Abstract
In response to a broad governmental referral, the French High Council for
Biotechnology has published an opinion on the use of genetically modified (GM) mosquitoes
for vector control [1].
Emerging techniques of vector control were developed to overcome (i) the lack
of therapies, preventive treatments and vaccines for most mosquito-borne diseases, and (ii)
the limitations of existing vector control techniques (the situation is particularly
critical regarding insecticides: in France, essentially only one insecticide is used against
adult mosquitoes (deltamethrin), and its efficacy decreases due to resistance evolution in
mosquito populations).
To date, only one GM mosquito-based technique has been developed to an
operational level, Oxitec's RIDL technique, which seeks to reduce a mosquito population by
repeated mass releases of sterilising transgenic males
[2]. Two other techniques under development rely on CRISPR-based gene drive,
seeking to spread a genetic trait in a wild population, either to eliminate the population
by spreading sterility [3] or to make the target
mosquitoes incapable of transmitting pathogens
[4].
To identify the specific benefits and limitations of the different GM
mosquito-based techniques, a cross-analysis of different vector control techniques was
conducted with respect to possible objectives, efficacy and sustainability, technical
constraints and risks to health and the environment. Consideration was given to both
existing techniques (chemical, biological, physical, and environmental) and emerging
techniques based on release of mosquitoes, whether GM (RIDL and the different gene drive
techniques) or non-GM–irradiated (standard sterile insect technique (SIT)) or carrying
Wolbachia
1
(incompatible insect technique (IIT) and spread of pathogen interference (PI) technique).
As specified by the referral, we considered the mosquito-borne diseases and
vector species present across France, including overseas territories. The French territories
being dispersed across the world, the most notable mosquito-borne diseases worldwide were
considered, namely dengue, chikungunya, Zika, yellow fever, West Nile fever, for the viral
diseases, and malaria and lymphatic filariasis for the parasitic diseases. We focused on the
corresponding local vector species: mainly Aedes aegypti and Aedes
albopictus, and species of Anopheles and Culex.
These vector species have very distinct features, not only in distribution and
vector competence, but also in bio-ecology (reproduction modes, potential for survival, host
preferences, peaks and sites of aggressiveness, invasive potential…). The vector systems
themselves (the triad mosquito/pathogen/vertebrate host), as well as the diversity of
situations encountered across the territories add another layer of complexity. This overall
complexity must be understood and taken into account in order to design the most appropriate
vector control strategy.
Cross-analysis of the different vector control techniques has been conducted in
great detail and has made it possible to identify specific features and relative benefits
and limitations of each of these techniques. Detailed results are developed in HCB's opinion
(HCB, 2017).
At a more general level, we found:
– no divide between GM and non-GM techniques or between emerging and existing
techniques (Fig. 1);
– shared characteristics within different sets of techniques, i.e. (i)
techniques based on release of mosquitoes, (ii) population reduction techniques
2
vs. population modification techniques
3
, (iii) self-limiting techniques
4
vs self-sustaining techniques
5
;
– complementarity of the techniques.
Lastly, we found that the benefits and limitations of these vector control
techniques cannot be treated in a generic manner, but will depend on the target vector
species, the intended objective, and the broader context (epidemiological, environmental and
socio-economic context, including available human and financial resources).
Key highlights for each of these broad conclusion points are developed below.
Because they operate through mating between released mosquitoes and field
mosquitoes, a key feature of all techniques based on mosquito release is an unprecedented
specificity of action, confined to the released mosquito species and any interfertile
(sub)species. This has the major benefit of minimizing the direct impact of vector control
on health and the environment. It does, however, entail as many individual interventions as
there are species of non-interfertile vector mosquitoes to be targeted on a given site.
Population reduction techniques, whether or not they use mosquito release, and
whether or not the released mosquitoes are GM, have in common:
– an environmental impact associated with the reduction of target mosquito
population density and depending on the target species’ role in the ecosystem. This impact
varies according to, amongst other factors, whether the relevant species is autochthonous or
invasive, whether its habitat is urban or natural, whether specialist predators exist, the
extent to which the population is reduced (simple reduction, local elimination, or
eradication of the species
6
), the duration of the effects of a technique (depending, amongst other things, on how
isolated the treated area is), and the specificity of the technique (techniques involving
mosquito release being the most specific);
– the potential for unintended replacement of the target population by the
population of another vector species, which increases the more the target population is
reduced and the more this reduction persists over time.
Population modification techniques, whether or not they use GM mosquitoes, have
in common:
– less of an impact, in principle, with regard to environmental and health
risks, since they should not affect the density of mosquito populations. An assessment of
the risks associated with the induced modification is still necessary;
– persistence and varying invasiveness of the modifications induced, with the
need to consider the evolution and long-term effects of the factors responsible for these
modifications (Wolbachia, transgenes), including their potential for
transfer to other species.
Self-limiting techniques, whether or not they make use of mosquito release, and
whether or not the released mosquitoes are GM, have in common:
– the advantage of being controllable and adjustable in the light of monitoring
data;
– the drawback of calling for demanding maintenance in the long-term.
Self-sustaining techniques, whether or not they use GM mosquitoes, have in
common:
– the advantage of not calling for maintenance or large-scale infrastructure;
– the drawback of being fairly inflexible, or even without the possibility of
control (e.g., of intended spread affecting a whole species).
Complementarity of existing and emerging vector control techniques is well
illustrated in Fig. 2, which represents the
efficiency of the techniques depending on target population density.
Fig. 2
illustrates that:
– the efficacy of conventional methods of vector control is independent of
density beyond a certain density threshold of the target mosquito population. Below this
threshold, it declines with density until it is nullified before it can lead to elimination;
– conversely, reduction techniques such as the sterile insect technique SIT and
the derived techniques such as RIDL and IIT can only be effective below a certain density
threshold of the target mosquito population (depending on the ratio of released males to
wild males and on the competitiveness of the males released in comparison with wild males).
Beneath this threshold, they are all the more effective when the density is lower, thus
leading to local elimination (referred to as “Eradication” on the figure) of the population.
These different context-dependent efficacy profiles for the various vector
control techniques mean that compatible, complementary techniques ought to be combined in an
integrated vector control approach.
As of now, gene drive techniques are still under development. Additional
research is required before considering any field application, including reducing
development of resistance, developing knowledge and procedures for assessing the long-term
effects of gene drive on ecosystems, and strategies for controlling the spread of gene
drive.
Self-limiting sterile insect techniques (SIT, RIDL, IIT) could be tested step
by step on a precautionary basis for the purpose of contributing to vector control in French
territories, depending on the vectors concerned, in combination with the conventional
techniques currently used for integrated vector management. If successful, employing IIT,
SIT or the RIDL technique would in particular help reduce insecticide use. In addition to a
lesser risk of exposure for humans and ecosystems, lower insecticide use owing to the use of
techniques based on mosquito release would preserve insecticide efficacy by lessening
pressure for selection of resistance. This would thus enable insecticide use to be reserved
specifically for epidemics and public health emergencies.
More generally, the choice between different existing and emerging vector
control techniques or combinations of techniques should be informed by the intended
objective, by vector biology and behavior, and by the epidemiological, environmental, and
socio-economic context.
