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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 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 -
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 -
Frontiers in Immunology 2023Parasitic nematodes responsible for filarial diseases cause chronic disablement in humans worldwide. Elimination programs have substantially reduced the rate of...
Parasitic nematodes responsible for filarial diseases cause chronic disablement in humans worldwide. Elimination programs have substantially reduced the rate of infection in certain areas, but limitations of current diagnostics for population surveillance have been pointed out and improved assays are needed to reach the elimination targets. While serological tests detecting antibodies to parasite antigens are convenient tools, those currently available are compromised by the occurrence of antibodies cross-reactive between nematodes, as well as by the presence of residual antibodies in sera years after treatment and clearance of the infection. We recently characterized the N-linked and glycosphingolipid derived glycans of the parasitic nematode and revealed the presence of various antigenic structures that triggered immunoglobulin G (IgG) responses in infected individuals. To address the specificity of IgG binding to these glycan antigens, we screened microarrays containing glycans with plasma from uninfected individuals and from individuals infected with , , and , four closely related filarial nematodes. IgG to a restricted subset of cross-reactive glycans was observed in infection plasmas from all four species. In plasma from and infected individuals, IgG binding to many more glycans was additionally detected, resulting in total IgG responses similar to the ones of infected individuals. For these infection groups, , and , we further studied the different IgG subclasses to glycans. In all three infections, IgG1 and IgG2 appeared to be the major subclasses involved in response to glycan antigens. Interestingly, in infected individuals, we observed a marked reduction in particular in IgG2 to parasite glycans post-treatment with anthelminthic, suggesting a promising potential for diagnostic applications. Thus, we compared the IgG response to a broad repertoire of glycans in individuals infected with various filarial nematodes. We identified broadly cross-reactive and more specific glycan targets, extending the currently scarce knowledge of filarial nematode glycosylation and host anti-glycan antibody response. We believe that our initial findings could be further exploited to develop disease-specific diagnostics as part of an integrated approach for filarial disease control.
Topics: Humans; Animals; Filariasis; Antibodies, Helminth; Brugia malayi; Antigens; Immunoglobulin G
PubMed: 36949937
DOI: 10.3389/fimmu.2023.1102344 -
Seizure Apr 2023Onchocerciasis-associated epilepsy (OAE) is an important but neglected public health problem in onchocerciasis-endemic areas with insufficient or inadequate... (Review)
Review
Onchocerciasis-associated epilepsy (OAE) is an important but neglected public health problem in onchocerciasis-endemic areas with insufficient or inadequate onchocerciasis control. Hence, there is a need for an internationally accepted, easy-to-use epidemiological case definition of OAE to identify areas of high Onchocerca volvulus transmission and disease burden requiring treatment and prevention interventions. By including OAE as a manifestation of onchocerciasis, we will considerably improve the accuracy of the overall onchocerciasis disease burden, which is currently underestimated. Hopefully, this will lead to increased interest and funding for onchocerciasis research and control interventions, notably the implementation of more effective elimination measures and treatment and support for affected individuals and their families.
Topics: Humans; Onchocerciasis; Nodding Syndrome; Epilepsy; Public Health; Cost of Illness; Prevalence
PubMed: 37023626
DOI: 10.1016/j.seizure.2023.03.024 -
Global Mental Health (Cambridge,... 2019Until recently, nodding syndrome (NS) was considered as a mysterious disease of unknown etiology. A link between onchocerciasis and epilepsy was suspected for a long... (Review)
Review
BACKGROUND
Until recently, nodding syndrome (NS) was considered as a mysterious disease of unknown etiology. A link between onchocerciasis and epilepsy was suspected for a long time. However, onchocerciasis was not considered as the cause of NS because NS was believed to occur only in onchocerciasis-endemic regions in Uganda, South Sudan, and Tanzania. In October 2015, with funding from the European Research Council, the NSETHIO group launched a trans-disciplinary, multi-country research project to identify the cause of NS and to study the link between onchocerciasis and epilepsy.
METHODS
We reviewed NSETHIO activities as well as all published papers, and compared project findings with results of previous research on NS.
RESULTS
Findings from the NSETHIO project showed that NS is only one of the clinical manifestations in the wide spectrum of onchocerciasis-associated epilepsy (OAE) that could be prevented by strengthening onchocerciasis elimination programs. NSETHIO demonstrated that OAE is an important neglected public health problem in onchocerciasis-endemic areas with no or a sub-optimally functioning onchocerciasis control strategies.
CONCLUSIONS
Today there is overwhelming evidence that NS together with the Nakalanga syndrome is clinical presentations of OAE, a condition that could be prevented by strengthening onchocerciasis elimination programs. While research needs to continue to elucidate the pathophysiological mechanisms causing NS, new strategies to accelerate onchocerciasis elimination coupled with community-based surveillance and treatment programs for epilepsy are urgently needed in areas of high transmission.
PubMed: 31807310
DOI: 10.1017/gmh.2019.24 -
Parasites & Vectors Nov 2021The onchocerciasis focus surrounding the lower Mbam and Sanaga rivers, where Onchocerca volvulus is transmitted by Simulium damnosum s.l. (Diptera: Simuliidae), was...
Onchocerca volvulus transmission in the Mbam valley of Cameroon following 16 years of annual community-directed treatment with ivermectin, and the description of a new cytotype of Simulium squamosum.
BACKGROUND
The onchocerciasis focus surrounding the lower Mbam and Sanaga rivers, where Onchocerca volvulus is transmitted by Simulium damnosum s.l. (Diptera: Simuliidae), was historically the largest in the southern regions of Cameroon. Annual community-directed treatment with ivermectin (CDTI) has been taking place since 2000, but recent studies have shown that new infections are occurring in children. We aimed to investigate blackfly biting and O. volvulus transmission rates along the lower Mbam river 16 years after the formal onset of annual CDTI.
METHODS
Black flies were collected for three consecutive days each month between July 2016 and June 2017 at two riverside villages and two inland sites situated 4.9 km and 7.9 km from the riverside. Specimens collected at each site were dissected on one of the three collection days each month to estimate parity rates and O. volvulus infection rates, while the remaining samples were preserved for pool screening.
RESULTS
In total, 93,573 S. damnosum s.l. black flies were recorded biting humans and 9281 were dissected. Annual biting rates of up to 606,370 were estimated at the riverside, decreasing to 20,540 at 7.9 km, while, based on dissections, annual transmission potentials of up to 4488 were estimated at the riverside, decreasing to 102 and 0 at 4.9 km and 7.9 km, respectively. However, pool screening showed evidence of infection in black flies at the furthest distance from the river. Results of both methods demonstrated the percentage of infective flies to be relatively low (0.10-0.36%), but above the WHO threshold for interruption of transmission. In addition, a small number of larvae collected during the dry season revealed the presence of Simulium squamosum E. This is the first time S. squamosum E has been found east of Lake Volta in Ghana, but our material was chromosomally distinctive, and we call it S. squamosum E2.
CONCLUSIONS
Relatively low O. volvulus infection rates appear to be offset by extremely high densities of biting black flies which are sustaining transmission along the banks of the lower Mbam river.
Topics: Animals; Cameroon; Female; Humans; Insect Control; Insect Vectors; Insecticides; Ivermectin; Male; Onchocerca volvulus; Onchocerciasis; Rural Health; Seasons; Simuliidae
PubMed: 34727965
DOI: 10.1186/s13071-021-05072-y -
Vaccines Jul 2023Onchocerciasis remains a debilitating neglected tropical disease. Due to the many challenges of current control methods, an effective vaccine against the causative agent...
Onchocerciasis remains a debilitating neglected tropical disease. Due to the many challenges of current control methods, an effective vaccine against the causative agent is urgently needed. Mice and cynomolgus macaque non-human primates (NHPs) were immunized with a vaccine consisting of a fusion of two protein antigens, -103 and -RAL-2 (-FUS-1), and three different adjuvants: Advax-CpG, alum, and AlT4. All vaccine formulations induced high antigen-specific IgG titers in both mice and NHPs. Challenging mice with L3 contained within subcutaneous diffusion chambers demonstrated that -FUS-1/Advax-CpG-immunized animals developed protective immunity, durable for at least 11 weeks. Passive transfer of sera, collected at several time points, from both mice and NHPs immunized with -FUS-1/Advax-CpG transferred protection to naïve mice. These results demonstrate that -FUS-1 with the adjuvant Advax-CpG induces durable protective immunity against in mice and NHPs that is mediated by vaccine-induced humoral factors.
PubMed: 37515028
DOI: 10.3390/vaccines11071212 -
Acta Tropica Jun 2021This review summarises more than a century of research on onchocerciasis, also known as river blindness, and its control. River blindness is an infection caused by the... (Review)
Review
This review summarises more than a century of research on onchocerciasis, also known as river blindness, and its control. River blindness is an infection caused by the tissue filaria Onchocerca volvulus affecting the skin, subcutaneous tissue and eyes and leading to blindness in a minority of infected persons. The parasite is transmitted by its intermediate hosts Simulium spp. which breed in rivers. Featured are history and milestones in onchocerciasis research and control, state-of-the-art data on the parasite, its endobacteria Wolbachia, on the vectors, previous and current prevalence of the infection, its diagnostics, the interaction between the parasite and its host, immune responses and the pathology of onchocerciasis. Detailed information is documented on the time course of control programmes in the afflicted countries in Africa and the Americas, a long road from previous programmes to current successes in control of the transmission of this infectious disease. By development, adjustment and optimization of the control measures, transmission by the vector has been interrupted in foci of countries in the Americas, in Uganda, in Sudan and elsewhere, followed by onchocerciasis eliminations. The current state and future perspectives for control, elimination and eradication within the next 20-30 years are described and discussed. This review contributes to a deeper comprehension of this disease by a tissue-dwelling filaria and it will be helpful in efforts to control and eliminate other filarial infections.
Topics: Animals; Humans; Insect Vectors; Onchocerciasis, Ocular; Prevalence
PubMed: 32857984
DOI: 10.1016/j.actatropica.2020.105677