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Showing papers on "Vector (molecular biology) published in 2022"


Journal ArticleDOI
01 Feb 2022-Cell
TL;DR: Dynamo as discussed by the authors is an analytical framework that infers absolute RNA velocity, reconstructs continuous vector fields that predict cell fates, employs differential geometry to extract underlying regulations, and ultimately predicts optimal reprogramming paths and perturbation outcomes.

94 citations


Journal ArticleDOI
TL;DR: In this article , the authors discuss the biology, distribution, and life cycle, the blood-feeding process, and the Leishmania-sand fly interactions that govern parasite transmission, and highlight some outstanding questions that need to be answered for the complete understanding of parasite-vector-host interactions in leishmaniasis.
Abstract: Blood-sucking arthropods transmit a variety of human pathogens acting as disseminators of the so-called vector-borne diseases. Leishmaniasis is a spectrum of diseases caused by different Leishmania species, transmitted quasi worldwide by sand flies. However, whereas many laboratories focus on the disease(s) and etiological agents, considerably less study the respective vectors. In fact, information on sand flies is neither abundant nor easy to find; aspects including basic biology, ecology, and sand-fly-Leishmania interactions are usually reported separately. Here, we compile elemental information on sand flies, in the context of leishmaniasis. We discuss the biology, distribution, and life cycle, the blood-feeding process, and the Leishmania-sand fly interactions that govern parasite transmission. Additionally, we highlight some outstanding questions that need to be answered for the complete understanding of parasite-vector-host interactions in leishmaniasis.

39 citations


Journal ArticleDOI
TL;DR: This article presented an overview of pre-clinical and clinical data on recombinant viral vector vaccines and discussed the advantages and limitations of the different viral vector platforms, including DNA plasmid vaccines, mRNA vaccines, and recombinant virus vectors.
Abstract: Vaccines represent the single most cost-efficient and equitable way to combat and eradicate infectious diseases. While traditional licensed vaccines consist of either inactivated/attenuated versions of the entire pathogen or subunits of it, most novel experimental vaccines against emerging infectious diseases employ nucleic acids to produce the antigen of interest directly in vivo. These include DNA plasmid vaccines, mRNA vaccines, and recombinant viral vectors. The advantages of using nucleic acid vaccines include their ability to induce durable immune responses, high vaccine stability, and ease of large-scale manufacturing. In this review, we present an overview of pre-clinical and clinical data on recombinant viral vector vaccines and discuss the advantages and limitations of the different viral vector platforms.

37 citations


Journal ArticleDOI
TL;DR: This document proposes and discusses the aspects and steps of a holistic approach, referenced as the Circular Policy, for national and local IVM strategies to be effective and adaptable, capable of providing the optimum outcomes.
Abstract: Integrated Vector Management (IVM) has yielded exemplary results in combating and preventing vector-borne diseases (VBDs) and their vectors. It’s success and positive outcomes depend on the sound planning, implementation, enforcement, and validation of the locally adapted vector control efforts from the involved national sectors and stakeholders. Nevertheless, current realities create several implications impeding IVM’s performance. Hence, there is a need to adjust local IVM plans to several factors, such as (i) the rapidly changing and unpredictable environmental conditions (i.e., climate change, shift on species distribution, invasive species—Anopheles stephensi, Aedes aegypti and Ae. albopictus); (ii) the environmental impacts from human activities (i.e., fossil fuel use, food sources, industry, land use, urbanization and deforestation); (iii) changes in human demographics and the international movement of people (travelers and forcibly displaced persons due to conflicts and severe weather) increasing the risk of contracting and transmitting vector-borne diseases and shifting humanitarian emergencies and societal demands; (iv) the SARS-CoV2 pandemic outbreak and the implication on national public health systems; (v) the continuous flow of technological advancements and newly acquired knowledge; (vi) the realization of the strong link between planetary health and public health. Addressing these factors in IVM can become difficult, taking into consideration the numerous involved sectors, stakeholders, and fields in the management of vectors and vector-borne diseases (VBD). This document proposes and discusses the aspects and steps of a holistic approach, referenced as the Circular Policy, for national and local IVM strategies to be effective and adaptable, capable of providing the optimum outcomes.

36 citations


Journal ArticleDOI
TL;DR: This paper presented an overview of pre-clinical and clinical data on recombinant viral vector vaccines and discussed the advantages and limitations of the different viral vector platforms, including DNA plasmid vaccines, mRNA vaccines, and recombinant virus vectors.
Abstract: Vaccines represent the single most cost-efficient and equitable way to combat and eradicate infectious diseases. While traditional licensed vaccines consist of either inactivated/attenuated versions of the entire pathogen or subunits of it, most novel experimental vaccines against emerging infectious diseases employ nucleic acids to produce the antigen of interest directly in vivo. These include DNA plasmid vaccines, mRNA vaccines, and recombinant viral vectors. The advantages of using nucleic acid vaccines include their ability to induce durable immune responses, high vaccine stability, and ease of large-scale manufacturing. In this review, we present an overview of pre-clinical and clinical data on recombinant viral vector vaccines and discuss the advantages and limitations of the different viral vector platforms.

35 citations


Journal ArticleDOI
TL;DR: In this paper , the basic properties of an Ad vector, Ad vector induced innate immunity and immune responses to Ad vector-produced transgene products are described. And development of novel Ad vectors which can overcome the drawbacks of conventional Ad vector vaccines and clinical application of Ad vector vaccine to several infectious diseases are also discussed.

32 citations


Journal ArticleDOI
TL;DR: In this paper , Bhatt et al. reviewed the latest developments in both symbionts and gene drive-based methods, as well as distinctions and obstacles relating to these promising technologies.

24 citations


Journal ArticleDOI
TL;DR: In this article , the authors discuss the importance of these invasions in the context of broader challenges facing malaria control in Africa and argue against addressing it as an isolated problem, instead of tackling this vector species as a stand-alone threat.
Abstract: Abstract There are increasing reports of the Asian malaria mosquito, Anopheles stephensi invading and spreading in Eastern Africa. We discuss the importance of these invasions in the context of broader challenges facing malaria control in Africa and argue against addressing it as an isolated problem. Anopheles stephensi is only one of multiple biological threats facing malaria control in the region—and is itself an indication of wide-ranging weaknesses in vector surveillance and control programs. Expanded investigations are needed in both urban and rural areas, especially in countries serviced by the Indian Ocean trade routes, to establish the full extent and future trajectories of the problem. More importantly, instead of tackling this vector species as a stand-alone threat, affected countries should adopt more integrated and multi-sectorial initiatives that can sustainably drive and keep out malaria.

21 citations


Journal ArticleDOI
TL;DR: Most of the critical complications occur in patients who are treated with very high vector doses indicating that the use of more efficient AAV vectors to allow for dose sparing or giving smaller doses repeatedly, the latter in conjunction with antibody or B cell depleting measures, should be explored.
Abstract: Gene transfer using adeno-associated viral (AAV) vectors has made tremendous progress in the last decade and has achieved cures of debilitating diseases such as hemophilia A and B. Nevertheless, progress is still being hampered by immune responses against the AAV capsid antigens or the transgene products. Immunosuppression designed to blunt T cell responses has shown success in some patients but failed in others especially if they received very high AAV vectors doses. Although it was initially thought that AAV vectors induce only marginal innate responses below the threshold of systemic symptoms recent trials have shown that complement activation can results in serious adverse events. Dorsal root ganglia toxicity has also been identified as a complication of high vector doses as has severe hepatotoxicity. Most of the critical complications occur in patients who are treated with very high vector doses indicating that the use of more efficient AAV vectors to allow for dose sparing or giving smaller doses repeatedly, the latter in conjunction with antibody or B cell depleting measures, should be explored.

21 citations


Journal ArticleDOI
TL;DR: In this article , the dynamics of Malaria illness among human persons and vectors are examined in a MATLAB software, where the impact of the vector (mosquito) on disease transmission is also taken into account.
Abstract: Many fatal diseases spread through vertical transmission while some of them spread through horizontal transmission and others transmit through both modes of transmission. Horizontal transmission illnesses are usually carried by a vector, which might be an animal, a bird, or an insect. Plasmodium parasites that dwell in red blood cells produce malaria, an infectious illness. This parasite is mostly transmitted to humans via mosquitoes. The dynamics of Malaria illness among human persons and vectors are examined in this study. The impact of the vector (mosquito) on disease transmission is also taken into account. The problem is described using nonlinear ODEs that are then generalized using the Atangana–Baleanu fractional derivative. Some theoretical analyses such as existence and uniqueness and stability via Ulam–Hyres stability analysis and optimal control strategies have been done. The numerical solution has been achieved via a numerical technique by implementing MATLAB software. Results of fractional, as well as classical order, are portrayed through different graphs while some figures are displayed for the global asymptotical stability of the model. From the graphical results, it can be noticed that the control parameters drastically decrease the number of infected human and vector population which will off course minimize the spread of infection among the human population. In addition to that, from the graphical results, it also be noticed that our model is globally asymptomatically stable as the solution converges to its equilibrium. Moreover, the use of bednets and insecticides can reduce the spread of infection dramatically while the impact of medication and treatment on the control of infection is comparatively less.

20 citations


Journal ArticleDOI
TL;DR: In this paper , different approaches to improve Adeno-associated virus (AAV) vectors for gene therapy with a focus on AAV capsid selection and engineering, strategies to overcome anti-AAV immune response, and vector genome design are discussed.

Journal ArticleDOI
TL;DR: Results show that vectors originating from the same construct design that were manufactured by the rBV/Sf9 system produced a higher degree of truncated and unresolved species that those generated by pTx/HEK293 production, and shed new light on vector efficacy, safety, and how clinical vectors should be quantified and evaluated.
Abstract: In the past two decades, adeno-associated virus (AAV) vector manufacturing has made remarkable advancements to meet large-scale production demands for pre-clinical and clinical trials. In addition, AAV vectors have been extensively studied for their safety and efficacy. In particular, the presence of empty AAV capsids and particles containing "inaccurate" vector genomes in preparations have been a subject of concern. Several methods exist to separate empty capsids from full particles; but thus far, no single technique can produce vectors that are free of empty or intermediate (non-unit length) capsids. Unfortunately, the exact genome compositions of full, intermediate, and empty capsids remain largely unknown. In this work, we used AAV-Genome Population sequencing (AAV-GPseq) to explore the compositions of DNase-resistant, encapsidated vector genomes produced by two common production pipelines: plasmid transfection in human embryonic kidney cells (pTx/HEK293) and baculovirus expression vectors in Spodoptera frugiperda insect cells (rBV/Sf9). Intriguingly, our results show that vectors originating from the same construct design that were manufactured by the rBV/Sf9 system produced a higher degree of truncated and unresolved species that those generated by pTx/HEK293 production. We also demonstrate that empty particles purified by CsCl gradient ultracentrifugation are not truly empty, but are instead packaged with genomes comprised of a single truncated and/or unresolved inverted terminal repeat (ITR). Our data suggest that the frequency of these "mutated" ITRs correlate with the abundance of inaccurate genomes in all fractions. These surprising findings shed new light on vector efficacy, safety, and how clinical vectors should be quantified and evaluated.

Journal ArticleDOI
TL;DR: In this article , the authors explore how Plasmodium falciparum, the deadliest malaria parasite, associates with one of its most important natural mosquito hosts, Anopheles gambiae, and discuss the implications of these findings for parasite transmission and vector control strategies currently in development.

Journal ArticleDOI
TL;DR: In this article , the authors present the current knowledge about the pathogens including their astonishing ability to overcome various host immune responses, regarding the main vector in Europe Ixodes ricinus, and the disease caused by Borreliae.
Abstract: Beside mosquitoes, ticks are well-known vectors of different human pathogens. In the Northern Hemisphere, Lyme borreliosis (Eurasia, LB) or Lyme disease (North America, LD) is the most commonly occurring vector-borne infectious disease caused by bacteria of the genus Borrelia which are transmitted by hard ticks of the genus Ixodes. The reported incidence of LB in Europe is about 22.6 cases per 100,000 inhabitants annually with a broad range depending on the geographical area analyzed. However, the epidemiological data are largely incomplete, because LB is not notifiable in all European countries. Furthermore, not only differ reporting procedures between countries, there is also variation in case definitions and diagnostic procedures. Lyme borreliosis is caused by several species of the Borrelia (B.) burgdorferi sensu lato (s.l.) complex which are maintained in complex networks including ixodid ticks and different reservoir hosts. Vector and host influence each other and are affected by multiple factors including climate that have a major impact on their habitats and ecology. To classify factors that influence the risk of transmission of B. burgdorferi s.l. to their different vertebrate hosts as well as to humans, we briefly summarize the current knowledge about the pathogens including their astonishing ability to overcome various host immune responses, regarding the main vector in Europe Ixodes ricinus, and the disease caused by borreliae. The research shows, that a higher standardization of case definition, diagnostic procedures, and standardized, long-term surveillance systems across Europe is necessary to improve clinical and epidemiological data.

Journal ArticleDOI
TL;DR: Analysis of the available reports shows clear evidence of an increasing annual incidence of babesiosis across Europe in both humans and animals that is changing in line with similar increases in the incidence of other tick-borne diseases.
Abstract: There is now considerable evidence that in Europe, babesiosis is an emerging infectious disease, with some of the causative species spreading as a consequence of the increasing range of their tick vector hosts. In this review, we summarize both the historic records and recent findings on the occurrence and incidence of babesiosis in 20 European countries located in southeastern Europe (Bosnia and Herzegovina, Croatia, and Serbia), central Europe (Austria, the Czech Republic, Germany, Hungary, Luxembourg, Poland, Slovakia, Slovenia, and Switzerland), and northern and northeastern Europe (Lithuania, Latvia, Estonia, Iceland, Denmark, Finland, Sweden, and Norway), identified in humans and selected species of domesticated animals (cats, dogs, horses, and cattle). Recorded cases of human babesiosis are still rare, but their number is expected to rise in the coming years. This is because of the widespread and longer seasonal activity of Ixodes ricinus as a result of climate change and because of the more extensive use of better molecular diagnostic methods. Bovine babesiosis has a re-emerging potential because of the likely loss of herd immunity, while canine babesiosis is rapidly expanding in central and northeastern Europe, its occurrence correlating with the rapid, successful expansion of the ornate dog tick (Dermacentor reticulatus) populations in Europe. Taken together, our analysis of the available reports shows clear evidence of an increasing annual incidence of babesiosis across Europe in both humans and animals that is changing in line with similar increases in the incidence of other tick-borne diseases. This situation is of major concern, and we recommend more extensive and frequent, standardized monitoring using a “One Health” approach.

Journal ArticleDOI
TL;DR: The role of the immune system, its molecules, and responses in the establishment, development, and outcome of Leishmaniasis are discussed, focusing on innate immune cells and Leishmania major interactions.
Abstract: Leishmaniasis is a parasitic, widespread, and neglected disease that affects more than 90 countries in the world. More than 20 Leishmania species cause different forms of leishmaniasis that range in severity from cutaneous lesions to systemic infection. The diversity of leishmaniasis forms is due to the species of parasite, vector, environmental and social factors, genetic background, nutritional status, as well as immunocompetence of the host. Here, we discuss the role of the immune system, its molecules, and responses in the establishment, development, and outcome of Leishmaniasis, focusing on innate immune cells and Leishmania major interactions.

Journal ArticleDOI
01 Mar 2022-Biology
TL;DR: A countrywide spread of An.
Abstract: Simple Summary Climate change increases the suitability of some environments for the establishment of newly introduced insects and is a major driver for the spread of mosquitoes that transmit diseases. Anopheles stephensi is a disease vector mosquito that transmits malaria and is naturally endemic in Asia. This vector newly emerged in Africa (first report from Djibouti in 2012), where annual malaria infections and deaths are the highest worldwide. This mosquito has different ecology and behavior from previously known malaria vectors in Africa, which makes control difficult for local under-resourced health systems. Considering the capacity of this vector to transmit at least two malaria-causing parasites (Plasmodium falciparum and Plasmodium vivax), we investigated its distribution and population structure in Sudan and assessed the potential risk of its further spread into neighboring countries. Using morphological and genomic sequencing techniques, we confirmed the presence of Anopheles stephensi along the borders of six countries previously assumed as free, including Chad, Egypt, Eritrea, Libya, Republic of Central Africa, and South Sudan. African countries need to enhance vector surveillance and control services and utilize genomics tools for tracking the dynamics of invasive disease vectors. Abstract Anopheles stephensi is an invasive Asian malaria vector that initially emerged in Africa in 2012 and was reported in Sudan in 2019. We investigated the distribution and population structure of An. stephensi throughout Sudan by using sequencing and molecular tools. We confirmed the presence of An. stephensi in eight border-states, identifying both natural and human-made breeding sites. Our analysis revealed the presence of 20 haplotypes with different distributions per state. This study revealed a countrywide spread of An. stephensi in Sudan, with confirmed presence in borders states with Chad, Egypt, Eritrea, Ethiopia, Libya, Republic of Central Africa, and South Sudan. Detection of An. stephensi at points of entry with these countries, particularly Chad, Libya, and South Sudan, indicates the rapid previously undetected spread of this invasive vector. Our phylogenetic and haplotype analysis suggested local establishment and evolutionary adaptation of the vector to different ecological and environmental conditions in Sudan. Urgent engagement of the global community is essential to control and prevent further spread into Africa.

Journal ArticleDOI
22 Mar 2022-Ecology
TL;DR: The model predicts that the optimum temperature for transmission suitability is similar for the four mosquito–parasite combinations assessed in this study, but may differ at the thermal limits, and mapped risk to illustrate the number of months various areas in Africa and Asia predicted to be suitable for malaria transmission based on this suitability metric.
Abstract: Abstract Extrinsic environmental factors influence the spatiotemporal dynamics of many organisms, including insects that transmit the pathogens responsible for vector‐borne diseases (VBDs). Temperature is an especially important constraint on the fitness of a wide variety of ectothermic insects. A mechanistic understanding of how temperature impacts traits of ectotherms, and thus the distribution of ectotherms and vector‐borne infections, is key to predicting the consequences of climate change on transmission of VBDs like malaria. However, the response of transmission to temperature and other drivers is complex, as thermal traits of ectotherms are typically nonlinear, and they interact to determine transmission constraints. In this study, we assess and compare the effect of temperature on the transmission of two malaria parasites, Plasmodium falciparum and Plasmodium vivax, by two malaria vector species, Anopheles gambiae and Anopheles stephensi. We model the nonlinear responses of temperature dependent mosquito and parasite traits (mosquito development rate, bite rate, fecundity, proportion of eggs surviving to adulthood, vector competence, mortality rate, and parasite development rate) and incorporate these traits into a suitability metric based on a model for the basic reproductive number across temperatures. Our model predicts that the optimum temperature for transmission suitability is similar for the four mosquito–parasite combinations assessed in this study, but may differ at the thermal limits. More specifically, we found significant differences in the upper thermal limit between parasites spread by the same mosquito (A. stephensi) and between mosquitoes carrying P. falciparum. In contrast, at the lower thermal limit the significant differences were primarily between the mosquito species that both carried the same pathogen (e.g., A. stephensi and A. gambiae both with P. falciparum). Using prevalence data, we show that the transmission suitability metric ST calculated from our mechanistic model is consistent with observed P. falciparum prevalence in Africa and Asia but is equivocal for P. vivax prevalence in Asia, and inconsistent with P. vivax prevalence in Africa. We mapped risk to illustrate the number of months various areas in Africa and Asia predicted to be suitable for malaria transmission based on this suitability metric. This mapping provides spatially explicit predictions for suitability and transmission risk.

Journal ArticleDOI
TL;DR: The results indicated that increasing air travel and uncontrolled mosquito vector populations were mostly responsible for the population's decline in health, and studies on VBD prediction models should be included to aid practitioners and patients in making medical decisions.

Journal ArticleDOI
TL;DR: In this article , the feasibility and efficiency of the surgical approach and vector delivery in a nonhuman primate model was reported, where five rhesus macaques were injected with AAV1 or Anc80L65 expressing eGFP using a transmastoid posterior tympanotomy approach to access the round window membrane.
Abstract: Inner ear gene therapy using adeno-associated viral vectors (AAV) promises to alleviate hearing and balance disorders. We previously established the benefits of Anc80L65 in targeting inner and outer hair cells in newborn mice. To accelerate translation to humans, we now report the feasibility and efficiency of the surgical approach and vector delivery in a nonhuman primate model. Five rhesus macaques were injected with AAV1 or Anc80L65 expressing eGFP using a transmastoid posterior tympanotomy approach to access the round window membrane after making a small fenestra in the oval window. The procedure was well tolerated. All but one animal showed cochlear eGFP expression 7-14 days following injection. Anc80L65 in 2 animals transduced up to 90% of apical inner hair cells; AAV1 was markedly less efficient at equal dose. Transduction for both vectors declined from apex to base. These data motivate future translational studies to evaluate gene therapy for human hearing disorders.

Journal ArticleDOI
TL;DR: In this paper , the authors highlighted the effects of the COVID-19 pandemic, growing political instability and violence, and socioeconomic, demographic, and geographical inequalities on malaria burden.
Abstract: Global challenges and opportunities for malaria control were perfectly outlined in The Lancet Microbe's Editorial,1 emphasising the effects of the COVID-19 pandemic; growing political instability and violence; and socioeconomic, demographic, and geographical inequalities on malaria burden. Another serious threat to the global health effort in Africa is rapidly developing: the emergence and spread of the invasive malaria vector, Anopheles stephensi (An stephensi).2 An stephensi is a competent vector of Plasmodium vivax and Plasmodium falciparum and a probable vector of zoonotic malaria parasites (appendix p 1).

Journal ArticleDOI
TL;DR: In this article , an adenine base editor (ABE) using a compact Cas9 from Neisseria meningitidis (Nme2Cas9) was proposed.
Abstract: Base editors (BEs) have opened new avenues for the treatment of genetic diseases. However, advances in delivery approaches are needed to enable disease targeting of a broad range of tissues and cell types. Adeno-associated virus (AAV) vectors remain one of the most promising delivery vehicles for gene therapies. Currently, most BE/guide combinations and their promoters exceed the packaging limit (∼5 kb) of AAVs. Dual-AAV delivery strategies often require high viral doses that impose safety concerns. In this study, we engineered an adenine base editor (ABE) using a compact Cas9 from Neisseria meningitidis (Nme2Cas9). Compared with the well-characterized Streptococcus pyogenes Cas9-containing ABEs, ABEs using Nme2Cas9 (Nme2-ABE) possess a distinct protospacer adjacent motif (N4CC) and editing window, exhibit fewer off-target effects, and can efficiently install therapeutically relevant mutations in both human and mouse genomes. Importantly, we show that in vivo delivery of Nme2-ABE and its guide RNA by a single AAV vector can efficiently edit mouse genomic loci and revert the disease mutation and phenotype in an adult mouse model of tyrosinemia. We anticipate that Nme2-ABE, by virtue of its compact size and broad targeting range, will enable a range of therapeutic applications with improved safety and efficacy due in part to packaging in a single-vector system.

Journal ArticleDOI
TL;DR: In this article , the authors review how increased knowledge of microbial ecology and vector-host interactions is driving the emergence of new concepts and tools for vector and pathogen control and present anti-microbiota vaccines as a tool to manipulate the vector microbiota and interfere with the development of pathogens within their vectors.
Abstract: Human and animal pathogens that are transmitted by arthropods are a global concern, particularly those vectored by ticks (e.g. Borrelia burgdorferi and tick-borne encephalitis virus) and mosquitoes (e.g. malaria and dengue virus). Breaking the circulation of pathogens in permanent foci by controlling vectors using acaricide-based approaches is threatened by the selection of acaricide resistance in vector populations, poor management practices and relaxing of control measures. Alternative strategies that can reduce vector populations and/or vector-mediated transmission are encouraged worldwide. In recent years, it has become clear that arthropod-associated microbiota are involved in many aspects of host physiology and vector competence, prompting research into vector microbiota manipulation. Here, we review how increased knowledge of microbial ecology and vector-host interactions is driving the emergence of new concepts and tools for vector and pathogen control. We focus on the immune functions of host antibodies taken in the blood meal as they can target pathogens and microbiota bacteria within hematophagous arthropods. Anti-microbiota vaccines are presented as a tool to manipulate the vector microbiota and interfere with the development of pathogens within their vectors. Since the importance of some bacterial taxa for colonization of vector-borne pathogens is well known, the disruption of the vector microbiota by host antibodies opens the possibility to develop novel transmission-blocking vaccines.

Journal ArticleDOI
TL;DR: In this paper , a parallel, cluster-randomized controlled trial was conducted in Iquitos, Peru, to quantify the impact of a transfluthrin-based spatial repellent on human ABV infection.
Abstract: Over half the world's population is at risk for viruses transmitted by Aedes mosquitoes, such as dengue and Zika. The primary vector, Aedes aegypti, thrives in urban environments. Despite decades of effort, cases and geographic range of Aedes-borne viruses (ABVs) continue to expand. Rigorously proven vector control interventions that measure protective efficacy against ABV diseases are limited to Wolbachia in a single trial in Indonesia and do not include any chemical intervention. Spatial repellents, a new option for efficient deployment, are designed to decrease human exposure to ABVs by releasing active ingredients into the air that disrupt mosquito-human contact. A parallel, cluster-randomized controlled trial was conducted in Iquitos, Peru, to quantify the impact of a transfluthrin-based spatial repellent on human ABV infection. From 2,907 households across 26 clusters (13 per arm), 1,578 participants were assessed for seroconversion (primary endpoint) by survival analysis. Incidence of acute disease was calculated among 16,683 participants (secondary endpoint). Adult mosquito collections were conducted to compare Ae. aegypti abundance, blood-fed rate, and parity status through mixed-effect difference-in-difference analyses. The spatial repellent significantly reduced ABV infection by 34.1% (one-sided 95% CI lower limit, 6.9%; one-sided P value = 0.0236, z = 1.98). Aedes aegypti abundance and blood-fed rates were significantly reduced by 28.6 (95% CI 24.1%, ∞); z = -9.11) and 12.4% (95% CI 4.2%, ∞); z = -2.43), respectively. Our trial provides conclusive statistical evidence from an appropriately powered, preplanned cluster-randomized controlled clinical trial of the impact of a chemical intervention, in this case a spatial repellent, to reduce the risk of ABV transmission compared to a placebo.

Journal ArticleDOI
TL;DR: In this article , the authors identify the Mayaro virus (MAYV) infecting Aedes aegypti mosquitoes in Goiânia, the capital of state of Goiás, Brazil.

Journal ArticleDOI
TL;DR: In this paper , the authors presented a method based on deep learning of mid-infrared spectra of mosquito cuticle that simultaneously identifies the species and age class of three main malaria vectors in natural populations.
Abstract: The malaria parasite, which is transmitted by several Anopheles mosquito species, requires more time to reach its human-transmissible stage than the average lifespan of mosquito vectors. Monitoring the species-specific age structure of mosquito populations is critical to evaluating the impact of vector control interventions on malaria risk. We present a rapid, cost-effective surveillance method based on deep learning of mid-infrared spectra of mosquito cuticle that simultaneously identifies the species and age class of three main malaria vectors in natural populations. Using spectra from over 40, 000 ecologically and genetically diverse An. gambiae, An. arabiensis, and An. coluzzii females, we develop a deep transfer learning model that learns and predicts the age of new wild populations in Tanzania and Burkina Faso with minimal sampling effort. Additionally, the model is able to detect the impact of simulated control interventions on mosquito populations, measured as a shift in their age structures. In the future, we anticipate our method can be applied to other arthropod vector-borne diseases.

Journal ArticleDOI
TL;DR: The present review address and discuss the main targeting ligands used to functionalize liposomes for improving gene delivery with potential application in cancer treatment.
Abstract: Cancer is the second most frequent cause of death worldwide, with 28.4 million new cases expected for 2040. Despite de advances in the treatment, it remains a challenge because of the tumor heterogenicity and the increase in multidrug resistance mechanisms. Thus, gene therapy has been a potential therapeutic approach owing to its ability to introduce, silence, or change the content of the human genetic code for inhibiting tumor progression, angiogenesis, and metastasis. For the proper delivery of genes to tumor cells, it requires the use of gene vectors for protecting the therapeutic gene and transporting it into cells. Among these vectors, liposomes have been the nonviral vector most used because of their low immunogenicity and low toxicity. Furthermore, this nanosystem can have its surface modified with ligands (e.g., antibodies, peptides, aptamers, folic acid, carbohydrates, and others) that can be recognized with high specificity and affinity by receptor overexpressed in tumor cells, increasing the selective delivery of genes to tumors. In this context, the present review address and discuss the main targeting ligands used to functionalize liposomes for improving gene delivery with potential application in cancer treatment.

Journal ArticleDOI
TL;DR: In this paper , the authors review how increased knowledge of microbial ecology and vector-host interactions is driving the emergence of new concepts and tools for vector and pathogen control and present anti-microbiota vaccines as a tool to manipulate the vector microbiota and interfere with the development of pathogens within their vectors.
Abstract: Human and animal pathogens that are transmitted by arthropods are a global concern, particularly those vectored by ticks (e.g. Borrelia burgdorferi and tick-borne encephalitis virus) and mosquitoes (e.g. malaria and dengue virus). Breaking the circulation of pathogens in permanent foci by controlling vectors using acaricide-based approaches is threatened by the selection of acaricide resistance in vector populations, poor management practices and relaxing of control measures. Alternative strategies that can reduce vector populations and/or vector-mediated transmission are encouraged worldwide. In recent years, it has become clear that arthropod-associated microbiota are involved in many aspects of host physiology and vector competence, prompting research into vector microbiota manipulation. Here, we review how increased knowledge of microbial ecology and vector-host interactions is driving the emergence of new concepts and tools for vector and pathogen control. We focus on the immune functions of host antibodies taken in the blood meal as they can target pathogens and microbiota bacteria within hematophagous arthropods. Anti-microbiota vaccines are presented as a tool to manipulate the vector microbiota and interfere with the development of pathogens within their vectors. Since the importance of some bacterial taxa for colonization of vector-borne pathogens is well known, the disruption of the vector microbiota by host antibodies opens the possibility to develop novel transmission-blocking vaccines.

Journal ArticleDOI
TL;DR: In this paper , the authors compared three commonly used proxies of arboviral transmission, namely, the presence of virus in mosquito legs, in salivary glands (SG) and in saliva collected in capillary tubes using forced salivation, with direct transmission estimates from mosquitoes to suckling mice.
Abstract: Arthropod-borne viruses (arboviruses) impose a major health and economic burden on human populations globally, with mosquitoes serving as important vectors. Measuring the ability of a mosquito population to transmit an arbovirus is important in terms of evaluating its public health risk. In the laboratory, a variety of methods are used to estimate arboviral transmission by mosquitoes, including indirect methods involving viral detection from mosquito saliva collected by forced salivation. The accuracy of indirect methods to estimate arbovirus transmission to live animal hosts has not been fully evaluated.We compared three commonly used proxies of arboviral transmission, namely, the presence of virus in mosquito legs, in salivary glands (SG) and in saliva collected in capillary tubes using forced salivation, with direct transmission estimates from mosquitoes to suckling mice. We analyzed five vector-virus combinations, including Aedes aegypti infected with chikungunya virus, West Nile virus and Zika virus; Culex quinquefasciatus infected with West Nile virus; and Aedes triseriatus infected with La Crosse virus.Comparatively, the methods of detecting virus infection in mosquito legs and in SG were equally accurate in predicting transmission. Overall, the presence of virus in mosquito legs was a more accurate predictor of transmission than the commonly implemented viral detection method using forced salivation into a capillary tube, and was subject to less technical variation.These results suggest that, in general, forced salivation methods tend to underestimate virus transmission, and they provide confidence in the use of mosquito leg screens to evaluate the transmission potential of a mosquito population.

Journal ArticleDOI
TL;DR: In this paper , a review focusing on triatomine distributions and animal infections in the southern United States is presented. But the authors focus on the distribution of triatomines in the United States and not on the number of hosts involved in the transmission of the parasite.
Abstract: Chagas disease, a neglected tropical disease present in the Americas, is caused by the parasite Trypanosoma cruzi and is transmitted by triatomine kissing bug vectors. Hundreds of vertebrate host species are involved in the ecology of Chagas disease. The sylvatic nature of most triatomines found in the United States accounts for high levels of animal infections but few reports of human infections. This review focuses on triatomine distributions and animal infections in the southern United States. A quantitative synthesis of available US data from triatomine bloodmeal analysis studies shows that dogs, humans, and rodents are key taxa for feeding triatomines. Imperfect and unvalidated diagnostic tools for wildlife complicate the study of animal T. cruzi infections, and integrated vector management approaches are needed to reduce parasite transmission in nature. The diversity of animal species involved in Chagas disease ecology underscores the importance of a One Health approach for disease research and management.