Unit: Insects and Infectious Diseases
Director: REITER Ian paulNo summary.
Genetic control of the dengue vector, Aedes aegypti
An estimated 2.5 billion people live in areas at risk of epidemic dengue; it is by far the most important mosquito-borne viral disease of humans. At present, mosquito control is the only option for reducing transmission, but conventional methods are increasingly ineffective. There is therefore an urgent need for new and innovative approaches.
Bio-engineering is a major focus of research in insect control. Ae. aegypti, the principal urban vector of dengue and yellow fever, is an excellent candidate. Our collaborators (Oxford University and OXITECH, a biotechnology company) have produced a strain of Ae. aegypti that includes a dominant gene which kills the aquatic stages of the mosquito when they have at least one copy. In the presence of tetracycline, however, the gene is repressed. Thus, the mosquitoes can survive in the laboratory but not in the field, where tetracycline is absent. The current objective is develop a transgenic strain that can compete with wild strains in nature; males will be released to mate with wild females, whose progeny will die because of the absence of tetracycline. The ultimate aim is to develop a sex-linked transgene that will restrict lethality to female progeny, thus providing a driver' of the gene in the field. In August 2005, the GATES foundation awarded OXITECH US$4.8 million for further research in this field. IMI was a co-member of the 11-institute consortium that applied for this funding, and is now a key player in laboratory and field-orientated research led by OXITECH.
At present we are comparing the fitness of transgenic males to that of a long-established laboratory strain (ROCK) by studies of competition, survival and reproductive capacity. We are also assessing the likelihood of emergence of a " resistant " strain in nature by monitoring the efficacy of the transgene in the presence of low concentrations of tetracycline. The transgene is linked to a gene for colour (fluorescent red) that enables us to separate transgenic from non-transgenic larvae. The Carl-Zeiss company are keen to work with us to develope a method to quantify fluorescence using a new model of fluorescence microscope (steREO Lumar). We hope to use this technique to discriminate between heterozygote and homozygote carriers of the transgene.
We are also back-crossing the transgene with a wild strain collected in San Juan, Puerto Rico. After successive generations of crossing, we hope to obtain a transgenic strain that resembles the wild strain in all respects except for the presence of the transgene. At that point we will be able to test competition and fitness in the presence of the original wild strain. Lastly, we are concluding a series of background studies of insemination success by ROCK males and diets for improving their survival in the laboratory.
A PhD student funded by OXITECH has been selected to continue laboratory development of a mark-release technique using our new atomic emission spectrophotometer. He will then conduct several short field trials of survival and dispersal, key factors in the efficacy and dissemination of future releases of the transgene. A Master's student has also been selected to work on the viral competence of transgenic strains in our P3 insectary. Lastly, we are providing expert advice on conventional dengue control to the Government of Singapore, who will also include transgenic mosquitoes in their research programme.
Epidemiology of West Nile virus in Europe
West Nile virus (WN) is the world's most widely distributed arbovirus. In the past decade, transmission has been documented at many sites in the Old World, and there have been major urban epidemics in Bucharest and Volgograd. The dramatic spread and remarkable prevalence of the virus in the Americas since its appearance there in 1999 has received great attention, and has given rise to fears of the emergence of a new public health problem in Europe. In truth, apart from the reasonable assumption that the virus has been present for a long time, little is known of its ecology and transmission dynamics.
The European Community has funded an €11.4million project named EDEN (Emerging Diseases in a Changing Environment) that addresses five endemic zoonoses. IMI is a participant in the 6-member steering committee of the project, and is responsible for the design and direction of the €1.4million WN research programme (see: http://www.eden-fp6project.net/diseases/west_nile_virus). The five-year project, which began in February 2005, is an 11-team comparative study of WN transmission at sites in Spain (Guadilquivir delta), France (Camargue), Italy (Padule de Fucecchio), Czech Republic (Danube basin) and Romania (Bucharest and the Danube Delta).
Ongoing field studies in the five countries include the recognition of potential vector species, characterization of mosquito-bird/mosquito-human and mosquito-horse transmission cycles, seroprevalence in resident and migratory birds, seroprevalence and seroconversion in horses, assessment of the role of ectoparasites in viral maintenance, overwintering of mosquitoes in urban areas, tests for virus in those mosquitoes, and the role of environmental factorsparticularly climatein viral ecology and the incidence of disease.
In Paris, IMI is responsible for laboratory studies of vector competence, vertical transmission and overwintering of mosquitoes identified as putative vectors by our field teams. A visiting PhD student has selected three such vectors in the Camargue and is conducting preliminary studies in our P3 insectary. A full time PhD student will continue his work in Spring, 2006. Institut Pasteur, Lyon, is responsible for quality control of diagnostic routines in the five countries, and for laboratory processing of samples collected by our teams in France. A " horizontal " component of the study will use satellite-derived information and Geographic Information Systems (GIS) to model present and future transmission.
Vertical transmission of dengue virus
Recent evidence suggests that inter-generation transmission of dengue virus via the egg stage may be more significant in the field than apparant in the laboratory. We are investigating factors that may have been overlooked in previous laboratory studies.
Asian Tiger Mosquito (Ae. albopictus) in northern Italy
This vector of dengue and Chikungunya viruses, imported to Europe from Asia via the United States, is a major problem throughout in Italy and has recently appeared in Nice. In collaboration with Institut Pasteur, La Sapienza University, Rome, we have developed a new surveillance/control device and are now organizing trials in Puerto Rico and Singapore.
Epidemic malaria in the Sahel
In areas of unstable malaria, high morbidity and mortality occur during epidemic transmission. The factors that precipitate epidemics are poorly understood, but rainfall and hydrology are probably critical. IMI and CERMES (Institute Pasteur in Niger) are co-partners with the Massachusetts Institute of Technology and Harvard School of Public Health in a projectfunded by the US National Oceanic and Atmospheric Administration (NOAA)that seeks to develope a statistical model epidemic transmission.
Paul Reiter, Marie Vazeille and Blandine Massonnet,17 October 2005