Mosquito-borne%20Zoonotic%20Diseases

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Mosquito-borne Zoonotic Diseases

• CMED/EPI 526Spring Quarter 2009
• Anthony A Marfin, MD, MPH, MA
• State Epidemiologist
• Washington Department of Health
• April 15, 2009
• University of Washington
• School of Public Health

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Overview

• Zoonotic diseases
• Definitions for vector-borne disease
• Role of dipterans in vector-borne diseases
• Japanese encephalitis serocomplex
• West Nile virus in North America
• ArboNET surveillance
• Mosquito-borne viruses in the blood supply
• Disease control

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• Zoonoses refer to diseases infections
  naturally transmitted between vertebrate animals
  man with or without an arthropod intermediate
  (WHO, 1956)

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Why worry about vector-borne zoonoses?

• Negative impact on commerce, travel, economies
  (e.g., Rift Valley fever, yellow fever)
• Explosive debilitating outbreaks (e.g., yellow
  fever)
• Developing nations, diseases of major public
  health significance (e.g., yellow fever,
  leishmaniasis)
• Preventable cause of human illness death
• Human impact on environment can ? incidence
  (e.g., Japanese encephalitis)

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Mosquito-borne diseases that are NOT zoonotic

• Human is only vertebrate host
• Question if there is a sylvatic reservoir
  (e.g., non-human primate species)
• Examples include
• Malaria (protozoa) Anopheles spp.
• Dengue (flavivirus) Aedes aegypti, Ae.
  albopictus
• Filiriasis (nematode) Aedes aegypti
• Chikungunya (alphavirus) Aedes spp.

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Vector-Borne Infectious Diseases Are More Complex

• Multiple interconnected complex cycles
• Pathogens adapted to vertebrate invertebrate
  species
• Vector interacts with host agent
• Environment affects vector abundance ability to
  transmit infection
• Multiple host species

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Commonalities of Mosquito-Borne Zoonoses

• Humans rarely develop high titer of pathogens in
  blood, CSF, or tissue (i.e., do not amplify).
• Large outbreaks rare but can be explosive
• Clinical cases usually severe
• High mortality
• Finding source of infection (reservoir)
  important for disease control (source reduction,
  depopulation)

Excluding yellow fever virus
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Big Concepts Definitions Unique to Vector-Borne
Diseases

• Vector Does not itself cause disease. Instead,
  vectors transmit infection by moving pathogen
  from one host to another. Infection generally
  lasts vectors life can kill vector.
• Bridging vector Mosquito feeds on amplifying
  hosts other species causing infections in other
  hosts. Bridge between one cycle another.

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Bridging mosquito species in yellow fever
Bridging
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Different Types of Hosts

• Amplifying host Host (usually vertebrate) in
  which pathogens replicate to high levels
  (titer) leading to infection of more vectors.
• Reservoir hosts Host that allows persistence of
  pathogen in nature when active transmission is
  not occurring.
• Dead-end hosts Host that does not develop
  high titer of pathogens. Consequently, will not
  infect vectors. AKA incidental hosts.
• Definitive host Host in which pathogen reaches
  maturity (generally applies to protozoal
  nematodal infections, not viral bacterial
  infections)

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Advanced knowledge of mosquito-borne zoonotic
diseases

• Extrinsic incubation period Time interval
  between infection of vector first transmission
  of pathogen by vector.
• Transovarial transmission Infection of eggs in
  ovaries of an infected female vector leading to
  new vector infection (vertical transmission)
• Mosquito Infection Rate (MIR) Minimum estimate
  of number of infected mosquitoes. Usually
  expressed per 1,000 mosquitoes.

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Over-wintering mechanisms Viral persistence
strategies

• Allow re-emergence of pathogen in next year
  despite unfavorable environmental conditions
• Reintroduction by migratory birds
• Alternate arthropod vectors
• Long-term survival of infected, dormant females
• Continued feeding transmission year-around
• Chronic infection of vertebrate hosts
• Transovarial transmission

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Factors that strongly affect pathogen
transmission by mosquitoes

• Vector competence (ability to get infected
  transmit)
• Extrinsic incubation period (influenced by
  temperature)
• Vector contact with critical host
• Population indices of vector hosts
• Diurnal feeding habits of vector
• Pathogen replication in host (intrinsic
  incubation period)
• Host feeding preferences
• Vector longevity
• Precipitation flooding drought
• Temperature
• Proximity of vectors/reservoirs to human
  populations

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Dipteran Vectors of Human Disease

• Insects
• True flies (di ptera two wings)
• 240K spp of mosquitoes, sandflies, black flies
• Major insect orders for human health economies
• Example mosquitoes are primary vectors for
  malaria, dengue, West Nile virus, yellow fever,
  multiple viruses causing encephalitis

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Mosquitoes, Sandflies, Black flies (Order
Diptera, Suborder Nematocera)

• Primitive flies
• Not common house fly
• Aquatic larval forms (important for control)
• Vectors other than mosquitoes in suborder
  disease
• Black flies - Onchocerca volvulus, nematode
  causing river blindness
• Deer flies - Francisella tularensis (tularemia,
  rabbit fever)
• Phlebotamine sandflies Toscana, SFF Sicily,
  SFF Naples viruses (Phlebovirus, Bunyaviridae)
• Biting midges Blue tongue virus (Orbivirus,
  Reoviridae) other diseases of livestock

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Infectious Disease TransmissionThe
Epi-Triangle
Viruses Bacteria Protozoans Nematodes
Agent
Vectors
MosquitoesSand fly
Environment
Hosts
Vertebrates Humans, horses, rodents, birds,
reptiles
Temperature, humidity, rainfall
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Mosquitoes, Sandflies Human Disease
Infectious Disease Agents Infectious Disease Agents Infectious Disease Agents
Vector genera Virus Bacterial Protozoal
Anopheles Onyong-nyong (Alphavirus) ?? Plasmodium (Malaria)
Aedes / Ochlerotatus (Stegomyia) Yellow fever Dengue (Flavivirus) Chikungunya virus (Alphavirus) Francisella tularensis ??
Culex West Nile virus Japanese encephalitis virus St. Louis encephalitis virus Francisella tularensis ??
Phelbotomus Lutzomyia Sandfly Fever (Phlebovirus) Bartonella (Oroya Fever) Leishmania (Kala Azar)
Mechanical transfer of bacteria
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Todays Discussion
Infectious Disease Agents Infectious Disease Agents Infectious Disease Agents
Vector genera Virus Bacterial Protozoal
Anopheles
Aedes/Ochlerotatus (Stegomyia)
Culex Japanese encephalitis serocomplex (Flaviviruses)
Phelbotomus
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Japanese encephalitis serocomplex (14 viruses)

• Viruses that cause human encephalitis
• Japanese encephalitis virus
• West Nile virus (Variant Kunjin)
• St. Louis encephalitis virus
• Murray Valley encephalitis virus (Variant Alfuy)
• Rocio virus
• Ilheus virus
• Bussuquara virus (?)
• Viruses that do not cause human encephalitis but
  may cause animal infections/illnesses
• Usutu (?), Cacipacore, Koutango, Yaounde,
  Stratford viruses

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Commonality of Viruses in JE Serocomplex

• Human infections
• Most asymptomatic
• Small number of rash-fever or febrile illness
  cases
• lt 1 associated with central nervous system
  illness
• Very low virus titer in human serum CSF
• No human-mosquito-human transmission
• No human-to-human transmission
• Surface Envelope protein similar across complex
• Culex mosquitoes are vectors
• Amplifying hosts Birds
• JE MVE Ardeid birds
• In JE, pigs also serve as amplifying hosts
• WNV SLE Passerine birds

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West Nile virus was first isolated in 1937 from
the blood of a febrile woman in the West Nile
province of Uganda
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West Nile Virus Epidemics

• Endemic transmission with periodic epidemics
• First recorded epidemic Israel, 1951-1954 1957
• France 1962
• South Africa 1974
• Massive (75K), 1 case of encephalitis reported
• Romania 1996
• Italy 1998
• Russia 1999
• ? rate of WNND, ? case fatality rate

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West Nile Virus Approximate Geographic Range in
1998
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1999 1st WNV outbreak in North America

• New York City, June October 1999
• Initially, two separate investigations
• Epizootic beginning June 1999
• Epidemic beginning August 1999
• Begins with the astute clinician
• Veterinary medical clinicians
• Tracey McNamara, Bronx Zoo
• Debbie Asnis, Flushing Hospital
• Links between investigations established in
  September 1999

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West Nile Virus, New York City, 1999, Timeline

• June July 1999
• Epizootic begins, dead crow reports
• Veterinarian (Flushing/Brooklyn) finds crows with
  signs of nervous system disorders
• No human illnesses identified (retrospective
  review)
• August 1999
• Epizootic Bronx zoo birds die (8/25). Samples
  to NYS Department of Environmental Conservation
  (DEC)
• Epidemic begins in 1st week
• 8/2 First human infection (retrospective)
• 8/12 First case admitted to Flushing hospital
• 8/23 5th case admitted, Hospital contacts
  NYC-DOH
• 8/31 Samples arrive at NYS-DOH lab

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WNV in NYC in 1999

• September 1999
• Epizootic
• Avian samples to USGS USDA. Unidentified virus
  isolated.
• Connecticut Virus isolated from crow brain
• Isolates sent to CDC
• Epidemic
• 9/1 NYS-DOH lab Antibody to Flavivirus (SLE?)
• 9/3 CDC DVBID confirms SLE NYC starts vector
  control
• Autopsy samples to UC Irvine
• Late September 1999 Investigations come
  together
• Virus identified as Flavivirus by CDC (WNV-like)
  UC Irvine (Kunjin)
• Repeat serology, high-titer antibody against WNV
• Complete sequence identifies West Nile virus from
  birds/humans
• WNV identified from mosquitoes collected in NYC

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NYC 1999 isolate essentially identical to 1998
isolate from Israel
(Epidemic transmission)
(Low level, zoonotic transmission)
Lanciotti et al. 1999. Origin of the West Nile
virus responsible for an outbreak of encephalitis
in the northeastern U.S. Science 2862333-337.
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WNV in NYC in 1999

• October 1999
• Equine outbreak on Long Island reported
• WNV-positive dead crow found in Baltimore
• Jan-Feb 2000
• WNV found in overwintering dormant female Cx.
  pipiens in NYC

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WNV transmission (Eastern U.S.)
Culex quinquefasciatus Culex pipiens
Enzootic vector
Enzootic vector (Maintenance/Amplification)
Amplifying hosts
Primary Enzootic Cycle
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WNV transmission
Incidental hosts Humans Horses Other mammals
Enzootic vector
Enzootic vector
Bridge vectors Cx salinarius Cx
nigripalpus Ochlerotatus sollicitans Oc
taeniorhynchus Aedes vexans Ae albopictus Cx
tarsalis
Amplifying hosts
Epidemic potential
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What About Crows?

• High mortality throughout region
• Short time from infection to death
• Intermediate virus titer
• Unlikely to be amplifying host driving epidemic
  epizootic
• Unlikely to be reservoir host allowing seasonal
  persistence

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I love the smell of malathion in the morning
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West Nile Virus Human Illness
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West Nile neuroinvasive disease(WNND) Encephalitis
, meningitis, myelitis Increased risk with age
co-morbid conditions Reportable condition
lt1 infections
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West Nile fever (WNF) No overt CNS
involvement Fever, rash, headache, myalgia,
arthralgia Not a reportable condition
10 -30 infections
WNF (10-30)
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Asymptomatic infection Not reportable
condition Same virus / antibody kinetics
Life-long immunity Potential problem for blood
banking organ donation
70-90 infections
Asymptomatic WN infection (70-90)
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Clinical Spectrum of WNV Illness Revised
WN Meningitis
WN Fever
WN Encephalitis
WN Poliomyelitis
Inflammatory Neuropathy
Radiculopathy / plexopathy
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Surveillance for mosquito-borne zoonoses

• Weather conditions (temperature precipitation
• Wild-bird population
• Sick/dead birds test for virus (WNV, Usutu)
• Healthy birds test for antibodies
• Sentinel chicken flocks test for antibodies
• Mosquito collections test for virus
• Horses encephalitis test for antibodies
• Human illnesses
• Viremic blood donors (WNV)

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WNV Disease Surveillance
http//diseasemaps.usgs.gov/
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1999
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2000
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2001
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2002
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2003
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2004
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2005
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2006
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2007
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2008
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West Nile Virus Neuroinvasive Disease Cases in
United States (by year)
Regional epidemics
Average 1295/yr
(As of 11/18/2008)
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First Reported WNV Activity by State, 1999-2008
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Average Annual Incidence of WNND,by County,
U.S., 2004-2007
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Human WNV Cases in Washington State, 2006-2008
Whatcom
Pend Oreille
Ferry
San Juan
Okanogan
Skagit
Stevens
Island
Snohomish
Clallam
Chelan
Jefferson
Douglas
Lincoln
Spokane
Kitsap
King (1 human)
Grays Harbor
Mason
Grant
Kittitas
Pierce (2 humans)
Thurston
Adams
Whitman
Lewis
Franklin
Pacific
Yakima (2 humans)
Garfield
Benton
Asotin
Cowlitz
Columbia
Walla Walla
Wahkiakum
Skamania
Klickitat
Clark (1 human)
WNV-infected human identified in county
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Culex tarsalis

• The vector of irrigated lands in arid west
• Efficient WNV transmitter in lab
• Long distance flier
• Feed equally on birds mammals
• High infection rates in 2003

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Estimated Number of WNV Infections Fever Cases,
U.S., 1999-2008

• Reports of WNV fever vary widely
• WNND best indicator of WNV transmission among
  humans
• 11,807 cases of neuroinvasive disease in 10 years
• Based on serosurveys
• 140 WNV infections per 1 WNND case
• 28 WNV fever cases per 1 WNND case

140 x 11,807 WNND 1.65 million infections
28 x 11,807 WNND 331,000 WNV fever
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West Nile Virus - The most widespread of the JE
serocomplex flaviviruses
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Transmission of WNV Without Mosquitoes
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Viremia
WNV-CNS tissue
Serum CSF IgM Ab
IgG Nt Ab
Concentration
Infection
D4 D6 illness
1Y after illness
Illness onset
D14 D21 illness
Incubation 2-15 days
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Surveillance for Asymptomatic WNViremic Blood
Donors

• 23 transfusion-associated WNV infections
  identified in 2002
• Beginning 2003, all blood donations screened
  using NAT
• Presumed Viremic Donors (PVD) reported to state
  health departments which report cases to ArboNET

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WNV Transfusion- Transplantation-Associated
Disease

• 2002-2008, 32 transfusion (TFX)-associated WNV
  illnesses reported
• Last documented TFX-associated cases in 2006
• 2002-2008, 7 transplantation-associated WNV
  illnesses reported
• 4 cases in 2002, 3 cases in 2005
• Last documented TFX-associated cases in 2005

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Disease Control
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Strategies to prevent arboviral infections

• Alter environment
• Reduce mosquito breeding habitats
• Screen windows/doors
• Kill mosquitoes
• Larvicide/ Bacillus thuringienis applications
• Aerial spraying (adulticide)
• Tailor to habits of specific vector
• Mosquito fish copepods
• Humans personal protection
• Restrict outdoor activity at dawn dusk
• Wear long-length clothing
• Mosquito repellant use

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Human-Driven Ecological Changes That Alter
Incidence of Mosquito-Borne Zoonoses

• Deforestation
• Large-scale water projects
• Global climate change
• Urbanization
• Industrial agriculture practices
• Industrial animal husbandry practices
• Widespread use of pesticides
• Water pollution
• Introduction of exotic species
• Tendency towards monoculture

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Environmental Change Potential Changes to
Mosquito-Borne Zoonotic Diseases

• Increase amplifying hosts
• Example Hog farms that ? Japanese encephalitis
  virus transmission in Southeast Asia
• Example Rice monoculture in peri-urban areas of
  SE Asian cities
• Increase vector species
• Example Irrigation practices that ? West Nile
  virus transmission in CO NE