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"river blindness"
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Chancey of the Maury River
After being abandoned, Chancey, an albino Appaloosa horse, finds a new home with Claire who needs him as much as he needs her, but as his eyesight deteriorates, he and Claire start anew as a therapeutic team.
Book
Patent infections with soil-transmitted helminths and Schistosoma mansoni are not associated with increased prevalence of antibodies to the Onchocerca volvulus peptide epitopes OvMP-1 and OvMP-23
Background
Ov16 serology is considered a reference method for
Onchocerca volvulus
epidemiological mapping. Given the suboptimal sensitivity of this test and the fact that seroconversion takes more than a year after infection, additional serological tests might be needed to guide onchocerciasis elimination programmes. Recently, two linear epitopes encoded in OvMP-1 and OvMP-23 peptides were introduced as serological markers, but the observed antibody cross-reactivity in samples originating from
Onchocerca volvulus
non-endemic areas required further investigation.
Methods
We evaluated both peptide markers in an
O. volvulus
hypo-endemic setting in Jimma Town, Ethiopia using peptide ELISA. For all individuals (
n
= 303), the infection status with soil-transmitted helminths and
Schistosoma mansoni
was known.
Results
We found that 11 (3.6%) individuals were positive for anti-Ov16 IgG4 antibodies, while 34 (11.2%) and 15 (5.0%) individuals were positive for OvMP-1 and OvMP-23, respectively. Out of the 34 OvMP-1 positive samples, 33 were negative on the Ov16 IgG4 ELISA. Similarly, out of the 15 OvMP-23 positive samples, 14 scored negative on this reference method. No difference in seroprevalence for all three markers could be observed between uninfected individuals and individuals infected with different soil-transmitted helminths or
S. mansoni
. Moreover, the intensity of the response to OvMP-1, OvMP-23 or Ov16 was not significantly stronger in individuals carrying patent STH or
S. mansoni
infections, nor was there any correlation between the intensities of the responses to the three different antigens.
Conclusions
This study demonstrates that a patent infection with either soil-transmitted helminths or
S. mansoni
does not lead to increased antibody recognition of both OvMP-1 and OvMP23.
Journal Article
Modelling the Spread of River Blindness Disease via the Caputo Fractional Derivative and the Beta-derivative
Information theory is used in many branches of science and technology. For instance, to inform a set of human beings living in a particular region about the fatality of a disease, one makes use of existing information and then converts it into a mathematical equation for prediction. In this work, a model of the well-known river blindness disease is created via the Caputo and beta derivatives. A partial study of stability analysis was presented. The extended system describing the spread of this disease was solved via two analytical techniques: the Laplace perturbation and the homotopy decomposition methods. Summaries of the iteration methods used were provided to derive special solutions to the extended systems. Employing some theoretical parameters, we present some numerical simulations.
Journal Article
Macrofilaricidal Efficacy of Repeated Doses of Ivermectin for the Treatment of River Blindness
Mass drug administration (MDA) with ivermectin is the cornerstone of efforts to eliminate human onchocerciasis by 2020 or 2025. The feasibility of elimination crucially depends on the effects of multiple ivermectin doses on Onchocerca volvulus. A single ivermectin (standard) dose clears the skin-dwelling microfilarial progeny of adult worms (macrofilariae) and temporarily impedes the release of such progeny by female macrofilariae, but a macrofilaricidal effect has been deemed minimal. Multiple doses of ivermectin may cumulatively and permanently reduce the fertility and shorten the lifespan of adult females. However, rigorous quantification of these effects necessitates interrogating longitudinal data on macrofilariae with suitably powerful analytical techniques.
Using a novel mathematical modeling approach, we analyzed, at an individual participant level, longitudinal data on viability and fertility of female worms from the single most comprehensive multiple-dose clinical trial of ivermectin, comparing 3-monthly with annual treatments administered for 3 years in Cameroon.
Multiple doses of ivermectin have a partial macrofilaricidal and a modest permanent sterilizing effect after 4 or more consecutive treatments, even at routine MDA doses (150 µg/kg) and frequencies (annual). The life expectancy of adult O. volvulus is reduced by approximately 50% and 70% after 3 years of annual or 3-monthly (quarterly) exposures to ivermectin.
Our quantification of macrofilaricidal and sterilizing effects of ivermectin should be incorporated into transmission models to inform onchocerciasis elimination efforts in Africa and residual foci in Latin America. It also provides a framework to assess macrofilaricidal candidate drugs currently under development.
Journal Article
Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity
Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.
Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.
This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations.
Journal Article
Modelling the impact of ivermectin on River Blindness and its burden of morbidity and mortality in African Savannah: EpiOncho projections
BACKGROUND: The African Programme for Onchocerciasis Control (APOC) has refocused its goals on the elimination of infection where possible, seemingly achievable by 15–17 years of annual mass distribution of ivermectin in some African foci. Previously, APOC had focused on the elimination of onchocerciasis as a public health problem. Timeframes have been set by the World Health Organization, the London Declaration on Neglected Tropical Diseases and the World Bank to achieve these goals by 2020–2025. METHODS: A novel mathematical model of the dynamics of onchocercal disease is presented which links documented associations between Onchocerca volvulus infection and the prevalence and incidence of morbidity and mortality to model outputs from our host age- and sex-structured onchocerciasis transmission framework (EpiOncho). The model is calibrated for African savannah settings, and used to assess the impact of long-term annual mass administration of ivermectin on infection and ocular and skin disease and to explore how this depends on epidemiological and programmatic variables. RESULTS: Current onchocerciasis disease projections, which do not account for excess mortality of sighted individuals with heavy microfilarial loads, underestimate disease burden. Long-term annual ivermectin treatment is highly effective at reducing both the morbidity and mortality associated with onchocerciasis, and this result is not greatly influenced by treatment coverage and compliance. By contrast, impact on microfilarial prevalence and intensity is highly dependent on baseline endemicity, treatment coverage and systematic non-compliance. CONCLUSIONS: The goals of eliminating morbidity and infection with ivermectin alone are distinctly influenced by epidemiological and programmatic factors. Whilst the former goal is most certainly achievable, reaching the latter will strongly depend on initial endemicity (the higher the endemicity, the greater the magnitude of inter-treatment transmission), advising caution when generalising the applicability of successful elimination outcomes to other areas. The proportion of systematic non-compliers will become far more influential in terms of overall success in achieving elimination goals.
Journal Article
Short- and Long-Range Dispersal by Members of the Simulium damnosum Complex (Diptera: Simuliidae), Vectors of Onchocerciasis: A Review
Blackfly members of the Simulium damnosum complex are major vectors of the parasite that causes onchocerciasis in Africa and Yemen, with other vector species involved in a few localized areas of Africa and in the Neotropics. Although the life cycle of these blackflies is linked to fast-flowing rivers, they can travel long distances (up to at least 500 km), calling into question how transmission zones are defined. Knowledge of the short- and long-range dispersal of these vectors could inform where control interventions and monitoring are necessary if targets for onchocerciasis elimination are to be met. Yet, research on blackfly dispersal has been limited and fragmented over the last 70 years. Here, we review the literature on the dispersal of onchocerciasis vectors, and we show the need for further research to establish how far larvae can travel downstream; the extent to which adults invade transmission zones; and whether adults migrate in a series of successive short movements or in single long-distance shifts, or use both methods.
Journal Article
Presumed Onchocerciasis Chorioretinitis Spilling over into North America, Europe and Middle East
Background: Newer generation ophthalmologists practicing in the developed world are not very familiar with some tropical ocular diseases due to the absence of reports in the ophthalmic literature over the past thirty years. Because of world globalization or due to influx of immigrants from sub-Saharan Africa, exotic retinal diseases are being encountered more often in ophthalmology clinics. Methods: A multicenter case series of chorioretinitis or optic neuritis with obscure etiology that used serial multimodal imaging. Results: Four cases qualified with the diagnosis of presumed ocular onchocerciasis based on their residence near fast rivers in endemic areas, multimodal imaging, long term follow-up showing progressive disease and negative workup for other diseases. Characteristic findings include peripapillary choroiditis with optic neuritis or atrophy, subretinal tracts of the microfilaria, progressive RPE atrophy around heavily pigmented multifocal chorioretinal lesions of varying shapes, subretinal white or crystalline dots, and response to ivermectin. Typical skin findings are often absent in such patients with chorioretinitis rendering the diagnosis more challenging. Conclusions: Familiarity with the myriad ocular findings of onchocerciasis, and a high-degree of suspicion in subjects residing in endemic areas can help in the correct diagnosis and implementation of appropriate therapy. Onchocercal chorioretinitis is a slow, insidious, progressive, and prolonged polymorphous disease.
Journal Article
Prediction and validation of the structural features of Ov58GPCR, an immunogenic determinant of Onchocerca volvulus
Onchocerciasis is a severely debilitating yet neglected tropical disease (NTD) that creates social stigma, generates and perpetuates poverty, and leads ultimately in some cases to irreversible unilateral or bilateral blindness if untreated. Consequently, the disease is a major impediment to socioeconomic development. Many control programs have been launched for the disease with moderate successes achieved. This mitigated hit is partially due to the lingering need for reliable, non-invasive and easily applicable tools for mapping endemic regions and post-elimination surveillance. In this work, bioinformatics analyses combined with immunological assays were applied in a bid to develop potential tools for diagnosis and assessing the success of drug treatment programs. We report that (i) the O. volvulus antigen, Ov58GPCR is a G-protein coupled receptor (GPCR) conserved in related nematodes, (ii) synthetic peptides predicted to be in the extracellular domain (ECD) of Ov58GPCR are indeed immunogenic epitopes in actively-infected individuals, (iii) synthetic peptide cocktails discriminate between actively-infected individuals, treated individuals and healthy African controls, (iv) polyclonal antibodies against one of the peptides or against the bacterially-expressed ECD reacted specifically with the native antigen of O. volvulus total and surface extracts, (v) Ov58GPCR is transcribed in both larvae and adult parasite stages, (vi) IgG and IgE responses to the recombinant ECD decline with ivermectin treatment. All these findings suggest that the extracellular domain and synthetic peptides of Ov58GPCR, as well as the specific immune response generated could be harnessed in the context of disease diagnosis and surveillance.
Journal Article
River-specific macrogenomic diversity in Simulium guianense s. l. (Diptera: Simuliidae), a complex of tropical American vectors associated with human onchocerciasis
Simulium guianense Wise is a Latin American vector complex of black flies associated with transmission of the causal agent of human onchocerciasis (river blindness). An analysis of the chromosomal banding patterns of 607 larvae of S. guianense s. l. revealed a high level of variation involving 83 macrogenomic rearrangements across 25 populations in Brazil, French Guiana, and Venezuela. The 25 populations were assigned to 13 cytoforms (A1, A2, B1-B4, C, D, E1-E4, and F), some of which are probably valid species. Based on geographical proximity, a member of the B group of cytoforms probably represents the name-bearing type specimen of S. guianense and the primary vector in the last-remaining onchocerciasis foci in the Western Hemisphere. Cytoform B3 in Amapá State is implicated as an anthropophilic simuliid in an area currently and historically free of onchocerciasis. Distributions of cytoforms are associated with geography, elevation, and drainage basin, and are largely congruent with ecoregions. Despite extraordinarily large larval populations of S. guianense s. l. in big rivers and consequent production of female flies for dispersal, the cytoforms maintain their chromosomal distinction within individual rivers, suggesting a high degree of fidelity to the specialized breeding habitats-rocky shoals-of the natal rivers.
Journal Article