insects
Article
Risk Assessment on the Release of Wolbachia-Infected Aedes aegypti in Yogyakarta, Indonesia
Damayanti Buchori 1,2,* , Amanda Mawan 3 , Indah Nurhayati 4, Aryati Aryati 5, Hari Kusnanto 6 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
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 2022, 13, 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/).
Insects 2022, 13, 924. https://doi.org/10.3390/insects13100924 https://www.mdpi.com/journal/insects
Insects 2022, 13, 924
2 of 20
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 aegypti, Ae. albopictus and other mosquitoes [1–3] 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
Insects 2022, 13, x FOR PEER REVIEW 3 of 20
Insects 2022, 13, 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 Wolbachia, dengue 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
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 Wolbachia- Wolbachia-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
WeeuusseeddaarirsiskkaannaalylyssisisfrfraameewoorrkkddeevveelolopeedbbyytthheeAuussttrraalliiaanOfffificceettootthheeGeennee
TTeecchhnnoolologgyyRReegguulalatotorr(O(OGTTR))totoaassseesssaalllppoosssibibiliiltiiteiessaannddsscceennaarrioiossooffuunnpprreecceeddeenntteedd
hhaarrmththaattmmayayococucrurwwithitihninthtehneenxetx3t03y0eyaresairfsbioftbhoftehmfeamlealnedanmdalme aWleolWbaochlbia-cihnifae-cintefedcAteed.
aAegey.pateigwypetriewrelreeasredle.aTsehde.aTsshessamssenstsmweanstcownadsucotendutoctevdaltuoaetveathlueaftaecthoresftahcatot rinsflthuaetncine-
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.
Insects 2022, 13, 924
4 of 20
1 Ecological effects
2 Genetic biodiversity change
3 Change in genetic diversity
4
Transfer of Wolbachia genome to
invertebrates
5 Transfer of Wolbachia genome to
vertebrates
6 New mosquito species evolves
7
Selection for more virulent arboviruses
8 Vector change
9 Increased vector density
10 Increased host biting
11 Female biased sex ratio
12 Increased mosquito host range
13 Increased filarial fitness
14 Replacement of dengue vectors
15 Transfer of other pathogens
16 Environmental change
17 Ecosystem service change
18 Ecological niche
19 Geographic distribution
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.
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.
Insects 2022, 13, 924
5 of 20
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.
Increased difficulty to mosquito control
21
22 Mosquito behaviour change
23 Increased resistance to insecticide
24 Strain selection
25 More dengue infections occur
26 Increased dengue virulence
27 Increased biting
28 Household control
29 Avoidance strategy
30 Complacency
31 Standards of public health
32
Interference with other dengue control
33 Severity of disease
34 More dengue cases
35 Dengue transmission
36 Nuisance biting
37
Other pathogens (transmission of
nondengue pathogens)
38 Dengue evolution
39 Dengue vector competence
40 Feeding frequency
41 Mosquito density
42 Host preference
43 Nondengue vector competence
44 Economic and sociocultural impacts
45 Economic change
46 Health care cost
47 Tourism
48 Loss income
49 Expense change
50 Socio-behavioural change
51 Scapegoating
52 Migration
53 Adverse media
54 Social conflict
55 Class action
56 Social fear
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
Insects 2022, 13, 924
6 of 20
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
Insects 2022, 13, 924
7 of 20
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.
Likelihood
Insects 2022, 13, 924
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-
8 of 20
agement efficacy and public health standard (as shown in Figure 2). Therefore, the total number of hazards became 58.
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. aegypti. of Wolbachia-infected Ae. aegypti.
InIsnescetsct2s02022,21,31,39,2x4FOR PEER REVIEW 9oof f2020
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
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.
Insects 2022, 13, x FOR PEER REVIEW 11 of 20
Insects 2022, 13, 924
11 of 20
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.
Insects 2022, 13, x FOR PEER REVIEW 12 of 20 InInsseecctsts2200222, ,1133, ,9x24FOR PEER REVIEW 12 of 2200
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. .
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.
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.
Insects 2022, 13, 924
13 of 20
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”.
No Hazard/Node
1 Ecological effect
2 Genetic biodiversity change
3 Change in genetic diversity
4 Invertebrate transfer and Wolbachia genome
5 Vertebrate transfer and Wolbachia genome
6 New mosquito species evolves
7 Selection for more virulent arboviruses
8 Vector change
9 Vector density
10 Increased host biting
11 Female biased sex ratio
12 Mosquito host range
13 Increase filarial fitness
14 Replacement of dengue
vectors
15 Transfer of other
arboviruses or pathogens
16 Environmental change
17 Ecosystem service change
18 Ecological niche
19 Geographic distribution
change
20 Mosquito management
efficacy
21 Increased difficulty to control
22 Mosquito behaviour change
23 Insecticide resistance
24 Strain selection
25 More dengue infections
occur
26 Increased dengue
virulence
27 Household control
28 Avoidance strategies
29 Complacency
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
Insects 2022, 13, 924
14 of 20
No Hazard/Node
31 Interference with other dengue controls
32 Severity of disease
33 More dengue cases
34 Increased biting
35 Dengue transmission
36 Nuisance biting
37 Other pathogens
38 Dengue evolution
39 Dengue vector
competence
40 Feeding frequency
41 Mosquito density
42 Host preference
43 Nondengue vector
competence
44 Economic and
sociocultural effect
45 Economic change
46 Health care
47 Tourism
48 Lost income
49 Expense change
50 Social-behavioural change
51 Scapegoating
52 Migration
53 Adverse media
54 Social conflict
55 Class action
56 Social fear
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
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).
Insects 2022, 13, 924
15 of 20
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 [20–22]. 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
Insects 2022, 13, 924
16 of 20
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
Insects 2022, 13, 924
17 of 20
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.
Insects 2022, 13, 924
18 of 20
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;
Insects 2022, 13, 924 19 of 20
References
Agnes Kurniawan; Rosichon Ubaidillah, Endang Srimurni Kusmintarsih, Susi Soviana, Isra Wahid, Andi Atu Sanusi, Tejo Sasmono, Rizalinda, Endang Sri Ratna, Syahri Bulan, Subagyo Yotopranoto.
Conflicts of Interest: The authors declare no conflict of interest.
World Health Organization Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention and Control 1997. Available online:https://apps.who.int/iris/handle/10665/41988 (accessed on 26 June 2017).
Rigau-Pérez, J.G.; Clark, G.G.; Gubler, D.J.; Reiter, P.; Sanders, E.J.; Vance Vorndam, A. Dengue and dengue haemorrhagic fever. Lancet 1998, 352, 971–977. [CrossRef]
Centers for Disease Control and Prevention Epidemiology Dengue Homepage. Available online: https://www.cdc.gov/dengue/ epidemiology/index.html (accessed on 1 July 2017).
World Health Organization. Global Strategy for Dengue Prevention and Control, 2012–2020; Velayudhan, R., Ed.; World Health Organization: Geneva, Switzerland, 2012; ISBN 978-92-4-150403-4.
Martina, B.E.E.; Penelope, K.; Osterhaus, A.D.M.E. Dengue virus pathogenesis: An integrated view. Clin. Microbiol. Rev. 2009, 22, 564–581. [CrossRef] [PubMed]
Karyanti, M.R.; Hadinegoro, S.R. Perubahan epidemiologi demam berdarah dengue di Indonesia 2009. Sari Pediatr. 2009, 10, 424–432. [CrossRef]
Indrayani, Y.A.; Wahyudi, T. Situasi Penyakit Demam Berdarah di Indonesia Tahun 2017; InfoDATIN Pusat Data dan Informasi Kementerian Kesehatan RI: Jakarta, Republic of Indonesia, 2018.
Ministry of Health. Data DBD Indonesia; Ministry of Health: Jakarta, Republic of Indonesia, 2021.
Direktorat Jenderal Pengendalian Penyakit dan Penyehatan Lingkungan. Profil Pengendalian Penyakit dan Penyehatan Lingkungan
Tahun 2013; Direktorat Jenderal Pengendalian Penyakit dan Penyehatan Lingkungan: Jakarta, Republic of Indonesia, 2014.
World Health Organization. Zika Strategic Response Plan; World Health Organization: Geneva, Switzerland, 2016.
Perlman, S.J.; Hunter, M.S.; Zchori-Fein, E. The emerging diversity of Rickettsia. Proc. Biol. Sci. 2006, 273, 2097–2106. [CrossRef]
Turley, A.P.; Moreira, L.A.; O’Neill, S.L.; McGraw, E.A. Wolbachia infection reduces blood-feeding success in the dengue fever
mosquito. Aedes aegypti. PLoS Negl. Trop. Dis. 2009, 3, e516. [CrossRef]
Ye, Y.H.; Carrasco, A.M.; Frentiu, F.D.; Chenoweth, S.F.; Beebe, N.W.; van den Hurk, A.F.; Simmons, C.P.; O’Neill, S.L.; McGraw,
E.A. Wolbachia Reduces the Transmission Potential of Dengue-Infected Aedes aegypti. PLoS Negl. Trop. Dis. 2015, 9, e0003894.
[CrossRef]
Murray, J.V.; Jansen, C.C.; De Barro, P. Risk associated with the release of Wolbachia-infected Aedes aegypti mosquitoes into the
environment in an effort to control dengue. Front. Public Health 2016, 4, 43. [CrossRef]
Siu, N.O.; Kelly, D.L. Bayesian parameter estimation in probabilistic risk assessment. Reliab. Eng. Syst. Saf. 1998, 62, 89–116.
[CrossRef]
Neapolitan, R.E. Learning Bayesian Network; Prentice Hall: Upper Saddle River, NJ, USA, 2003.
Severtson, D.J.; Burt, J.E. The influence of mapped hazards on risk beliefs: A proximity-based modeling approach. Risk Anal.
2012, 32, 259–280. [CrossRef]
Langseth, H.; Portinale, L. Bayesian networks in reliability. Reliab. Eng. Syst. Saf. 2007, 92, 92–108. [CrossRef]
Mkrtchyan, L.; Podofillini, L.; Dang, V.N. Bayesian belief networks for human reliability analysis: A review of applications and
gaps. Reliab. Eng. Syst. Saf. 2015, 139, 1–16. [CrossRef]
Hoffmann, A.A.; Montgomery, B.L.; Popovici, J.; Iturbe-Ormaetxe, I.; Johnson, P.H.; Muzzi, F.; Greenfield, M.; Durkan, M.; Leong,
Y.S.; Dong, Y.; et al. Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission. Nature 2011,
476, 454–457. [CrossRef] [PubMed]
Walker, T.; Johnson, P.H.; Moreira, L.A.; Iturbe-Ormaetxe, I.; Frentiu, F.D.; McMeniman, C.J.; Leong, Y.S.; Dong, Y.; Axford, J.;
Kriesner, P.; et al. The wMel Wolbachia strain blocks dengue and invades caged Aedes aegypti populations. Nature 2011, 476,
450–453. [CrossRef]
Mains, J.W.; Kelly, P.H.; Dobson, K.L.; Petrie, W.D.; Dobson, S.L. Localized Control of Aedes aegypti (Diptera: Culicidae) in
Miami, FL, via Inundative Releases of Wolbachia-Infected Male Mosquitoes. J. Med. Entomol. 2019, 56, 1296–1303. [CrossRef]
McMeniman, C.J.; Lane, A.M.; Fong, A.W.C.; Voronin, D.A.; Iturbe-Ormaetxe, I.; Yamada, R.; McGraw, E.A.; O’Neill, S.L. Host adaptation of a Wolbachia strain after long-term serial passage in mosquito cell lines. Appl. Environ. Microbiol. 2008, 74, 6963–6969.
[CrossRef]
McMeniman, C.J.; Lane, R.V.; Cass, B.N.; Fong, A.W.C.; Sidhu, M.; Wang, Y.-F.; O’Neill, S.L. Stable introduction of a life-shortening
Wolbachia infection into the mosquito Aedes aegypti. Science 2009, 323, 141–144. [CrossRef]
Moreira, L.A.; Saig, E.; Turley, A.P.; Ribeiro, J.M.C.; O’Neill, S.L.; McGraw, E.A. Human probing behavior of Aedes aegypti when
infected with a life-shortening strain of Wolbachia. PLoS Negl. Trop. Dis. 2009, 3, e568. [CrossRef] [PubMed]
Sim, S.; Ramirez, J.L.; Dimopoulos, G. Dengue virus infection of the Aedes aegypti salivary gland and chemosensory apparatus
induces genes that modulate infection and blood-feeding behavior. PLoS Pathog. 2012, 8, e1002631. [CrossRef]
Raquin, V.; Lambrechts, L. Dengue virus replicates and accumulates in Aedes aegypti salivary glands. Virology 2017, 507, 75–81.
[CrossRef]
Insects 2022, 13, 924 20 of 20
Weeks, A.R.; Tracy Reynolds, K.; Hoffmann, A.A. Wolbachia dynamics and host effects: What has (and has not) been demon- strated? Trends Ecol. Evol. 2002, 17, 257–262. [CrossRef]
Higa, Y. Dengue vectors and their spatial distribution. Trop. Med. Health 2011, 39, S17–S27. [CrossRef] [PubMed]
Rosen, L.; Rozeboom, L.E.; Sweet, B.H.; Sabin, A.B. The transmission of dengue by Aedes polynesiensis marks. Am. J. Trop. Med.
Hyg. 1954, 3, 878–882. [CrossRef] [PubMed]
Moore, P.R.; Johnson, P.H.; Smith, G.A.; Ritchie, S.A.; Van Den Hurk, A.F. Infection and dissemination of dengue virus type 2 in
Aedes aegypti, Aedes albopictus, and Aedes scutellaris from the Torres Strait, Australia. J. Am. Mosq. Control Assoc. 2007, 23,
383–388. [CrossRef] [PubMed]
Rogers, D.J.; Wilson, A.J.; Hay, S.I.; Graham, A.J. The global distribution of yellow fever and dengue. In Global Mapping of Infectious
Diseases: Methods, Examples and Emerging Applications; Hay, S.I., Graham, A., Rogers, D.J., Eds.; Academic Press: Cambridge, MA,
USA, 2006; Volume 62, pp. 181–220, ISBN 0065-308X.
Shaw, W.R.; Marcenac, P.; Childs, L.M.; Buckee, C.O.; Baldini, F.; Sawadogo, S.P.; Dabiré, R.K.; Diabaté, A.; Catteruccia, F.
Wolbachia infections in natural Anopheles populations affect egg laying and negatively correlate with Plasmodium development.
Nat. Commun. 2016, 7, 11772. [CrossRef] [PubMed]
Pfarr, K.; Foster, J.; Slatko, B.; Hoerauf, A.; Eisen, J.A. On the taxonomic status of the intracellular bacterium Wolbachia pipientis:
Should this species name include the intracellular bacteria of filarial nematodes? Int. J. Syst. Evol. Microbiol. 2007, 57, 1677–1678.
[CrossRef] [PubMed]
Wang, D.Y.; Kumar, S.; Hedges, S.B. Divergence time estimates for the early history of animal phyla and the origin of plants,
animals and fungi. Proc. Biol. Sci. 1999, 266, 163–171. [CrossRef]
Tapia-Conyer, R.; Méndez-Galván, J.; Burciaga-Zúñiga, P. Community participation in the prevention and control of dengue: The
patio limpio strategy in Mexico. Paediatr. Int. Child Health 2012, 32 (Suppl. S1), 10–13. [CrossRef]
Dieng, H.; Saifur, R.G.M.; Ahmad, A.H.; Salmah, M.R.C.; Aziz, A.T.; Satho, T.; Miake, F.; Jaal, Z.; Abubakar, S.; Morales, R.E. Unusual developing sites of dengue vectors and potential epidemiological implications. Asian Pac. J. Trop. Biomed. 2012, 2,
228–232. [CrossRef]
Ouédraogo, S.; Benmarhnia, T.; Bonnet, E.; Somé, P.-A.; Barro, A.S.; Kafando, Y.; Soma, D.D.; Dabiré, R.K.; Saré, D.; Fournet, F.;
et al. Evaluation of effectiveness of a community-based intervention for control of dengue virus vector, Ouagadougou, Burkina
Faso. Emerg. Infect. Dis. 2018, 24, 1859–1867. [CrossRef]
Caballero-Anthony, M.; Cook, A.D.B.; Amul, G.G.H.; Sharma, A. Health Governance and Dengue in Indonesia; S. Rajaratnam School
of International Studies: Singapore, 2015.
Kusriastuti, R.; Sutomo, S. Evolution of Dengue Prevention and Control Programme in Indonesia. Dengue Bull. 2005, 29, 1–7.
Sasmita, H.I.; Neoh, K.-B.; Yusmalinar, S.; Anggraeni, T.; Chang, N.-T.; Bong, L.-J.; Putra, R.E.; Sebayang, A.; Silalahi, C.N.;
Ahmad, I.; et al. Ovitrap surveillance of dengue vector mosquitoes in Bandung City, West Java Province, Indonesia. PLoS Negl.
Trop. Dis. 2021, 15, e0009896. [CrossRef] [PubMed]
Zouache, K.; Voronin, D.; Tran-Van, V.; Mousson, L.; Failloux, A.-B.; Mavingui, P. Persistent Wolbachia and cultivable bacteria
infection in the reproductive and somatic tissues of the mosquito vector Aedes albopictus. PLoS ONE 2009, 4, e6388. [CrossRef] [PubMed]
No comments:
Post a Comment