Viral Metagenomics on Blood-Feeding Arthropods as a Tool for Human Disease Surveillance.

Surveillance and monitoring of viral pathogens circulating in humans and wildlife, together with the identification of emerging infectious diseases (EIDs), are critical for the prediction of future disease outbreaks and epidemics at an early stage. It is advisable to sample a broad range of vertebrates and invertebrates at different temporospatial levels on a regular basis to detect possible candidate viruses at their natural source. However, virus surveillance systems can be expensive, costly in terms of finances and resources and inadequate for sampling sufficient numbers of different host species over space and time. Recent publications have presented the concept of a new virus surveillance system, coining the terms "flying biological syringes", "xenosurveillance" and "vector-enabled metagenomics". According to these novel and promising surveillance approaches, viral metagenomics on engorged mosquitoes might reflect the viral diversity of numerous mammals, birds and humans, combined in the mosquitoes' blood meal during feeding on the host. In this review article, we summarize the literature on vector-enabled metagenomics (VEM) techniques and its application in disease surveillance in humans. Furthermore, we highlight the combination of VEM and "invertebrate-derived DNA" (iDNA) analysis to identify the host DNA within the mosquito midgut.

Ecologically and medically important black flies of the genus Simulium: Identification of biogeographical groups according to similar larval niches.

The black fly genus Simulium includes medically and ecologically important species, characterized by a wide variation of ecological niches largely determining their distributional patterns. In a rapidly changing environment, species-specific niche characteristics determine whether a species benefits or not. With aquatic egg, larval and pupal stages followed by a terrestrial adult phase, their spatial arrangements depend upon the interplay of aquatic conditions and climatic-landscape parameters in the terrestrial realm. The aim of this study was to enhance the understanding of the distributional patterns among Simulium species and their ecological drivers. In an ecological niche modelling approach, we focused on 12 common black fly species with different ecological requirements. Our modelling was based on available distribution data along with five stream variables describing the climatic, land-cover, and topographic conditions of river catchments. The modelled freshwater habitat suitability was spatially interpolated to derive an estimate of the adult black flies' probability of occurrence. Based on similarities in the spatial patterns of modelled habitat suitability we were able to identify three biogeographical groups, which allows us to confirm old assessments with current occurrence data: (A) montane species, (B) broad range species and (C) lowland species. The five veterinary and human medical relevant species Simulium equinum, S. erythrocephalum, S. lineatum, S. ornatum and S. reptans are mainly classified in the lowland species group. In the course of climatic changes, it is expected that biocoenosis will slightly shift towards upstream regions, so that the lowland group will presumably emerge as the winner. This is mainly explained by wider ecological niches, including a higher temperature tolerance and tolerance to various pollutants. In conclusion, these findings have significant implications for human and animal health. As exposure to relevant Simulium species increases, it becomes imperative to remain vigilant, particularly in investigating the potential transmission of pathogens.

The Others: A Systematic Review of the Lesser-Known Arboviruses of the Insular Caribbean.

The Caribbean enjoys a long-standing eminence as a popular tourist destination; however, over the years it has also amassed the sobriquet "arbovirus hotspot". As the planet warms and vectors expand their habitats, a cognizant working knowledge of the lesser-known arboviruses and the factors that influence their emergence and resurgence becomes essential. The extant literature on Caribbean arboviruses is spread across decades of published literature and is quite often difficult to access, and, in some cases, is obsolete. Here, we look at the lesser-known arboviruses of the insular Caribbean and examine some of the drivers for their emergence and resurgence. We searched the scientific literature databases PubMed and Google Scholar for peer-reviewed literature as well as scholarly reports. We included articles and reports that describe works resulting in serological evidence of the presence of arboviruses and/or arbovirus isolations in the insular Caribbean. Studies without serological evidence and/or arbovirus isolations as well as those including dengue, chikungunya, Zika, and yellow fever were excluded. Of the 545 articles identified, 122 met the inclusion criteria. A total of 42 arboviruses were identified in the literature. These arboviruses and the drivers that affect their emergence/resurgence are discussed.

On the use of inhibitors of 4-hydroxyphenylpyruvate dioxygenase as a vector-selective insecticide in the control of mosquitoes.

BACKGROUND: Blood-sucking insects incorporate many times their body weight of blood in a single meal. Because proteins are the major component of vertebrate blood, its digestion in the gut generates extremely high concentrations of free amino acids. Previous reports showed that the tyrosine degradation pathway plays an essential role in adapting these animals to blood feeding. Inhibition of 4-hydroxyphenylpyruvate dioxygenase (HPPD), the rate-limiting step of tyrosine degradation, results in the death of insects after a blood meal. Therefore, it has been suggested that compounds that block the catabolism of tyrosine could act selectively on blood-feeding insects. Here, we evaluated the toxicity against mosquitoes of three HPPD inhibitors currently used as herbicides and in human health. RESULTS: Of the compounds tested, nitisinone (NTBC) proved to be more potent than mesotrione (MES) and isoxaflutole (IFT) in Aedes aegypti. NTBC was lethal to Ae. aegypti in artificial feeding assays [median lethal dose (LD50 ): 4.53 µm] and in topical application (LD50 : 0.012 nmol/mosquito). NTBC was also lethal to Ae. aegypti populations that were resistant to neurotoxic insecticides, and to other mosquito species (Anopheles and Culex). CONCLUSION: HPPD inhibitors, particularly NTBC, represent promising new drugs for mosquito control. Because they affect only blood-feeding organisms, they represent a safer and more environmentally friendly alternative to conventional neurotoxic insecticides. © 2021 Society of Chemical Industry.

Arboviruses in Free-Ranging Birds and Hematophagous Arthropods (Diptera, Nematocera) from Forest Remnants and Urbanized Areas of an Environmental Protection Area in the Amazon Biome.

The rapid and disorderly urbanization in the Amazon has resulted in the insertion of forest fragments into cities, causing the circulation of arboviruses, which can involve hematophagous arthropods and free-ranging birds in the transmission cycles in urban environments. This study aimed to evaluate the circulation of arboviruses in free-ranging birds and hematophagous arthropods captured in an Environmental Protection Area in the Belem metropolitan area, Brazil. Birds were captured using mist nets, and hematophagous arthropods were collected using a human protected attraction technique and light traps. The birds' sera were subjected to a hemagglutination inhibition test to detect antibodies against 29 arbovirus antigens. Arthropod macerates were inoculated into C6/36 and VERO cell cultures to attempt viral isolation and were tested using indirect immunofluorescence, subsequent genetic sequencing and submitted for phylogenetic analysis. Four bird sera were positive for arbovirus, and one batch of Psorophora ferox was positive for Flavivirus on viral isolation and indirect immunofluorescence. In addition, the Ilheus virus was detected in the sequencing and phylogenetic analysis. The presence of antibodies in sera from free-ranging birds and the isolation of Ilheus virus in Psorophora ferox indicate the circulation of arboviruses in forest remnants in the urban center of Belem.

Depicting the RNA Virome of Hematophagous Arthropods from Belgrade, Serbia.

Hematophagous arthropods are important vectors for zoonotic pathogens. To date, a huge number of viruses have been identified in these arthropods, with a considerable proportion of them being human pathogens. However, the viromes of hematophagous arthropods are still largely unresearched. In this study, a number of arthropods were collected from Belgrade, Serbia including mosquitoes, ticks and bedbugs. The viromes of these arthropods were identified and characterized using Illumina MiSeq sequencing. In total, 21 viruses belonging to 11 families were characterized, with 11 of them representing novel species. These results may contribute to our knowledge of RNA viruses in arthropods and the discovery of novel human pathogens.

Who Bites Me? A Tentative Discriminative Key to Diagnose Hematophagous Ectoparasites Biting Using Clinical Manifestations.

Arthropod blood feeders are vectors of several human pathogenic agents, including viruses (e.g., yellow fever, chikungunya, dengue fever), parasites (e.g., malaria, leishmaniasis, lymphatic filariasis), or bacteria (e.g., plague). Besides their role as a vector of pathogens, their biting activities cause a nuisance to humans. Herein, we document clinical symptoms associated with the biting of ten clusters of hematophagous arthropods, including mosquitoes, biting midges and sandflies, lice, ticks, tsetse flies, blackflies, horse flies, fleas, triatomine and bed bugs. Within the framework of clinical history and entomo-epidemiological information, we propose a tentative discriminative key that can be helpful for practicing physicians in identifying hematophagous arthropods biting humans and delivering treatment for the associated clinical disorders.

Heme Oxygenase-1 Induction by Blood-Feeding Arthropods Controls Skin Inflammation and Promotes Disease Tolerance.

Hematophagous vectors lacerate host skin and capillaries to acquire a blood meal, resulting in leakage of red blood cells (RBCs) and inflammation. Here, we show that heme oxygenase-1 (HO-1), a pleiotropic cytoprotective isoenzyme that mitigates heme-mediated tissue damage, is induced after bites of sand flies, mosquitoes, and ticks. Further, we demonstrate that erythrophagocytosis by macrophages, including a skin-residing CD163+CD91+ professional iron-recycling subpopulation, produces HO-1 after bites. Importantly, we establish that global deletion or transient inhibition of HO-1 in mice increases inflammation and pathology following Leishmania-infected sand fly bites without affecting parasite number, whereas CO, an end product of the HO-1 enzymatic reaction, suppresses skin inflammation. This indicates that HO-1 induction by blood-feeding sand flies promotes tolerance to Leishmania infection. Collectively, our data demonstrate that HO-1 induction through erythrophagocytosis is a universal mechanism that regulates skin inflammation following blood feeding by arthropods, thus promoting early-stage disease tolerance to vector-borne pathogens.

DOPA decarboxylase is essential for cuticle tanning in Rhodnius prolixus (Hemiptera: Reduviidae), affecting ecdysis, survival and reproduction.

Cuticle tanning occurs in insects immediately after hatching or molting. During this process, the cuticle becomes dark and rigid due to melanin deposition and protein crosslinking. In insects, different from mammals, melanin is synthesized mainly from dopamine, which is produced from DOPA by the enzyme DOPA decarboxylase. In this work, we report that the silencing of the RpAadc-2 gene, which encodes the putative Rhodnius prolixus DOPA decarboxylase enzyme, resulted in a reduction in nymph survival, with a high percentage of treated insects dying during the ecdysis process or in the expected ecdysis period. Those treated insects that could complete ecdysis presented a decrease in cuticle pigmentation and hardness after molting. In adult females, the knockdown of AADC-2 resulted in a reduction in the hatching of eggs; the nymphs that managed to hatch failed to tan the cuticle and were unable to feed. Despite the failure in cuticle tanning, knockdown of the AADC-2 did not increase the susceptibility to topically applied deltamethrin, a pyrethroid insecticide. Additionally, our results showed that the melanin synthesis pathway did not play a major role in the detoxification of the excess (potentially toxic) tyrosine from the diet, an essential trait for hematophagous arthropod survival after a blood meal.

Hard ticks (Acari: Ixodidae) from Colombia, a review to its knowledge in the country / Garrapatas duras (acari: ixodidae) de colombia, una revisión a su conocimiento en el país

RESUMEN Las garrapatas son artrópodos de gran impacto sobre la economía pecuaria y la salud humana debido a las pérdidas generadas en la producción, y a su capacidad de transmitir microorganismos. Pese a la evidencia de circulación de una gran diversidad de garrapatas en Colombia, no se cuenta con compilaciones actualizadas de la variedad de especies presentes, por lo cual los autores presentan una revisión de literatura sobre las garrapatas de la familia Ixodidae reportadas en Colombia incluyendo su distribución geográfica, sus hospederos y los microorganismos reportados en aquellas especies registradas en este país. En la recopilación se evidenció la presencia en Colombia de diferentes especies de garrapatas de los géneros Amblyomma, Ixodes, Haemaphysalis, Rhipicephalus y Dermacentor. El género con mayor variedad fue Amblyomma con 29 especies, seguido de Ixodes con 11 especies, y de los géneros Dermacentor, Haemaphysalis y Rhipicephalus se reportaron dos especies para cada uno. Las especies se distribuyeron en la mayoría de los departamentos de Colombia y en una amplia diversidad de hospederos entre los cuales se incluyen animales domésticos, sinantrópicos y silvestres. Adicionalmente se encontró que algunas garrapatas reportadas podrían jugar un papel como vectores potenciales de diversos microorganismos que pueden afectar a la salud publica y veterinaria. Esperamos que este trabajo sea un aporte para apoyar la investigación en garrapatas y el estudio de los agentes transmitidos por estas en Colombia.

ABSTRACT Ticks are arthropods with significant impact on the economy of livestock and public health, due to losses generated in production, and their ability to transmit microorganisms. Despite the evidence of circulation of different tick species in the country, there are no updates concerning the variety of existing species, therefore, the authors of this manuscript offer a literature review on ticks from the Ixodidae family reported in Colombia including their geographical distribution, their hosts and the microorganisms they carry and might transmit in Colombia. In this manuscript, we described the presence in the country of different species of ticks of the genera Amblyomma, Ixodes, Haemaphysalis, Rhipicephalus, and Dermacentor. The genus with the greatest variety was Amblyomma with 29 species, followed by Ixodes with 11 species, and of the genus Dermacentor, Haemaphysalis and Rhipicephalus two species were reported for each. These species are distributed in most departments and a wide variety of hosts, including domestic, synanthropic and wild animals. Additionally, it was found that some reported ticks could play a role as potential vectors of various microorganisms that could affect public and veterinary health. We expect that this work will be a contribution to support tick research and the study of tick-borne agents in Colombia.

Arboviruses pathogenic for domestic and wild animals.

The objective of this chapter is to provide an updated and concise systematic review on taxonomy, history, arthropod vectors, vertebrate hosts, animal disease, and geographic distribution of all arboviruses known to date to cause disease in homeotherm (endotherm) vertebrates, except those affecting exclusively man. Fifty arboviruses pathogenic for animals have been documented worldwide, belonging to seven families: Togaviridae (mosquito-borne Eastern, Western, and Venezuelan equine encephalilitis viruses; Sindbis, Middelburg, Getah, and Semliki Forest viruses), Flaviviridae (mosquito-borne yellow fever, Japanese encephalitis, Murray Valley encephalitis, West Nile, Usutu, Israel turkey meningoencephalitis, Tembusu and Wesselsbron viruses; tick-borne encephalitis, louping ill, Omsk hemorrhagic fever, Kyasanur Forest disease, and Tyuleniy viruses), Bunyaviridae (tick-borne Nairobi sheep disease, Soldado, and Bhanja viruses; mosquito-borne Rift Valley fever, La Crosse, Snowshoe hare, and Cache Valley viruses; biting midges-borne Main Drain, Akabane, Aino, Shuni, and Schmallenberg viruses), Reoviridae (biting midges-borne African horse sickness, Kasba, bluetongue, epizootic hemorrhagic disease of deer, Ibaraki, equine encephalosis, Peruvian horse sickness, and Yunnan viruses), Rhabdoviridae (sandfly/mosquito-borne bovine ephemeral fever, vesicular stomatitis-Indiana, vesicular stomatitis-New Jersey, vesicular stomatitis-Alagoas, and Coccal viruses), Orthomyxoviridae (tick-borne Thogoto virus), and Asfarviridae (tick-borne African swine fever virus). They are transmitted to animals by five groups of hematophagous arthropods of the subphyllum Chelicerata (order Acarina, families Ixodidae and Argasidae-ticks) or members of the class Insecta: mosquitoes (family Culicidae); biting midges (family Ceratopogonidae); sandflies (subfamily Phlebotominae); and cimicid bugs (family Cimicidae). Arboviral diseases in endotherm animals may therefore be classified as: tick-borne (louping ill and tick-borne encephalitis, Omsk hemorrhagic fever, Kyasanur Forest disease, Tyuleniy fever, Nairobi sheep disease, Soldado fever, Bhanja fever, Thogoto fever, African swine fever), mosquito-borne (Eastern, Western, and Venezuelan equine encephalomyelitides, Highlands J disease, Getah disease, Semliki Forest disease, yellow fever, Japanese encephalitis, Murray Valley encephalitis, West Nile encephalitis, Usutu disease, Israel turkey meningoencephalitis, Tembusu disease/duck egg-drop syndrome, Wesselsbron disease, La Crosse encephalitis, Snowshoe hare encephalitis, Cache Valley disease, Main Drain disease, Rift Valley fever, Peruvian horse sickness, Yunnan disease), sandfly-borne (vesicular stomatitis-Indiana, New Jersey, and Alagoas, Cocal disease), midge-borne (Akabane disease, Aino disease, Schmallenberg disease, Shuni disease, African horse sickness, Kasba disease, bluetongue, epizootic hemorrhagic disease of deer, Ibaraki disease, equine encephalosis, bovine ephemeral fever, Kotonkan disease), and cimicid-borne (Buggy Creek disease). Animals infected with these arboviruses regularly develop a febrile disease accompanied by various nonspecific symptoms; however, additional severe syndromes may occur: neurological diseases (meningitis, encephalitis, encephalomyelitis); hemorrhagic symptoms; abortions and congenital disorders; or vesicular stomatitis. Certain arboviral diseases cause significant economic losses in domestic animals-for example, Eastern, Western and Venezuelan equine encephalitides, West Nile encephalitis, Nairobi sheep disease, Rift Valley fever, Akabane fever, Schmallenberg disease (emerged recently in Europe), African horse sickness, bluetongue, vesicular stomatitis, and African swine fever; all of these (except for Akabane and Schmallenberg diseases) are notifiable to the World Organisation for Animal Health (OIE, 2012).