The efficacy of rifampicin plus albendazole against river blindness (onchocerciasis) in Cameroon

2021 ◽  
Author(s):  
Samuel Wanji ◽  
Achim Hoerauf ◽  
Ute Klarmann-Schulz
Keyword(s):  
2017 ◽  
Vol 65 (12) ◽  
pp. 2026-2034 ◽  
Author(s):  
Martin Walker ◽  
Sébastien D S Pion ◽  
Hanwei Fang ◽  
Jacques Gardon ◽  
Joseph Kamgno ◽  
...  

2016 ◽  
Vol 113 (5) ◽  
pp. E644-E653 ◽  
Author(s):  
Nurit Degani-Katzav ◽  
Revital Gortler ◽  
Lilach Gorodetzki ◽  
Yoav Paas

The invertebrate glutamate-gated chloride-selective receptors (GluClRs) are ion channels serving as targets for ivermectin (IVM), a broad-spectrum anthelmintic drug used to treat human parasitic diseases like river blindness and lymphatic filariasis. The native GluClR is a heteropentamer consisting of α and β subunit types, with yet unknown subunit stoichiometry and arrangement. Based on the recent crystal structure of a homomeric GluClαR, we introduced mutations at the intersubunit interfaces where Glu (the neurotransmitter) binds. By electrophysiological characterization of these mutants, we found heteromeric assemblies with two equivalent Glu-binding sites at β/α intersubunit interfaces, where the GluClβ and GluClα subunits, respectively, contribute the “principal” and “complementary” components of the putative Glu-binding pockets. We identified a mutation in the IVM-binding site (far away from the Glu-binding sites), which significantly increased the sensitivity of the heteromeric mutant receptor to both Glu and IVM, and improved the receptor subunits’ cooperativity. We further characterized this heteromeric GluClR mutant as a receptor having a third Glu-binding site at an α/α intersubunit interface. Altogether, our data unveil heteromeric GluClR assemblies having three α and two β subunits arranged in a counterclockwise β-α-β-α-α fashion, as viewed from the extracellular side, with either two or three Glu-binding site interfaces.


Science ◽  
1993 ◽  
Vol 259 (5095) ◽  
pp. 593-593
Author(s):  
Eliot Marshall
Keyword(s):  

2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Rubén Santiago Nicholls ◽  
Sofía Duque ◽  
Luz Adriana Olaya ◽  
Myriam Consuelo López ◽  
Sol Beatriz Sánchez ◽  
...  

Nature ◽  
1987 ◽  
Vol 329 (6142) ◽  
pp. 752-752 ◽  
Author(s):  
David Lindley
Keyword(s):  
New Drug ◽  

2006 ◽  
Vol 24 (3) ◽  
pp. 176-180 ◽  
Author(s):  
Claes D. Enk
Keyword(s):  

2020 ◽  
Author(s):  
Melaine A. Kuenemann ◽  
Phyo Phyo Zin ◽  
Sravya Kuchibhotla ◽  
Denis Fourches

<p></p><p>Onchocerciasis (also known as river blindness<i>)</i> is a neglected tropical disease caused by the <i>Onchocerca volvulus</i> parasitic nematode. Currently, the only approved drug for treating this disease is ivermectin, which is a broad-spectrum antiparasitic agent. However, signs of resistance towards ivermectin have started to emerge. New therapeutic agents are thus urgently needed. The OvCHT1 chitinase enzyme from <i>O. volvulus</i> has been established as a relevant biological target for combatting river blindness. The veterinary anthelmintic drug closantel has been found to be a potent, micro-molar OvCHT1 inhibitor. Herein, we investigated the chemical space of closantel and all its synthesized analogues, focusing on the analysis of their potential binding modes towards OvCHT1. First, we conducted an unsupervised hierarchical clustering to group highly similar analogues and explore structure-activity relationships. Second, we conducted a structure-based molecular docking to predict and study the binding modes of all 57 closantel analogues in the active site of OvCHT1. Third, we screened more than 4 million lead-like compounds from the ZINC library to identify other structurally similar ligands that could potentially bind to OvCHT1. The cheminformatics analysis of the closantel analogues illustrated how minor structural changes in closantel analogues can impact their OvCHT1 activity.</p><p></p>


2021 ◽  
Author(s):  
Jean-Claude MAKENGA BOF ◽  
Paul MANSIANGI ◽  
Josué ZANGA ◽  
Félicien ILUNGA ◽  
Yves COPPIETERS

Abstract Background Onchocerciasis, a parasitic disease caused by the filarial worm Onchocerca volvulus transmitted through the bite of Simulium (black flies), is a cause of global concern, with the African population being majorly affected. This study focused on the bite rates, bite cycle, and transmission potential of Simulium damnosum s.l. in two sites with river blindness outbreaks in Kinshasa, DRC: Gombe (S1) and Mont-Ngafula at Kimwenza (S2). Methods From August 1, 2019, to July 31, 2020, we captured adult female black flies near breeding sites along the Congo River at S1 and Lukaya Valley at S2. Collections using human baits at the two sites were conducted for five days/month. Results A total of 6082 black flies of species Simulium squamosum (classified based on other entomological surveys) were captured during the study period. The daily cycle of aggression revealed two peaks: one between 8 and 9 a.m. and the other between 4 and 5 p.m. Low bite rates were observed between 11 a.m. and 1 p.m. The annual biting rate/person reached 13,463 in S1 and 23,638 in S2, with a total of 37,101 bites/person. The average daily biting rate, 37 ± 10 and 69 ± 23 bites/day/person in S1 and S2, respectively, did not differ significantly (P = 0.8901). The high density of the host population can disrupt the transmission of vector-borne diseases by diluting the transmission indices. There was no evidence of onchocerciasis transmission at the study sites because of inadequate laboratory facilities in the DRC. Various larval supports have been identified: at Gombe: aquatic plants, plastic bags, dead leaves, and rocks; at Kimwenza: Ledermaniella ledermanii (the most abundant species at the site), plastic bags, artificial waste, and aquatic plants. Conclusions The study provides further evidence for the need for alternative strategies to eliminate the parasite in the formerly hyper-endemic foci.


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