging Infections: Microbial Threats to Health in the United States. Joshua Lederberg, Robert E. Shope, and Stanley C.Oaks, Jr., Editors; Committee on Emerging Microbial Threats to Health, Institute of Medicine (1992)

  4. Atlantic Monthly, 1997 Outline • Drivers of emerging / re-emerging diseases • Re/emerging flavivirus • West Nile • Re/emerging alphavirus • Chikungunya

  5. Re/emerging infectious diseases • Define the concept. EIDs are infections that have newly appeared in a population, or have existed but are rapidly increasing in incidence or geographic range (Morse 1995) • Process • Introduction of agent • Establishment and dissemination

  6. Introduction: The ‘Zoonotic Pool’ Assuming 50,000 vertebrates, each with 20 endemic viruses. There are likely 1,000,000 vertebrate viruses. 99.8% of vertebrate viruses remain to be discovered Large potential for future zoonotic emergence! S Morse 1993

  7. Question What leads to selection or emergence a new agent?

  8. Genetic and biological factors Physical and environmental factors Vectors Ecological factors Socal, political and economic factors Modified from Jones et al 2008 Nature 451:990.

  9. Underlying factors in emergence: • Genetic and biologic factors Microbial genetics and adaptation Host susceptibility to infection • Physical environmental factor Climate and weather Economic development and land use • Ecological factors • Changing ecosystems • Human demographics and behavior • Social, political, and economic factors • International travel and commerce • Poverty and society inequity • War and famine • Intent to harm Modified from King L CDC 2008

  10. Population in millions http://esa.un.org/unpp/

  11. There is nowhere that is too remote to reach Global Aviation Network Most frequent Least frequent no. passengers / day Hufnagel et al, 2004 PNAS

  12. 400 ) ) 350 5 ( 300 ( e t a s 4 250 g n i v o e a i l b l n i o 200 b l m 3 G u n i c e r 150 n i h C t o 2 i t o a t 100 l u s y p a o 1 50 P D d l r 0 o 0 W 2000 1850 1900 1950 Year Speed of Global Travel in Relation to World Population Growth 6 Murphy and Nathanson Sems Virol 5, 87, 1994

  13. Percentage of Population Without Reasonable Access to Safe Drinking Water Earth Dispatch

  14. What is an Arbovirus? • Arthropod-borne • Group of viruses spread by arthropods • Many are zoonotic • Infection spread to incidental hosts that are not essential to the life cycle.

  15. Outline • Drivers in emerging diseases • Re/emerging flaviviruses • West Nile • Dengue • Japanese encephalitis • Yellow fever • Kyassanur Forest • Re/emerging alphavirus • Chikungunya

  16. Flavivirus: Flaviviridae (~70 members) 11 kb WNV modified from Kuhn RJ in Kramer LD et al. Lancet Neurology 2007

  17. Flavivirus: Flaviviridae (~70 members) • Human pathogens • Hemorrhagic fevers (flavi=yellow) • Encephalitis • Febrile illness • 3 phylogenetic clusters • No known vector • Tick-borne • Mosquito borne • Japanese encephalitis serocomplex • Includes JEV, SLEV, WNV • Primarily bird viruses • Humans not “amplifying” host • Other serocomplexes include YFV, DENV

  18. Japanese encephalitis serogroup WNV SLEV KUNV JEV MVEV

  19. Smithburn JS, Hughes TP, Burke AW, Paul JH. A neurotropic virus isolated from the blood of a native of Uganda. Am J Trop Med Hyg. 1940;20:471–92. Medical Department of the Uganda Protectorate International Health Division of The Rockefeller Foundation.

  20. West Nile 1994-2003 France 2000 2003 1999 Morocco Bucarest 1996 2003 2000 1994 Italy 1998 1996 1997 2003 1998 2000 Tunisia 2003 Israel 2003 2002 Modified from the French National Reference Center for Arboviruses, Pasteur Institute,Lyon, France Horses Humans Birds

  21. WNV geographic distribution Pre-1999 distribution Post-1999 distribution

  22. West Nile Virus in North America: Background • Discovered in 1999 in New York City during an outbreak of meningitis and encephalitis in humans and an accompanying epizootic in birds • Emergence during heat wave

  23. West Nile Virus In New York - 1999 NYC - 1795 Yellow Fever Outbreak 730 Deaths

  24. “I love the smell of malathion in the morning”

  25. Buzz City by Barry Blitt The New Yorker Sept. 27, 2000

  26. The Bite of Spring by Peter de Seve The New Yorker April 17, 2000

  27. Possible pathways of introduction of WNV into the USA • Infected Human • Human-transported vertebrate host • Legal • Illegal • Human-transported mosquito vector • Storm-transported vertebrate host (bird) • Intentional introduction (terrorist event)

  28. Lanciotti et al. 1999. Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern U.S. [Science 286:2333-337.]

  29. West Nile Virus Transmission Cycle Mosquito vectors Culex species Epidemic Secondary Hosts Epizootic Amplification hosts

  30. WNV Surveillance, United States,1999-2008*: Summary of Mosquito and Dead Bird Data • 64WNV-positive mosquito species reported • Culex species account for >98% of the total reported • 317 WNV-positive dead bird spp. • reported • 2006: American crows and blue jays • accounted for 62% of the dead birds • reported A Hitchcock, The Birds * Reported as of 3/2009

  31. Spatio-temporal Declines, American Crow North American Breeding Bird Survey S LaDeau; Nature. 2007. 447(7145):710-3

  32. 16000 14000 12000 10000 8000 6000 4000 2000 0 1999 2000 2001 2002 2003 2004 2005 2006 2007 Equine Cases, United States, 1999-2007 Total Equine: 24,681cases Vaccine introduced Equine Case Reports Year CDC/NCID/DVBID

  33. WN disease

  34. (1294) 2005 (1495) 2006 (1173) 2007 Reported incidence of West Nile virus disease by county, United States, 1999–2007 (Total cases) (21) (62) (66) (4156) (9862) (2539) Hayes EB et al. EID 2006

  35. Risk of WN disease in humansseroprevalence studies in US (CDC) 1 of 140 infections neurologic disease 1 of 5 infections febrile illness 4 of 5 infections subclinical Most mosquito bites not by infected mosquito

  36. Regional epidemics Avg = 1295/year WNV neuroinvasive disease cases in United States (by year) No. NID cases Year

  37. WNV neuroinvasive disease cases and deaths No. of NID cases % mortality

  38. 11,820 WNND Cases x 140 infections/WNND ~ 1.65 Million Infections Reported WNND Cases and WNV Deaths in Humans,United States, 1999-2008* WNV Widespread and Pervasive in Environment Produced Widespread and Pervasive Impact * Reported as of 11/04/2008

  39. West Nile virus neuroinvasive disease cases by age group and gender, 1999-2006* 25 Male Incidence 20 Female Incidence 15 Incidence per 100,000 10 5 0 0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 80-89 90-99 Age Group (yr) * Reported as of 5/2/2007 Sejvar J CDC

  40. 0.8 0.7 0.6 0.5 0.4 Proportion with WNF 0.3 0.2 0.1 0 18-29 30-39 40-49 50-59 60-69 70-79 Age Group Proportion of viremic blood donorsdeveloping West Nile feverColorado, 2003 Vector Borne Zoonotic Dis 2007;7:479

  41. Risk factors for neuroinvasive disease • Strong evidence • Age • Risk increases ~1.5 times per decade • Organ transplant recipients • ~40% develop neuroinvasive disease (>40 times the risk as population-at-large)* • Hematological malignancies • Experimental infection and individual case reports (risk remains undefined) * Kumar et al. Am J Transplant 2004;4:1883-8

  42. Risk factors for neuroinvasive disease • Weaker evidence • Diabetes • Hypertension • Alcohol abuse • Chronic renal disease • Cardiovascular disease

  43. The West Nile Virus “Iceberg” - 2 Acute WNV WNV long term effects Sejvar CDC

  44. Temporal profile of recovery—WNV “Poliomyelitis” BaselineStrength 100 80 Level of recovery (18) 60 40 20 0 Sejvar J CDC

  45. Greatest risk – exposure to mosquito bite !! Novel modes of virus transmission • Transfused blood • Blood supply screening began in 2003 • More than 1000 viremic blood donors identified 2003 - 2004 • Transplanted organs • Breast milk • One case, infant asymptomatic • Transplacental transmission • Single case 2002 with severe outcome to infant • Percutaneous, occupational exposure • Dialysis?

  46. Conclusions 1 – North America • Rapid spread across USA (<4 years to Pacific Coast) • Bird migration and random bird movements • Many possible important avian hosts and competent mosquito vectors (unprecedented infection prevalence) • Significant impact on wildlife and domestic animals. • Persistent seasonal outbreaks. Incidence varies regionally. • High infection incidence in humans has led to unusual modes of transmission. • Age and immunosuppression highly significant risk factors for neuroinvasive disease. Role of other risk factors unclear, but possibly important.

  47. West Nile Virus in Latin America 2002 – 2004 2006

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