Transcript Infectious Disease Transmission: The “Epi-Triangle”

Mosquito-borne Zoonotic Diseases
CMED/EPI 526
Spring Quarter 2009
Anthony A Marfin, MD, MPH, MA
State Epidemiologist
Washington Department of Health
April 15, 2009
University of Washington
School of Public Health
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
Zoonoses refer to diseases & infections
naturally transmitted between vertebrate
animals & man with or without an arthropod
intermediate (WHO, 1956)
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)
Mosquito-borne diseases that are NOT zoonotic



Human is only vertebrate host
Question if there is a “sylvatic” reservoir (e.g., nonhuman primate species)
Examples include:
• Malaria (protozoa) – Anopheles spp.
• Dengue (flavivirus) – Aedes aegypti, Ae. albopictus
• Filiriasis (nematode) – Aedes aegypti
• Chikungunya (alphavirus) – Aedes spp.
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
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
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 vector’s life & can kill vector.
Bridging vector – Mosquito feeds on amplifying hosts & other
species causing infections in other hosts. “Bridge” between
one cycle & another.
“Bridging” mosquito species in yellow fever
“Bridging”
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)
“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.”
“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 yeararound
• Chronic infection of vertebrate hosts
• Transovarial transmission
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
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
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
Infectious Disease Transmission:
The “Epi-Triangle”
Agent
“Vectors”
Viruses
Bacteria
Protozoans
Nematodes
Mosquitoes
Sand fly
Hosts
Vertebrates – Humans, horses, rodents, birds,
& reptiles
Environment
Temperature, humidity, rainfall
Mosquitoes, Sandflies & Human Disease
Infectious Disease Agents
Vector genera
Virus
Bacterial
Protozoal
Anopheles
Onyong-n’yong (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
Today’s Discussion
Infectious Disease Agents
Vector genera
Virus
Anopheles
Aedes/Ochlerotatus
(Stegomyia)
Culex
Phelbotomus
Japanese encephalitis
serocomplex
(Flaviviruses)
Bacterial
Protozoal
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
Commonality of Viruses in JE Serocomplex




Human infections:
• Most asymptomatic
• Small number of rash-fever or febrile illness cases
• < 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
“…West Nile virus was first
isolated in 1937 from the
blood of a febrile woman in
the West Nile province of
Uganda…”
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
West Nile Virus
Approximate Geographic Range in 1998
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
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
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
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 286:2333-337.
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
WNV transmission (Eastern U.S.)
Culex quinquefasciatus
Enzootic
vector Culex pipiens
Enzootic vector
(Maintenance/Amplification)
Amplifying hosts
Primary Enzootic Cycle
WNV transmission
Enzooticvector
vector
Enzootic
Incidental hosts
Humans
Horses
Other mammals
Bridge vectors*
Amplifying hosts
Cx salinarius
Cx nigripalpus
Ochlerotatus sollicitans
Oc taeniorhynchus
Aedes vexans
Ae albopictus
Cx tarsalis
* Epidemic potential
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
“I love the smell of malathion in the morning”
West Nile Virus Human Illness
<1% infections
West Nile neuroinvasive
disease(WNND)
Encephalitis, meningitis, myelitis
Increased risk with age & co-morbid
conditions
Reportable condition
10 -30% infections
West Nile fever (WNF)
No “overt” CNS involvement
WNF (10-30%)
Fever, rash, headache, myalgia, arthralgia
Not a reportable condition
70-90% infections
Asymptomatic infection
Not reportable condition
Same virus / antibody kinetics
WN
Life-longAsymptomatic
immunity
(70-90%)
Potentialinfection
problem for
blood
banking & organ donation
Clinical Spectrum of WNV
Illness: Revised
WN Meningitis
WN Fever
WN Encephalitis
WN “Poliomyelitis”
Inflammatory Neuropathy
Radiculopathy / plexopathy
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)
WNV Disease Surveillance
http://diseasemaps.usgs.gov/
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
West Nile Virus Neuroinvasive Disease
Cases in United States (by year)
Regional epidemics
WNND Cases
3000
Average = 1295/yr
2500
2000
1500
1000
2007
2006
2005
2004
2003
2002
2001
2008*
(*As of 11/18/2008)
2000
0
1999
500
First Reported WNV Activity by State, 1999-2008
1999
2000
2001
2002
2003
2004
Average Annual Incidence of WNND,
by County, U.S., 2004-2007
Human WNV Cases in
Washington State, 2006-2008
Whatcom
Okanogan
Skagit
Stevens
Island
Snohomish
Clallam
Chelan
Jefferson
Kitsap
Grays Mason
Harbor
Thurston
Pacific
Wahkiakum
Pend
Oreille
Ferry
San Juan
Douglas
King
(1 human)
Pierce
(2 humans)
Kittitas
Lewis
Yakima
(2 humans)
Cowlitz
Skamania
Clark
(1
human)
Lincoln
Spokane
Grant
Adams
Whitman
Franklin
Garfield
Benton
Walla Columbia
Walla
Asotin
Klickitat
WNV-infected human identified in county
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
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
140 x 11,807 WNND = ~1.65 million infections
• 28 WNV fever cases per 1 WNND case

28 x 11,807 WNND = ~331,000 WNV fever
West Nile Virus - The most widespread of the JE
serocomplex flaviviruses
Transmission of WNV Without
Mosquitoes
Viremia
Concentration
WNV-CNS tissue
Serum & CSF IgM Ab
IgG & Nt Ab
Infection
Illness onset
Incubation: 2-15 days
D4 – D6 illness
1Y after illness
D14 – D21 illness
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
WNV Transfusion- & TransplantationAssociated 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
Disease Control
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
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
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