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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 -
Journal of Special Operations Medicine... 2009
Topics: Africa South of the Sahara; Animals; Filaricides; Insect Vectors; Ivermectin; Onchocerca volvulus; Onchocerciasis; Simuliidae
PubMed: 19813355
DOI: No ID Found -
Cadernos de Saude Publica 2002Human onchocerciasis was recently discovered in Brazil among Yanomámi Indians living along the border region with Venezuela in the States of Amazonas and Roraima. The... (Review)
Review
Human onchocerciasis was recently discovered in Brazil among Yanomámi Indians living along the border region with Venezuela in the States of Amazonas and Roraima. The article reports on the history of the disease's discovery, its distribution, and incrimination of vector simuliid species. The literature that has been generated on the parasite, its vectors, and control of the disease is critically analyzed as well as the organization of epidemiological surveys and the control program developed by the Brazilian government and an international agency. Suggestions for future work are made.
Topics: Animals; Brazil; Disease Vectors; Humans; Indians, South American; Onchocerca; Onchocerca volvulus; Onchocerciasis; Simuliidae
PubMed: 12244349
DOI: 10.1590/s0102-311x2002000500009 -
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 -
Acta Tropica Sep 2023Simulium damnosum s.l., the most important vector of onchocerciasis in Africa, is a complex of sibling species described on the basis of differences in their larval... (Review)
Review
Simulium damnosum s.l., the most important vector of onchocerciasis in Africa, is a complex of sibling species described on the basis of differences in their larval polytene chromosomes. These (cyto) species differ in their geographical distributions, ecologies and epidemiological roles. In Togo and Benin, distributional changes have been recorded as a consequence of vector control and environmental changes (e.g. creation of dams, deforestation), with potential epidemiological consequences. We review the distribution of cytospecies in Togo and Benin and report changes observed from 1975 to 2018. The elimination of the Djodji form of S. sanctipauli in south-western Togo in 1988 seems to have had no long-term effects on the distribution of the other cytospecies, despite an initial surge by S. yahense. Although we report a general tendency for long-term stability in most cytospecies' distributions, we also assess how the cytospecies' geographical distributions have fluctuated and how they vary with the seasons. In addition to seasonal expansions of geographical ranges by all species except S. yahense, there are seasonal variations in the relative abundances of cytospecies within a year. In the lower Mono river, the Beffa form of S. soubrense predominates in the dry season but is replaced as the dominant taxon in the rainy season by S. damnosum s.str. Deforestation was previously implicated in an increase of savanna cytospecies in southern Togo (1975-1997), but our data had little power to support (or refute) suggestions of a continuing increase, partly because of a lack of recent sampling. In contrast, the construction of dams and other environmental changes including climate change seem to be leading to decreases in the populations of S. damnosum s.l. in Togo and Benin. If so, combined with the disappearance of the Djodji form of S. sanctipauli, a potent vector, plus historic vector control actions and community directed treatments with ivermectin, onchocerciasis transmission in Togo and Benin is much reduced compared with the situation in 1975.
Topics: Animals; Simuliidae; Seasons; Togo; Onchocerciasis; Benin; Insect Vectors
PubMed: 37339715
DOI: 10.1016/j.actatropica.2023.106970 -
Microbiology Spectrum Feb 2022Stress-associated dysbiosis of microbiome can have several configurations that, under an energy landscape conceptual framework, can change from one configuration to...
Stress-associated dysbiosis of microbiome can have several configurations that, under an energy landscape conceptual framework, can change from one configuration to another due to different alternating selective forces. It has been proposed-according to the Anna Karenina Principle-that in stressed individuals the microbiome are more dispersed (i.e., with a higher within-beta diversity), evidencing the grade of dispersion as indicator of microbiome dysbiosis. We hypothesize that although dysbiosis leads to different microbial communities in terms of beta diversity, these are not necessarily differently dispersed (within-beta diversity), but they form disrupted networks that make them less resilient to stress. To test our hypothesis, we select nutrient restriction (NR) stress that impairs host fitness but does not introduce overt microbiome selectors, such as toxic compounds and pathogens. We fed the polyphagous black soldier fly, , with two NR diets and a control full-nutrient (FN) diet. NR diets were dysbiotic because they strongly affected insect growth and development, inducing significant microscale changes in physiochemical conditions of the gut compartments. NR diets established new configurations of the gut microbiome compared to FN-fed guts but with similar dispersion. However, these new configurations driven by the deterministic changes induced by NR diets were reflected in rarefied, less structured, and less connected bacterial interactomes. These results suggested that while the dispersion cannot be considered a consistent indicator of the unhealthy state of dysbiotic microbiomes, the capacity of the community members to maintain network connections and stability can be an indicator of the microbial dysbiotic conditions and their incapacity to sustain the holobiont resilience and host homeostasis. Changes in diet play a role in reshaping the gut microbiome in animals, inducing dysbiotic configurations of the associated microbiome. Although studies have reported on the effects of specific nutrient contents on the diet, studies regarding the conditions altering the microbiome configurations and networking in response to diet changes are limited. Our results showed that nutrient poor diets determine dysbiotic states of the host with reduction of insect weight and size, and increase of the times for developmental stage. Moreover, the poor nutrient diets lead to changes in the compositional diversity and network interaction properties of the gut microbial communities. Our study adds a new component to the understanding of the ecological processes associated with dysbiosis, by disentangling consequences of diets on microbiome dysbiosis that is manifested with the disruption of microbiome networking properties rather than changes in microbiome dispersion and beta diversity.
Topics: Animal Feed; Animals; Bacteria; Biodiversity; Gastrointestinal Microbiome; Nutrients; Simuliidae
PubMed: 34985334
DOI: 10.1128/spectrum.01580-21 -
Waste Management (New York, N.Y.) Dec 2018Processing of biowaste with larvae of the black soldier fly, Hermetia illucens L. (Diptera: Stratiomyidae), is an emerging waste treatment technology. Larvae grown on... (Review)
Review
Processing of biowaste with larvae of the black soldier fly, Hermetia illucens L. (Diptera: Stratiomyidae), is an emerging waste treatment technology. Larvae grown on biowaste can be a relevant raw material for animal feed production and can therefore provide revenues for financially viable waste management systems. In addition, when produced on biowaste, insect-based feeds can be more sustainable than conventional feeds. Among others, the scalability of the technology will depend on the availability of large amounts of biowaste with a high process performance (e.g. bioconversion of organic matter to proteins and lipids) and microbial and chemical product safety. Currently, in contrast to other waste treatment technologies, such as composting or anaerobic digestion, the process performance is variable and the processes driving the decomposition of biowaste macronutrients, inactivation of microbes and fate of chemicals is poorly understood. This review presents the first summary of the most important processes involved in black soldier fly larvae (BSFL) treatment, based on the available knowledge concerning five well-studied fly species. This is a starting point to increase understanding regarding the processes of this technology, with the potential to increase its efficiency and uptake, and support the development of appropriate regulations. Based on this review, formulating different types of biowaste, e.g. to produce a diet with a similar protein content, a balanced amino acid profile and/or pre- and co-treatment of biowaste with beneficial microbes, has the potential to increase process performance. Following harvest, larvae require heat or other treatments for microbial inactivation and safety.
Topics: Animal Feed; Animals; Diptera; Larva; Nutrients; Simuliidae; Waste Management
PubMed: 30509593
DOI: 10.1016/j.wasman.2018.10.022 -
International Journal of Environmental... Jun 2022The components of blackfly (Diptera: Simuliidae) saliva secreted during feeding on humans and animals induce various pathological reactions manifested by skin lesions...
The components of blackfly (Diptera: Simuliidae) saliva secreted during feeding on humans and animals induce various pathological reactions manifested by skin lesions and systemic symptoms. In this study, we describe 43 cases of severe skin lesions induced by blackfly bites and analyze their potential causes. Based on the results of a survey of 418 patients, we identified periods with risk of blackfly attacks and their environmental determinants in the eastern part of the European Union. Especially strong inflammatory reactions after blackfly bites were reported in patients with concomitant cardiovascular diseases (mainly with venous insufficiency), metabolic diseases, and bacterial infections. Enhanced symptoms of simuliosis were also observed in other patients attacked by these insects only once or repeatedly. The greatest number of blackfly attacks in the study area is recorded from May to July, with a peak in June (38.73%) in the afternoon (37.10%) and evening (33.03%), when patients are in fields, forests, or their households. The case analysis indicates interactions of various factors in the development of severe inflammatory reactions in patients bitten by blackflies. Therefore, it is recommended that subjects exposed to the presence of blackflies during their work or rest should limit the length of their stay in a vulnerable environment during the highest seasonal and daily activity of these insects. It is also necessary to take measures to reduce the number of blackflies and popularize methods for prophylaxis of their attacks.
Topics: Animals; Bites and Stings; European Union; Humans; Simuliidae; Skin Diseases
PubMed: 35805269
DOI: 10.3390/ijerph19137610 -
Mitochondrial DNA. Part B, Resources 2022The complete mitochondrial genome of was sequenced and annotated, and its general features and base composition were analyzed. The mitogenome was 15,896 bp long,...
The complete mitochondrial genome of was sequenced and annotated, and its general features and base composition were analyzed. The mitogenome was 15,896 bp long, comprising 13 protein-coding genes, 22 transport RNA genes, 2 ribosomal RNA genes, and 1 control region. The phylogenetic relationships based on the concatenated nucleotide sequences of 17 metagenomes from families Chironomidae, Ceratopogonidae, and Simuliidae were reconstructed. According to the phylogenetic topologies, was closely related to ( + ) in the maximum likelihood tree.
PubMed: 36386026
DOI: 10.1080/23802359.2022.2122746 -
Frontiers in Immunology 2021In insects, a complex and effective immune system that can be rapidly activated by a plethora of stimuli has evolved. Although the main cellular and humoral mechanisms...
In insects, a complex and effective immune system that can be rapidly activated by a plethora of stimuli has evolved. Although the main cellular and humoral mechanisms and their activation pathways are highly conserved across insects, the timing and the efficacy of triggered immune responses can differ among different species. In this scenario, an insect deserving particular attention is the black soldier fly (BSF), (Diptera: Stratiomyidae). Indeed, BSF larvae can be reared on a wide range of decaying organic substrates and, thanks to their high protein and lipid content, they represent a valuable source of macromolecules useful for different applications (e.g., production of feedstuff, bioplastics, and biodiesel), thus contributing to the development of circular economy supply chains for waste valorization. However, decaying substrates bring the larvae into contact with different potential pathogens that can challenge their health status and growth. Although these life strategies have presumably contributed to shape the evolution of a sophisticated and efficient immune system in this dipteran, knowledge about its functional features is still fragmentary. In the present study, we investigated the processes underpinning the immune response to bacteria in larvae and characterized their reaction times. Our data demonstrate that the cellular and humoral responses in this insect show different kinetics: phagocytosis and encapsulation are rapidly triggered after the immune challenge, while the humoral components intervene later. Moreover, although both Gram-positive and Gram-negative bacteria are completely removed from the insect body within a few hours after injection, Gram-positive bacteria persist in the hemolymph longer than do Gram-negative bacteria. Finally, the activity of two key actors of the humoral response, i.e., lysozyme and phenoloxidase, show unusual dynamics as compared to other insects. This study represents the first detailed characterization of the immune response to bacteria of larvae, expanding knowledge on the defense mechanisms of this insect among Diptera. This information is a prerequisite to manipulating the larval immune response by nutritional and environmental factors to increase resistance to pathogens and optimize health status during mass rearing.
Topics: Animals; Bacteria; Immunity; Larva; Simuliidae
PubMed: 34867970
DOI: 10.3389/fimmu.2021.745160