Scott L. O'Neill - Eliminate Dengue
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The Use of Wolbachia by the World
Mosquito Program to Interrupt 24
Transmission of Aedes aegypti
Transmitted Viruses
Scott L. O’Neill
Abstract 14]. It has been of interest to basic biologists for
The biological control of mosquito transmis- many years due to the unusual ways it manipu-
sion by the use of the naturally occurring lates host insect reproduction to ensure its effi-
insect-specific bacterial endosymbiont cient transmission into populations. Wolbachia is
Wolbachia has been successfully tested in not infectious but instead is maternally inherited
small field trials. The approach has been trans- through the insect egg cytoplasm. It has evolved
lated successfully to larger field sites in mechanisms to transmit itself very efficiently
Townsville, Australia and expanded to more into host populations by either directly or indi-
than 10 countries through the Eliminate rectly favouring female insects that carry
Dengue Program. The broader application of Wolbachia to leave behind more offspring than
the program beyond limiting the transmission uninfected counterparts [12]. One of the best
of dengue and including other Aedes aegypti studied of these mechanisms is cytoplasmic
borne mosquitoes has seen the program grow- incompatibility (CI) in which embryonic devel-
ing into a global not-for-profit initiative to be opment is arrested in Wolbachia uninfected
known as the World Mosquito Program. embryos that are fertilised by sperm that have
matured in the presence of Wolbachia (Fig. 24.1),
Keywords or in embryos fertilized by sperm matured in the
World Mosquito Program · Biological presence of a different strain of Wolbachia than
mosquito control · Cytoplasmic in the female egg.
Incompatibility · wMel Wolbachia strain · The World Mosquito Program (WMP), far-
Randomised control cluster trial merly known as the Eliminate Dengue Program is
a non-profit research consortium operating in a
number of countries www.worldmosquitopro-
gram.org (Fig. 24.2). It aims to develop Wolbachia
Wolbachia is a naturally occurring bacterial as an intervention to control mosquito-transmitted
endosymbiont of insects that is estimated to viruses such as dengue, zika and chikungunya.
occur in up to 40–60% of all insect species [6, The key feature of the Eliminate Dengue Program
is the intentional release of Wolbachia-infected
S. L. O’Neill (*) mosquitoes into target areas that will then trans-
Institute Vector Borne Disease, Monash University, mit Wolbachia into wild Aedes mosquito popula-
Clayton, VIC, Australia tions [7]. CI provides the mechanism by which
e-mail: scott.oneill@monash.edu
© Springer Nature Singapore Pte Ltd. 2018 355
R. Hilgenfeld, S. G. Vasudevan (eds.), Dengue and Zika: Control and Antiviral Treatment
Strategies, Advances in Experimental Medicine and Biology 1062,
https://doi.org/10.1007/978-981-10-8727-1_24
356 S. L. O’Neill Fig. 24.1 Wolbachia infections induce a phenomenon infected females. This is done by reducing the reproduc- known as cytoplasmic incompatibility in infected hosts tive output of Wolbachia uninfected females in a popula- that acts as a drive mechanism to push Wolbachia into the tion which benefits the maternally transmitted Wolbachia host populations by indirectly favouring Wolbachia Fig. 24.2 Locations where Eliminate Dengue release activities are being undertaken as of 2016. A number of new sites will be added in 2017
24 The Use of Wolbachia by the World Mosquito Program to Interrupt Transmission of Aedes aegypti… 357
Wolbachia will establish and maintain itself in periods have been required if target mosquito
wild mosquito populations over a number of mos- populations are larger. Despite the need to release
quito generations once released, even if the females the experience to date has been that most
Wolbachia strain places a mild genetic load on the members of a community undergoing releases do
mosquito it infects [8]. Given that Wolbachia is not complain of increased biting pressure, pre-
quite ubiquitous in the natural environment it is sumably because nuisance biting by other species
somewhat intuitive that environmental or human dominates the personal experience of residents.
health risks associated with its introduction into Once a series of releases has been undertaken
urban areas should be minimal. This is supported Wolbachia is expected to then maintain itself in
by independent risk analysis [10]. the local population indefinitely under the action
The key attribute of Wolbachia that the World of CI. The deployment is predicted to be robust if
Mosquito Program is basing its intervention on is it becomes successfully established initially and
its demonstrated ability to interfere with the rep- is demonstrated from data from our earliest
lication of human pathogens in Wolbachia release sites in Northern Australia where
infected Aedes mosquitoes. This includes Wolbachia has sustained itself in local mosquito
Flaviviruses like dengue, West Nile and Zika [1, populations at frequencies above 80–90% since
3, 5, 9, 11], Alphaviruses like chikungunya [2] as establishment from 10 weeks of releases in 2011
well as a range of other viruses and parasites. (Fig. 24.3). This is an extremely important attri-
Analysis of dengue blocking data where mosqui- bute of the interventions that WMP is undertak-
toes have been fed on bloods from dengue ing as costs for implementing the intervention are
patients indicates that the establishment of essentially front loaded during releases and then
Wolbachia in Aedes aegypti populations can be restricted to periodic monitoring. This avoids the
predicted to reduce R0 for dengue by more than need for ongoing expenditure as is the case for
70%, which in most epidemiological settings other interventions such as vector suppression
should completely stop local dengue transmis- technologies or vaccines and makes the WMP
sion [4]. approach both sustainable and highly
To implement a World Mosquito Program cost-effective.
intervention it is necessary to release Wolbachia It can be noted from Fig. 24.3 that while
infected mosquitoes, both male and female, until Wolbachia maintains itself at a very high fre-
the local frequency of Wolbachia in wild Aedes quency in the wild mosquito population it is
aegypti mosquitoes surpasses an unstable equi- rarely at complete fixation. We presume that this
librium point estimated to be less than 0.3 for the is a result of some leakiness in maternal transmis-
wMel strain of Wolbachia. Once this unstable sion rates of Wolbachia, possibly through the
equilibrium point is surpassed it is expected that action of environmental heat in some breeding
Wolbachia will locally establish and if the estab- sites. Of particular note though is that frequen-
lishment area is sufficiently large then start to cies of Wolbachia of around 80–90% may be
slowly spread out from the release area. This more optimal for disease reduction than complete
theory has now been tested in five countries fixation. At lower infection levels we can expect
where establishment of wMel has been achieved incompatible crosses generated from Wolbachia
according to these principles. Typically, quite via the CI mechanism to put downward pressure
small numbers of mosquitoes need to be released on mosquito population sizes that should act in
to surpass the unstable equilibrium point. In concert with the transmission blocking properties
Northern Australia in the first release experi- of Wolbachia to enhance the effects of pathogen
ments undertaken 10 mosquitoes (both male and blocking. Even at frequencies of around 80% in
female) were released per house per week for populations the effects of reduced vector compe-
10 weeks and this was sufficient to achieve estab- tence should still have very large impacts on
lishment [7]. In other countries longer release358 S. L. O’Neill
Fig. 24.3 Results of Wolbachia monitoring in the first sampled wild mosquito population in both sites.
two sites in Northern Australia where wMel releases were Wolbachia has maintained itself at high frequency since
undertaken showing the frequency of Wolbachia in the introduction in 2011
transmission, consistent with the observational ment requiring community consent rather than
data gathered so far. individual informed consent. The deployment in
Pilot releases have now been successfully Townsville also successfully used community
undertaken in five countries including Australia, deployments to augment programmatic deploy-
Indonesia, Vietnam, Brazil and Colombia and ments. Community deployments featured the use
indicate that the wMel strain can be deployed of small mosquito release containers supplied
successfully in diverse settings both ecologically with Wolbachia mosquito eggs and fish food and
and culturally. Observational data from these required only the addition of water and place-
deployments supports large impacts on disease ment of the container in a suitable shady location
transmission as predicted by modelling. In all for 2–3 weeks until all mosquitoes had emerged.
areas where Wolbachia has now established in As part of the community release program a tar-
these five countries we have not detected any geted program also ran in schools where school
examples of local transmission of dengue to date, students undertook the releases in a citizen sci-
defined as clustering of dengue cases in time and ence experiment. An area of 95 km2 was targeted
space, despite local transmission occurring in in the city of Townsville (almost the entire city)
neighbouring areas. A key feature of all these and the intervention was successfully deployed
deployments is that they have all occurred with over three stages in 2.5 years providing the first
strong community support and virtually no oppo- indications that the method could be scaled effec-
sition. Similarly, there have been no adverse tively over small cities. As per earlier pilot
impacts identified in any of these deployments releases there have been no examples of locally
either human related or environmental. transmitted dengue cases in Townsville in any
In 2014 the WMP undertook its first scaled areas where Wolbachia has been established at
release over the entire city of Townsville using a the time of writing.
mixture of egg and adult deployments. This scale Within the last 2 years there has been consid-
up required a new form of community engage- erable alarm in the international community of24 The Use of Wolbachia by the World Mosquito Program to Interrupt Transmission of Aedes aegypti… 359
the enormity and difficulty in controlling the At the same time, we will have learned how to
South American outbreaks of Zika virus which deploy at the scale of very large cities and reduced
have now spread to nearly all the countries where our costs with a goal of reaching a target of US$1/
dengue transmission occurs. Given the similarity person protected. If the results on these studies
in the ecology of dengue and Zika we can expect continue to be positive then it will be our goal to
ultimately that Zika transmission should co-exist collaborate with governments in disease affected
with dengue transmission in the same geogra- areas to make this technology and best practice
phies that have the main transmission vector, methods for its deployment available to countries
Aedes aegypti. Since Zika virus is quite closely in need.
related to dengue viruses there was an expecta-
tion that Wolbachia should block Zika transmis-
sion in much the same way as dengue viruses and References
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The wMel Wolbachia strain blocks dengue and One 7:e38544You can also read
