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[
Comput Methods Programs Biomed,
1990]
ONCHOSIM is a computer program for modelling the transmission and control of the tropical parasitic disease onchocerciasis, or river blindness. It is developed in collaboration with the Onchocerciasis Control Programme in West Africa (OCP), and is used as a tool in the evaluation and planning of control operations. The model comprises a detailed description of the life history of the parasite Onchocerca volvulus and of its transmission from person to person by Simulium flies. The effects of different control strategies, based on larvicide application and chemotherapy (ivermectin), on the transmission and on the disease symptoms can be evaluated and predicted. In the program two simulation techniques are mixed. Stochastic microsimulation is used to calculate the life events of individual persons and inhabitant parasites, while the dynamics of the Simulium population and the development of the parasite in the flies are simulated deterministically. Output of ONCHOSIM conforms to the format in which data collected by the OCP are reported. This enables detailed checking of model specifications against empirical data. Output can also consist of summarizing key indices for the intensity of onchocerciasis infection, which is especially useful for comparing the effectivity of control strategies.
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Relini A, Airoldi C, Regonesi ME, Gatta E, Tortora P, Bonanomi M, Vertemara J, De Gioia L, Pellistri F, Visentin C, Natalello A, Penco A
[
Hum Mol Genet,
2017]
The protein ataxin-3 (ATX3) triggers an amyloid-related neurodegenerative disease when its polyglutamine stretch is expanded beyond a critical threshold. We formerly demonstrated that the polyphenol epigallocatechin-3-gallate (EGCG) could redirect amyloid aggregation of a full-length, expanded ATX3 (ATX3-Q55) towards non-toxic, soluble, SDS-resistant aggregates. Here, we have characterized other related phenol compounds, although smaller in size, i.e., (-)-epigallocatechin gallate (EGC), and gallic acid (GA). We analyzed the aggregation pattern of ATX3-Q55 and of the N-terminal globular Josephin domain (JD) by assessing the time course of the soluble protein, as well its structural features by FTIR and AFM, in the presence and the absence of the mentioned compounds. All of them redirected the aggregation pattern towards soluble, SDS-resistant aggregates. They also prevented the appearance of ordered side-chain hydrogen bonding in ATX3-Q55, which is the hallmark of polyQ-related amyloids. Molecular docking analyses on the JD highlighted three interacting regions, including the central, aggregation-prone one. All three compounds bound to each of them, although with different patterns. This might account for their capability to prevent amyloidogenesis. Saturation transfer difference NMR experiments also confirmed EGCG and EGC binding to monomeric JD. ATX3-Q55 pre-incubation with any of the three compound prevented its calcium-influx-mediated cytotoxicity towards neural cells. Finally, all the phenols significantly reduced toxicity in a transgenic Caenorhabditis elegans strain expressing an expanded ATX3. Overall, our results show that the three polyphenols act in a substantially similar manner. GA, however, might be more suitable for antiamyloid treatments due to its simpler structure and higher chemical stability.
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[
J Infect Dis,
1995]
Ivermectin is an effective drug for the treatment of human onchocerciasis, a disease caused by the parasitic filarial nematode Onchocerca volvulus. When humans are treated, the microfilariae normally found in the skin are rapidly and very nearly completely eliminated. Nonetheless, after a delay, microfilariae gradually reappear in the skin. This study is concerned with the causes of this delay. Hypotheses are tested by comparing the results of model calculations with skin microfilaria counts collected from 114 patients during a trial of five annual treatments in the focus area of Asubende, Ghana. The results obtained strongly suggest that annual treatment with ivermectin causes an irreversible decline in microfilariae production of approximately 30%/treatment. This result has important implications for public health strategies designed to eliminate onchocerciasis as a significant health hazard.
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[
J Med Entomol,
2004]
The relation between the number of microfilariae (mf) ingested by host-seeking vectors of human onchocerciasis and skin mf load is an important component of the population biology of Onchocerca volvulus, with implications for disease control and evaluation of the risk of transmission recrudescence. The microsimulation model ONCHOSIM has been used to assess such risk in the area of the Onchocerciasis Control Program (OCP) in West Africa, based on a strongly nonlinear relation between vector mf uptake and human mf skin density previously published. However, observed levels of recrudescence have exceeded predictions, warranting a recalibration of the model. To this end, we present the results of a series of fly-feeding experiments carried out in savanna and forest localities of West Africa. Flies belonging to Simulium damnosum s.s., S. sirbanum, S. soubrense, and S. leonense were fed on mf carriers and dissected to assess the number of ingested mf escaping imprisonment by the peritrophic matrix (the number of exo-peritrophic mf), a predictor of infective larval output. The method of instrumental variables was used to obtain (nearly) unbiased estimates of the parameters of interest, taking into account error in the measurement of skin mf density. This error is often neglected in these types of studies, making it difficult to ascertain the degree of density-dependence truly present in the relation between mf uptake and skin load. We conclude that this relation is weakly (yet significantly) nonlinear in savanna settings but indistinguishable from linearity in forest vectors. Exo-peritrophic mf uptake does not account for most of the density dependence in the transmission dynamics of the parasite as previously thought. The number of exo-mf in forest simuliids is at least five times higher than in the savanna vectors. Parasite abundance in human onchocerciasis is regulated by poorly known mechanisms operating mainly on other stages of the lifecycle.