2006 Highlights in Medical Entomology

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2006 Highlights in Medical Entomology

• Stephen L. Dobson
• Entomological Society of America
• Indianapolis, IN
• December 13, 2006

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Selection
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Aedes aegypti Genome

• Coming soon to a Top Tier Journal... Watch for
  a series of publications Expected publication
  early 07

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http//www.vectorbase.org
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Largest intron observed 329 Kb
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• Assembly Complicated
• Approximately 50 of Ae. aegypti genome appears
  to be transposable elements
• smaller contigs
• more fragmented
• no polytene chromosomes (cannot easily place
  scaffolds)

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• Assembly Complicated ... and yet progress
• The top 500 scaffolds cover 70 of the genome
• Conservative approach simply assign to
  chromosome arm until sufficient
  evidence to support more precise
  placement

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With alternate splicing estimate 16,789
proteins Transcriptional evidence for 80 of
the 15,419 genes 76 of the hypothetical genes
(i.e., no known function) Based upon three
independent platforms
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Expansion of Insect Genomics
Mosquito An. gambiae ( other Anopheles) Ae.
aegypti Cx. pipiens ( Cx. p. quinquefasciatus) T
ick Ixodes scapularis Boophilus microplus -
Proposed (J. Med. Ent. 43(1) 9-16, 2006) Sand
flies Lutzomyia longipalpis - In
Process Phlebotomus papatasi - Planned, not
started Bug Rhodnius prolixus - In
Process Louse Pediculus humanus humanus-
Proposed (J. Med. Ent. 43(6) 1103-1111,
2006) Tsetse Fly Glossina morsitans - In
Process Over 100K ESTs, 10K full length-cDNAs
and BAC sequencing data (Source Serap
Aksoy) House Fly Musca domestica
http//www.genome.gov http//www.vectorbase.or
g
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VectorPathogen Interaction
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VectorPathogen Interaction
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Down Syndrome Cell Adhesion Molecule (Dscam)
Dong et al., 2006
101 exons
31,920 splice forms with different binding
specificities
Infection responsive alternative splicing of Ig
domain exons Challenge with different pathogens
induces specific AgDscam splice form repertoires
Slide Credit to George Dimopoulous
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Down Syndrome Cell Adhesion Molecule (Dscam)
Dong et al., 2006
PHAGOCYTIC FACTOR
MEDIATE RESISTANCE TO INFECTION
A
D
F
E
B
C
HPC1068 A. bogorensis P. veronii total
Slide Credit to George Dimopoulous
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Down Syndrome Cell Adhesion Molecule (Dscam)
Functional relevance of infection responsive
alternative splicing
Dong et al., 2006
challenge challenge
Dscam responds to immune challenge with
production of pathogen interaction specific
splice form repertoires.
binding
Correlation between pathogen challenge responsive
splice form production and anti-pathogen activity.
Slide Credit to George Dimopoulous
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AgDscam depletion increases mosquito
susceptibility to Plasmodium
Down Syndrome Cell Adhesion Molecule (Dscam)
Plasmodium berghei
Control
Knock-down
plt0.05
Plt0.05
Slide Credit to George Dimopoulous
Dong et al., 2006
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P. berghei
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VectorPathogen Interaction

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Live Heat inactivated
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Molecular Assay Accessibility
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Molecular Assay Accessibility
Figure Credit
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Molecular Assay Accessibility
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Molecular Assay Accessibility
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Insecticides
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Insecticides
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The Innovative Vector Control Consortium
improved control of mosquito-borne
diseases Janet Hemingway, Barry J. Beaty, Mark
Rowland, Thomas W. Scott and Brian L. Sharp
Trends in Parasitology, Volume 22, Issue 7,
July 2006, Pages 308-312.
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Washington DC Dec. 14, 2006
The President's Malaria Initiative (PMI) is a
five-year, 1.2 billion program that challenges
the private sector to join the U.S. Government in
combating malaria in 15 of the hardest-hit
countries. The initiative aims to cut
malaria-related deaths by 50 percent in these 15
focus countries in Africa.
First three focus countries Tanzania, Angola and
Uganda Four additional focus countries announced
in June 2006 Malawi, Mozambique, Rwanda, and
Senegal Announcement of an additional 8
countries expected (Total 15
countries) Emphasis education and evaluation
programs, long-lasting mosquito nets,
anti-malarial drugs, mosquito-spraying programs
(indoor residual spraying including the possible
use of DDT )
www.whitehouse.gov/infocus/malaria
Source Tom Burkot, CDC
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Insecticide Treated Bed Nets
Planned distribution of 38M Long Lasting
Insecticidal nets through mid-2007, free of
charge, to 16 countries in Africa and Indonesia
(primarily linked to measles vaccination and
other health campaigns) Expected to result in
the prevention of gt500,000 deaths
210,000,000 /500,000 deaths averted 420/aver
ted death
Countries nets Ethiopia
18,210,000 9 West Central African countries
8,069,000 6 East and southern African
countries 10,070,000 Indonesia
2,050,000 TOTAL 38,399,000

• Estimate based on
• 75 of nets being used
• 1.7 children per net
• nets remaining effective for 3 years
• 5.5 deaths prevented per year for every 1000
  children using an insecticidal net
  (Lengeler, Cochrane Review, 2005)

Funding 210 million for the nets and their
delivery from GF, UNICEF, Carter Center, CIDA,
IFRC, ExxonMobil, PMI, ARC, WB, JICA, UNF, CRC,
DFID, MACEPA, Rotary, PSI Data from Mark
Grabowsky, Measles and Malaria Partnership and
Yemane Ye-ebiya, Centre for National Health
Development, Ethiopia
Source Chris Curtis, London School of Hygiene
and Tropical Medicine
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West Nile Virus
WNV Case data and temperature anomalies for 2006
Locations of human cases through Oct 06
largest epidemic so far in Idaho
Slide Credit Bill Reisen
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West Nile Virus
West Nile virus (WNV) was isolated from the
brains of 3 horses that died from encephalitis in
February 2006. The horses were from different
farms in central Argentina and had not traveled
outside the country. This is the first isolation
of WNV in South America. West Nile Virus
Isolation from Equines in Argentina, 2006 María
A. Morales, et al. Emerging Infectious
Diseases Vol. 12, No. 10, October 2006
WNV detected in Argentina with virus isolated
from horses and with serologically confirmed
human cases. Marks the entry of WNV
into temperate South America, with associated
human and horse cases not widely seen in the
tropical Americas. ProMed - April 26, 2006
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West Nile Virus

• Droplet size, rate of delivery and
  meteorological conditions were
  monitored.
• The target populations proved to be fully
  susceptible
• The roads in the test sites generally gave
  adequate opportunity for insecticidal
  coverage.
• The aerosol plume may have failed to contact
  the target mosquitoes
• Conclusion such insecticidal aerosols,
  delivered from the road, may not
  effectively reduce the force of transmission
  of WNV in our test sites

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Tick Borne Rickettsia
In 2005, NC reported 1/3 of all RMSF cases in US
(625 of 1843).

• Hypothesis
• Rickettsia amblyommii is a new spotted fever
  group rickettsia that is causing a mild to
  moderate illness that is being mistaken for RMSF
  in North Carolina
• Vector Amblyomma americanum

Presented at the 2006 ASTMH, Atlanta, GA
Source Charles Apperson
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Chikungunya

• Genus Alphavirus Family Togaviridae
• First isolated from the blood of a febrile
  patient in Tanzania in 1953
• Identified repeatedly in west, central and
  southern Africa and many areas of Asia

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Chikungunya

• Infection can cause a debilitating illness,
  most often characterized by fever, headache,
  fatigue, nausea, vomiting, muscle pain, rash, and
  joint pain. The term chikungunya is Swahili
  for that which bends up.

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Chikungunya

• Acute chikungunya fever typically lasts a few
  days to a couple of weeks, but some patients have
  prolonged fatigue lasting several weeks
• No vaccine or preventive drug recommendation
  vector control, vector avoidance

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Chikungunya
2004 - Kenya 2005 - Comoros Islands 2005, 2006 -
Réunion, Seychelles, Mauritius,
Madagascar, Mayotte, (other?)
some islands have played down the outbreak for
fear of an adverse impact on tourism
Dorothy Bonn, The Lancet, Vol. 6, Sept. 2006, 543
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Chikungunya
La Réunion Island (France)

• Virus detected in March 2005
• gt250,000 clinical cases (34 of the population)
• 237 deaths
• primary vector Aedes albopictus

Number of Cases
Weeks (2006)
Reiter, P. Fontenille, D. and Paupy, C., The
Lancet, pp. 463-464, Vol. 6, August
2006. Graph http//www.who.int/csr/don/2006_02_1
7a/en/
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Chikungunya
Genome Microevolution of Chikungunya Viruses
Causing the Indian Ocean Outbreak
Isabelle
Schuffenecker, et al. PLoS Medicine,
July
2006, Vol. 3, Issue 7, pp. 1058-1070.
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Chikungunya

• Five viral isolates from Réunion, one from
  Seychelles
• Outbreak began with a strain related to
  East-African strains that subsequently
  differentiated into multiple variants
• Change in E1 protein (position 226) predicted to
  affect cholesterol dependence of the
  virus

Genome Microevolution of Chikungunya Viruses
Causing the Indian Ocean Outbreak
Isabelle
Schuffenecker, et al. PLoS Medicine,
July
2006, Vol. 3, Issue 7, pp. 1058-1070.
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Chikungunya
French government has announced the creation of a
new research and surveillance center for emerging
diseases in the Indian Ocean. France has pledged
a start-up budget of 2.7 million, but details
are still sketchy. My dream is that it will be
open for researchers from around the world,
says Antoine Flahault, who coordinates
Frances chikungunya research program.
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Chikungunya

• From February 2006 to 10 Oct 2006, the WHO
  Regional Office for South-East Asia has reported
  151 districts in 8 states/provinces of India
  affected by chikungunya fever
• More than 1.25 million suspected cases
• In some areas reported attack rates have
  reached 45 percent.
• An entomological survey revealed high densities
  of Aedes albopictus in the affected
  areas as well as in areas not affected
  by the disease.
• ProMed - Oct. 17, 2006

Figure WHO http//www.who.int/csr/don/Regional_C
hykungunya_largeb.jpg
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Chikungunya

• The Sri Lankan government has confirmed that
  the viral fever spreading rapidly amongst people
  in Jaffna is the mosquito-borne chikungunya
  fever. It is suspected that more than 5000 people
  have been infected with the virus, now at
  epidemic levels.
• ProMED - Nov. 29, 2006

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Chikungunya
During 2005--2006, 12 cases of CHIK fever were
diagnosed serologically and virologically at CDC
in travelers who arrived in the United States
from areas known to be epidemic or endemic for
CHIK fever.
Chikungunya Infection in Travelers
Hochedez P, Jaureguiberry S, Debruyne M, Bossi P,
Hausfater P, Brucker G, et al. Chikungunya
infection in travelers. Emerg Infect Dis. 2006 Oct
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Chikungunya
... some risk exists that CHIKV might be
introduced into previously nonendemic areas by
travelers with viremia, leading to local
transmission of the virus, especially in tropical
or subtropical areas of the United States (e.g.,
the Gulf Coast and Hawaii) or its territories
(e.g., Guam, Puerto Rico, and the U.S. Virgin
Islands)
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Chikungunya
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Exotics Invasion/Elimination
Discovery of a widespread infestation of Aedes
albopictus in the Torres Strait, Australia.
Journal of the American Mosquito Control
Association 22(3) 358-365
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Lymphatic Filariasis Elimination
China has suggested the WHO send a team to
re-examine the regions which have reached the
criteria of filariasis elimination "The success
of China (and soon that of the Republic of Korea)
are proof that elimination of lymphatic
filariasis is possible if given the necessary
levels of political support, adequate funding and
public commitment."
- Dr. Shigeru Omi WHO Regional Director
for the Western Pacific Global Alliance to
Eliminate Lymphatic Filariasis Conference March
2006 Suva, Fiji Source Xinhua News Agency
April 5, 2006
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Vector Ecology
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Biocontrol
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Biocontrol
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Tools
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Tools
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NIH Funding

• electronic submission of R01s starting with the
  Feb. 5, 2007
• use of the SF 424 forms instead of the PHS 398
  forms
• new submission dates
• multiple PI grants
• the FY 2007 budget has not yet been approved by
  Congress, therefore, a definitive payline has not
  been established for NIAID
• currently operating on a temporary 10 payline
  for R01s
• Source Adriana Costero (NIAID/NIH)

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EDEN Project
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EDEN Project
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News
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and more to come in 2007
Thank you.