Sunday, February 18, 2024

Ireland's referendum: Vote No To Hold On To The Law

It takes too long to explain but 'woman' and 'man' have a meaning in law that is crucial for human rights on any level. The government are seeking to take out basically their responsibility to support families by simply changing the terms and then not recognising them. 


Here are some short discussions that will quickly put you in the picture: 

Darrren-Anthony: No To Taking 'Woman', 'Mother' and 'Family' from the Constitution


Emer and I discussing the Referendum on family and women


Darren-Anthony explaining the Ramifications



Thursday, February 8, 2024

Past Salisbury CND research should be enough to Stop Spending on Nuclear

Talk by Andy and Phil, both professors but I have long lost their proper titles, research for Salisbury CND talk 2nd April 2021.

Asking why is the UK government so committed to civil nuclear power, Andy gives the background.

As the years go by it is getting progressively more and more difficult to understand. This is especially in relation to their main argument that nuclear power is the way to achieve Climate Change mitigation goals.  


In criticism of the Energy policy, the existing nuclear power is manifestly slow in reducing climate change. The Hinkly Point C project is running very behind schedule. The government promised that Christmas dinners 2017 would be celebrated using power from the Hinkley Point nuclear power plant. And if not ‘the lights would go out’. It is already running 10 years late and it is the same in France and for Finnish nuclear projects and many have not yet been started.


The Modular reactors and other ‘New Generation’ nuclear projects proposed have not been piloted or tested. Now there is not even time for a development plan let alone delivery, as the UK government have promised a 68% reduction in carbon emissions by 2030 – just 9 years away. 


The government has, as well, made a commitment for Britain to be net zero by 2050 and has installed 10 gigawatts of offshore wind, alone. This does not account for on shore wind or solar. But it does already amount to more power than would be generated by ten of the new modular reactor plants in the proposed programme. Radical acceleration of renewable energy programmes is clearly possible.


The costs further compound the issue: For Hinkley Point C electricity, consumers will be forced to enter a 35 year contract. Even at current prices, charges will be £102 per Megawatt/hour. Current contract prices, in off-shore wind in comparison, are still going down and are already at £40 per MW/h. The problems of intermittency and inter-seasonality of renewables are talked about as a problem but found to not actually affect the cost greatly. The figures of 56-73 MW/h for on-shore wind, 53-56 MW/h for large scale solar and 69-85 MW/h per MWh for off-shore wind are ‘enhanced levelized costs’ by BEIS, which means that they include any pessimistic calculations as to intermittency of supply. Therefore, the argument is over on cost but the government, instead of revealing these figures, released its Energy White Paper in December 2020 with no costs on it. This is the first time such a White Paper has been delivered. 


Speculative nuclear programmes have always included escalating, not falling, future costs. There is very little evidence in history or experience that suggests that oncoming nuclear plants, which have always been more expensive, will turn out to be less so. 


Another cost problem is that spending on nuclear takes money away from spending on renewables, which could achieve the climate change goals faster.


Looking at trends and patterns over time also demonstrates that the efficacy gap of nuclear, for delivering electricity and mitigating climate change, is growing. Another group studying levelized costs note that solar and wind have gone down massively in the last ten years. In fact solar has gone down by 900% in its cost. Wind has gone down by 70%. In contrast, nuclear costs have gone up by 26%. So, over the passage of time, they are not going down.


Then there is this idea of firm nuclear power or baseload that the British are particularly caught up with. This idea proposed that the inflexibility of nuclear power, that it can’t go up or down in its output, is somehow an advantage. The CEO of the National Grid NGC called it an out-dated idea even back in 2015 and actually rigidly inflexible nuclear power is actually a disadvantage in smart grid sytems. 


On the other hand, the UK’s renewable resources are far larger than their foreseeable demand. This means that we cannot only deliver the electricity needs of the country but also the transport needs, via electricity, of the country from the available, viable renewable resource. 


There's often a clash between what they publish in background documents and what senior figures and scientists say. Official data confirms that renewables, with their intermittency, are capable of supplying the smart grids, which are being investigated by all sorts of demand management techniques. They show that the inflexible nature of nuclear power plants, becomes much more of a disadvantage. The idea that small modular reactors can be more flexible is actually also speculative. Even though modular reactors are already used like that in the military, there are safety implications in ramping up nuclear power and turning it up and down. France is already using nuclear in that way and we have yet to see what the regulatory repercussions are actually going to be. 


In short, renewables provide a domestic power supply that is safer, they are more diverse and they are more secure than nuclear power. 


Renewables and energy efficiency investments are also much more productive of UK jobs. So the picture really is stark, even when looking at the government's own data. So, why is it that the UK is so committed to nuclear power? It is actually obvious.


It is the military who perceive a need for the civil nuclear programme. It is not actually for nuclear weapons, but actually for nuclear submarine propulsion. These are very difficult artefacts to build. They need a massive nuclear industry. The companies and engineers for civil power are all involved in building the propulsion systems as well. What is remarkable is if you look at any of the Defence documents in the UK. The military are very clear that they need the civil nuclear power ‘at any cost’, in order to be able to build nuclear propelled submarines. In contrast, in the Energy Policy literature, there is a total silence. It is not acknowledged that it is the military that are the drivers. The UK government stick to their untenable and spurious argument that nuclear power is justified as an energy strategy and that nuclear is there for climate change. 


The upshot of this, because nuclear is so much more expensive than alternative zero carbon options, that consumers and taxpayers are paying tens of millions of pounds, hundreds of billions of pounds over the decades, of these contracts. This is in order to subsidise an industry that is only needed for military purposes. Remember that these contracts for electricity are regressive. It is the poorest households that are disproportionately charged for their electricity. 


This picture of costs is without even looking at the massive costs of development, research, decommissioning, waste management or security provision, such as the dedicated armed police force. They don’t include the cost of anti proliferation measures and to stop diversions of fissile materials that could complete a nuclear reaction. These are additional costs that are covered by all the UK nations including Scotland, where there is very strong opposition to nuclear power, which may become more significant. 


So investing in nuclear, rather than investing in renewables and efficiency is clearly impeding progress on climate change. Providing affordable energy and achieving climate targets are actually a legal duty on government. So, the official position of prioritising nuclear power is not only unjustified by evidence, it is actually arguably unlawful.


 The use of nuclear power, even where it is happening, is slow and it is costly. It is dishonest because the real reasons for pursuing it are not being given. It is undemocratic and it is unlawful. 


Phil will look in more detail at the civil military links.          One of the first places to look is at the broader international picture. There is a correlation between nuclear ambition and different types of geopolitical status. The leading global military powers are the most committed to large scale new nuclear bills. There is no global or regional military power that does not hold an active history of very strong pressures for civil nuclear power. No country, either with or planning nuclear weapons or submarines, is currently pursuing either a nuclear moratorium, or phase out. There really does seem to be a relationship and it becomes irrefutable when we look at the specifics.


The president of France, Emmanuel Macron says to oppose civilian nuclear, in terms of production and research does not make any sense for a country like theirs, because without civilian nuclear there’s no military nuclear and without military nuclear there’s no civilian nuclear. That was in December 2020.


The Atlantic Council, which is a large security think tank, describes how the US has a large educational Research and Development and industrial support system that underpins its civilian nuclear power sector. The same report goes on to actually quantify the level of subsidy that civilian nuclear power makes to military nuclear power; at least $42 billion is gathered annually, in the pursuit of US national security priorities. 


If there was a sustained decline in the commercial industry, it would also have a negative impact on the US nuclear naval programme. This is what was reported at the energy innovation reform project 2017 at the Centre for Strategic and International Studies.  


A former energy secretary said, in 2018, that naval nuclear capability is tied to the fate of the commercial nuclear sector, as long as a strong domestic supply chain is needed to provide the nuclear Navy requirements. This supply chain has a very strong overlap, which is very clear in France and in the US. It is a bit more hidden in the UK but if you get into the defence documents, you will find its acknowledgement. The Royal Academy of Engineering in 2009 said skills required in the design, build, operation and disposal of naval nuclear reactors are in short supply and the increasingly expensive decline of civil nuclear programmes, has forced the nuclear submarine programme to develop and fund its own expertise to remain operational. This points out that some of the costs were, before, being covered by the Civilian programme. 


Rolls Royce, in 2009, talked about skill synergies and said that skills are considered to be transferable between military propulsion and civil programmes. They said a larger involvement in the broader industry will also have a spill-over benefit to military capability, in skills, development and experience exchange. 


Doulton Institute says UK is not now in the position of having financial or personnel resources to develop either civilian or military nuclear programme in isolation. Rolls Royce, in their 2017 report, concluded that links between the civil and naval sector need to be encouraged – even though this has now been taken off their site. The report also described the advantage of small modular reactor systems for civilian nuclear power development as a subsidy to the military, to relieve the Defence Ministry of the burden of developing and retaining the skills and capability on the military side. That burden relates to costs. 


So a lot of the documentation or the information is to be found in the defence side of the policy documents. There is a crisis in military nuclear skills across the enterprise. The availability of deep specialist expertise is key and suitably qualified staff appear to be at the bare minimum necessary to deliver the programme. This was revealed by the Ministry of Defence in 2014, in a redacted Freedom of Information secret report, written for the submarine development programme. 


So, part of the crisis is in research capabilities. The Ministry of Defence's programme had been underwritten by civil nuclear research that has been dismantled and commercialised and expertise in these activities has atrophied. This was also in that secret documentation, only exposed through the FOI.

 

The government response was to say that the programme should seek imaginative methods to better engage with the emergent civil nuclear programme, to the benefit of defence. A research programme group was established to look at leveraging civil nuclear investment to maximum effect. The Ministry of Defence revisited the possible option of utilising other nuclear facilities, including those in the civil sector. This was taken up by the government in their nuclear sector deal that actually committed to increasing the opportunities for transferability between the civil and defence industries, to increase mobility to ensure resources are available. 


In contrast, the UK energy sector displays an odd and contrasting silence on the connection to military nuclear. The Oxford Economics Government Consulting report, in 2013, they state that naval and civil reactor industries are often viewed as separate, and to some extent unrelated. However, the timeline of the UK’s nuclear industry has clear interaction between the two, particularly from a supply chain development point of view. The Nuclear Research Institute says, though, this link does need to be carefully managed, to avoid the perception that civil and military nuclear programmes are one and the same. Nuclear submarines already suffer criticism because their through life costs cannot be absorbed or masked by other programmes as can be the case with fast jets or large standing land forces. The obvious implication, in light of the other information, is that the intention would be to mask those costs. 


The Ministry of Defence permanent secretary and lead civil nuclear contract negotiator confirmed that the UK is completing the build of the nuclear submarines, so there is very definitely an opportunity for the nation to grasp, in terms of building up its nuclear skills. He went on to say, he does not think that that was going to be happen by accident but it was going to require concerted government action to make it happen.


After many years without success, this year the link between the military and civil nuclear industries has been covered, in the newspapers in the BBC and The Daily Telegraph. In Scotland, it has been really picked up and there was a parliamentary motion in Scottish Government, where the links were highlighted. And yet, the silence continues from the UK Government. 

That is a problem for British democracy, as is the Energy white paper that came out with no costings on it, allowing the enthusiasm for nuclear to continues despite renewables being manifestly cheaper. 


It has been highlighted that there are strategic factors beyond Energy policy that explain not just the enthusiasm but the otherwise inexplicable UK policy on nuclear. It is clear that the military rationale is the most likely and yet the government does not officially acknowledge this. At about the same time that the 2020 White Paper came out, buried away in the Nuclear Intelligence Weekly, was a very candid interview with Rolls Royce, where they said that developing a UK small modular reactor programme would help Rolls Royce maintain UK capability for the military nuclear naval programme. It was also stated by an employee of Rolls Royce that it was complementary to have a thriving UK domestic civilian nuclear programme alongside the submarine programme, for the strongest skills base and the strongest supply chain. 


The fact that the interview was buried away; the incredible level of lobbying in favour of nuclear in the media and amount of nuclear advocacy - at the time when the case for nuclear is at its weakest – shows the extent of the problem for democracy. 


The Greens For Nuclear account was set up in 2019, with the sole purpose of intensely promoting nuclear. It involved a Twitter campaign by failed Green Party leadership candidate, Rosie Sexton, consistently urging the greens to reconsider their position on nuclear. They refused to listen to any evidence, in regard to the cost or the other weaknesses of a nuclear as an Energy solution. 


(FM: I couldn’t catch these names right or who was in which group! but I left this paragraph in, in case there was something important there) “In 2020, Lights was employed in the UK branch of nuclear lobbyist, Michael Scallon Berger’s environmental progress group - using the PR trope of the repentant critic. Clay claimed repeatedly without any without any evidence that she changed her mind on nuclear. It garnered incredible media attention in the Daily Mail, The Sun and the BBC News Daily as well. John Humphries wrote a full page for the Daily Mail advocating for new nuclear and giving favourable attention to Light’s change of mind.” 


There were several UK pro-nuclear power groups set up in 2020 including Mothers for nuclear energy, Liberal Democrats for nuclear, and Friends of Nuclear Energy. There were demonstrations by activists, such as Nuclear for Net Zero. Isn't it amazing that these activities should start to happen when the case for nuclear energy and for new nuclear is so weak. 


The same thing is happening in the US, with the reframing of nuclear. There is the so-called Good Energy Collective making the progressive case for nuclear. In fact, the collective is led by former members of the Brace Institute. 


Something very strange is going on in the UK in the moment in regards to nuclear and it is a serious problem in regards to democracy. What is the issue? Nuclear is slow, it is costly and it is dishonest, because the real drivers are not spoken about. This is undemocratic and unlawful. The main points: 

Existing nuclear power is slow in reducing climate change, new forms are even slower. 

Nuclear power is costly at reducing climate change, new forms are almost certainly costlier.

Renewables and energy efficiency are demonstrably faster and cheaper at averting climate disruption.

The established trend is that the nuclear competitiveness gap is growing, not

diminishing. 

Other arguments for inflexible nuclear output are acknowledged by industry to be out-dated. 

Whilst UK energy policy is silent, defence sources are clear that major nuclear drivers are military.

In the UK, massive government nuclear support is justified as energy strategy.  

The result is that many 10s of billions of pounds are directed from consumers and taxpayers.


 


Tuesday, February 6, 2024

Word Mosquito Program Risk Assessment and Omitted Risks


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insects

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Article

Risk Assessment on the Release of Wolbachia-Infected Aedes aegypti in Yogyakarta, Indonesia

Damayanti Buchori 1,2,* , Amanda Mawan , Indah Nurhayati 4, Aryati Aryati 5, Hari Kusnanto and Upik Kesumawati Hadi 7

1 2

3 4

5 6

7

Correspondence: damayanti@apps.ipb.ac.id

Simple Summary: Globally, the number of dengue cases reported to the WHO increased over 8- fold over the last 2 decades, from 505,430 cases in 2000 to over 2.4 million in 2010 to 5.2 million in 2019. Reported deaths between the years 2000 and 2015 increased from 960 to 4032, affecting mostly younger age groups. The latest data in November 2021 recorded that the cumulative number of dengue cases in Indonesia was 40,759 cases (incidence rate (IR) 14.76/100,000 population) and 402 deaths (l (CFR) 0.99%). Wolbachia-infected Aedes aegypti has been hailed as a new technology that can solve dengue fever disease. Infected females are unable to transmit the dengue virus and are reproductively incompatible with uninfected males. The aim of this study is to conduct risk assessment on the release of Wolbachia-infected Aedes aegypti in Yogyakarta, Indonesia. The assessment of the risks associated with the release of Wolbachia-infected Ae. aegypti used methodology developed by the Commonwealth Scientific Industrial Research Organization (CSIRO), Australia. In this paper, the Bayesian belief network (BBN) was used as the analysis method, and combined with the discussion results and analysis data of the local expert group, the risk assessment of the release of Wolbachia-infected Ae. aegypti was carried out. The results showed that the release of Wolbachia-infected Ae. aegypti led to negligible risk (0.0088).

Abstract: Wolbachia-infected Aedes aegypti is the latest technology that was developed to eliminate dengue fever. The Ministry of Research and Technology of the Republic of Indonesia (Kemenris- tekdikti) established an expert group to identify future potential risks that may occur over a period of 30 years associated with the release of Wolbachia-infected Ae. aegypti. The risk assessment consisted of identifying different hazards that may have impacts on humans and the environment. From the consensus among the experts, there were 56 hazards identified and categorized into 4 components, namely, ecological matters, efficacy in mosquito management, economic and sociocultural issues, and public health standards. There were 19 hazards in the ecological group. The overall likelihood in the ecology of the mosquito is very low (0.05), with moderate consequence (0.74), which resulted in negligible risk. For the efficacy in mosquito management group, there were 12 hazards that resulted in very low likelihood (0.11) with high consequence (0.85). The overall risk for mosquito management efficacy was very low (0.09). There were 14 hazards identified in the public health standard with very low likelihood (0.07), moderate consequence (0.50) and negligible risk (0.04). Lastly, 13 hazards were identified in the economic and sociocultural group with low likelihood (0.01) but of moderate conse- quence (0.5), which resulted in a very low risk (0.09). The risk severity level of the four components

Department of Plant Protection, Faculty of Agriculture, IPB University, Bogor 16680, Indonesia
Center for Transdisciplinary and Sustainability Science, Lembaga Penelitian dan Pengabdian kepada Masyarakat, IPB University, Bogor 16153, Indonesia
JF Blumenbach Institute of Zoology and Anthropology, Department of Animal Ecology, University of Göttingen, 37073 Göttingen, Germany
World Mosquito Program Yogyakarta, Centre for Tropical Medicine, Faculty of Medicine, Public Health and Nursing, University of Gadjah Mada, Yogyakarta 55281, Indonesia
Department of Clinical Pathology, Faculty of Medicine, Airlangga University, Surabaya 60286, Indonesia Department of Family and Community Medicine, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
Division of Parasitology and Medical Entomology, School of Veterinary Medicine and Biomedical Sciences, IPB University, Bogor 16680, Indonesia

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Citation: Buchori, D.; Mawan, A.; Nurhayati, I.; Aryati, A.; Kusnanto, H.; Hadi, U.K. Risk Assessment on the Release of Wolbachia-Infected Aedes aegypti in Yogyakarta, Indonesia. Insects 202213, 924. https://doi.org/10.3390/ insects13100924

Academic Editors: Robert Jones and Louisa Messenger

Received: 3 September 2022 Accepted: 8 October 2022 Published: 12 October 2022

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations.

Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

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Insects 202213, 924. https://doi.org/10.3390/insects13100924 https://www.mdpi.com/journal/insects

Insects 202213, 924

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leading to the endpoint risk of “cause more harm” due to releasing Wolbachia-infected Ae. aegypti is negligible (0.01).

Keywords: dengue fever; risk analysis; Wolbachia; Yogyakarta; eliminate dengue program

1. Introduction

Dengue haemorrhagic fever (DHF) is still a health problem in Indonesia, in both urban and semi-urban areas. Dengue virus (DENV) causes the wide spread of dengue fever in many regions across Indonesia. A number of cosmopolitan insects such as Aedes aegyptiAe. albopictus and other mosquitoes [13] are the primary vectors of DENV. According to the World Health Organization (WHO) [4], DENV infections are characterized by different fever symptoms, including dengue fever, DHF accompanied by shock known as dengue shock syndrome (DSS) [5], and other unusual manifestations such as encephalopathy and cardiomyopathy. The environmental conditions and communities’ behaviors can also affect the development of DHF transmitted by Ae. aegypti that affects the prevalence of DHF all year long. All age groups are vulnerable to the disease. This condition is common in tropical countries, including Indonesia.

Aedes aegypti was first reported to be found in Indonesia in 1968 in Jakarta and Surabaya. In that year, Karyanti and Hadinegoro [6] reported the first DHF case in Jakarta and Surabaya, and the disease spread widely throughout Indonesia. The number of deaths due to DHF in 2015 was 1071, with total reported cases of 129,650. Furthermore, the inci- dence rate (IR) per 100,000 people in Indonesia was 50.75%, and the case fatality rate (CFR) was 0.83%; in 2016, the number of deaths was 1598, with IR of 78.85% and CFR of 0.78% [7]. Based on the recent data from the Ministry of Health Republic of Indonesia, DHF cases in Indonesia in 2020 reached 95,893, with IR 38.15 per 100,000 people and CFR 0.70%. The most cases were in West Java (18,608 cases), Bali (11,964 cases), East Java (8483), Lampung (6372), and East Nusa Tenggara (5746) [8]. Almost all the regions with high case numbers are industrial or trade centers, which have denser populations with higher mobility.

In Indonesia, the most popular government dengue vector management program is the national Breeding Site Eradication (Pemberantasan Sarang Nyamuk/PSN), which focuses on the “3M plus” action of covering, draining, and burying discarded water containers. Other programs include improving the water supplies, mosquito biological control using natural enemies such as mosquito-eating fish, insecticides (spraying or fogging and larval control), and also health education and community empowerment [9]. Although mosquito eradication efforts have been conducted continuously, there is still a relatively high rate of DHF cases. As a result, a new technique for controlling DHF in Indonesia by introducing Wolbachia-infected mosquitoes was considered [10].

Wolbachia are Gram-negative bacteria that cause intracellular infections in invertebrates. Wolbachia belong to the order Rickettsiales and are classified as strains of one species (Wolbachia pipientis) [11]. Wolbachia, particularly the strain from Drosophila melanogaster population (wMel strain), causes the ‘bendy proboscis’ phenomenon in ageing female Ae. aegypti. With bendy proboscis, adult females cannot penetrate into human skin to feed on blood [12]. A study conducted by Ye et al. [13] showed that Wolbachia can reduce the transmission potential of dengue-infected Aedes aegypti. Their study showed that the presence of Wolbachia can significantly delay the time for the mosquito saliva to become infectious, reducing the frequency of dengue virus that was expectorated by mosquitoes and lowering the virus titer in mosquito saliva. Their work also showed that Wolbachia can reduce the number of infectious mosquitoes in a population while also delaying the arrival of virus in mosquitoes’ saliva.

In Indonesia, the Centre for Tropical Medicine, Faculty of Medicine, Gadjah Mada University, pioneered the use of Wolbachia in 2011. As a follow-up to this approach a risk assessment was conducted to evaluate the factors that influence the ecology of vectors; the

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Insects 202213, x FOR PEER REVIEW 3 of 20

Insects 202213, 924

In Indonesia, the Centre for Tropical Medicine, Faculty of Medicine, Gadjah Mada

University, pioneered the use of Wolbachia in 2011. As a follow-up to this approach a risk

assessment was conducted to evaluate the factors that influence the ecology of vectors;

the social, cultural, and economic impacts of the release; the mosquito management

and the public health. The endpoint of the assessment was to address the question whether

question whether the release of Wolbachia-infected Ae. aegypti would “cause more harm” the release of Wolbachia-infected Ae. aegypti would “cause more harm” or not. Therefore,

or not. Therefore, possibilities were identified concerning the likelihood that the release

possibilities were identified concerning the likelihood that the release of Wolbachia-infected of Wolbachia-infected Ae. aegypti will cause more harm to the ecology of mosquitoes,

Ae. aegypti will cause more harm to the ecology of mosquitoes, dengue virus and Wolbachiadengue virus and Wolbachia, efficacy of mosquitoes management, standards of public

efficacy of mosquitoes management, standards of public health, and the social, cultural

health, and the social, cultural and economic conditions of the local community in release

and economic conditions of the local community in release sites as well comparison of the

3 of 20

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social, cultural, and economic impacts of the release; the mosquito management efficacy;

efficacy; and the public health. The endpoint of the assessment was to address the

sites as well comparison of the current condition with the next 30 years.

current condition with the next 30 years.

2. Materials and Methods

2. Materials and Methods

The risk assessment core team consisted of four experts, in ecology, medical entomol-

The risk assessment core team consisted of four experts, in ecology, medical ento-

ogy, biological evolution, and medicine. In addition to the core team, 20 independent ex-

mology, biological evolution, and medicine. In addition to the core team, 20 indepen-

perts from universities, research institutes, nongovernment organisations, and the minis-

dent experts from universities, research institutes, nongovernment organisations, and the

terial agencies in different areas were selected to participate in the risk assessment discus-

ministerial agencies in different areas were selected to participate in the risk assessment

sions. The expert team was composed of one virologist, two microbiologists and epidemi-

discussions. The expert team was composed of one virologist, two microbiologists and

ologists, four entomologists (medical and agriculture), one biodiversity expert, one para-

epidemiologists, four entomologists (medical and agriculture), one biodiversity expert,

sitologist, one internist, one immunologist, one pediatrician, one psychologist, one public

one parasitologist, one internist, one immunologist, one pediatrician, one psychologist,

health expert, one economist, and one social scientist. The team conducted an assessment

one public health expert, one economist, and one social scientist. The team conducted an

of the risks associated with the release of Wolbachia-infected Ae. aegypti using a methodol- assessment of the risks associated with the release of Wolbachia-infected Ae. aegypti using

ogy that was developed by the Commonwealth Scientific Industrial Research Organiza-

a methodology that was developed by the Commonwealth Scientific Industrial Research

tion (CSIRO), Australia [14].

Organization (CSIRO), Australia [14].
Meetings and workshops were conducted to elicit opinions from experts and evi-

Meetings and workshops were conducted to elicit opinions from experts and evidence

dence to identify various hazards and analyze the risks associated with the release of

to identify various hazards and analyze the risks associated with the release of WolbachiaWolbachia-infected Ae. aegypti that may have impacts on humans and the environment.

infected Ae. aegypti that may have impacts on humans and the environment. 22.1.1.SttaageessiinRiisskkAssseesssmeentt

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TTeecchhnnoolologgyyRReegguulalatotorr(O(OGTTR))totoaassseesssaalllppoosssibibiliiltiiteiessaannddsscceennaarrioiossooffuunnpprreecceeddeenntteedd

hhaarrmththaattmmayayococucrurwwithitihninthtehneenxetx3t03y0eyaresairfsbioftbhoftehmfeamlealnedanmdalmaWleolWbaochlbia-cihnifae-cintefedcAteed.

aAegey.pateigwypetriewrelreeasredle.aTsehde.aTsshessamssenstsmweanstcownadsucotendutoctevdaltuoaetveathlueaftaecthoresftahcatorinsflthuaetncine-

vectors’ ecology; the social, cultural, and economic impacts of the release; the mosquito

fluence vectors’ ecology; the social, cultural, and economic impacts of the release; the mos-

management efficacy; and the public health. The endpoint of the assessment was to address

quito management efficacy; and the public health. The endpoint of the assessment was to

the question whether the release of Wolbachia-infected Ae. aegypti would cause more harm address the question whether the release of Wolbachia-infected Ae. aegypti would cause

or not compared with the current situation within a 30-year time frame. This assessment

more harm or not compared with the current situation within a 30-year time frame. This

covers several components including hazard identification, likelihood of risk, consequence

assessment covers several components including hazard identification, likelihood of risk,

of risk, and level of risk estimation (Figure 1).
consequence of risk, and level of risk estimation (Figure 1).

Figure 1. The framework of risk assessment on the release of Wolbachia-infected Aedes aegypti in Yogyakarta, Indonesia.

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Insects 202213, 924

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  1. 1  Ecological effects

  2. 2  Genetic biodiversity change

  3. 3  Change in genetic diversity

4

Transfer of Wolbachia genome to

invertebrates

  1. 5  Transfer of Wolbachia genome to

    vertebrates

  2. 6  New mosquito species evolves

7

Selection for more virulent arboviruses

  1. 8  Vector change

  2. 9  Increased vector density

  3. 10  Increased host biting

  4. 11  Female biased sex ratio

  5. 12  Increased mosquito host range

  6. 13  Increased filarial fitness

  7. 14  Replacement of dengue vectors

  8. 15  Transfer of other pathogens

  9. 16  Environmental change

  10. 17  Ecosystem service change

  11. 18  Ecological niche

  12. 19  Geographic distribution

  13. 20  Mosquito management efficacy

A Bayesian belief network (BBN) was used for visualizing and developing the risk analysis framework and combining the expert assessment with conditional probabilities to determine the endpoint risk value. Bayes’s theorem in BBN says that future events can be predicted using any previous events that have happened [15]. BBN is a probabilistic model described in a directed acyclic graph (DAG) to demonstrate the probabilistic link between any given events [16]. It was constructed using the software package Netica© 6.09 (Norsys Software Corp. (Vancouver, BC, Canada)).

2.2. Problem Formulation and Hazard Identification

Experts were grouped according to the four identified components of “cause more harm”, namely, negative effects on ecology, decreased mosquito management efficacy, worsened public health standards, and negative sociocultural and economic impacts. Each group discussed all potential hazards leading to each component of cause more harm in the context of releasing Wolbachia-infected Ae. aegypti for the next 30 years.

The expert elicitation on hazard identification and mapping was undertaken in several steps: identification of events, determination of possible states of the events, development of the hazards list and agreed definitions, and consensus about all hazards and their definitions. Hazard and risk are often used interchangeably. Severtson and Burt [17] defined a hazard as “an act or phenomenon that has the potential to cause harm to humans or what they value” and risk as “the probability an adverse event will occur”. However, in this assessment, a hazard is a potential source of harm for humans, communities, and ecosystems. Each of the hazards (depicted as node) definitions can be found in Table 1.

Table 1. Definition of identified hazards that may “cause more harm” upon the release of Wolbachia- infected Aedes aegypti within a 30-year time frame.

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No

Hazard/Node

Definition

Ecological impact of Wolbachia-infected Ae. aegypti release.
Changes in genetic of mosquitoes, virus and 
Wolbachia in their natural habitat. Changes in genetic diversity of Ae. aegypti species in nature.
Horizontal transfer of 
Wolbachia or some of their genomes to other invertebrates.

Horizontal transfer of Wolbachia or some of their genomes to vertebrates.

New species or strain of mosquito evolves.
Selection of more virulent arboviruses causing higher morbidity/damage and mortality.
Changes in vector species, including vector density, behaviour, biology, and reproduction.
Increased average number of mosquitoes per household due to possible changes in fecundity, longevity and vector population dynamic.
Increased frequency of host biting by 
Wolbachia-infected Ae. aegypti.
Changes in sex ratio, skewed to female mosquitoes, which leads to an increase in the mosquito vector population.
Increased number of hosts other than humans enhancing the likelihood of acquiring new viruses or pathogens.
Wolbachia-infected Ae. aegypti can enhance the filarial fitness to the mosquito. Ae. aegypti would no longer be dengue vector, replaced by other mosquito species or other organisms.
Ae. aegypti may be able to transfer other arboviruses or parasites e.g., Zika or filariasis.
Changes in geographical distribution, niche of 
Ae. aegypti habitat and ecosystem services in certain areas.
Changes in ecosystem structure, functions or services.
Changes of ecological niche of 
Ae. aegypti from being a domestic species to a broader or alternative niche.
Changes in geographical distribution of 
Ae. aegypti.
Management efficacy of Ae. aegypti control.

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Table 1. Cont. No Hazard/Node

Definition

Increased difficulty in mosquito control due to changes in breeding places of Wolbachia-infected Ae. aegypti.
Changes in behaviour of Wolbachia-infected Ae. aegypti related to dengue transmission and breeding places.

Increased resistance to dose and types of insecticide after Wolbachia-infected Ae. aegypti mosquitoes have been release and established.
Emergence of 
Ae. aegypti with higher vector capacity.
Increased transmission of dengue virus.

Worse clinical outcomes caused by dengue infection.
Increased the probability of the biting rate of Wolbachia-infected 
Ae. aegypti. Changes in dengue vector control activities by household members.
Changes in normal mosquito avoidance strategies.
Decreased community participation in dengue vector control due to perceived comfort and safety.
The overall standard of public health.
The presence of 
Wolbachia-infected Ae. aegypti has caused disruption to the larva free index indicators as part of the dengue contro program.
More severe manifestations of dengue infection, and elderly people affected by the disease.
Increased number of dengue cases.
The rate of dengue transmission increases compared to the situation before the release of 
Wolbachia-infected Ae. aegypti.
Increased pest status of Ae. aegypti, due to increased tendency to associate with people, uninhabited houses, severity of bites and mosquito population density. Increased capability of Ae. aegypti to transmit pathogens other than dengue virus.
Dengue virus evolves so that its transmission would be more effective.
Ae. aegypti becomes a more capable vector in transmitting dengue virus.
Ae. aegypti takes blood meal more frequently.
Average number of 
Ae. aegypti per household would be higher.
Increased variety of host animal infested with 
Ae. aegypti.
Increased vector competence as disease agents of other diseases than dengue. Economic and socio-cultural change due to the release of Wolbachia-infected Ae. aegypti.
Decreased income and increased expenses will negatively change the economy. The cost for health care in general will increase.
Local and international tourism will be affected by the release.
Individual and corporate businesses will lose lost their incomes.
Increased expenses due to monitoring and controlling mosquitoes.
Negative social behaviour and deterioration of local wisdom, such as increased social isolation and decreased community participation.
Negative collective defence mechanism as technology fails.
Changes in destination of migration area due to perceived safety or perceived threat.
Negative social media messages leading to concerns among the public. Contradictory opinions in the society based on different knowledge and beliefs.
Legal actions from individuals, groups, communities, and community organizations.
Collective mental confusions due to unintended consequences without proper assurance.

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Increased difficulty to mosquito control

21
22 Mosquito behaviour change

  1. 23  Increased resistance to insecticide

  2. 24  Strain selection

  3. 25  More dengue infections occur

  4. 26  Increased dengue virulence

  5. 27  Increased biting

  6. 28  Household control

  7. 29  Avoidance strategy

  8. 30  Complacency

  9. 31  Standards of public health

32

Interference with other dengue control

  1. 33  Severity of disease

  2. 34  More dengue cases

  3. 35  Dengue transmission

  4. 36  Nuisance biting

37

Other pathogens (transmission of

nondengue pathogens)

  1. 38  Dengue evolution

  2. 39  Dengue vector competence

  3. 40  Feeding frequency

  4. 41  Mosquito density

  5. 42  Host preference

  6. 43  Nondengue vector competence

  7. 44  Economic and sociocultural impacts

  8. 45  Economic change

  9. 46  Health care cost

  10. 47  Tourism

  11. 48  Loss income

  12. 49  Expense change

  13. 50  Socio-behavioural change

  14. 51  Scapegoating

  15. 52  Migration

  16. 53  Adverse media

  17. 54  Social conflict

  18. 55  Class action

  19. 56  Social fear

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Hazards/nodes with bold letters are the four identified components of “cause more harm”.

2.3. Development of the Predictive Risk Model

A BBN was used to obtain the probabilistic relationships between events and to provide graphical representation of those events (as nodes) with possible states and a DAG from the parent node (cause) to the child node (effect). A BBN usually consists of

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two main components, namely, a DAG and a conditional probability table (CPT). A DAG consists of nodes and links that depicts the relationships between the variables. Here, the nodes represent the variables being observed, the hazards. Each node is connected to another node with the links (also known as arcs or edges) to show indications of conditional dependence. A link between parent node and child node showed that the nodes were functionally related or statistically correlated. Each child node (i.e., a node linked to one or more parents) contained a CPT that showed the conditional probability of the node in a specific state given by the state configurations of its parent nodes. A conditional probability is the probability of one event’s occurring if another event occurred. It was used to calculate likelihood of each node. The absence of an arc between two nodes means that no CPT can be defined.

Bayes’s theorem was used to calculate the conditional probability at each node of an observed hazard and was applied according to the values in the CPT. The outcomes of the previous nodes were given within each node. The absolute probability as the final result was calculated by using all conditional probabilities that were previously obtained. Meanwhile, when the networks were compiled, it changed the probability distribution for the states at parent node which were also reflected in changes in the probability distribution for the states at child node.

The results of a BBN were often convincing and conclusive, even when sufficient data were not available [18]. BBN has often been used to represent knowledge and support in decision making under uncertainty [19]. It is suitable for estimating the probabilities of the occurrence of hazards caused by the release of Wolbachia-infected Ae. aegypti as a result of uncertainty (due to lack of knowledge of the long-term benefit of the presence of Wolbachia in natural environment).

Experts’ prior knowledge has a significant influence in hazard evaluation and the understanding of each hazard. These two factors are incorporated in the Risk Assess- ment using simulations that have different grades, thus ensuring that prior knowledge, assumptions and judgements are accounted in the Risk Assessment process.

2.4. Risk Calculation

The experts defined each hazard that may arise from the impact of Wolbachia-infected mosquitoes and the likelihood of each hazard based on the existing information. The consequence of a hazard was reached through discussions and consensus building based on expert assessment. Afterward, the overall risk was calculated. Here, risk was defined as an event of a particular level of severity and measured by the potential occurrence of a specific event (likelihood) multiplied by the level of resulting consequence or impact (consequence). In simple equation, risk = likelihood × consequence.

We used the risk scale from Murray et al. [14] as the reference in determining the probability of likelihood and consequence. The scale for likelihood and consequence estimation was determined in the group discussion using a participatory process. The experts agreed on scales to score the likelihood and consequence of the identified hazards (Table 2) and the definitions for each scale (Table 3).

Table 2. Scale for likelihood and consequence estimation used for calculating the risk of identified hazards with the endpoint of causing more harm.

Scale Negligible Very Low Low Moderate High Very High

Probability 0–0.01 0.02–0.10 0.11–0.40 0.41–0.74 0.75–0.89 0.90–1

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Negligible Very low Low Moderate High Very high

Negligible

Negligible risk Negligible risk Negligible risk Negligible risk Negligible risk Negligible risk

Very low

Negligible risk Negligible risk Negligible risk Negligible risk Very low risk Very low risk

Low

Negligible risk Negligible risk Negligible risk Very low risk Low risk

Low risk

Moderate

Negligible risk Negligible risk Very low risk Low risk Moderate risk Moderate risk

High

Negligible risk Very low risk Low risk Moderate risk High risk High risk

Very high

Very low risk Low risk Moderate risk High risk Extreme risk Extreme risk

Table 3. The definition of each scale that may result from each identified hazard with the endpoint of causing more harm.

Scale

Negligible Very low Low

Moderate

High

Very high

Definition

Almost no change.
Insignificant impact on human health and social economy.
Very low impact or no damage to the ecosystem.
Causes harm to human health but can be repaired, and the impact on socio-economic conditions is relatively small. The environmental damage or disturbance to local biodiversity is reversible and limited in space and time or in the amount of diversity that affected by the damage.
Adverse health effects are difficult to reverse but not life-threatening and have moderate socioeconomic impacts on communities.Long-term damage to the environment or disturbance to biodiversity that is still reversible. Adverse health effects that are severe, widespread, irreversible, life-threatening, and devastating to the socioeconomic conditions.Extensive damage to the environment or disturbances to biodiversity and ecosystems, communities, or the species that survive in those ecosystems and this is not easily reversible.

Discussion on the estimation of likelihoods and consequences in all groups of hazards used scales ranging from negligible to very high. Each value was calculated by considering the severity level of each hazard’s impacts on humans, the coverage and duration of the impacts, and the level of reversibility of each hazard. After determining the consequence values of each hazard, the experts then discussed the placement of each hazard into a risk matrix (Table 4).

Table 4. Matrix of the risk level of each identified hazard associated with “cause more harm”. Consequence

3. Results

3.1. Hazard Identification and Mapping

The identification and mapping of the hazards as the outcome of releasing the Wol- bachia-infected Ae. aegypti were based on expert elicitations and resulted in 56 hazards (nodes) excluding the end point of “cause more harm” (Figure 2). The hazards were mapped into four subcomponents of cause more harm: and altogether were combined, leading to the endpoint of “cause more harm”. The four main components were adverse impact on mosquito ecology, a lower standard of public health, decreased mosquito management effi- cacy, and economic and sociocultural impacts. The assessment team identified 19 ecological- related hazards including ecological effects as the endpoint (Figure 3), 12 efficacy-related hazards including mosquito management efficacy as the endpoint (Figure 4), 14 public health-related hazards including the standard of public health as the endpoint (Figure 5), and 13 economical and sociocultural hazards (Figure 6). While 56 hazards were identified (as shown in Table 1), there were two hazards (increased biting rate and transmission of non-dengue pathogens) that were shared by two groups, mosquito management efficacy and public health standard (as shown in Figure 2). Therefore, the total number of hazards became 58.

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Likelihood

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12 efficacy-related hazards including mosquito management efficacy as the endpoint (Fig- ure 4), 14 public health-related hazards including the standard of public health as the end- point (Figure 5), and 13 economical and sociocultural hazards (Figure 6). While 56 hazards were identified (as shown in Table 1), there were two hazards (increased biting rate and

transmission of non-dengue pathogens) that were shared by two groups, mosquito man-

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agement efficacy and public health standard (as shown in Figure 2). Therefore, the total number of hazards became 58.

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Figure 2. The Bayesian belief network for the endpoint “cause more harm”. Each node (box) repre- Figure 2. The Bayesian belief network for the endpoint “cause more harm”. Each node (box) sents probability of hazards that might occur within the next 30 years as the result of the release of represents probability of hazards that might occur within the next 30 years as the result of the release

Wolbachia-infected Ae. aegyptiof Wolbachia-infected Ae. aegypti.

InIsnescetsct2s02022,21,31,39,2x4FOR PEER REVIEW 9oof2020

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Figure 3. The Bayesian belief network for the endpoint “ecological effects”. Each node (box) repre- Figure 3. The Bayesian belief network for the endpoint “ecological effects”. Each node (box) repre-

sents probability of hazards that might occur within the next 30 years as the result of the release of

sents probability of hazards that might occur within the next 30 years as the result of the release of

Wolbachia-infected Ae. aegypti. Parent nodes are in the yellow boxes. Wolbachia-infected Ae. aegypti. Parent nodes are in the yellow boxes.

InIsnescetcst2s02202,21,31,39,2x4FOR PEER REVIEW 10ooff2020

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Figure 4. The Bayesian belief network for the endpoint “mosquito management efficacy”. Each node Figure 4. The Bayesian belief network for the endpoint “mosquito management efficacy”. Each node

(box) represents the probability of hazards that might occur within the next 30 years as the result of

(box) represents the probability of hazards that might occur within the next 30 years as the result of

the release of Wolbachia-infected Ae. aegypti. Parent nodes are in the yellow boxes. the release of Wolbachia-infected Ae. aegypti. Parent nodes are in the yellow boxes.

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Figure 5. The Bayesian belief network for the endpoint “standard of public health”. Each node (box)

represents the probability of hazards that might occur within the next 30 years as the result of the

Figure 5. The Bayesian belief network for the endpoint “standard of public health”. Each node (box) release of Wolbachia-infected Ae. aegypti. Parent nodes are in the yellow boxes.
represents the probability of hazards that might occur within the next 30 years as the result of the

release of Wolbachia-infected Ae. aegypti. Parent nodes are in the yellow boxes.

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Figure 6. The Bayesian belief network for the endpoint “economic and socio-cultural effects”.Each Figure 6. The Bayesian belief network for the endpoint “economic and socio-cultural effects”. Each

node (box) represents the probability of hazards that might occur within the next 30 years as resultsnnoodee((bbooxx))rreepprreesseenntststthheepprroobbaabbiliiltiytyooffhhaazzaarrddssththaattmigighhttoocccuurrwitihthinintthheenneexxtt3300yyeeaarrssaassrreessuultltss

of the release of Wolbachia-infected Ae. aegypti. Parent nodes are in the yellow boxes. oofftthheerreeleleaasseeooffWoolblbaacchhiaia-i-ninfefeccteteddAAee.aaeeggyypptit.i.Paarreennttnnooddeessaarreeininththeeyyeellolowbbooxxeess.

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3.2. Likelihood

3.2. Likelihood 3.2. Likelihood

The next step of BBN in this risk assessment was discussions about the hazard likeli-

The next step of BBN in this risk assessment was discussions about the hazard likeli- The next step of BBN in this risk assessment was discussions about the hazard likeli-

hood of the four main components of cause more harm. The estimation yielded negligible

hood of the four main components of cause more harm. The estimation yielded negligible hood of the four main components of cause more harm. The estimation yielded negligible

likelihood of 1.11% (Figure 7). The likelihoods of hazards from the four components were likelihood of 1.11% (Figure 7). The likelihoods of hazards from the four components were likelihood of 1.11% (Figure 7). The likelihoods of hazards from the four components were

4.74% for ecological effects and 6.96% for the standards of public health, indicating negligi-

4.74% for ecological effects and 6.96% for the standards of public health, indicating negli- 4.74% for ecological effects and 6.96% for the standards of public health, indicating negli-

ble likelihood, and mosquito management efficacy and economic and sociocultural effects

gible likelihood, and mosquito management efficacy and economic and sociocultural ef- gible likelihood, and mosquito management efficacy and economic and sociocultural ef-

had likelihoods of 10.5% and 18.3%, which demonstrates a very low likelihood of risk from

fects had likelihoods of 10.5% and 18.3%, which demonstrates a very low likelihood of fects had likelihoods of 10.5% and 18.3%, which demonstrates a very low likelihood of

the hazards if Wolbachia-infected Ae. aegypti are released to suppress DENV.
risk from the hazards if Wolbachia-infected Ae. aegypti are released to suppress DENV. risk from the hazards if Wolbachia-infected Ae. aegypti are released to suppress DENV.

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Figure 7. Estimated likelihood of the adverse impacts of the release of Wolbachia associated with Figure 7. Estimated likelihood of the adverse impacts of the release of Wolbachia associated with

Figure 7. Estimated likelihood of the adverse impacts of the release of Wolbachia associated with four

four identified hazards. four identified hazards.

identified hazards.

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3.3. Consequences

The expert solicitations of consequences that may arise due to the release of Wolbachia- infected Ae. aegypti were derived from a consensus on identified hazards: and among the 56 hazards, the four main components’ endpoints had moderate (ecology effects, public health, and economic and sociocultural effects) or high (mosquito management efficacy) consequences (Table 5).

Table 5. Consensus of estimation of likelihood, consequence and risk (ranked by risk) for the endpoint “cause more harm”.

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No Hazard/Node

  1. 1  Ecological effect

  2. 2  Genetic biodiversity change

  3. 3  Change in genetic diversity

  4. 4  Invertebrate transfer and Wolbachia genome

  5. 5  Vertebrate transfer and Wolbachia genome

  6. 6  New mosquito species evolves

  7. 7  Selection for more virulent arboviruses

  8. 8  Vector change

  9. 9  Vector density

  10. 10  Increased host biting

  11. 11  Female biased sex ratio

  12. 12  Mosquito host range

  13. 13  Increase filarial fitness

  14. 14  Replacement of dengue

    vectors

  15. 15  Transfer of other

    arboviruses or pathogens

  16. 16  Environmental change

  17. 17  Ecosystem service change

  18. 18  Ecological niche

  19. 19  Geographic distribution

    change

  20. 20  Mosquito management

    efficacy

  21. 21  Increased difficulty to control

  22. 22  Mosquito behaviour change

  23. 23  Insecticide resistance

  24. 24  Strain selection

  25. 25  More dengue infections

    occur

  26. 26  Increased dengue

    virulence

  27. 27  Household control

  28. 28  Avoidance strategies

  29. 29  Complacency

  30. 30  Standards of public

    health

Likelihood Likelihood Scale

0.05 Very low

0.01 Negligible

0.01 Negligible <0.01 Negligible <0.01 Negligible <0.01 Negligible

0.01 Negligible

0.10 Very low 0.05 Very low 0.01 Negligible 0.01 Negligible <0.01 Negligible <0.01 Negligible

0.05 Very low

<0.01 Negligible

0.11 Negligible <0.01 Negligible 0.02 Very low

0.04 Very low

0.11 Very low

0.03 Very low

0.10 Very low

0.05 Very low 0.05 Very low

0.08 Very low

0.04 Very low

0.16 Low 0.05 Very low 0.10 Very low

0.07 Very low

Consequence Consequence Consequence Consensus Scale Risk

0.74 Moderate 0.04

0.90 Very high 0.01

0.74 Moderate 0.01

0.75 High <0.01

0.95 Very high <0.01

0.95 Very high <0.01

0.75 High 0.01

0.90 Very high 0.09 0.75 High 0.04 0.89 Very high 0.01 0.57 Moderate 0.01 0.74 Moderate <0.01 0.75 High <0.01

0.90 Very high 0.05

0.75 High <0.01

0.90 Very high 0.01 0.74 Moderate <0.01 0.74 Moderate 0.02

0.57 Moderate 0.02

0.85 High 0.09

0.90 High 0.02

0.70 Moderate 0.07

0.20 Low 0.01 0.20 Low 0.01

0.80 High 0.07

0.80 High 0.03

0.60 Moderate 0.10 0.10 Very low 0.005 0.75 High 0.07

0.50 Moderate 0.04

Risk Matrix Scale

Negligible

Very low Negligible Negligible Very low Very low Negligible

Low Very low Negligible Negligible Negligible Negligible

Low

Negligible

Very low Negligible Negligible

Negligible

Very low

Very low

Negligible

Negligible Negligible

Very low

Very low

Very low Negligible Very low

Negligible

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No Hazard/Node

  1. 31  Interference with other dengue controls

  2. 32  Severity of disease

  3. 33  More dengue cases

  4. 34  Increased biting

  5. 35  Dengue transmission

  6. 36  Nuisance biting

  7. 37  Other pathogens

  8. 38  Dengue evolution

  9. 39  Dengue vector

    competence

  10. 40  Feeding frequency

  11. 41  Mosquito density

  12. 42  Host preference

  13. 43  Nondengue vector

    competence

  14. 44  Economic and

    sociocultural effect

  15. 45  Economic change

  16. 46  Health care

  17. 47  Tourism

  18. 48  Lost income

  19. 49  Expense change

  20. 50  Social-behavioural change

  21. 51  Scapegoating

  22. 52  Migration

  23. 53  Adverse media

  24. 54  Social conflict

  25. 55  Class action

  26. 56  Social fear

  27. 57  Cause more harm

0.10 Very low

0.01 Negligible 0.01 Negligible 0.01 Negligible 0.15 Low 0.15 Low 0.10 Very low 0.05 Very low

0.05 Very low

0.01 Negligible 0.10 Very low 0.10 Very low

0.05 Very low

0.18 Low

0.10 Very low 0.05 Very low 0.02 Very low 0.02 Very low 0.05 Very low 0.17 Low 0.30 Low 0.10 Very low 0.40 Low 0.50 Moderate 0.50 Moderate 0.50 Moderate 0.01 Negligible

0.50 Moderate 0.05

0.80 High 0.01 0.80 High 0.01 0.80 High 0.01 0.80 High 0.12 0.50 Moderate 0.07 0.50 Moderate 0.05 0.85 High 0.04

0.80 High 0.04

0.75 High 0.01 0.50 Moderate 0.05 0.85 High 0.09

0.85 High 0.04

0.5 Moderate 0.09

0.01 Negligible <0.01 0.01 Negligible <0.01 0.01 Negligible <0.01 0.01 Negligible <0.01 0.01 Negligible <0.01 0.20 Low 0.03 0.45 Moderate 0.14 0.08 Very low <0.01 0.75 High 0.30 0.75 High 0.38 0.75 High 0.38 0.60 Moderate 0.30 0.80 High 0.008

Table 5. Cont.
Likelihood Likelihood Consequence Consequence Consequence

Scale Consensus Scale Risk

Risk Matrix Scale

Negligible

Negligible Negligible Negligible Low

Very low Negligible Very low

Very low

Negligible Negligible Very low

Very low

Very low

Negligible Negligible Negligible Negligible Negligible Negligible Very low Negligible Low Moderate Moderate Low Negligible

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Hazards/nodes with bold letters are the four identified components of “cause more harm” and the endpoint “cause more harm”.

The ecology component had the most hazards, 19, including the endpoint. An amount of 18 hazards excluding the endpoint were estimated to have moderate (6 hazards), high (5 hazards), or very high (7 hazards) consequences with 57% to 90% consensus. The ecological effects as the endpoint of the ecology component had a moderate consequence with a value of 0.74. As for the mosquito management efficacy component, the expert solicitation of 10 hazards (including endpoint) resulted in a high consequence of 0.85 of the endpoints. Nine hazards, without the endpoint, were widely estimated to have very low consequence (one hazard), low consequence (two hazards), moderate consequence (two hazards), and high consequence (four hazards).

A total of 14 hazards in the public health standard component were identified due to the release of Wolbachia-infected Ae. aegypti, leading to an endpoint of 0.5, reflecting moderate consequence (Table 5). The expert solicitation of 13 hazards without the endpoint yielded a consensus of moderate consequence for four hazards and high consequence for nine hazards. The economic and sociocultural impacts resulted in a 0.5 (moderate consequence) of this component’s endpoint. Hazards in this component were calculated to have a negligible consequence (five hazards), very low consequence (one hazard), low consequence (one hazard), moderate consequence (two hazards), and high consequence (three hazards).

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3.4. Risk Calculation

Risk analysis workshops provided consensus concerning the estimation of the conse- quence and likelihood of hazards. The variables were combined to obtain the risk severity level of the four components, leading to the endpoint risk of causing more harm due to releasing Wolbachia-infected Ae. aegypti.

Overall, the expert solicitation results of the 56 hazards that may occur due to the release of Wolbachia-infected Ae. aegypti indicated an estimated high consequence (0.8) of the end point for cause more harm. The consequences for the 56 hazards ranged from negligible (5 hazards), very low (3), low (3), moderate (17), high (23), and very high consequence (6). The hazards had consensus scores of 1% to 95% for likelihood that were dominated by negligible likelihood.

Each consensus was afterwards grouped based on the risk matrix to obtain the severity levels of the risks: negligible risk, 33 hazards; very low risk, 17 hazards; low risk, 5 hazards; and moderate risk, 2 hazards (Table 5). Among the four cause more harm components, eco- logical influence and standard of public health were estimated to have negligible risk while efficacy of mosquito management and economic and sociocultural impacts components were estimated to have very low risk. Based on the risk estimation of 56 hazards related to the cause more harm endpoint, the release of Wolbachia-infected Ae. aegypti has negligible likelihood (0.011) and high consequence (0.8), which leads to negligible risk (0.0088).

4. Discussion

In this risk assessment, vector change is defined as the changes in the density, behavior, biology, and reproduction of vectors. Studies indicated that the presence of Wolbachia in Ae. aegypti mosquitoes suppresses the population size due to cytoplasmic incompatibility (CI) and suppress dengue viral transmission through the pathogen blocking effect that caused by Wolbachia [2022]. Ae. aegypti infected by wMelPop showed a declining growth rate indicated by reduced fecundity and egg viability in Ae. aegypti [23,24]. In addition, wMelPop causes changes in the behavior of Ae. aegypti, as indicated by Turrey et al. [12] and Moreira et al. [25], which showed that wMelPop-infected mosquitoes fed on less blood meal than uninfected mosquitoes. Because the older mosquitoes spent more time in pre- probing and probing, in addition to shaking and bendy proboscis, this behavior leads to a decline in saliva production. Saliva production is associated with the DENV that accumulates in the salivary glands of Ae. aegypti [26,27], thus indirectly affecting DENV transmission. It also indicates that although the presence of wMelPop strain may cause an increased blood-feeding intensity among female adults, the mosquitoes’ ability to find blood meals also declines. Despite that, the experts assigned a relatively high score of likelihood because Weeks et al. [28] indicated that after 20 years, naturally occurring Wolbachia-infected Drosophila simulans exhibited a 10% increase in fecundity compared with that in flies that were not infected by Wolbachia. In other words, the bacterium characteristic changed from being parasitic to more mutualistic.

The second low-risk hazard from the ecology component was the possibility of dengue vector replacement. In addition to Ae. Aegypti, mosquito species such as Ae. Albopictus [29], Ae. Polynesiensis [30], and Ae. scutellaris [31] are primary dengue vectors, although to date, Ae. aegypti are still the most effective primary vector in the transmission of DENV. History indicates that Ae. aegypti was first identified as the primary vector of yellow fever in 1648 in Mexico and Guadeloupe (France) [32]. The first epidemic of dengue fever transmitted by Ae. aegypti was recorded in 1779. Yellow fever started to become an epidemic at the beginning of the 21st century, while the dengue fever epidemic started in the 1950s. Both viruses belong to the Flaviviridae family. However, they are never found at the same time in one particular endemic area [32]. Based on this information, experts concluded that in the next 30 years, there is a likelihood that there is a very low occurrence of vector replacement because of Wolbachia-infected Ae. aegypti.

Another hazard that was concluded to have negligible risk and moderate consequence was the female-biased sex ratio. The assessment team defined this hazard as the possibility

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that the existence of Wolbachia could cause changes in Ae. aegypti sex ratio that might skew toward female mosquitoes, which could increase the mosquito population, which would lead to increased DHF incidence. So far, there have been no reports on the influence of Wolbachia on the sex ratio of Ae. aegypti mosquitoes or Aedes genus. However, Shaw et al. [33] reported that the infection of Wolbachia to the natural population of Anopheles did not influence the sex ratio of the offspring. This result outlines the relatively low influence of Wolbachia on the sex ratio of Ae. aegypti mosquitoes. To prove this, further in-depth exploration of the sex ratio of Ae. aegypti, after being infected with Wolbachia, needs to be conducted.

In the course of the hazard formulations, concerns arose regarding the possibility of the evolution of Wolbachia in Ae. aegypti that could lead to the increased fitness of filarial nematodes in mosquitoes. The consensus on increased filarial nematode fitness as a hazard indicated that there might be a negligible risk in the future. Pfarr et al. [34] concluded that Wolbachia that infect arthropods are distinct from Wolbachia that infect filarial nematodes. Pfarr et al. [34] also explained that Wolbachia is a parasite in arthropods but mutualists in filarial nematodes. Furthermore, arthropods and nematodes originate from different phyla, which is the risk of the evolution of Wolbachia present in Ae. aegypti in association with filarial nematodes are very low or very unlikely to happen [35].

The experts agreed that the release of Wolbachia-infected Ae. aegypti in a particular area could lead to adverse impacts on the mosquito management efficacy, but they assessed the risks as negligible (five hazards) or very low (five hazards). The five hazards with very low risk were increased difficulty to control, increased dengue virulence, household control, increased complacency, and more dengue occurrences.

In dengue management control, sustainable vector control interventions are necessary to significantly reduce dengue transmission [4]. Community participation in dengue control needs to be continuously promoted to ensure that community members can successfully maintain their individual household environments free from dengue vectors [36]. The release of Wolbachia-infected Ae. aegypti may discourage preventive measures by the community through mosquito management. In addition, it can also increase difficulty in Ae. aegypti control due to the development of cryptic breeding sites [37].

Increasing the difficulty of controlling mosquitoes also became a critical hazard that needs to be considered mainly because it is related to Wolbachia-infected Ae. aegypti behavior changes. The changes in mosquitoes’ behavior result from the presence of Wolbachia, was defined by experts as changes in dengue transmission and breeding places (Table 1). However, this hazard had a very low likelihood, and moderate consequences resulted in a negligible risk. Furthermore, increased complacency at the household level due to Wolbachia-infected Ae. aegypti control may increase mosquito density, mosquito biting frequency, and a greater possibility of dengue transmission. At the community level, complacency can lead to decreased caution on the presence of Ae. aegypti. This particular hazard had a very low likelihood but a high consequence. This means that the hazard may have a significant influence on the success in Ae. aegypti mosquito management. Successful community-based vector mosquito control is influenced by numerous factors, including the community’s alert and literacy of mosquito population distribution and virus transmission rate in their respective areas [38].

Insecticide resistance is one of the hazards in the mosquito management efficacy component. At first, the experts considered this an essential issue that needed to be addressed. Since Ae. aegypti is a primary vector of dengue disease with a cosmopolitan range, meaning that it can be found in many tropical cities worldwide. Thus far, mosquito disease vector control has been the most effective measure in addressing dengue disease. In Indonesia, control measures have been promoted through the 3M plus (covering, draining, and burying unused water containers) program as shown in the declining DHF incidence rate [39,40]. However, available data have indicated that mosquito populations remain high [41], so that pesticides are still commonly used as an alternative measure in mosquito

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control in many locations in Indonesia. Therefore, the experts agreed that it has a very low likelihood with a low consequence, which resulted in a negligible risk of severity level.

Public health did not affect the release of Wolbachia-infected Ae. aegypti because the consensus from experts estimated a negligible risk with a very low likelihood and moderate consequence. The severity level of 13 hazards, excluding lower standard of public health, varied from negligible to low risk with 7 hazards have negligible risks. Increasing dengue transmission was the only hazard with a low-risk severity level. It is defined as the rate of dengue transmission increases compared with the situation before the release of Wolbachia-infected Ae. aegypti. So far, the results from studies on the rate of dengue transmission by Wolbachia-infected Ae. aegypti have indicated a decline. One of the primary factors influencing mosquitoes’ ability to transmit DENV is the extrinsic incubation period (EIP). EIP is the developmental time required for the virus to reach the mosquito’s saliva glands after an infectious blood meal. The earlier the virus appears in the saliva, the more opportunities for the mosquito to transmit DENV to humans. Ye et al. [13] reported that wMel lengthens the EIP, reducing the virus’s transmission frequency through the saliva. Moreover, the study also showed that Wolbachia-infected Ae. aegypti mosquito’s saliva had less DENV copy compared with wild-type mosquitoes that were not infected by Wolbachia. The mosquito salivary gland is the primary way for virus transmission. Wolbachia is mostly found in the mosquito midgut and salivary glands, both essential in transmitting the virus [42]. Therefore, the lower density of DENV in mosquito salivary glands may suggest reduced virus transmission.

The last component of this assessment was the economic, social, and cultural impact of the release of Wolbachia-infected Ae. aegypti. Initially, the group of experts focused their discussion on social and economic aspects only, but as the discussion went on, they also considered the cultural impact associated with the release of Wolbachia-infected Ae. aegypti. Since in real life, the social, behavioral, and economic factors are intertwined. The experts came to a consensus that it had a very low risk of severity level. It had 12 hazards with 7 negligible risks, 1 very low risk (scapegoating), 2 low risks (adverse media and social fear), and 2 moderate risks (class action and social conflict). Sociocultural hazards were estimated to have a higher risk than the economic ones. The sociocultural hazards may likely happen when information concerning technologies for controlling Wolbachia is not available in detail and does not reach all society elements, who are the main actors in community-based control. Experience from the first limited release in 2014 indicated that there were differences in opinion among the communities on whether Wolbachia-infected mosquitoes were safe to be released or not [39]. These differences could potentially lead to disharmony among communities. Hence, during the expert team discussion, the feedback was that awareness-raising activities are essential for preventing disharmony and conflict among the communities. There were other concerns that were raised during the discussion, e.g., the limited knowledge about the biology and evolution of Wolbachia, the interaction ofWolbachia with other species, and the nontarget impacts of the release of Wolbachia-infected Ae. aegypti on the health of the communities and the environment, which may have included the probability of an increase of filariasis as a result of the release of Wolbachia-infected Ae. aegypti. These factors need to be further understood in the future.

The finding of Wolbachia was a novel breakthrough due to its innovation in addressing problematic mosquito vector control. The decline in Ae. aegypti mosquito populations due to cytoplasmic incompatibility (CI) and reduced vector competence is considered key in addressing the mosquito population’s problems, which have never been successfully addressed. However, the technology’s novelty needs to be assessed with caution as there is limited knowledge of the ecology of Wolbachia. To this point, research in some countries has indicated that Wolbachia-infected Ae. aegypti mosquitoes do not show any distinct behavior compared with the wild-type population that is not infected by Wolbachia. However, the future is still beyond prediction, and therefore, a risk assessment was considered necessary to ensure that all potential adverse impacts can be anticipated.

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The risk assessment conducted in Indonesia estimated that over the next 30 years, there would be a negligible risk of causing more harm due to the release of Wolbachia-infected Ae. aegypti. The focus group discussion results indicated considerable critical feedback, in- cluding that continuous monitoring should be conducted after releasing Wolbachia-infected Ae. aegypti to prevent hazards identified in the assessment from happening in the natu- ral environment. Extreme caution must be taken in responding to the result of the risk assessment. Relatively high values were assigned to the likelihoods and consequences of the identified hazards, especially the economic and sociocultural hazards (likelihood: moderate, consequence: high, risk: moderate) and social conflict (likelihood: moderate, consequence: high, risk: moderate). The experts argued that both hazards pose a danger that high value has been assigned despite the lack of scientific evidence that such hazards may occur. This indicates the high level of caution that the assessment exercised.

5. Limitation

Uncertainties concerning the risks associated with the release of Wolbachia- infected mosquitos were thoroughly discussed. Some of the uncertainties arose because of the limitted knowledge that are available in the literatures, which then resulted in the differ- ences in the expert judgement. Several factors can influence this different interpretation, including personal experience of the adverse impact under observation, social-cultural background and beliefs, ability to exercise control over a particular risk, access to infor- mation from different sources, and a tendency to overestimate very low risk sometimes to under-estimate very high ones. At this stage in the process, a risk must be considered a potential risk because it is unknown if it occurs in existing ecosystems. Additionally, there are probabilities of different perceptions of risks due to limited knowledge on Wolbachia and infected mosquitoes. The complexity of an ecosystem related to biodiversity and its interaction in the natural environment still contains many un knowns.

6. Conclusions

Most of the concerns regarding the release of Wolbachia-infected Ae. aegypti stem from the lack of current knowledge on Wolbachia. However, scientific data have been able to address these concerns that enable experts to reach consensus on the negligible risks. The expert team conducted risk analysis based on global evidence and expert judgment resulting from comprehensive experience in health entomology, evolution ecology, public health, mosquito management, physiology, philosophy, economy, and social issues. It can be said that this assessment has covered all aspects and potential hazards of the release of Wolbachia-infected Ae. aegypti in an integrated manner. However, up-to-date knowledge should be followed and taken into consideration for the program to be able to immediately respond to changes in hazards or potential increases in risk.

Author Contributions: Conceptualization, D.B.; methodology, D.B., A.A., U.K.H., and H.K.; analysis, I.N., D.B. and A.M.; investigation, D.B., A.A, U.K.H., and H.K.; data curation, A.M.; writing—original draft preparation, D.B., A.A, U.K.H., H.K., and A.M.; writing—review and editing, D.B. and A.M.; visualization, I.N. and A.M.; supervision, D.B., A.A, U.K.H., and H.K.; All authors have read and agreed to the published version of the manuscript.

Funding: This research was funded by TAHIJA Foundation, grant number 058/YT/Agr/2016. Data Availability Statement: The data presented in this study are available on request from the

corresponding author.

Acknowledgments: TAHIJA Foundation for research fund (grant number 058/YT/Agr/2016). CSIRO for providing training on risk assessment methodology. Thank you to WMP Monash Univer- sity for providing expert judgment, to WMP Yogyakarta, Indonesia, Centre for Tropical Medicine, the Faculty of Medicine, Gadjah Mada University (UGM). Kemenristek DIKTI for establishing The Indonesian Risk Assessment (RA) team: Irawan Yusuf, Johanna Endang Prawitasari; Hadiyono; Teguh Triono; Karlina Supelli, Andi Trisyono; Thomas Suroso; Hajar Hasan; Parwati; Usman Hadi;

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Conflicts of Interest: The authors declare no conflict of interest.

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