Genetic control and transgenic mosquitoes

Diverse approaches have been considered for genetic control of nuisance or vector mos-quito populations. Genetic control consists of the release of genetically modified indivi-duals in the field, to reduce or modify the composition of natural populations of target insects. It is based on a number of approaches (Asman, McDonald & Prout, 1981; Grover, 1985; Alphey et al., 2002):

•the introduction of sterility in males by irradiation or chemicals (the so-called sterile insect technique);

•sterility induced by hybridization (sterility inherited by crossing sibling species);

of WNV transmission seasonal screening of individual samples and restricting screening to blood donations designated for immunocompromised recipients was most cost effec-tive (Korves, Goldie & Murray, 2006).

Efforts are in progress to develop a vaccine against WNV (Chang et al., 2004; Hall &

Khromykh, 2004). However, a cost–effectiveness analysis calculated for the United States indicated that universal vaccination would be unlikely to result in societal monetary savings, compared with the cost per case of illness under the present disease incidence rates (Zohrabian, Hayes & Petersen, 2006). According to this analysis, at a cost of US$ 8.7 billion in a hypothetical population of 100 million people, vaccination would prevent 256000 cases of illness (including neuroinvasive diseases, lifetime disabilities and deaths) from WNV during a 10-year period, given an average cost per case of illness of about US$ 34000. Under these assumptions, a universal vaccination programme would be cost effective only when the incidence of disease increased substantially or the costs of vacci-nation were below US$ 12 per person (in the analysis, baseline vaccivacci-nation costs were assumed to be US$ 100).

The economic impact of mosquitoes, in particular of mosquito-borne diseases, must also be expanded to the animal industry. Horses are highly susceptible to infection with WNV, and many infections end in their death (Murgue et al., 2001). Thus, for example, WNV cost the equine industries in Colorado and Nebraska more than US$ 1.25 million in 2002, with an additional US$ 2.75 million estimated for preventive measures (USDA, 2003).

Older data, from 1965, tell that American losses from mosquito attacks on livestock rea-ched US$ 25 million that year, including a US$ 10 million decline in milk production (Rodhain & Perez, 1985).

11.10. Benchmarks

Mosquitoes are virtually ubiquitous – that is, they are adapted to a wide range of envi-ronmental conditions and develop in numerous different types of water bodies, inclu-ding organically polluted ones and small and often concealed aquatic habitats. Also, the ability of adult females, including infected ones, to disperse some distance from their lar-val habitats in search of a blood-meal threatens many localities with their bites, disease transmission or both. According to the species, biting can take place indoors or outdoors, during the day, and in the evening or at night-time. Control measures can usually only reduce mosquito abundances and mosquito–human contacts. This can be achieved through a variety of methods, including personal protection through the use of bednets, window screens, appropriate clothing and insect repellents.

Public efforts to control mosquitoes, however, should be implemented when:

•autochthonous mosquito-borne infections in people have been identified and endemic transmission poses a threat; or

•an intolerable level of mosquito biting is reached.

As with other pests, various items contribute to their economic burden – such as mos-quito control, medical treatment and health care (in the case of associated diseases), and loss of productivity – and additional costs may be incurred for preventive medicinal mea-sures. For example, health authorities throughout the United States recently introduced mandatory screening for WNV in blood from blood donors (Bren, 2003). Despite the lack of systematic studies, representative data are available to illustrate the huge econo-mic impact of mosquitoes.

Mosquitoes can affect people’s livelihoods and property values, as illustrated in the follo-wing example from Germany. The German Mosquito Control Association is a semi-pri-vate and semi-public institution responsible for mosquito control in the Upper Rhine Valley of Germany. The area it covers stretches 300 km along the Rhine and covers about 6000 km². With regard to mosquito breeding sites, it is a particularly sensitive region, because of the varying river levels and its vast floodplains. Several times a year, some 2.5million residents are at risk for mosquito nuisances. The Association has an annual budget of about €2 million, derived from public taxes. According to a cost–effectiveness analysis, the economic loss to be expected in the absence of mosquito control is a factor of 3.7 greater than this budget or about €7.5 million (N. Becker, German Mosquito Control Association, personal communication, 2006). Without mosquito control, this eco-nomic burden would be due mainly to losses in the gastroeco-nomic trade and recreational sectors and to expenditures for private mosquito control. Without mosquito control, busi-ness volume in gastronomy would be reduced by 25% during the peak summer season and by about 10% for the whole year. Moreover, due to mosquito control, property values have increased in this region, although figures are not available.

At present, the most important disease transmitted by mosquitoes in Europe and North America is West Nile fever. In 2002, 329 of a total of 4156 West Nile fever cases reported in the United States were from Louisiana. Of the people infected in Louisiana, 204 had an illness that involved the central nervous system and 24 of them died. According to a conversion of hospital charges to economic costs, using Medicare cost-to-charge ratios, the estimated cost of the Louisiana WNV epidemic was US$ 20.1 million from June 2002 to February 2003 (Zohrabian et al., 2004). This figure can be divided into two compo-nents: (1) a US$ 10.9 million cost of illness, comprising US$ 4.4 million in medical costs and US$ 6.5 million in nonmedical costs (such as loss of productivity, illness-related costs for transport and child care costs.); and (2) a US$ 9.2 million cost for the public health response, such as control of the epidemic.

The spread of WNV and evidence of transmission by transfusion (CDC, 2004a) promp-ted the Unipromp-ted States Food and Drug Administration to institute mandatory screening of the nation’s blood supplies and to regulate the routine screening of blood donations for the virus. A prospective cost analysis, on the basis of 2 million transfusions, was cal-culated to be between US$ 7 million and US$ 19 million, depending on the specific test applied and on the period of the year the blood samples were to be screened – that is, year-round screening or only screening during months of high incidences of WNV.

However, screening by a blood donor questionnaire alone in low-transmission areas with short WNV seasons was the most cost-effective strategy, whereas in areas with high levels

Public Health Significance of Urban Pests Mosquitoes

11.11. Conclusions

For decades, in the high- and middle-income parts of the world, the field of medical ento-mology has been neglected in many countries in temperate climate zones, because no urgent demands for specialists were apparent. However, for various and partly unknown reasons and for some time, we have been encountering increasingly more problems with arthropod nuisances and disease transmission. It is therefore essential to re-intensify research in medical entomology and to train medical entomologists to deal with vector-borne diseases and their control. These arguments apply particularly to mosquitoes, which are (next to ticks) the most ubiquitous and medically important arthropods.

Therefore, not only cases of mosquito-borne diseases, but also the distribution and abun-dance of mosquitoes have to be monitored regularly by specialized, government-autho-rized institutions.

With regard to the distribution of possible vectors and the occurrence of vector-borne diseases, it is necessary to intensify international and European collaboration, both on the legislative and executive levels. In Europe, notification systems should be standardized and notifications reported to a central agency, such as the ECDC. Like the CDC in the United States, this institution should be further promoted, and its duties should be exten-ded, to collect and analyse vector-related epidemiological data and to disseminate them The borderline between acceptable and unacceptable infestation levels may vary from

region to region, from time to time and from culture to culture and must be determined (and occasionally reassessed) according to actual requirements.

With some exceptions, the mosquito nuisance in Europe and the United States is usually rather limited, because of reasonable water management systems within urban areas. In more rural residential areas that have insufficient water management or have experien-ced floods, the mass emergence of adult mosquitoes may follow, which may cause increa-sed biting or disease transmission, both in rural areas and urban or suburban areas. As a consequence, mosquito control programmes should be implemented. However, the appropriate facilities for controlling such outbreaks of mosquitoes are not commonly available. The choice of management strategy for controlling mosquitoes should be made according to the specific situation and according to preset national or federal guidelines.

It always should be based on an IPM philosophy – that is, various approaches (physical, biological, biochemical and chemical) should be combined, and applications of pesticides should be minimized as much as possible. Experts are therefore essential for both plan-ning control programmes and implementing them. These programmes must include:

•monitoring and identifying mosquito species;

•locating their breeding sites;

•continuously assessing adult or larval (or both) densities; and

•having a clear strategy of control goals.

Information (such as the risks associated with the application of various pesticides) and educating the public (such as on how to prevent unintentional provision of breeding sites in the urban residential environment) are fundamental for effective control.

Also, ongoing climate and environmental changes should be observed carefully, as they may ameliorate conditions for mosquito development – for example, mosquito seasons may be extended, and mosquito habitats and densities may increase, which may lead to a greater impact on health. Furthermore, increased international travel and traffic in consumer items and animals increase the risk of introducing pathogens. This is especially true of viruses, when competent mosquito vectors are already present or when, in addi-tion to the introducaddi-tion of new viruses, mosquito vectors are also introduced. Permanent surveillance for autochthonous vectors and also for introduced potential vectors and pathogens will allow better risk assessment and management. The complex interactions between mosquitoes, people and the environment, and the impact mosquitoes may have on public health (Fig. 11.6), calls for more international cooperation in legislative, exe-cutive and research matters.

Fig. 11.6. Public health related interactions between mosquitoes, environment and people

References¹

Adhami J, Reiter P (1998). Introduction and establishment of Aedes (Stegomyia) albopic-tusSkuse (Diptera: Culicidae) in Albania. Journal of the American Mosquito Control Association, 14:340–343.

Alphey L et al. (2002). Malaria control with genetically manipulated insect vectors.

Science, 298:119–121.

Aranda C, Eritja R, Roiz D (2006). First record and establishment of Aedes (Stegomyia) albopictus in Spain. Medical and Veterinary Entomology, 20:150–152.

Asman SM, McDonald PT, Prout T (1981). Field studies of genetic control systems for mosquitoes. Annual Review of Entomology, 26:289–318.

Autorino GL et al. (2002). West Nile virus epidemic in horses, Tuscany region, Italy.

Emerging Infectious Diseases, 8:1372–1378.

Bae HG et al. (2005). Analysis of two imported cases of yellow fever infection from Ivory Coast and The Gambia to Germany and Belgium. Journal of Clinical Virology, 33:274–280.

Baldari M et al. (1998). Malaria in Maremma, Italy. Lancet, 351:1246–1247.

Barnard DR (2000). Global collaboration for development of pesticides for public health: repel-lents and toxicants for personal protection: position paper. Geneva, World Health Organization (document WHO/CDC/WHOPES/GCDPP/2000.5;

http://whqlibdoc.who.int/hq/2000/WHO_CDS_WHOPES_GCDPP_2000.5.pdf, acces-sed 5 October 2006).

Beaty ME et al. (2005). Travel-associated dengue infections – United States, 2001–2004.

Morbidity and Mortality Weekly Report, 54:556–558.

Becker N et al. (2003). Mosquitoes and their control. New York, Kluwer Academic/Plenum Publishers.

Benedict MQ, Robinson AS (2003). The first releases of transgenic mosquitoes: an argu-ment for the sterile insect technique. Trends in Parasitology, 19:349–355.

Bennett JK et al. (2005). New state record for the Asian tiger mosquito, Aedes albopictus (Skuse). Journal of the American Mosquito Control Association, 21:341–343.

to the public. Its duties may also include coordinating public health research program-mes. For example, more epidemiological data about mosquito-borne virus activity in Europe, such as that about WNV, are urgently needed. Moreover, there is hardly any information on the temporal and spatial circulation of encephalitis viruses; thus, the etio-logy of cases of summer encephalitides should be followed up.

To minimize the risk of establishing and spreading newly introduced exotic vectors in the WHO Europe Region, such as the Asian tiger mosquito, it is necessary to support colla-boration between European surveillance teams, which is getting under way within the EMCA. Furthermore, it is very important to provide legal requirements for adequate tyre storage (indoors or at places not exposed to rainfall) and tyre traceability. It is also necessary to implement more efficient control of international animal transport and to strengthen guidelines and directives for such control. Moreover, aircraft and ship disin-fection should be reassessed, and compulsory international rules should be established.

Mosquito control management, as a consequence of mosquito monitoring, should be effi-cient and at the same time ecologically sound. Governments would benefit from esta-blishing a network of centres in each country or state to gather information and form monitoring and operational (control) tasks. To avoid the formation of mosquito breeding sites by city management or landscaping (such as through the restoration of large tracts of land along rivers to a natural state), it is essential for building authorities to collaborate with biologists who are knowledgeable about the occurrence, biology and ecology of the indigenous culicid species. It is strongly recommended to harmonize mosquito control practices, to reduce unwelcome environmental impacts. Ecological risks posed by insec-ticides can be checked in the laboratory, but risk monitoring in the field will provide fur-ther knowledge for making decisions about the implementation of mosquito control in the framework of sustainable management of wetlands.

Within the EU, guidelines for insecticide review and application should be harmonized between the Member States. Formation of an insecticide panel, to facilitate effective control of a biting nuisance or vector transmission, must be guaranteed for the future.

However, possible health hazards caused by control activities must not exceed those of the pests they are intended to control.

1The authors selected the reference works that appear here according to their best knowledge. Whenever possible, peer-reviewed journals were cited. In very few cases, information or data were available only through other documents, but renowned institutions or organizations or authors published these.

Public Health Significance of Urban Pests Mosquitoes

CDC (2000). Map: distribution of Aedes albopictus in the United States, by county, 2000 [web site]. Fort Collins, CO, National Center for Infectious Diseases, Centers for Disease Control and Prevention (http://www.cdc.gov/ncidod/dvbid/arbor/albopic_97_sm.htm, accessed 4 October 2006).

CDC (2001). Arboviral encephalitides [web site]. Fort Collins, CO, National Center for Infectious Diseases, Centers for Disease Control and Prevention (http://www.cdc.gov/nci-dod/dvbid/arbor/cases-sle-1964-2000.htm, accessed 3 October 2006).

CDC (2003). Epidemic/enzootic West Nile virus in the United States: guidelines for sur-veillance, prevention and control, 3rd revision [online monograph]. Fort Collins, CO, National Center for Infectious Diseases, Centers for Disease Control and Prevention (http://www.cdc.gov/ncidod/dvbid/westnile/resources/wnv-guidelines-aug-2003.pdf, accessed 6 December 2006).

CDC (2004a). Update: West Nile virus screening of blood donations and transfusion-associated transmission – United States, 2003. Morbidity and Mortality Weekly Report, 53:281–284.

CDC (2004b). Mosquito-borne diseases [web site]. Fort Collins, CO, National Center for Infectious Diseases, Centers for Disease Control and Prevention (http://www.cdc.gov/nci-dod/diseases/list_mosquitoborne.htm, accessed 8 October 2006).

CDC (2005). West Nile virus: entomology [web site]. Fort Collins, CO, National Center for Infectious Diseases, Centers for Disease Control and Prevention (http://www.cdc.gov/ncidod/dvbid/westnile/mosquitoSpecies.htm, accessed 3 October 2006).

CDC (2006). West Nile virus: statistics, surveillance, and control [web site]. Fort Collins, CO, National Center for Infectious Diseases, Centers for Disease Control and Prevention (http://www.cdc.gov/ncidod/dvbid/westnile/surv&control.htm, accessed 3 October 2006).

CDHS/M&VCAC/UC (2004). California mosquito-borne virus surveillance & response plan.

Sacramento, CA, California Department of Health Services, Mosquito & Vector Control Association of California, and University of California. (http://westnile.ca.gov/web-site/publications/2005_ca_mosq_response_plan.pdf, accessed 12 January 2007).

Chang GJ et al. (2004). Recent advancement in flavivirus vaccine development. Expert Review of Vaccines, 3:199–220.

Chavasse DC, Yap HH (1997). Chemical methods for the control of vectors and pests of public health importance. Geneva, World Health Organization (document WHO/CTD/WHOPES/97.2;

http://whqlibdoc.who.int/hq/1997/WHO_CTD_WHOPES_97.2.pdf, accessed 5 October 2006).

Blair CD, Adelman ZN, Olson KE (2000). Molecular strategies for interrupting arthro-pod-borne virus transmission by mosquitoes. Clinical Microbiology Reviews, 13:651–661.

Brault AC et al. (2004). Differential virulence of West Nile strains for American crows.

Emerging Infectious Diseases, 10:2161–2168.

Bren L (2003). West Nile virus: reducing the risk. FDA Consumer, 37:20–27.

Brook JH et al. (1994). Brief report: malaria probably locally acquired in New Jersey. The New England Journal of Medicine, 331:22–23.

Bruce-Chwatt LJ, de Zulueta J (1980). The rise and fall of malaria in Europe. Oxford, Oxford University Press.

Buckley A et al. (2003). Serological evidence of West Nile virus, Usutu virus and Sindbis virus infection of birds in the UK. The Journal of General Virology, 84:2807–2817.

Ça˘glar SS, Alten B (2000). Malaria situation and its vectors in Turkey. In: Ça˘glar SS, Alten B, Özer N, eds. Proceedings of the 13th European Society for Vector Ecology Meeting, Belek-Antalya, Turkey, 24–29 September 2000. Ankara, DTP:234–245.

Callot J, Delécolle JC (1972). Notes d’entomologie – VI. Localisation septentrionale d’Aedes aegypti. Annales de Parasitologie, 47:665.

Cancrini G et al. (2003a). Aedes albopictus is a natural vector of Dirofilaria immitis in Italy.

Veterinary Parasitology, 118:195–202.

Cancrini G et al. (2003b). First finding of Dirofilaria repens in a natural population of Aedes albopictus. Medical and Veterinary Entomology, 17:448–451.

Cardamatis JP (1929). La dengue en Grèce. Bulletin de la Société Pathologie Exotique, 22:272–292.

Carlson DA et al. (1995). Molecular genetic manipulation of mosquito vectors. Annual Review of Entomology, 40:359–388.

Castelli F et al. (1993). ‘Baggage malaria’ in Italy: cryptic malaria explained. Transactions of the Royal Society of Tropical Medicine and Hygiene, 87:394.

Catteruccia F, Godfray HCJ, Crisanti A (2003). Impact of genetic manipulation on the fit-ness of Anopheles stephensi mosquitoes. Science, 299:1225–1227.

CDC (1995). Local transmission of Plasmodium vivax malaria – Houston, Texas, 1994.

Morbidity and Mortality Weekly Report, 44:295, 301–303.

(http://www.who.int/docstore/bulletin/pdf/2000/issue8/99-0285.pdf, accessed 7 October 2006).

Grover KK (1985). Chemosterilization trials against Aedes aegypti. In: Laird M, Milnes JJ, eds. Integrated mosquito control methodologies. Vol. 2. London, Academic Press: 79–116.

Guillet P et al. (1998). Origin and prevention of airport malaria in France. Tropical Medicine & International Health, 3:700–705.

Hall P et al. (2002). Fatal yellow fever in a traveller returning from Amazonas, Brazil, 2002. Morbidity and Mortality Weekly Report, 51:324–325.

Hall RA, Khromykh AA (2004). West Nile virus vaccines. Expert Opinion on Biological Therapy, 4:1295–1305.

Halstead SB et al. (1969a). Dengue and chikungunya virus infection in man in Thailand, 1962–1964. IV. Epidemiologic studies in the Bangkok metropolitan area. The American Journal of Tropical Medicine and Hygiene, 18:997–1021.

Halstead SB et al. (1969b). Dengue and chikungunya virus infection in man in Thailand, 1962–1964. V. Epidemiologic observations outside Bangkok. The American Journal of Tropical Medicine and Hygiene, 18:1022–1033.

Hemingway J (1999). Insecticide resistance in malaria vectors: a new approach to an old subject. Parassitologia, 41:315–318.

Hermosilla C et al. (2006). First autochthonous case of canine ocular Dirofilaria repens infection in Germany. The Veterinary Record, 158:134–135.

Higgs S, Snow K, Gould EA (2004). The potential of West Nile virus to establish outside of its natural range: a consideration of potential mosquito vectors in the United Kingdom.

Transactions of the Royal Society of Tropical Medicine and Hygiene, 98:82–87.

Hubálek Z, Halouzka J (1999). West Nile fever – a re-emerging mosquito-borne viral

Hubálek Z, Halouzka J (1999). West Nile fever – a re-emerging mosquito-borne viral