Culex Hybrid Debate (5) - Letter to Science & Response

[See WestNileVirus-L postings from March 6, 18, 19 and 23 of 2004 for
previous contributions to the debate prompted by the Fonseca et al.
article (Emerging Vectors in the Culex pipiens Complex) published March
5 2004 in Science: 1535-1538.]

OUTBREAK OF WEST NILE VIRUS IN NORTH AMERICA
Science 306 (5701):1473-1475. 26 November 2004

The Report "Emerging vectors in the Culex pipiens complex" by D. M.
Fonseca et al. (5 Mar., p. 1535) advances sweeping extrapolations
concerning mosquito blood-feeding behavior and West Nile virus (WNV)
transmission. These findings led Fonseca to conclude (1) that a
European introduction of Nearctic mosquitoes could "radically change
the dynamics of WNV in Europe" and to state "[t]his is a plea for more
control of the movements of these disease vectors."

Fonseca et al. find that certain microsatellite markers distinguish
Palearctic from Nearctic C. pipiens and interpret this observation as
supporting the idea that the former feeds solely on birds and the
latter indiscriminately on birds and mammals. Cited references (2, 3),
however, permit no such suggestion, while other publications (4-13)
indicate that Nearctic C. pipiens seek hosts no differently than do
Palearctic forms. Their epidemiological interpretation of this
analysis, therefore, is incorrect.

The most reasonable explanation for the relative severity of WNV in the
United States rests on the novelty of the event and the pathogenicity
of the introduced strain. Until recently, Nearctic birds remained
nonimmune against this virus and had not adapted to its presence. In
addition, other more effective vectors, such as C. tarsalis, transmit
WNV in many intensely affected Nearctic sites (14). This report,
therefore, fails to explain the unique features of the American WNV
outbreak and cannot justify imposition of European quarantine measures
against American mosquitoes.

A. Spielman,
Harvard University, Boston, MA 02115, USA.

T. G. Andreadis,
Connecticut Agriculture Experiment Station, New Haven, CT 06504, USA.

C. S. Apperson,
North Carolina State University, Raleigh, NC 27695, USA.

A. J. Cornel,
University of California, Davis, CA 95616, USA.

J. F. Day,
University of Florida, Vero Beach, FL 32962, USA.

J. D. Edman,
University of California, Davis, CA 95616,USA.

D. Fish,
Yale University, New Haven, CT 06520, USA.

L. C. Harrington,
Cornell University, Ithaca, NY 14853, USA.

A. E. Kiszewski,
Harvard University, Boston, MA 02115, USA.

R. Lampman,
Illinois Natural History Survey, Champaign, IL 61820, USA.

G. C. Lanzaro,
University of California, Davis, CA 95616, USA.

F.-R. Matuschka,
Humboldt University, 10099 Berlin, Germany.

L. E. Munstermann,
Yale University, New Haven, CT 06520, USA.

R. S. Nasci,
Centers for Disease Prevention and Control, Fort Collins, CO 80522, USA.

D. E. Norris,
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205,
USA.

R. J. Novak,
Illinois Natural History Survey, Champaign, IL 61820, USA.

R. J. Pollack,
Harvard University, Boston, MA 02115, USA.

W. K. Reisen,
University of California, Davis, CA 95616, USA.

P. Reiter,
Pasteur Institute, 75724 Paris Cedex 15, France.

H. M. Savage,
Centers for Disease Prevention and Control, Fort Collins, CO 80522, USA.

W. J. Tabachnick,
University of Florida, Vero Beach, FL 32962, USA.

D. M. Wesson
Tulane University, New Orleans, LA 70118, USA.

References

    1. D. MacKenzie, "Hybrid mosquitoes blamed for U.S. West Nile
disease," NewScientist.com, 5 March 2004 (available at
www.newscientist.com/news/news.jsp?id=ns99994748).
    2. A. G. Richards, Entomol. News 52, 211 (1941).
    3. A. Spielman, Ann. N.Y. Acad. Sci. 951, 220 (2001).
    4. C. Apperson et al., J. Med. Entomol. 39, 777 (2002).
    5. C. Apperson et al., Vector-Borne Zoonot. Dis. 4, 71 (2004).
    6. W. Crans, Proc. N.J. Mosq. Exterm. Assoc. 51, 51 (1964).
    7. G. Ekis, J. N.Y. Entomol. Soc. 79, 190 (1972).
    8. R. Hayes, Mosq. News 21, 179 (1961).
    9. A. D. Hess, R. O. Hayes, Am. J. Trop. Med. Hyg. 19, 327 (1970).
   10. L. A. Magnarelli, Am. J. Trop. Med. Hyg. 26, 547 (1977).
   11. R. Nasci, J. Edman, J. Med. Entomol. 6, 493 (1981).
   12. C. Tempelis et al., Am. J. Trop. Med. Hyg. 16, 111 (1967).
   13. C. Tempelis, J. Med. Entomol. 11, 635 (1975).
   14. D. R. O'Leary et al., Vector-Borne Zoonot. Dis. 4, 61 (2004).

---
RESPONSE
Citing studies where only U.S. specimens were examined, Spielman et al.
state that Nearctic and Palearctic Culex pipiens "seek hosts no
differently." On the basis of the combined evidence of our genetic
analyses and host preference studies performed in the United States,
Europe, Africa, and the Middle East, we propose that they do.
In our Report, we used a panel of 8 highly polymorphic microsatellite
loci to demonstrate that the two previously known forms of Cx. pipiens
in Northern Europe [Cx. pipiens form (f.) "pipiens" and f. "molestus"]
(1) are genetically distinct and do not interbreed there. We also
demonstrated that all U.S. populations examined contain many
individuals with hybrid genetic signatures ("pipiens" x "molestus")
alongside specimens with a "pipiens" signature. No hybrid signatures
were seen in Northern European populations, although a few hybrids were
detected in Southern France in late summer. Spielman et al. do not
contest these findings.
European Cx. pipiens f. "pipiens" have been found to feed
overwhelmingly on birds (2, 3) and ignore humans (4). We showed that
populations of Cx. pipiens f. "molestus" from Northern Europe have the
same genetic signature as North African and Middle Eastern populations
that feed almost exclusively on mammals (2, 5), especially humans (5).
These data support the hypothesis that there are two genetically
distinct forms of Cx. pipiens in northern Europe that differ radically
in their host preference.
In contrast, references (4-13) in the Spielman et al. Letter show that
although birds are preferred by U.S. Cx. pipiens, 38% of the blood
meals in a northeastern population were from mammalian sources (over
10% human) (6). Thus, U.S. Cx. pipiens, although mostly preferring
birds, includes many individuals that will bite mammals. This is
consistent with our finding that the U.S. populations examined have
individuals with a hybrid signature ("pipiens" x "molestus") alongside
individuals with a "pipiens" signature.
Because human cases of West Nile virus (WNV) require vectors willing to
bite birds and then mammals, we proposed that hybrids of the two
behavioral forms contributed to the unique features of the U.S.
outbreak (7). The demonstrated different geographic distribution of
forms and hybrids within Cx. pipiens and the concordance of hybrid
status and reports of host preference make the summary dismissal of our
epidemiological interpretation by Spielman et al. premature, to say the
least. The combined evidence led us also to state that the introduction
of U.S. Cx. pipiens hybrids "has the potential to radically change the
dynamics of WNV in Europe," but we did not advocate the imposition of
quarantine measures against U.S. mosquitoes. Introduced disease vectors
can, however, have large health, economic, and ecological impacts. The
traffic of insecticide-resistant mosquitoes (8) has rendered powerful
insecticides useless, and diseases transmitted by introduced mosquitoes
threaten ecosystems [bird malaria, avian pox (9), WNV (10)], as well as
human populations [yellow fever (11), dengue (12), WNV (13)]. This was
the drive behind the statements made by D. M. Fonseca to the New
Scientist.
The novelty and pathogenicity of WNV to U.S. birds are almost certainly
important factors in the U.S. epidemic, but WNV would remain a bird or
wildlife disease without vectors willing to bite birds and then humans.
Indeed, Cx. tarsalis is considered a good vector of arboviruses to
humans because it shifts from a predominantly bird feeder to mammal
feeder during the breeding season (14). Such a clear pattern in host
preference has not been found in U.S. Cx. pipiens, which instead show a
high degree of geographic variation in host preference (6, 14)
consistent with a heterogeneous hybrid ancestry.
The complexity of forms in Cx. pipiens has long been debated (15) and
it is clear that the ability to identify Cx. pipiens populations
differing in host preference and physiology is needed for informed
epidemiological studies. Combining classical field and laboratory
methodology with new technologies like those used in our study offers a
way forward.
Dina M. Fonseca,
The Academy of Natural Sciences,
1900 Benjamin Franklin Parkway,
Philadelphia, PA 19103,
USA.
Genetics Program,
Smithsonian Institution,
3001 Connecticut Avenue, NW,
Washington, DC 20008-0551,
USA.
Nusha Keyghobadi,
Okanagan University College,
Kelowna, BC V1V 1V7,
Canada.
Colin A. Malcolm,
School of Biological Sciences,
Queen Mary,
University of London,
London E1 4NS,
UK.
Francis Schaffner,
Adege,
EID Méditerranée,
34184 Montpellier Cedex 4,
France.
Motoyoshi Mogi,
Saga Medical School,
Nabeshima 5-1-1,
Saga 849-8501,
Japan.
Robert C. Fleischer,
Genetics Program,
Smithsonian Institution,
3001 Connecticut Avenue, NW,
Washington, DC 20008-0551,
USA.
Richard C. Wilkerson
Walter Reed Army Institute of Research,
503 Robert Grant Avenue,
Silver Spring, MD 20910-7500,
USA.
References
    1. R. E. Harbach, B. A. Harrison, A. M. Gad, Proc. Entomol. Soc.
Wash 86, 521 (1984).
    2. A. Gabinaud et al., Cah. Orstom Sér. Ent. Méd. Parasitol. 23, 123
(1985).
    3. T. G. Jaenson, Med. Vet. Entomol. 4, 221 (1990).
    4. P. S. Cranston, C. D. Ramsdale, K. R. Snow, G. B. White, "Keys to
the adults, male hypogpygia, fourth instar larvae and pupae of British
mosquitoes (Culicidae) with notes on their ecology and medical
importance" (Publication 48, Freshwater Biological Association,
Ambleside, Cumbria, UK 1987).
    5. J. H. Zimmerman, H. A. Hanafi, M. M. Abbassy, J. Med. Entomol.
22, 82 (1985).
    6. C. S. Apperson et al., Vector Borne Zoonot. Dis. 4, 71 (2004).
    7. C. G. Hayes, Ann. N.Y. Acad. Sci. 951, 25 (2001).
    8. M. Raymond, A. Callaghan, P. Fort, N. Pasteur, Nature 350, 151
(1991).
    9. T. L. Benning, D. LaPointe, C. T. Atkinson, P. M. Vitousek, Proc.
Natl. Acad. Sci. U.S.A. 99, 14246 (2002).
   10. R. G. McLean, S. R. Ubico, D. Bourne, N. Komar, Curr. Top.
Microbiol. Immunol. 267, 271 (2002).
   11. P. Van der Stuyft et al., Lancet 353, 1558 (1999).
   12. J. G. Rigau-Perez, D. J. Gubler, A. V. Vorndam, G. G. Clark, J.
Travel Med. 4, 65 (1997).
   13. B. P. Granwehr et al., Lancet Infect. Dis. 4, 547 (2004).
   14. C. H. Tempelis, J. Med. Entomol. 11, 635 (1975).
   15. E. B. Vinogradova, Culex pipiens pipiens Mosquitoes: Taxonomy,
Distribution, Ecology, Physiology, Genetics, Applied Importance and
Control (Pensoft, Moscow, 2000).
Copyright © 2004 by The American Association for the Advancement of
Science. All rights reserved.
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