-
Microorganisms Aug 2022Arthropods' vectors-those of a large variety of families, including Culicidae, Simuliidae, Psychodidae, Ixodidae, Agarsidae, Pulicidae, Glossinidae, Reduviidae, and...
Arthropods' vectors-those of a large variety of families, including Culicidae, Simuliidae, Psychodidae, Ixodidae, Agarsidae, Pulicidae, Glossinidae, Reduviidae, and Tabanidae [...].
PubMed: 36013973
DOI: 10.3390/microorganisms10081555 -
Research and Reports in Tropical... 2018Mansonellosis is a filarial disease caused by three species of filarial (nematode) parasites (, , and ) that use humans as their main definitive hosts. These parasites... (Review)
Review
Mansonellosis is a filarial disease caused by three species of filarial (nematode) parasites (, , and ) that use humans as their main definitive hosts. These parasites are transmitted from person to person by bloodsucking females from two families of flies (Diptera). Biting midges (Ceratopogonidae) transmit all three species of , but blackflies (Simuliidae) are also known to play a role in the transmission of in parts of Latin America. and are endemic in western, eastern, and central Africa, and is also present in the neotropical region from equatorial Brazil to the Caribbean coast. has a patchy distribution in Latin America and the Caribbean. Mansonellosis infections are thought to have little pathogenicity and to be almost always asymptomatic, but occasionally causing itching, joint pains, enlarged lymph glands, and vague abdominal symptoms. In Brazil, infections are also associated with corneal lesions. Diagnosis is usually performed by detecting microfilariae in peripheral blood or skin without any periodicity. There is no standard treatment at present for mansonellosis. The combination therapy of diethylcarbamazine plus mebendazole for microfilaremia is presently one of the most widely used, but the use of ivermectin has also been proven to be very effective against microfilariae. Recently, doxycycline has shown excellent efficacy and safety when used as an antimicrobial against endosymbiotic bacteria harbored by some strains of and . Diethylcarbamazine and ivermectin have been used effectively to treat infection. There are at present no estimates of the disease burden caused by mansonellosis, and thus its importance to many global health professionals and policy makers is presently limited to how it can interfere with diagnostic tools used in modern filarial disease control and elimination programs aimed at other species of filariae.
PubMed: 30050351
DOI: 10.2147/RRTM.S125750 -
Research and Reports in Tropical... 2021Mansonellosis is caused by three filarial parasite species from the genus that commonly produce chronic human microfilaraemias: and . The disease is widespread in... (Review)
Review
Mansonellosis is caused by three filarial parasite species from the genus that commonly produce chronic human microfilaraemias: and . The disease is widespread in Africa, the Caribbean and South and Central America, and although it is typically asymptomatic it has been associated with mild pathologies including leg-chills, joint-pains, headaches, fevers, and corneal lesions. No robust mansonellosis disease burden estimates have yet been made and the impact the disease has on blood bank stocks and the monitoring of other filarial diseases is not thought to be of sufficient public health importance to justify dedicated disease management interventions. Mansonellosis´s Ceratopogonidae and Simuliidae vectors are not targeted by other control programmes and because of their small size and out-door biting habits are unlikely to be affected by interventions targeting other disease vectors like mosquitoes. The ivermectin and mebendazole-based mass drug administration (iMDA and mMDA) treatment regimens deployed by the WHO´s Elimination of Neglected Tropical Diseases (ESPEN) programme and its forerunners have, however, likely impacted significantly on the mansonellosis disease burden, principally by reducing the transmission of in Africa. The increasingly popular plan of using iMDA to control malaria could also affect parasite prevalence and transmission in Latin America in the future. However, a potentially far greater mansonellosis disease burden impact is likely to come from short-course curative anti- therapeutics, which are presently being developed for onchocerciasis and lymphatic filariasis treatment. Even if the WHO´s ESPEN programme does not choose to deploy these drugs in MDA interventions, they have the potential to dramatically increase the financial and logistical feasibility of effective mansonellosis management. There is, thus, now a fresh and urgent need to better characterise the disease burden and eco-epidemiology of mansonellosis so that effective management programmes can be designed, advocated for and implemented.
PubMed: 34079424
DOI: 10.2147/RRTM.S274684 -
International Journal of Infectious... Mar 2021Nodding syndrome is one of several forms of onchocerciasis-associated epilepsy (OAE) seen among children in areas formerly hyperendemic for the transmission of... (Review)
Review
Nodding syndrome is one of several forms of onchocerciasis-associated epilepsy (OAE) seen among children in areas formerly hyperendemic for the transmission of Onchocerca volvulus. These forms of epilepsy are highly prevalent and clustered in certain villages located close to blackfly (Diptera: Simuliidae) breeding sites. OAE presents with a wide spectrum of seizures, including generalized tonic-clonic and head nodding seizures, impaired cognitive function, growth stunting and delayed puberty. In 2014, the present authors published a perspective paper in this journal which hypothesized that nodding syndrome may be caused by either a neurotropic virus transmitted by blackflies or an endosymbiont present within the O. volvulus parasite. Seven years later, this critical review presents progress in nodding syndrome research, and assesses whether it is still plausible that a neurotropic virus or endosymbiont could be the cause.
Topics: Animals; Biomedical Research; Humans; Nodding Syndrome; Onchocerca volvulus; Onchocerciasis; Prevalence
PubMed: 33556614
DOI: 10.1016/j.ijid.2021.02.006 -
Expert Review of Anti-infective Therapy Apr 2017Onchocerca volvulus infects in excess of 15 million people. The vectors are Simulium blackflies, varieties of which differ in their ecologies, behavior and vectorial... (Review)
Review
Onchocerca volvulus infects in excess of 15 million people. The vectors are Simulium blackflies, varieties of which differ in their ecologies, behavior and vectorial abilities. Control of the vectors and mass administrations of ivermectin have succeeded in reducing prevalences with elimination achieved in some foci, particularly in Central and southern America. In Africa, progress towards elimination has been less successful. Areas covered: Even with community directed treatment with ivermectin (CDTI), control has been difficult in African areas with initial prevalences in excess of 55%, especially if only annual treatments are dispensed. This is partly attributable to insufficient coverage, but the appearance of incipiently resistant non-responding parasites and lack of attention to vector biology in modeling and planning outcomes of intervention programmes have also played their parts, with recrudescence now appearing in some treated areas. Expert commentary: The biology of onchocerciasis is complex involving different vectors with differing abilities to transmit parasites, diverse pathologies related to geographical and parasite variations and endosymbionts in both parasite and vector. Modeling to predict epidemiological and control outcomes is addressing this complexity but more attention needs to be given to the vectors' roles to further understanding of where and when control measures will succeed.
Topics: Africa; Albendazole; Animals; Anthelmintics; Central America; Doxycycline; Humans; Insect Vectors; Insecticides; Ivermectin; Macrolides; Onchocerca volvulus; Onchocerciasis; Simuliidae; South America
PubMed: 28117596
DOI: 10.1080/14787210.2017.1286980 -
Frontiers in Immunology 2023Salivary glands from blood-feeding arthropods secrete several molecules that inhibit mammalian hemostasis and facilitate blood feeding and pathogen transmission. The...
BACKGROUND
Salivary glands from blood-feeding arthropods secrete several molecules that inhibit mammalian hemostasis and facilitate blood feeding and pathogen transmission. The salivary functions from , the main vector of Onchocerciasis in South America, remain largely understudied. Here, we have characterized a salivary protease inhibitor (Guianensin) from the blackfly .
MATERIALS AND METHODS
A combination of bioinformatic and biophysical analyses, recombinant protein production, in vitro and in vivo experiments were utilized to characterize the molecula mechanism of action of Guianensin. Kinetics of Guianensin interaction with proteases involved in vertebrate inflammation and coagulation were carried out by surface plasmon resonance and isothermal titration calorimetry. Plasma recalcification and coagulometry and tail bleeding assays were performed to understand the role of Guianensin in coagulation.
RESULTS
Guianensin was identified in the sialotranscriptome of adult flies and belongs to the Kunitz domain of protease inhibitors. It targets various serine proteases involved in hemostasis and inflammation. Binding to these enzymes is highly specific to the catalytic site and is not detectable for their zymogens, the catalytic site-blocked human coagulation factor Xa (FXa), or thrombin. Accordingly, Guianensin significantly increased both PT (Prothrombin time) and aPTT (Activated partial thromboplastin time) in human plasma and consequently increased blood clotting time . Guianensin also inhibited prothrombinase activity on endothelial cells. We show that Guianensin acts as a potent anti-inflammatory molecule on FXa-induced paw edema formation in mice.
CONCLUSION
The information generated by this work highlights the biological functionality of Guianensin as an antithrombotic and anti-inflammatory protein that may play significant roles in blood feeding and pathogen transmission.
Topics: Mice; Humans; Animals; Simuliidae; Hemostatics; Endothelial Cells; Hemostasis; Anti-Inflammatory Agents; Inflammation; Salivary Proteins and Peptides; Mammals
PubMed: 37469515
DOI: 10.3389/fimmu.2023.1163367 -
PLoS Neglected Tropical Diseases Mar 2022Onchocerciasis ("river blindness"), is a neglected tropical disease caused by the filarial nematode Onchocerca volvulus and transmitted to humans through repeated bites... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Onchocerciasis ("river blindness"), is a neglected tropical disease caused by the filarial nematode Onchocerca volvulus and transmitted to humans through repeated bites by infective blackflies of the genus Simulium. Moxidectin was approved by the United States Food and Drug Administration in 2018 for the treatment of onchocerciasis in people at least 12 years of age. The pharmacokinetics of orally administered moxidectin in 18- to 60-year-old men and women infected with Onchocerca volvulus were investigated in a single-center, ivermectin-controlled, double-blind, randomized, single-ascending-dose, ascending severity of infection study in Ghana.
METHODOLOGY/PRINCIPAL FINDINGS
Participants were randomized to either a single dose of 2, 4 or 8 mg moxidectin or ivermectin. Pharmacokinetic samples were collected prior to dosing and at intervals up to 12 months post-dose from 33 and 34 individuals treated with 2 and 4 mg moxidectin, respectively and up to 18 months post-dose from 31 individuals treated with 8 mg moxidectin. Moxidectin plasma concentrations were determined using high-performance liquid chromatography with fluorescence detection. Moxidectin plasma AUC0-∞ (2 mg: 26.7-31.7 days*ng/mL, 4 mg: 39.1-60.0 days*ng/mL, 8 mg: 99.5-129.0 days*ng/mL) and Cmax (2mg, 16.2 to17.3 ng/mL, 4 mg: 33.4 to 35.0 ng/mL, 8 mg: 55.7 to 74.4 ng/mL) were dose-proportional and independent of severity of infection. Maximum plasma concentrations were achieved 4 hours after drug administration. The mean terminal half-lives of moxidectin were 20.6, 17.7, and 23.3 days at the 2, 4 and 8 mg dose levels, respectively.
CONCLUSION/SIGNIFICANCE
We found no relationship between severity of infection (mild, moderate or severe) and exposure parameters (AUC0-∞ and Cmax), T1/2 and Tmax for moxidectin. Tmax, volume of distribution (V/F) and oral clearance (CL/F) are similar to those in healthy volunteers from Europe. From a pharmacokinetic perspective, moxidectin is an attractive long-acting therapeutic option for the treatment of human onchocerciasis.
Topics: Administration, Oral; Adolescent; Adult; Animals; Female; Humans; Ivermectin; Macrolides; Male; Middle Aged; Onchocerca volvulus; Onchocerciasis; Simuliidae; Young Adult
PubMed: 35333880
DOI: 10.1371/journal.pntd.0010005 -
Mitochondrial DNA. Part B, Resources 2022The complete mitochondrial genome of (Meigen 1818) was sequenced and annotated, and its general features and base composition were analyzed. The phylogenetic...
The complete mitochondrial genome of (Meigen 1818) was sequenced and annotated, and its general features and base composition were analyzed. The phylogenetic relationships of the families Chironomidae, Simuliidae, Sciaridae and Culicidae based on 25 metagenomes were reconstructed using maximum likelihood (ML) methods based on the concatenated nucleotide sequences, the phylogenetic analysis showed that belongs family Chironomidae, which is consistent with the traditional morphological classification.
PubMed: 35097216
DOI: 10.1080/23802359.2022.2029604 -
Toxics Jul 2022This study is the first to investigate the ingestion of microplastics (MPs), plasticizers, additives, and particles of micro-litter < 100 μm by larvae of Simuliidae...
This study is the first to investigate the ingestion of microplastics (MPs), plasticizers, additives, and particles of micro-litter < 100 μm by larvae of Simuliidae (Diptera) in rivers. Blackflies belong to a small cosmopolitan insect family whose larvae are present alongside river courses, often with a torrential regime, up to their mouths. Specimens of two species of blackfly larvae, Simulium equinum and Simulium ornatum, were collected in two rivers in Central Italy, the Mignone and the Treja. Small microplastics (SMPs, <100 μm), plasticizers, additives, and other micro-litter components, e.g., natural and non-plastic synthetic fibers (APFs) ingested by blackfly larvae were, for the first time, quantified and concurrently identified via MicroFTIR. The pretreatment allowed for simultaneous extraction of the ingested SMPs and APFs. Strong acids or strong oxidizing reagents and the application of temperatures well above the glass transition temperature of polyamide 6 and 6.6 (55−60 °C) were not employed to avoid further denaturation/degradation of polymers and underestimating the quantification. Reagent and procedural blanks did not show any SMPs or APFs. The method’s yield was >90%. Differences in the abundances of the SMPs and APFs ingested by the two species under exam were statistically significant. Additives and plasticizers can be specific to a particular polymer; thus, these compounds can be proxies for the presence of plastic polymers in the environment.
PubMed: 35878288
DOI: 10.3390/toxics10070383 -
Tropical Medicine & International... Feb 2015We aim to review the current epidemiology of nodding syndrome (NS) and discuss relevant gaps in research. NS and convulsive epilepsy of unknown aetiology are clustered... (Review)
Review
We aim to review the current epidemiology of nodding syndrome (NS) and discuss relevant gaps in research. NS and convulsive epilepsy of unknown aetiology are clustered within the same villages and families in onchocerciasis-endemic areas. They are therefore potentially different clinical expressions of the same disease. It has been difficult to perform full autopsies on NS patients who die in remote villages. Adequate fixation of tissue immediately after death is critical for the examination of brain tissue. Therefore, post-mortem transsphenoidal brain biopsies, performed immediately after death by trained nurses, will provide the best option for obtaining tissue for analysis. We suspect that certain blackflies in onchocerciasis-endemic areas may transmit a novel pathogen that could cause NS and epilepsy. This is supported by a recent drop in the number of new NS cases coinciding with vector control activities aimed at reducing blackfly populations in northern Uganda. We propose that metagenomic studies of human samples, blackflies and microfilariae are conducted to screen for pathogens, and that a clinical trial is planned to evaluate the impact of larviciding against NS and epilepsy epidemics.
Topics: Animals; Epilepsy, Generalized; Food Parasitology; Humans; Metagenomics; Nodding Syndrome; Onchocerciasis; Research; Simuliidae; Uganda
PubMed: 25348848
DOI: 10.1111/tmi.12421