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Bioorganic & Medicinal Chemistry Letters Aug 2017The Neglected Tropical Disease onchocerciasis is a parasitic disease. Despite many control programmes by the World Health Organization (WHO), large communities in West...
The Neglected Tropical Disease onchocerciasis is a parasitic disease. Despite many control programmes by the World Health Organization (WHO), large communities in West and Central Africa are still affected. Besides logistic challenges during biannual mass drug administration, the lack of a robust, point-of-care diagnostic is limiting successful eradication of onchocerciasis. Towards the implementation of a non-invasive and point-of-care diagnostic, we have recently reported the discovery of the biomarker N-acetyltyramine-O-glucuronide (NATOG) in human urine samples using a metabolomics-mining approach. NATOG's biomarker value was enhanced during an investigation in a rodent model. Herein, we further detail the specificity of NATOG in active onchocerciasis infections as well as the co-infecting parasites Loa loa and Mansonella perstans. Our results measured by liquid chromatography coupled with mass spectrometry (LC-MS) reveal elevated NATOG values in mono- and co-infection samples only in the presence of the nematode Onchocerca volvulus. Metabolic pathway investigation of l-tyrosine/tyramine in all investigated nematodes uncovered an important link between the endosymbiotic bacterium Wolbachia and O. volvulus for the biosynthesis of NATOG. Based on these extended studies, we suggest NATOG as a biomarker for tracking active onchocerciasis infections and provide a threshold concentration value of NATOG for future diagnostic tool development.
Topics: Animals; Biomarkers; Chromatography, Liquid; Glucuronides; Humans; Limit of Detection; Mass Spectrometry; Metabolomics; Neglected Diseases; Onchocerca volvulus; Onchocerciasis; Tyramine
PubMed: 28600214
DOI: 10.1016/j.bmcl.2017.05.082 -
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 -
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 -
BMJ (Clinical Research Ed.) Jan 2003
Review
Topics: Animals; Anti-Bacterial Agents; Doxycycline; Forecasting; Humans; Onchocerca volvulus; Onchocerciasis; Rickettsiaceae Infections; Wolbachia
PubMed: 12543839
DOI: 10.1136/bmj.326.7382.207 -
BMC Microbiology Jan 2021During the last two decades research on animal filarial parasites, especially Onchocerca ochengi, infecting cattle in savanna areas of Africa revealed that O. ochengi as...
BACKGROUND
During the last two decades research on animal filarial parasites, especially Onchocerca ochengi, infecting cattle in savanna areas of Africa revealed that O. ochengi as an animal model has biological features that are similar to those of O. volvulus, the aetiological agent of human onchocerciasis. There is, however, a paucity of biochemical, immunological and pathological data for O. ochengi. Galectins can be generated by parasites and their hosts. They are multifunctional molecules affecting the interaction between filarial parasites and their mammalian hosts including immune responses. This study characterized O. ochengi galectin, verified its immunologenicity and established its immune reactivity and that of Onchocerca volvulus galectin.
RESULTS
The phylogenetic analysis showed the high degree of identity between the identified O. ochengi and the O. volvulus galectin-1 (ß-galactoside-binding protein-1) consisting only in one exchange of alanine for serine. O. ochengi galectin induced IgG antibodies during 28 days after immunization of Wistar rats. IgG from O. ochengi-infected cattle and O. volvulus-infected humans cross-reacted with the corresponding galectins. Under the applied experimental conditions in a cell proliferation test, O. ochengi galectin failed to significantly stimulate peripheral blood mononuclear cells (PBMCs) from O. ochengi-infected cattle, regardless of their parasite load.
CONCLUSION
An O. ochengi galectin gene was identified and the recombinantly expressed protein was immunogenic. IgG from Onchocerca-infected humans and cattle showed similar cross-reaction with both respective galectins. The present findings reflect the phylogenetic relationship between the two parasites and endorse the appropriateness of the cattle O. ochengi model for O. volvulus infection research.
Topics: Animals; Cattle; Cloning, Molecular; Female; Galectins; Gene Expression Profiling; Helminth Proteins; Humans; Immunization; Immunoglobulin G; Leukocytes, Mononuclear; Onchocerca; Phylogeny; Rats; Rats, Wistar; Recombinant Proteins; Sequence Analysis, DNA
PubMed: 33407120
DOI: 10.1186/s12866-020-02064-3 -
Parasitology Research Apr 2018Onchocerca ochengi is a nodule-forming filarial nematode parasite of cattle. It is the closest known relative of the human parasite Onchocerca volvulus, with which it...
Onchocerca ochengi is a nodule-forming filarial nematode parasite of cattle. It is the closest known relative of the human parasite Onchocerca volvulus, with which it shares the black fly vector Simulium damnosum. Onchocerca sp. "Siisa" was described in black flies and in cattle and, based on limited mitochondrial sequence information, appeared to be about equally phylogenetically distant from O. ochengi and O. volvulus. Based on molecular genetic markers and apparent interbreeding, we later proposed that O. sp. "Siisa" belongs to the species O. ochengi. However, we did not demonstrate directly that the hybrids were fertile, and we were still unable to resolve the phylogenetic relationship of O. ochengi, O. sp. "Siisa," and O. volvulus, leaving some concerns with the conclusion mentioned above. Here, we present fully assembled, manually curated mitochondrial genomes of O. ochengi and O. sp. "Siisa," and we compare multiple individuals of these two taxa with respect to their whole mitochondrial and nuclear genomes. Based on the mitochondrial genomes, O. ochengi and O. sp. "Siisa" are phylogenetically much closer to each other than to O. volvulus. The differences between them are well within the range of what is expected for within-species variation. The nuclear genome comparison provided no indication of genetic separation of O. ochengi and O. sp. "Siisa." From this, in combination with the earlier literature, we conclude that O. ochengi and O. sp. "Siisa" should be considered one species.
Topics: Animals; Cattle; Cattle Diseases; Genome, Mitochondrial; Genome, Protozoan; Humans; Insect Vectors; Mitochondria; Onchocerca; Onchocerciasis; Phylogeny; Polymorphism, Single Nucleotide; Simuliidae; Skin
PubMed: 29404746
DOI: 10.1007/s00436-018-5783-0 -
The American Journal of Tropical... Oct 2020In the United States and Europe, human onchocerciasis is a rare disease caused by zoonotic or anthropophilic parasites in the genus . The zoonotic species identified in...
In the United States and Europe, human onchocerciasis is a rare disease caused by zoonotic or anthropophilic parasites in the genus . The zoonotic species identified in focal areas of Europe and United States is , and , the anthroponotic species, may be found among people who had lived in endemic areas of Africa, the Arabian Peninsula, or Latin America. Onchocerciasis due to is an emergent parasitic disease, with limited diagnostic methods, in addition to the lack of information on its biology, transmission, and epidemiology. Cutaneous nodules are the disease's most prevalent manifestation but lack diagnostic specificity. To address the diagnosis of onchocerciasis at reference laboratories, we developed a duplex TaqMan real-time PCR (qPCR) method, targeting the cytochrome oxidase subunit I locus which has species-specific probes to identify and differentiate from . . We determined the performance of the duplex with a panel of 45 samples: 11 positives for , six for , five samples with negative results for spp., and 23 non- nematodes. The duplex qPCR correctly detected 10 of 11 . - and six of six . -positive specimens. The new duplex assay allowed the simultaneous detection and discrimination of . and . in clinical specimens, expediting and facilitating the clinical diagnosis of . in non-endemic settings where the disease is an infrequent finding.
Topics: Animals; Diagnosis, Differential; Dog Diseases; Dogs; Humans; Onchocerca; Onchocerca volvulus; Onchocerciasis; Real-Time Polymerase Chain Reaction; Species Specificity; Zoonoses
PubMed: 32748784
DOI: 10.4269/ajtmh.20-0113 -
PLoS Neglected Tropical Diseases Aug 2023Previous studies have described the association of onchocerciasis (caused by Onchocerca volvulus) with epilepsy, including nodding syndrome, although a clear etiological...
Previous studies have described the association of onchocerciasis (caused by Onchocerca volvulus) with epilepsy, including nodding syndrome, although a clear etiological link is still missing. Cases are found in different African countries (Tanzania, South Sudan, Uganda, Democratic Republic of the Congo, Central African Republic and Cameroon). In our study we investigated immunological parameters (cytokine, chemokine, immunoglobulin levels) in individuals from the Mahenge area, Tanzania, presenting with either epilepsy or nodding syndrome with or without O. volvulus infection and compared them to O. volvulus negative individuals from the same endemic area lacking neurological disorders. Additionally, cell differentiation was performed using blood smears and systemic levels of neurodegeneration markers, leiomodin-1 and N-acetyltyramine-O, β-glucuronide (NATOG) were determined. Our findings revealed that cytokines, most chemokines and neurodegeneration markers were comparable between both groups presenting with epilepsy or nodding syndrome. However, we observed elevated eosinophil percentages within the O. volvulus positive epilepsy/nodding syndrome patients accompanied with increased eosinophilic cationic protein (ECP) and antigen-specific IgG levels in comparison to those without an O. volvulus infection. Furthermore, highest levels of NATOG were found in O. volvulus positive nodding syndrome patients. These findings highlight that the detection of distinct biomarkers might be useful for a differential diagnosis of epilepsy and nodding syndrome in O. volvulus endemic areas. Trial-registration: NCT03653975.
Topics: Animals; Humans; Onchocerciasis; Onchocerca volvulus; Nodding Syndrome; Intestinal Volvulus; Epilepsy; Uganda; Cytokines
PubMed: 37535695
DOI: 10.1371/journal.pntd.0011503 -
Tropical Biomedicine Mar 2020The nuisance bites of blackflies and transmission of Onchocerca volvulus, which causes onchocerciasis, constitutes a threat to public health and an impediment to food...
The nuisance bites of blackflies and transmission of Onchocerca volvulus, which causes onchocerciasis, constitutes a threat to public health and an impediment to food production in rural and riverine communities in Nigeria. The entomological profile of onchocerciasis at Adani, Nigeria, was investigated from August 2010 to January 2011 to determine the transmission of O. volvulus after 15 years of ivermectin distribution in the area. A total of 548 adult female blackflies of the Simulium damnosum complex were caught using human baits and dissected. Of this number, 248 flies were caught in the wet season (August to October), while 300 flies were caught in the dry season (November to January). The relative abundance of flies at Adani varied from 21 in December to 243 in January. The monthly catches between September and October and between December and January were significantly different. The monthly population density of the flies ranged from 0.5Flies/Man/Hour (FMH) in December to 5.5FMH in January. The diurnal biting pattern of the S. damnosum complex at the site showed a bimodal peak of activity with the evening peak being higher than the morning peak except in October when the morning peak was higher than the evening peak. The morning peaks were observed between 7.00 am and 10.00 am, whereas the evening peaks occurred between 4.00 pm and 6.00 pm. The morning and evening biting peaks in all the months were not significantly different. Nulliparous flies accounted for 75.7% of the total catch, whereas 24.3% of the flies caught were parous. The infection, infective bites and transmission of O. volvulus during the study period were zero. This study suggests that transmission of O. volvulus has been halted and the flies are presently more nuisance biters than disease vectors since no stage of O. volvulus was found in the flies dissected.
Topics: Animals; Female; Humans; Insect Bites and Stings; Insect Vectors; Ivermectin; Mass Drug Administration; Nigeria; Onchocerca volvulus; Onchocerciasis; Seasons; Simuliidae
PubMed: 33612728
DOI: No ID Found -
Acta Tropica May 2018The Mahenge Mountains onchocerciasis focus in south eastern Tanzania was historically one of the most heavily infected areas in the country. The vectors of Onchocerca...
The Mahenge Mountains onchocerciasis focus in south eastern Tanzania was historically one of the most heavily infected areas in the country. The vectors of Onchocerca volvulus are mainly Simulium damnosum complex blackflies, but a species of the Simulium neavei group may also contribute to transmission in some areas. The only detailed studies of parasite transmission in Mahenge were conducted in the late 1960s. The taxonomy of the S. damnosum complex has since been revised and onchocerciasis control through annual community directed treatment with ivermectin (CDTI) commenced in 1997. This study aimed to provide a cytogenetic and molecular update of the S. damnosum complex cytoforms present in Mahenge, and to evaluate the current status of O. volvulus transmission by blackflies following 19 years of annual CDTI. Rivers were surveyed to identify sites of S. damnosum s.l. breeding among the eastern slopes of the mountains, and human landing collections of adult female blackflies were made close to breeding sites. Identification of S. damnosum complex cytoforms was by cytotaxonomy of late-instar larvae and ITS1 amplicon size polymorphisms of larvae and adults. Adult blackflies were pool screened for O. volvulus infection using a triplex real-time PCR. The cytoforms 'Nkusi', Simulium kilibanum and 'Turiani' were found breeding in perennial rivers. 'Nkusi' and S. kilibanum were collected on human bait at 7/7 catch sites and possessed ITS1 profiles most closely resembling the molecular forms 'Nkusi J' and S. kilibanum 'T'. Whereas 'Turiani' was present in rivers, it was not collected on human bait and appears to be zoophilic. Simulium nyasalandicum was collected in low numbers on human bait at 3/7 catch sites. In total, 12,452 S. damnosum s.l. were pool screened and O. volvulus infection was detected in 97/104 pools of bodies and 51/104 pools of heads. The estimated percentage of S. damnosum s.l. carrying infective L3 stage parasites was 0.57% (95% CI 0.43%-0.74%). Onchocerca volvulus transmission by S. damnosum s.l. is continuing in the Mahenge Mountains after 19 years of annual CDTI. Infection rates appear similar to those reported in the 1960s, but a more detailed study is required to fully understand the epidemiological significance of the ongoing transmission. These results provide further evidence that annual CDTI may be insufficient to eliminate the parasite in formerly hyperendemic foci.
Topics: Adult; Animals; Breeding; Female; Humans; Insect Vectors; Ivermectin; Onchocerca volvulus; Onchocerciasis; Rivers; Simuliidae; Tanzania
PubMed: 29410302
DOI: 10.1016/j.actatropica.2018.01.009