Malaria vector control tools in emergency settings: What do experts think? Results from a DELPHI survey.

BACKGROUND: The use and implementation of novel tools for malaria control such as long lasting impregnated bednets (LLINs) and Indoor Residual Spraying (IRS) over the last decade has contributed to a substantial reduction in malaria burden globally. However numerous challenges exist particularly in relation to vector control in emergency settings. This study seeks to explore expert opinion on the utility of existing tools within the emergency context setting and to better understand the attitude towards emerging and innovative tools (including Genetically Modified Mosquitoes) to augment current approaches. METHODS: 80 experts in the field of malaria and vector control were invited to participate in a two-round Delphi survey. They were selected through a combination of literature (academic and policy publications) review and snowball sampling reflecting a range of relevant backgrounds including vector control experts, malaria programme managers and emergency response specialists. The survey was conducted online through a questionnaire including the possibility for free text entry, and concentrated on the following topics: 1. Utility and sustainability of current vector control tools, both in and outside emergency settings 2. Feasibility, utility and challenges of emerging vector control tools, both in and outside emergency settings 3. Current and unmet research priorities in malaria vector control and in malaria control in general. RESULTS: 37 experts completed the first round and 31 completed the second round of the survey. There was a stronger consensus about the increased utility of LLIN compared to IRS in all settings, while insecticide-treated covers and blankets ranked very high only in emergency settings. When considering the combination of tools, the ones deemed most interesting always involved LLINs and IRS regardless of the setting, and the acceptability and the efficacy at reducing transmission are essential characteristics. Regarding perceptions of tools currently under development, consensus was towards improvement of existing tools rather than investing in novel approaches and the majority of respondents expressed distrust for genetic approaches. CONCLUSION: Malaria vector control experts expressed more confidence for tools whose efficacy is backed up by epidemiological evidence, hence a preference for the improvement rather than the combination of existing tools. Moreover, while several novel tools are under development, the majority of innovative approaches did not receive support, particularly in emergency settings. Stakeholders involved in the development of novel tools should involve earlier and raise awareness of the potential effectiveness amongst a wider range of experts within the malaria community to increase acceptability and improve early adoption once the evidence base is established.

Insecticide resistance profiles in malaria vector populations from Sud-Kivu in the Democratic Republic of the Congo.

BACKGROUND: Insecticide resistance has become a widespread problem causing a decline in the effectiveness of vector control tools in sub-Saharan Africa. In this situation, ongoing monitoring of vector susceptibility to insecticides is encouraged by the WHO to guide national malaria control programmes. Our study was conducted from April to November 2018 in Tchonka (Sud-Kivu, Democratic Republic of the Congo) and reported primary data on the resistance status of Anopheles funestus and Anopheles gambiae. METHODS: Insecticide susceptibility bioassays were performed on wild populations of A. funestus and A. gambiae using WHO insecticide-impregnated papers at discriminating concentration. In addition, PCR was performed to identify mosquito species and to detect kdr and ace-1R mutations involved in insecticide resistance. RESULTS: Bioassay results show resistance to all tested insecticides except pirimiphos-methyl, propoxur, fenitrothion and malathion with a mortality rate ranging from 95.48 to 99.86%. The addition of piperonyl butoxide (PBO) increased the susceptibility of vectors to deltamethrin and alpha-cypermethrin by exhibiting a mortality ranging from 91.50 to 95.86%. The kdr mutation was detected at high frequencies (approximately 0.98) within A. gambiae while ace-1R was not detected. CONCLUSIONS: This study provides useful data on the insecticide resistance profiles of malaria vector populations to better manage vector control. Our results highlight that, despite the high level of resistance, organophosphorus compounds and pyrethroids + PBO remain effective against the vectors.

Evaluating the probability of CRISPR-based gene drive contaminating another species.

The probability D that a given clustered regularly interspaced short palindromic repeats (CRISPR)-based gene drive element contaminates another, nontarget species can be estimated by the following Drive Risk Assessment Quantitative Estimate (DRAQUE) Equation: D = h y b + t r a n s f × e x p r e s s × c u t × f l a n k × i m m u n e × n o n e x t i n c t with hyb = probability of hybridization between the target species and a nontarget species; transf = probability of horizontal transfer of a piece of DNA containing the gene drive cassette from the target species to a nontarget species (with no hybridization); express = probability that the Cas9 and guide RNA genes are expressed; cut = probability that the CRISPR-guide RNA recognizes and cuts at a DNA site in the new host; flank = probability that the gene drive cassette inserts at the cut site; immune = probability that the immune system does not reject Cas9-expressing cells; nonextinct = probability of invasion of the drive within the population. We discuss and estimate each of the seven parameters of the equation, with particular emphasis on possible transfers within insects, and between rodents and humans. We conclude from current data that the probability of a gene drive cassette to contaminate another species is not insignificant. We propose strategies to reduce this risk and call for more work on estimating all the parameters of the formula.

Needs and Challenges in Modelling Malaria for Emergency Contexts.

While modelling is an essential component for an understanding of the epidemiology of malaria, and for designing better control measures, it rarely considers the particular contexts encountered in emergency settings. By linking these situations with the transmission parameters our aim is to correct this bias and call for a better collaboration between relief actors.

Strategies of host resistance to pathogens in spatially structured populations: An agent-based evaluation.

There is growing theoretical evidence that spatial structure can affect the ecological and evolutionary outcomes of host-parasite interactions. Locally restricted interactions have been shown in particular to affect host resistance and tolerance. In this study we investigate the evolution of several types of host disease resistance strategies, alone or in combination, in spatially structured populations. We construct a spatially explicit, individual-based stochastic model where hosts and parasites interact with each other in a spatial lattice, and interactions are restricted to a given neighbourhood of varying size. We investigate several host resistance strategies, including constitutive (expressed in all resistant hosts), induced (expressed only upon infection), and combinations thereof. We show that a costly constitutive resistance cannot reach fixation, whereas an inducible resistance strategy may become fixed in the population if the cost remains low, particularly if it impacts host recovery. We also demonstrate that mixed strategies can be maintained in the host population, and that a higher investment in a recovery-boosting inducible resistance allows for a higher investment in a constitutive response. Our simulations reveal that the spatial structure of the population impacts the selection for resistance in a complex fashion. While single strategies of resistance are generally favoured in less structured populations, mixed strategies can sometimes prevail only in highly structured environments, e.g. when combining constitutive and transmission-blocking induced responses Overall these results shed new light on the dynamics of disease resistance in a spatially-structured host-pathogen system, and advance our theoretical understanding of the evolutionary dynamics of disease resistance, a necessary step to elaborate more efficient and sustainable strategies for disease management.

Technoscience and Biodiversity Conservation.

The discovery of CRISPR/Cas9 has opened new avenues in gene editing. This system, usually considered as molecular scissors, permits the cutting of the DNA at a targeted site allowing the introduction of new genes or the removal or the modification of existing ones. The genome-editing, involving gene drive or not, is then considered with a strong interest in a variety of fields ranging from agriculture to public health and conservation biology. Given its controversial aspects, it is then no surprise that actors in biodiversity conservation do express conflicting views on this emerging and disruptive technology. The positions are ranging from a request for a moratorium to the will to test and deploy it in strategies aiming at eradicating invasive species of mammals on islands. Reviewing some of its recent developments brings light on the conflicts of interest, the financial support, and lobbying currently occurring in this growing field of biotechnology. While an optimistic view on the use of gene drive for ecosystem conservation was first promoted by several molecular biologists, the risks and uncertainties associated have now led to some reservations. Overall, the eventual use of this novel approach for conservation raises concerns related to the engagement of the public, the communication between scientists, and the public and the risk of a manufactured consent. There are also a series of essential ethical and philosophical questions on the relations we have with Nature that needs to be answered.

Bats and Academics: How Do Scientists Perceive Their Object of Study?

Bats are associated with conflicting perceptions among humans, ranging from affection to disgust. If these attitudes can be associated with various factors among the general public (e.g. social norms, lack of knowledge), it is also important to understand the attitude of scientists who study bats. Such reflexive information on the researchers community itself could indeed help designing adequate mixed communication tools aimed at protecting bats and their ecosystems, as well as humans living in their vicinity that could be exposed to their pathogens. Thus, we conducted an online survey targeting researchers who spend a part of their research activity studying bats. Our aim was to determine (1) how they perceive their object of study, (2) how they perceive the representation of bats in the media and by the general population, (3) how they protect themselves against pathogen infections during their research practices, and (4) their perceptions of the causes underlying the decline in bat populations worldwide. From the 587 completed responses (response rate of 28%) having a worldwide distribution, the heterogeneity of the scientists' perception of their own object of study was highlighted. In the majority of cases, this depended on the type of research they conducted (i.e. laboratory versus field studies) as well as their research speciality. Our study revealed a high level of personal protection equipment being utilised against pathogens during scientific practices, although the role bats play as reservoirs for a number of emerging pathogens remains poorly known. Our results also disclosed the unanimity among specialists in attributing a direct role for humans in the global decline of bat populations, mainly via environmental change, deforestation, and agriculture intensification. Overall, the present study suggests the need for better communication regarding bats and their biology, their role within the scientific community, as well as in the general public population. As a consequence, increased knowledge regarding scientists' perceptions of bats should improve the role scientists play in influencing the perception of bats by the general public.

Biodiversity and health: Lessons and recommendations from an interdisciplinary conference to advise Southeast Asian research, society and policy.

Southeast Asia is an economic, biodiverse, cultural and disease hotspot. Due to rapid socio-economic and environmental changes, the role of biodiversity and ecosystems for human health ought to be examined and communicated to decision-makers and the public. We therefore summarized the lessons and recommendations from an interdisciplinary conference convened in Cambodia in 2014 to advise Southeast Asian societies on current research efforts, future research needs, and to provide suggestions for improved education, training and science-policy interactions. First, we reviewed several examples of the important role of ecosystems as 'sentinels' in the sense that potentially harmful developments for human health become first apparent in ecosystem components. Other ecosystem services which also benefit human well-being are briefly summarized. Second, we summarized the recommendations of the conference's roundtable discussions and added recent developments in the science-policy interface. The recommendations were organized along five themes: Ethical and legal considerations; implementation of the One Health approach; education, training, and capacity building; future research priorities; and potential science-policy interactions. While the role of biodiversity for human health needs further research, especially for zoonoses and emerging diseases, many direct and indirect benefits to human health are already apparent, but have yet to filter down to the science-policy interface in order to influence legislation and enforcement. Therefore, efforts to strengthen the interface in Southeast Asia should become a high priority in order to strengthen the health and resilience of Southeast Asian societies.

Engaging scientists: An online survey exploring the experience of innovative biotechnological approaches to controlling vector-borne diseases.

BACKGROUND: Pioneering technologies (e.g., nanotechnology, synthetic biology or climate engineering) are often associated with potential new risks and uncertainties that can become sources of controversy. The communication of information during their development and open exchanges between stakeholders is generally considered a key issue in their acceptance. While the attitudes of the public to novel technologies have been widely considered there has been relatively little investigation of the perceptions and awareness of scientists working on human or animal diseases transmitted by arthropods. METHODS: Consequently, we conducted a global survey on 1889 scientists working on aspects of vector-borne diseases, exploring, under the light of a variety of demographic and professional factors, their knowledge and awareness of an emerging biotechnology that has the potential to revolutionize the control of pest insect populations. RESULTS: Despite extensive media coverage of key developments (including releases of manipulated mosquitoes into human communities) this has in only one instance resulted in scientist awareness exceeding 50% on a national or regional scale. We document that awareness of pioneering releases significantly relied on private communication sources that were not equally accessible to scientists from countries with endemic vector-borne diseases (dengue and malaria). In addition, we provide quantitative analysis of the perceptions and knowledge of specific biotechnological approaches to controlling vector-borne disease, which are likely to impact the way in which scientists around the world engage in the debate about their value. CONCLUSIONS: Our results indicate that there is scope to strengthen already effective methods of communication, in addition to a strong demand by scientists (expressed by 79.9% of respondents) to develop new, creative modes of public engagement.

Scientists and public involvement: a consultation on the relation between malaria, vector control and transgenic mosquitoes.

Among the hopes for vector-based malaria control, the use of transgenic mosquitoes able to kill malaria parasites is seen as a potential way to interrupt malaria transmission. While this potential solution is gaining some support, the ethical and social aspects related to this high-tech method remain largely unexplored and underestimated. Related to those latter points, the aim of the present survey is to determine how scientists working on malaria and its vector mosquitoes perceive public opinion and how they evaluate public consultations on their research. This study has been performed through a questionnaire addressing questions related to the type of research, the location, the nationality and the perception of the public involvement by scientists. The results suggest that even if malaria researchers agree to interact with a non-scientific audience, they (especially the ones from the global North) remain quite reluctant to have their research project submitted in a jargon-free version to the evaluation and the prior-agreement by a group of non-specialists. The study, by interrogating the links between the scientific community and the public from the perspective of the scientists, reveals the importance of fostering structures and processes that could lead to a better involvement of a non specialist public in the actual debates linking scientific, technological and public health issues in Africa.

Anopheles mosquitoes: not just flying malaria vectors... especially in the field.

The polymorphism of genes involved in the immunity of malaria vectors has been the subject of several recent studies with mosquitoes from natural populations. Most of the genes examined are known for their role against Plasmodium berghei and not necessarily for their role against Plasmodium falciparum. It seems, therefore, to be highly important not only to be cautious when linking natural selection with malaria epidemiology but also to consider the importance of other parasites and the environment on the mosquito genome.

Can transgenic mosquitoes afford the fitness cost?

In a recent study, SM1-transgenic Anopheles stephensi, which are resistant partially to Plasmodium berghei, had higher fitness than non-transgenic mosquitoes when they were maintained on Plasmodium-infected blood. This result should be interpreted cautiously with respect to malaria control using transgenic mosquitoes because, despite the evolutionary advantage conferred by the transgene, a concomitant cost prevents it from invading the entire population. Indeed, for the spread of a resistance transgene in a natural situation, the transgene's fitness cost and the efficacy of the gene drive will be more crucial than any evolutionary advantage.