-
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 -
PLoS Neglected Tropical Diseases Jan 2019Benzimidazole anthelmintics have long been employed for the control of soil-transmitted helminth infections. Flubendazole (FBZ) was approved in 1980 for the treatment of... (Review)
Review
Benzimidazole anthelmintics have long been employed for the control of soil-transmitted helminth infections. Flubendazole (FBZ) was approved in 1980 for the treatment of gastrointestinal nematode infections in both veterinary and human medicine. It has also long been known that parenteral administration of FBZ can lead to high macrofilaricidal efficacy in a variety of preclinical models and in humans. As part of an effort to stimulate the discovery and development of new macrofilaricides, particularly for onchocerciasis, research has recently been devoted to the development of new formulations that would afford high oral bioavailability of FBZ, paving the way for potential clinical development of this repurposed drug for the treatment of human filariases. This review summarizes the background information that led to this program and summarizes some of the lessons learned from it.
Topics: Albendazole; Animals; Diethylcarbamazine; Elephantiasis, Filarial; Filaricides; Gastrointestinal Diseases; Humans; Ivermectin; Mebendazole; Microfilariae; Onchocerca volvulus; Onchocerciasis; Wuchereria bancrofti
PubMed: 30650160
DOI: 10.1371/journal.pntd.0006436 -
Parasite Epidemiology and Control May 2018, and are widespread helminth parasites in the tropics. Their distribution remains difficult to determine as it may change during national disease control programs and...
BACKGROUND
, and are widespread helminth parasites in the tropics. Their distribution remains difficult to determine as it may change during national disease control programs and with regional mass drug administration (MDA). Epidemiological surveys are of importance to evaluate the geographical distribution of these helminth parasites and the diseases they may cause, however, up to date epidemiological evaluations on and in Togo are rare, and surveys on are important especially under the aspect of MDA of ivermectin which is performed since decades.
METHODS
Dry blood samples ( = 924) were collected from rural populations in the Régions Central and Plateaux in Togo, and analyzed by parasite-specific real-time PCR and ELISA techniques.
RESULTS
Dry blood samples from 733 persons where investigated by real-time PCR tested for DNA of blood-circulating microfilaria, and a prevalence of 14.9% was detected. Distinct differences were observed between genders, positivity was higher in men increasing with age, and prevalence was highest in the Région Plateaux in Togo. IgG4 responses to antigen (OvAg) were studied in 924 persons and 59% were found positive. The distribution of parasite infestation between age and gender groups was higher in men increasing with age, and regional differences were detected being highest in the Région Plateaux. The diagnostic approach disclosed 64,5% positive IgG4 responses to infective third-stage larvae-specific antigen (SsL3Ag) in the surveyed regions. Antigen cross reactivity of SsL3Ag with parasite co-infections may limit the calculated prevalence. Singly IgG4 positive for SsL3Ag were 13.9%, doubly positive for OvAg and SsL3Ag were 35.5% and triply positive for , and were 9.9%.
CONCLUSIONS
Mansonelliasis, onchocerciasis and strongyloidiasis remain prevalent in the surveyed regions, yet with local differences. Our observations suggest that transmission of , may be ongoing. The degree of positive test results in the examined rural communities advocate for the continuation of MDA with ivermectin and albendazole, and further investigations should address the intensity of transmission of these parasites.
PubMed: 29774301
DOI: 10.1016/j.parepi.2018.03.001 -
PLoS Neglected Tropical Diseases Nov 2021The neglected tropical disease onchocerciasis, or river blindness, is caused by infection with the filarial nematode Onchocerca volvulus. Current estimates indicate that...
The neglected tropical disease onchocerciasis, or river blindness, is caused by infection with the filarial nematode Onchocerca volvulus. Current estimates indicate that 17 million people are infected worldwide, the majority of them living in Africa. Today there are no non-invasive tests available that can detect ongoing infection, and that can be used for effective monitoring of elimination programs. In addition, to enable pharmacodynamic studies with novel macrofilaricide drug candidates, surrogate endpoints and efficacy biomarkers are needed but are non-existent. We describe the use of a multimodal untargeted mass spectrometry-based approach (metabolomics and lipidomics) to identify onchocerciasis-associated metabolites in urine and plasma, and of specific lipid features in plasma of infected individuals (O. volvulus infected cases: 68 individuals with palpable nodules; lymphatic filariasis cases: 8 individuals; non-endemic controls: 20 individuals). This work resulted in the identification of elevated concentrations of the plasma metabolites inosine and hypoxanthine as biomarkers for filarial infection, and of the urine metabolite cis-cinnamoylglycine (CCG) as biomarker for O. volvulus. During the targeted validation study, metabolite-specific cutoffs were determined (inosine: 34.2 ng/ml; hypoxanthine: 1380 ng/ml; CCG: 29.7 ng/ml) and sensitivity and specificity profiles were established. Subsequent evaluation of these biomarkers in a non-endemic population from a different geographical region invalidated the urine metabolite CCG as biomarker for O. volvulus. The plasma metabolites inosine and hypoxanthine were confirmed as biomarkers for filarial infection. With the availability of targeted LC-MS procedures, the full potential of these 2 biomarkers in macrofilaricide clinical trials, MDA efficacy surveys, and epidemiological transmission studies can be investigated.
Topics: Animals; Biomarkers; Chromatography, Liquid; Female; Humans; Male; Mass Spectrometry; Onchocerca volvulus; Onchocerciasis; Plasma; Urine
PubMed: 34843471
DOI: 10.1371/journal.pntd.0009999 -
Nature Microbiology Nov 2016Ongoing elimination efforts have altered the global distribution of Onchocerca volvulus, the agent of river blindness, and further population restructuring is expected...
Ongoing elimination efforts have altered the global distribution of Onchocerca volvulus, the agent of river blindness, and further population restructuring is expected as efforts continue. Therefore, a better understanding of population genetic processes and their effect on biogeography is needed to support elimination goals. We describe O. volvulus genome variation in 27 isolates from the early 1990s (before widespread mass treatment) from four distinct locales: Ecuador, Uganda, the West African forest and the West African savanna. We observed genetic substructuring between Ecuador and West Africa and between the West African forest and savanna bioclimes, with evidence of unidirectional gene flow from savanna to forest strains. We identified forest:savanna-discriminatory genomic regions and report a set of ancestry informative loci that can be used to differentiate between forest, savanna and admixed isolates, which has not previously been possible. We observed mito-nuclear discordance possibly stemming from incomplete lineage sorting. The catalogue of the nuclear, mitochondrial and endosymbiont DNA variants generated in this study will support future basic and translational onchocerciasis research, with particular relevance for ongoing control programmes, and boost efforts to characterize drug, vaccine and diagnostic targets.
Topics: Africa, Western; Animals; Ecuador; Gene Flow; Genetic Variation; Genotype; Onchocerca volvulus; Phylogeography; Uganda; Wolbachia
PubMed: 27869792
DOI: 10.1038/nmicrobiol.2016.207 -
The Journal of the Louisiana State... 2015Several factors acting in concert now place US residents, returning travelers, and expatriates at risks of contracting ocular filariasis including increasing... (Review)
Review
Several factors acting in concert now place US residents, returning travelers, and expatriates at risks of contracting ocular filariasis including increasing seroprevalence rates of zoonotic filariasis, international travel bringing tourists to and expatriates from filariasis-endemic regions, and warming temperatures extending distribution ranges of arthropod vectors. To describe the epidemiology and outcomes of ocular filariasis and to recommend strategies for the diagnosis, management, and prevention of ocular filariasis, internet search engines were queried with the key words in order to examine case reports and series of ocular filariasis in the US and elsewhere. Descriptive epidemiological, morphological, and molecular evidence now support increasing cases of ocular filariasis in domestic and wild animals and humans, with most cases caused by filarial worms including Dirofilaria repens and other zoonotic Dirofilaria species and Onchocerca lupi and other zoonotic Onchocerca species. Clinicians should maintain early suspicion of ocular filariasis in US residents, returning travelers, and expatriates who complain of combinations of red eye, eye pain, foreign body sensation, reduced visual acuity, and migrating ocular worms, even without significant peripheral eosinophilia or microfilaremia. Microfilariae of Wuchereria bancrofti, Brugia malayi, and O. volvulus may traverse the eye, but can usually be treated medically. Mobile adult worms trapped in the subconjunctiva or anterior chamber should be removed by ophthalmologists to permit species identification, prevent posterior uveitis and iritis, and stop worm migration into the posterior chamber which could require lens removal and vitrectomy for worm extraction causing further eye damage.
Topics: Animals; Brugia malayi; Eye Infections, Parasitic; Filariasis; Humans; Microfilariae; Onchocerca volvulus; Seroepidemiologic Studies; Transients and Migrants; Travel; United States; Wuchereria bancrofti
PubMed: 27159510
DOI: No ID Found -
Trends in Parasitology Mar 2018A high prevalence of epilepsy has been observed in onchocerciasis-endemic regions with high onchocerciasis transmission. Recent epidemiological studies suggest that... (Review)
Review
A high prevalence of epilepsy has been observed in onchocerciasis-endemic regions with high onchocerciasis transmission. Recent epidemiological studies suggest that Onchocerca volvulus infection is the trigger causing the seizures, which appear in previously healthy children between the ages of 3 and 18 years. Persons with onchocerciasis-associated epilepsy present with a wide spectrum of seizures, including atonic and myoclonic neck seizures; but also absences and most frequently generalized tonic-clonic seizures. Often individuals present with intellectual disabilities and psychiatric disorders and occasionally with 'Nakalanga' features such as severe stunting with delayed or absent external signs of sexual development. Onchocerciasis-associated epilepsy, because of its importance as a public health problem, is an additional reason for strengthening onchocerciasis elimination programs.
Topics: Animals; Disease Eradication; Epilepsy; Humans; Onchocerca volvulus; Onchocerciasis; Seizures
PubMed: 29288080
DOI: 10.1016/j.pt.2017.11.009 -
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 -
Pathogens (Basel, Switzerland) Mar 2020We investigated urinary N-acetyltyramine-O,β-glucuronide (NATOG) levels as a biomarker for active infection in an onchocerciasis-endemic area in the Democratic...
We investigated urinary N-acetyltyramine-O,β-glucuronide (NATOG) levels as a biomarker for active infection in an onchocerciasis-endemic area in the Democratic Republic of Congo with a high epilepsy prevalence. Urinary NATOG was measured in non-epileptic men with and without infection, and in infected persons with epilepsy (PWE). Urinary NATOG concentration was positively associated with microfilarial density ( < 0.001). The median urinary NATOG concentration was higher in PWE (3.67 µM) compared to men without epilepsy (1.74 µM), = 0.017; and was higher in persons with severe (7.62 µM) compared to mild epilepsy (2.16 µM); = 0.008. Non-epileptic participants with and without infection had similar NATOG levels (2.23 µM and 0.71 µM, = 0.426). In a receiver operating characteristic curve analysis to investigate the diagnostic value of urinary NATOG, the area under the curve was 0.721 (95% CI: 0.633-0.797). Using the previously proposed cut-off value of 13 µM to distinguish between an active infection and an uninfected state, the sensitivity was 15.9% and the specificity 95.9%. In conclusion, an infection is associated with an increased urinary NATOG concentration, which correlates with the individual parasitic load. However, the NATOG concentration has a low discriminating power to differentiate between infected and uninfected individuals.
PubMed: 32151038
DOI: 10.3390/pathogens9030191 -
PLoS Neglected Tropical Diseases Oct 2014The bacterium Wolbachia (order Rickettsiales) is probably the world's most successful vertically-transmitted symbiont, distributed among a staggering 40% of terrestrial... (Review)
Review
The bacterium Wolbachia (order Rickettsiales) is probably the world's most successful vertically-transmitted symbiont, distributed among a staggering 40% of terrestrial arthropod species. Wolbachia has great potential in vector control due to its ability to manipulate its hosts' reproduction and to impede the replication and dissemination of arboviruses and other pathogens within haematophagous arthropods. In addition, the unexpected presence of Wolbachia in filarial nematodes of medical and veterinary importance has provided an opportunity to target the adult worms of Wuchereria bancrofti, Onchocerca volvulus, and Dirofilaria immitis with safe drugs such as doxycycline. A striking feature of Wolbachia is its phenotypic plasticity between (and sometimes within) hosts, which may be underpinned by its ability to integrate itself into several key processes within eukaryotic cells: oxidative stress, autophagy, and apoptosis. Importantly, despite significant differences in the genomes of arthropod and filarial Wolbachia strains, these nexuses appear to lie on a continuum in different hosts. Here, we consider how iron metabolism may represent a fundamental aspect of host homeostasis that is impacted by Wolbachia infection, connecting disparate pathways ranging from the provision of haem and ATP to programmed cell death, aging, and the recycling of intracellular resources. Depending on how Wolbachia and host cells interact across networks that depend on iron, the gradient between parasitism and mutualism may shift dynamically in some systems, or alternatively, stabilise on one or the other end of the spectrum.
Topics: Animals; Apoptosis; Arthropods; Autophagy; Heme; Homeostasis; Humans; Iron; Oxidative Stress; Wolbachia
PubMed: 25329055
DOI: 10.1371/journal.pntd.0003224