Download Virus Reservoirs and Vectors

Virus Reservoirs and
Vectors
Thomas P. Monath MD
Chief Scientific Officer & Chief Operating Officer,
ID Division, NewLink Genetics Corp.
Agenda
• Potential changes in vector distribution and vectorial efficiency
with climate change
• Potential for establishment of an enzootic transmission cycle in
the Americas
• Role of direct human-to-human transmission in the Zika
epidemic
• Critical gaps in Zika knowledge and research priorities
Temperatures in the
Continental US
http://www3.epa.gov/climatechange/science/indi
cators/weather-climate/temperature.html
Temperature and Rainfall are the Most Important
Factors Limiting Virus Transmission
• Temperature prolongs adult mosquito survivorship and
shortens extrinsic incubation period
– Virus transmission requires that longevity exceed EIP
– Population size of adult mosquitoes dependent on survival through a
gonotrophic cycle
• In multiple models, temperature and rainfall significantly
and independently associated with dengue
transmission
• However, link between climate change and dengue
(chikungunya) incidence is largely speculative
– Longer transmission seasons in temperate areas
– Northward extension of Ae. aegypti and Ae. albopictus
(Europe)
– Increasing frequency of El Niño events,
other extreme climatic events
Temperature suitability for dengue transmission
Peak suitability in
warmest regions
100-1000 x the value in
tropics vs. temperate
regions
Ae. aegypti
100-1000 more
mosquitoes required to
sustain transmission in
temperate areas
Ae. albopictus
Isolations of Zika virus from mosquito species
Known vector of
Ae. aegypti
Ae. africanus
Ae. luteocephalus
Ae. furcifer
Ae. taylori
Ae. vittatus
Ae. metallicus
Ae. dalzielli
Ae. hirsutus
Ae. unilinaetus
An. gambiae
An. coustani
Ma. uniformis
Cx. perfuscus
Yellow fever
Chikungunya
Dengue
Ae aegypti
Aedes aegypti
Ae. vittatus
Ae. furcifer
Aedes africanus
Ae. apicoargenteus
Aedes luteocephalus
Aedes albopictus
Aedes africanus
Risk of establishment of an enzootic Zika
transmission cycle in the Americas
•
Yellow fever was introduced into
tropical America 400 years ago.
–
•
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–
•
Zika virus was introduced into
tropical America only 1 1/2 years
ago
•
A sylvatic cycle could be initiated at
the forest/suburban ecotone by the
same mechanism
The introduction must have been
through the agency of viremic
humans or infected Ae. aegypti
A sylvatic cycle was established in
nonhuman primates
–
•
“Reverse” jungle YF event(s):
infection of Haemagogus spp.
mosquitoes feeding at ground level
on humans with subsequent
transmission to monkeys in the
canopy
Haemagogus and Sabethes spp.
highly competent vectors in
econiche for transmission
Vertical transmission in
Haemagogus
Some neotropical monkeys (notably
Alouatta) develop fatal YF, whereas
coevolved African species have
inapparent infections
–
Haemagogus spp. (and monkeys)
distributed widely from South
America to Mexico through areas
affected by Zika
–
No data on neotropical mosquito
vector competence
Vertical transmission in Ae.
luteocephalus, Ae. furcifer-taylori
(no data on neotropical spp.)
–
•
No data on susceptibility of
neotropical monkeys to Zika; African
monkeys (and Orangutans) have
inapparent infections
Jungle Yellow Fever Distribution in 19501953 Epizootic Extended to the US border
Potential Zika distribution if
escapes into sylvatic cycle
1952
2016
Experts investigate a Zika link to
mysterious monkey deaths in Nicaragua
In recent months, around 60 howler monkeys have been found dead or dying in
the tropical rainforests of Nicaragua. The animals have CNS signs, hepatitis and
renal failure. Studies are in progress.
Feb. 10 Global Post
Limitations on Laboratory Investigations
of Wildlife Disease Samples
• Multiple primatologists are working in the
Neotropics and constitute a valuable
surveillance network
• CITES permits required for shipping samples
from endangered species
• Export permits
• Import permits
• Facilitation of laboratory support needed by
international agencies
Potential for Persistence of Zika Virus
•
•
•
Maintenance in human-mosquito cycle
Persistent virus infections, immunologically privileged sites, direct contact or
sexual transmission
Sylvatic cycle involving NHP
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Confined to tropical, subtropical areas with wild NHP populations
Could constitute a persistent threat of reintroduction to urban cycle
Could involve border regions Mexico, Central America
Not a direct threat to CONUS (primate centers too small to sustain transmission)
Vertical transmission in Aedes vectors
Alternate vectors
– Studies in tropical America show substantial feeding on NHPs of mosquitoes of
minor importance to YF cycle, suggesting that more research is needed on sylvatic
vectors
•
Other vertebrate hosts
– Zika and YF Virus isolated from multiple mosquito species in Africa with
generalized feeding preferences: involvement of non-primate hosts?
•
•
No evidence in Africa for alternative hosts
Some unusual findings (YF isolates from ticks, bat) suggest more research required
– New World mammals should be investigated if a sylvatic cycle is established
(especially marsupials, sloths)
Zika Virus Transmission
Cycle
Urban/
Sexual transmission
Congenital
Transfusion
?Direct contact
Nonhuman
Primates
Tree-hole breeding Aedes spp.
Domestic breeding
Aedes aegypti
Aedes albopictus
Ae. hensilli ?
Viremia Levels and Duration are
determinants of Ro
RNA copies
Infectious units
Infectious units
?
Zika Virus Adaptation to
Humans
Asian
African
Zika Virus Viremia and Shedding
•
•
Low, transient viremia after onset, suggests effective viremia may
occur principally during incubation period
Prolonged shedding of virus or viral RNA in saliva and urine
indicates potential for direct contact spread
– Virus isolation from serum, saliva, urine day 6, Canadian traveler
(Fonseca et al., 2014)
– RNA detected in urine for >10 days (viremia ceased day 4), 6
patients (Gourinat et al, 2015)
Zika Virus Viremia and Shedding
Proportion of patients (%)
– RNA detected in saliva for 5-7 days, n=182 patients with Zika
symptoms -, Tahiti, 2014 (Musso et al, 2015)
Days after onset
Critical Gaps in Zika Knowledge and Research Priorities
1
• Respective contributions of Ae. aegypti and Ae. albopictus
to ZIKV transmission?
– Define MID50’s
• Will other mosquito vectors play a significant role in
transmission?
– Susceptibility of Haemagogus spp.?
• Could ZIKV adaptation for more efficient transmission by
Aedes or humans explain its recent emergence?
• What is the magnitude of risk for mosquito-borne
transmission in the different regions of U.S.?
• What are the prospects for reducing ZIKV transmission and
spread through vector control?
– New approaches, Toxorrhynchites, aerial spraying
Critical Gaps in Zika Knowledge and Research Priorities
2
• What is the role of asymptomatically infected people as
amplifying hosts for mosquito transmission?
– Define ZIKV viremia in humans.
• What is the contribution of human-to-human transmission?
– Quantitate magnitude and duration of shedding and epi studies
• What is the potential for an enzootic cycle in primates or
other vertebrates in the Americas?
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Experimental studies of Neotropical NHP, other species
Field studies, surveillance
Enlist primatologists and facilitate diagnostic sampling
Long-term impact on human disease, vaccine policy,
surveillance?
• What are the interactions between ZIKV and heterologous
flaviviruses?
– Competition in vectors, cross-protection in humans, immune
enhancement