Green cities and vector-borne diseases: emerging concerns and opportunities.

Aligned with the Sustainable Development Goals, nature-based solutions such as urban greening e.g. public gardens, urban forests, parks and street trees, which aim to protect, sustainably manage or restore an ecosystem, have emerged as a promising tool for improving the health and well-being of an ever-increasing urban population. While urban greening efforts have undeniable benefits for human health and the biological communities inhabiting these green zones, disease vector populations may also be affected, possibly promoting greater pathogen transmission and the emergence of infectious diseases such as dengue, West Nile fever, malaria, leishmaniosis and tick-borne diseases. Evidence for the impact of urban green areas on vector-borne disease (VBD) transmission is scarce. Furthermore, because of vast disparities between cities, variation in green landscapes and differing scales of observation, findings are often contradictory; this calls for careful assessment of how urban greening affects VBD risk. Improved understanding of the effect of urban greening on VBDs would support planning, monitoring and management of green spaces in cities to sustainably mitigate VBD risks for surrounding urban populations.

Invasive hematophagous arthropods and associated diseases in a changing world.

Biological invasions have increased significantly with the tremendous growth of international trade and transport. Hematophagous arthropods can be vectors of infectious and potentially lethal pathogens and parasites, thus constituting a growing threat to humans-especially when associated with biological invasions. Today, several major vector-borne diseases, currently described as emerging or re-emerging, are expanding in a world dominated by climate change, land-use change and intensive transportation of humans and goods. In this review, we retrace the historical trajectory of these invasions to better understand their ecological, physiological and genetic drivers and their impacts on ecosystems and human health. We also discuss arthropod management strategies to mitigate future risks by harnessing ecology, public health, economics and social-ethnological considerations. Trade and transport of goods and materials, including vertebrate introductions and worn tires, have historically been important introduction pathways for the most prominent invasive hematophagous arthropods, but sources and pathways are likely to diversify with future globalization. Burgeoning urbanization, climate change and the urban heat island effect are likely to interact to favor invasive hematophagous arthropods and the diseases they can vector. To mitigate future invasions of hematophagous arthropods and novel disease outbreaks, stronger preventative monitoring and transboundary surveillance measures are urgently required. Proactive approaches, such as the use of monitoring and increased engagement in citizen science, would reduce epidemiological and ecological risks and could save millions of lives and billions of dollars spent on arthropod control and disease management. Last, our capacities to manage invasive hematophagous arthropods in a sustainable way for worldwide ecosystems can be improved by promoting interactions among experts of the health sector, stakeholders in environmental issues and policymakers (e.g. the One Health approach) while considering wider social perceptions.

Infravec2 guidelines for the design and operation of containment level 2 and 3 insectaries in Europe.

With the current expansion of vector-based research and an increasing number of facilities rearing arthropod vectors and infecting them with pathogens, common measures for containment of arthropods as well as manipulation of pathogens are becoming essential for the design and running of such research facilities to ensure safe work and reproducibility, without compromising experimental feasibility. These guidelines and comments were written by experts of the Infravec2 consortium, a Horizon 2020-funded consortium integrating the most sophisticated European infrastructures for research on arthropod vectors of human and animal diseases. They reflect current good practice across European laboratories with experience of safely handling different mosquito species and the pathogens they transmit. As such, they provide experience-based advice to assess and manage the risks to work safely with mosquitoes and the pathogens they transmit. This document can also form the basis for research with other arthropods, for example, midges, ticks or sandflies, with some modification to reflect specific requirements.

Development and Implementation of an Interprofessional Digital Platform to Increase Therapeutic Adherence: Protocol for a Mixed Design Study.

BACKGROUND: Adherence to care plans is a major issue in health care systems. Improved adherence has several potential benefits such as ensuring treatment effectiveness and control of chronic diseases. There is currently a lack of tools to maximize treatment adherence in an integrated manner, that is, covering multiple aspects of patients' health continuously throughout their medical care. To ensure better adherence, such tools must meet the needs of patients with chronic conditions as well as those of health care professionals. Acknowledging the health issues associated with nonadherence to treatment, an industry-research-clinical partnership aims to adapt a digital platform-facilitating patient-health care professional interactions-to improve therapeutic adherence in patients with chronic illnesses. The platform allows for exchanges between patients and health care professionals to facilitate the timing of medication use or chronic disease management and maximize patient adherence. OBJECTIVE: This study aims to (1) identify the needs of patients living with a chronic condition and their health professionals concerning their interactions regarding treatment; (2) codevelop an adaptation of an interactive patient-professional platform that meets the needs identified; and (3) then test the platform and document its effects and acceptability in a clinical setting. METHODS: The study will use a creative design thinking process based on the needs expressed by users (patients and health professionals) concerning treatment adherence for chronic diseases (eg, diabetes, asthma, high blood pressure, depression and anxiety, chronic obstructive pulmonary disease). A mixed method evaluation research design will be used to develop and evaluate the platform. Qualitative data will be used to assess user needs and acceptability of the platform, and quantitative data will provide the necessary insights to document its effects. RESULTS: Technological development of the platform has been completed. Recruitment for the first part of Phase 1 started in May 2022. The results of this project to codevelop an interprofessional digital platform to increase therapeutic adherence will be relevant to clinicians and managers seeking contemporary solutions that support patient adherence to treatment for chronic diseases. These results will enable optimal use of the platform and identify areas for improvement in interactive patient-health care professional apps. CONCLUSIONS: The adoption of an interactive digital platform to facilitate effective exchanges between patients and health care professionals in primary care settings could improve adherence to treatment. The platform tested in this project takes a first step in this direction by ensuring that the technological product is developed according to the needs of patients as well as the health professionals who are likely to use it. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34463.

On the need for integrating cancer into the One Health perspective.

Recent pandemics have highlighted the urgency to connect disciplines studying animal, human, and environment health, that is, the "One Health" concept. The One Health approach takes a holistic view of health, but it has largely focused on zoonotic diseases while not addressing oncogenic processes. We argue that cancers should be an additional key focus in the One Health approach based on three factors that add to the well-documented impact of humans on the natural environment and its implications on cancer emergence. First, human activities are oncogenic to other animals, exacerbating the dynamics of oncogenesis, causing immunosuppressive disorders in wildlife with effects on host-pathogen interactions, and eventually facilitating pathogen spillovers. Second, the emergence of transmissible cancers in animal species (including humans) has the potential to accelerate biodiversity loss across ecosystems and to become pandemic. It is crucial to understand why, how, and when transmissible cancers emerge and spread. Third, translating knowledge of tumor suppressor mechanisms found across the Animal Kingdom to human health offers novel insights into cancer prevention and treatment strategies.

Effects of insemination and blood-feeding on locomotor activity of wild-derived females of the malaria mosquito Anopheles coluzzii.

BACKGROUND: Behavioural shifts in the canonical location and timing of biting have been reported in natural populations of anopheline malaria vectors following the implementation of insecticide-based indoor vector control interventions. These modifications increase the likelihood of human-vector contact and allow mosquitoes to avoid insecticides, both conditions being favourable to residual transmission of the malarial parasites. The biting behaviour of mosquitoes follows rhythms that are under the control of biological clocks and environmental conditions, modulated by physiological states. In this work we explore modifications of spontaneous locomotor activity expressed by mosquitoes in different physiological states to highlight phenotypic variability associated to circadian control that may contribute to explain residual transmission in the field. METHODS: The F10 generation progeny of field-collected Anopheles coluzzii from southwestern Burkina Faso was tested using an automated recording apparatus (Locomotor Activity Monitor, TriKinetics Inc.) under LD 12:12 or DD light regimens in laboratory-controlled conditions. Activity recordings of each test were carried out for a week with 6-day-old females belonging to four experimental treatments, representing factorial combinations of two physiological variables: insemination status (virgin vs inseminated) and gonotrophic status (glucose fed vs blood fed). Chronobiological features of rhythmicity in locomotor activity were explored using periodograms, diversity indices, and generalized linear mixed modelling. RESULTS: The average strength of activity, onset of activity, and acrophase were modulated by both nutritional and insemination status as well as by the light regimen. Inseminated females showed a significant excess of arrhythmic activity under DD. When rhythmicity was observed in DD, females displayed sustained activity also during the subjective day. CONCLUSIONS: Insemination and gonotrophic status influence the underlying light and circadian control of chronobiological features of locomotor activity. Overrepresentation of arrhythmic chronotypes as well as the sustained activity of inseminated females during the subjective day under DD conditions suggests potential activity of natural populations of A. coluzzii during daytime under dim conditions, with implications for residual transmission of malarial parasites.

Evaluating metrics in link streams.

We seek to understand the topological and temporal nature of temporal networks by computing the distances, latencies and lengths of shortest fastest paths. Shortest fastest paths offer interesting insights about connectivity that were unknowable until recently. Moreover, distances and latencies tend to be computed by separate algorithms. We developed four algorithms that each compute all those values efficiently as a contribution to the literature. Two of those methods compute metrics from a fixed source temporal node. The other two, as a significant contribution to the literature, compute the metrics between all pairs of source and destination temporal nodes. The methods are also grouped by whether they work on paths with delays or not. Proofs of correctness for our algorithms are presented as well as bounds on their temporal complexities as functions of temporal network parameters. Experimental results show the algorithms presented perform well against the state of the art and terminate in decent time on real-world datasets. One purpose of this study is to help develop algorithms to compute centrality functions on temporal networks such as the betweenness centrality and the closeness centrality.

Data-driven and interpretable machine-learning modeling to explore the fine-scale environmental determinants of malaria vectors biting rates in rural Burkina Faso.

BACKGROUND: Improving the knowledge and understanding of the environmental determinants of malaria vector abundance at fine spatiotemporal scales is essential to design locally tailored vector control intervention. This work is aimed at exploring the environmental tenets of human-biting activity in the main malaria vectors (Anopheles gambiae s.s., Anopheles coluzzii and Anopheles funestus) in the health district of Diébougou, rural Burkina Faso. METHODS: Anopheles human-biting activity was monitored in 27 villages during 15 months (in 2017-2018), and environmental variables (meteorological and landscape) were extracted from high-resolution satellite imagery. A two-step data-driven modeling study was then carried out. Correlation coefficients between the biting rates of each vector species and the environmental variables taken at various temporal lags and spatial distances from the biting events were first calculated. Then, multivariate machine-learning models were generated and interpreted to (i) pinpoint primary and secondary environmental drivers of variation in the biting rates of each species and (ii) identify complex associations between the environmental conditions and the biting rates. RESULTS: Meteorological and landscape variables were often significantly correlated with the vectors' biting rates. Many nonlinear associations and thresholds were unveiled by the multivariate models, for both meteorological and landscape variables. From these results, several aspects of the bio-ecology of the main malaria vectors were identified or hypothesized for the Diébougou area, including breeding site typologies, development and survival rates in relation to weather, flight ranges from breeding sites and dispersal related to landscape openness. CONCLUSIONS: Using high-resolution data in an interpretable machine-learning modeling framework proved to be an efficient way to enhance the knowledge of the complex links between the environment and the malaria vectors at a local scale. More broadly, the emerging field of interpretable machine learning has significant potential to help improve our understanding of the complex processes leading to malaria transmission, and to aid in developing operational tools to support the fight against the disease (e.g. vector control intervention plans, seasonal maps of predicted biting rates, early warning systems).

Sterile Insect Technique (SIT) against Aedes Species Mosquitoes: A Roadmap and Good Practice Framework for Designing, Implementing and Evaluating Pilot Field Trials.

Aedes albopictus and Aedes aegypti are invasive mosquito species that impose a substantial risk to human health. To control the abundance and spread of these arboviral pathogen vectors, the sterile insect technique (SIT) is emerging as a powerful complement to most commonly-used approaches, in part, because this technique is ecologically benign, specific, and non-persistent in the environment if releases are stopped. Because SIT and other similar vector control strategies are becoming of increasing interest to many countries, we offer here a pragmatic and accessible 'roadmap' for the pre-pilot and pilot phases to guide any interested party. This will support stakeholders, non-specialist scientists, implementers, and decision-makers. Applying these concepts will ensure, given adequate resources, a sound basis for local field trialing and for developing experience with the technique in readiness for potential operational deployment. This synthesis is based on the available literature, in addition to the experience and current knowledge of the expert contributing authors in this field. We describe a typical path to successful pilot testing, with the four concurrent development streams of Laboratory, Field, Stakeholder Relations, and the Business and Compliance Case. We provide a graphic framework with criteria that must be met in order to proceed.

A PCR-RFLP method for genotyping of inversion 2Rc in Anopheles coluzzii.

BACKGROUND: Genotyping of polymorphic chromosomal inversions in malaria vectors such as An. coluzzii Coetzee & Wilkerson is important, both because they cause cryptic population structure that can mislead vector analysis and control and because they influence epidemiologically relevant eco-phenotypes. The conventional cytogenetic method of genotyping is an impediment because it is labor intensive, requires specialized training, and can be applied only to one gender and developmental stage. Here, we circumvent these limitations by developing a simple and rapid molecular method of genotyping inversion 2Rc in An. coluzzii that is both economical and field-friendly. This inversion is strongly implicated in temporal and spatial adaptations to climatic and ecological variation, particularly aridity. METHODS: Using a set of tag single-nucleotide polymorphisms (SNPs) strongly correlated with inversion orientation, we identified those that overlapped restriction enzyme recognition sites and developed four polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) assays that distinguish alternative allelic states at the tag SNPs. We assessed the performance of these assays using mosquito population samples from Burkina Faso that had been cytogenetically karyotyped as well as genotyped, using two complementary high-throughput molecular methods based on tag SNPs. Further validation was performed using mosquito population samples from additional West African (Benin, Mali, Senegal) and Central African (Cameroon) countries. RESULTS: Of four assays tested, two were concordant with the 2Rc cytogenetic karyotype > 90% of the time in all samples. We recommend that these two assays be employed in tandem for reliable genotyping. By accepting only those genotypic assignments where both assays agree, > 99% of assignments are expected to be accurate. CONCLUSIONS: We have developed tandem PCR-RFLP assays for the accurate genotyping of inversion 2Rc in An. coluzzii. Because this approach is simple, inexpensive, and requires only basic molecular biology equipment, it is widely accessible. These provide a crucial tool for probing the molecular basis of eco-phenotypes relevant to malaria epidemiology and vector control.

Strategic Approach, Advances, and Challenges in the Development and Application of the SIT for Area-Wide Control of Aedes albopictus Mosquitoes in Reunion Island.

The global expansion of Aedes albopictus, together with the absence of specific treatment and vaccines for most of the arboviruses it transmits, has stimulated the development of more sustainable and ecologically acceptable methods for control of disease transmission through the suppression of natural vector populations. The sterile insect technique (SIT) is rapidly evolving as an additional tool for mosquito control, offering an efficient and more environment-friendly alternative to the use of insecticides. Following the devastating chikungunya outbreak, which affected 38% of the population on Reunion Island (a French overseas territory in the southwest of the Indian Ocean), there has been strong interest and political will to develop effective alternatives to the existing vector control strategies. Over the past 10 years, the French Research and Development Institute (IRD) has established an SIT feasibility program against Ae. albopictus on Reunion Island in collaboration with national and international partners. This program aimed to determine whether the SIT based on the release of radiation-sterilized males is scientifically and technically feasible, and socially acceptable as part of a control strategy targeting the local Ae. albopictus population. This paper provides a review of a multi-year and a particularly broad scoping process of establishing the scientific and technological feasibility of the SIT against Ae. albopictus on Reunion Island. It also draws attention to some prerequisites of the decision-making process, through awareness campaigns to enhance public understanding and support, social adoption, and regulatory validation of the SIT pilot tests.

First report of Anopheles (Cellia) multicolor during a study of tolerance to salinity of Anopheles arabiensis larvae in Nouakchott, Mauritania.

BACKGROUND: Anopheles multicolor is known to be present in the arid areas of Africa north of the Sahara Desert, especially in oases. To date, its presence in Mauritania has not been reported. Here, we present the first record of its presence in Nouakchott, the capital of Mauritania. The larvae of An. multicolor, together with those of An. arabiensis, the major malaria vector in the city, were found thriving in highly saline surface water collections. METHODS: Entomological surveys were carried out during 2016-2017 in Nouakchott. Mosquito larval habitats were investigated through larval surveys while indoor resting culicid fauna were collected using hand-held aspirator. Physicochemical parameters of the larval habitats were measured on-site, at the time mosquitoes were collected. Larvae and pupae were reared to adults in the insectaries. Morphological and polymerase chain reaction (PCR)-based methods were used to identify newly emerged adults. Batches of fourth-instar larvae were used to assess salinity tolerance by exposing them to increasing concentrations of NaCl, and mortality was monitored throughout development. RESULTS: Morphological and molecular results confirmed that the specimens were An. multicolor and An. arabiensis. Sequences of 24 An. multicolor adult mosquitoes showed 100% nucleotide identity with the published sequences of An. multicolor from Iran. The physicochemical analysis of the water from the two larval habitats revealed highly saline conditions, with NaCl content ranging between 16.8 and 28.9 g/l (i.e. between c.50-80% seawater). Anopheles multicolor and An. arabiensis fourth-instar larvae survival rates at 17.5 g/l NaCl were 86.5% and 75%, respectively. Anopheles arabiensis larvae showed variable levels of salt tolerance according to the larval habitat. Adult An. multicolor specimens were collected resting indoor at low frequency (0.7%) compared to the other culicid mosquitoes. CONCLUSIONS: To the best of our knowledge, this paper is the first report of An. multicolor in Mauritania, extending the known distributional range of the species to the south, as well as to the west. Highly salt-tolerant populations of An. arabiensis and An. multicolor were observed. Because salt-water collections are widespread in Nouakchott, the relevance of these findings for the dynamics and epidemiology of malaria transmission needs to be assessed.

Cancer and mosquitoes - An unsuspected close connection.

Cancer is a major public health issue and represents a significant burden in countries with different levels of economic wealth. In parallel, mosquito-borne infectious diseases represent a growing problem causing significant morbidity and mortality worldwide. Acknowledging that these two concerns are both globally distributed, it is essential to investigate whether they have a reciprocal connection that can fuel their respective burdens. Unfortunately, very few studies have examined the link between these two threats. This review provides an overview of the possible links between mosquitoes, mosquito-borne infectious diseases and cancer. We first focus on the impact of mosquitoes on carcinogenesis in humans including the transmission of oncogenic pathogens through mosquitoes, the immune reactions following mosquito bites, the presence of non-oncogenic mosquito-borne pathogens, and the direct transmission of cancer cells. The second part of this review deals with the direct or indirect consequences of cancer in humans on mosquito behaviour. Thirdly, we discuss the potential impacts that natural cancers in mosquitoes can have on their life history traits and therefore on their vector capacity. Finally, we discuss the most promising research avenues on this topic and the integrative public health strategies that could be envisioned in this context.

A new species in the major malaria vector complex sheds light on reticulated species evolution.

Complexes of closely related species provide key insights into the rapid and independent evolution of adaptive traits. Here, we described and studied Anopheles fontenillei sp.n., a new species in the Anopheles gambiae complex that we recently discovered in the forested areas of Gabon, Central Africa. Our analysis placed the new taxon in the phylogenetic tree of the An. gambiae complex, revealing important introgression events with other members of the complex. Particularly, we detected recent introgression, with Anopheles gambiae and Anopheles coluzzii, of genes directly involved in vectorial capacity. Moreover, genome analysis of the new species allowed us to clarify the evolutionary history of the 3La inversion. Overall, An. fontenillei sp.n. analysis improved our understanding of the relationship between species within the An. gambiae complex, and provided insight into the evolution of vectorial capacity traits that are relevant for the successful control of malaria in Africa.

Is Perceived Exposure to Mosquitoes Associated with Actual Exposure? Results from Studies in High-Risk and Low-Risk Geographic Areas.

Perceived exposure to mosquitoes plays a fundamental role in the adoption of a range of protective behaviors aiming to prevent and control mosquito-borne disease. However, it is largely unknown in the present literature to what extent perceived exposure is associated with actual exposure. Moreover, the perception of nuisance may depend on the natural environment in which human populations are living, and especially its epidemiological context. In this study, the hypothesis that perceived exposure is driven by mosquito abundance was tested in two different geographic areas. We compared a range of perceived nuisance measures-collected through questionnaires-with egg number measured within ovitraps located in the south of France, which has been recently colonized by an arbovirus vector, and La Martinique island, a tropical French territory, which has a long history of outbreaks of mosquito-borne pathogens. Unexpectedly, only the nuisance due to mosquito noise was correlated with ovitrap activity in southern France. All other perceived exposure measures, both in the south of France and in Martinique, were not correlated with egg number surrounding households investigated. These results suggest the existence of habituation effects that may disturb the engagement in adaptive behaviors in the face of change in the entomological conditions.

Natural Wolbachia infections are common in the major malaria vectors in Central Africa.

During the last decade, the endosymbiont bacterium Wolbachia has emerged as a biological tool for vector disease control. However, for long time, it was believed that Wolbachia was absent in natural populations of Anopheles. The recent discovery that species within the Anopheles gambiae complex host Wolbachia in natural conditions has opened new opportunities for malaria control research in Africa. Here, we investigated the prevalence and diversity of Wolbachia infection in 25 African Anopheles species in Gabon (Central Africa). Our results revealed the presence of Wolbachia in 16 of these species, including the major malaria vectors in this area. The infection prevalence varied greatly among species, confirming that sample size is a key factor to detect the infection. Moreover, our sequencing and phylogenetic analyses showed the important diversity of Wolbachia strains that infect Anopheles. Co-evolutionary analysis unveiled patterns of Wolbachia transmission within some Anopheles species, suggesting that past independent acquisition events were followed by co-cladogenesis. The large diversity of Wolbachia strains that infect natural populations of Anopheles offers a promising opportunity to select suitable phenotypes for suppressing Plasmodium transmission and/or manipulating Anopheles reproduction, which in turn could be used to reduce the malaria burden in Africa.

Oasis Malaria, Northern Mauritania1.

A malaria survey was conducted in Atar, the northernmost oasis city in Mauritania, during 2015-2016. All febrile patients in whom malaria was suspected were screened for malaria by using rapid diagnostic testing and microscopic examination of blood smears and later confirmed by PCR. Of 453 suspected malaria cases, 108 (23.8%) were positive by rapid diagnostic testing, 154 (34.0%) by microscopic examination, and 162 (35.7%) by PCR. Malaria cases were observed throughout the year and among all age groups. Plasmodium vivax was present in 120/162 (74.1%) cases, P. falciparum in 4/162 (2.4%), and mixed P. falciparum-P. vivax in 38/162 (23.4%). Malaria is endemic in northern Mauritania and could be spreading farther north in the Sahara, possibly because of human-driven environmental changes. Further entomologic and parasitologic studies and monitoring are needed to relate these findings to major Anopheles mosquito vectors and to design and implement strategies for malaria prevention and control.

Potential of Aedes albopictus as a bridge vector for enzootic pathogens at the urban-forest interface in Brazil.

The invasive species Aedes albopictus is present in 60% of Brazilian municipalities, including at the interfaces between urban settings and forests that are zoonotic arbovirus hotspots. We investigated Ae. albopictus colonization, adult dispersal and host feeding patterns in the anthropic-natural interface of three forested sites covering three biomes in Brazil in 2016. To evaluate whether an ecological overlap exists between Ae. albopictus and sylvatic yellow fever virus (YFV) in forests, we performed similar investigations in seven additional urban-forest interfaces where YFV circulated in 2017. We found Ae. albopictus in all forested sites. We detected eggs and adults up to 300 and 500 m into the forest, respectively, demonstrating that Ae. albopictus forest colonization and dispersal decrease with distance from the forest edge. Analysis of the host identity in blood-engorged females indicated that they fed mainly on humans and domestic mammals, suggesting rare contact with wildlife at the forest edge. Our results show that Ae. albopictus frequency declines as it penetrates into the forest and highlight its potential role as a bridge vector of zoonotic diseases at the edge of the Brazilian forests studied.