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[
Infect Dis Poverty,
2016]
BACKGROUND: There is compelling evidence that not only do anti-filarials significantly reduce larval forms, but that host immune responses also contribute to the clearance of filarial parasites; however, the underlying mechanisms have not been fully elucidated. MAIN TEXT: Filarial infections caused by Wuchereria bancrofti and Brugia species (lymphatic filariasis) and Onchocerca volvulus (onchocerciasis) affect almost 200 million individuals worldwide and pose major public health challenges in endemic regions. Indeed, the collective disability-adjusted life years for both infections is 3.3 million. Infections with these thread-like nematodes are chronic and, although most individuals develop a regulated state, a portion develop severe forms of pathology. Mass drug administration (MDA) programmes on endemic populations focus on reducing prevalence of people with microfilariae, the worm's offspring in the blood, to less than 1 %. Although this has been successful in some areas, studies show that MDA will be required for longer than initially conceived. CONCLUSION: This paper highlights the mode of action of the various antifilarial treatment strategies and role of host immune response.
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[
WormBook,
2013]
Receptors of the Notch family mediate cell-cell interactions during animal development, and aberrations in Notch signaling have been implicated in human disease. Studies in Caenorhabdits elegans have made essential contributions towards understanding the biological roles and molecular mechanism of this fundamental signaling system. A major development in the field since the original version of this chapter (LIN-12/Notch signaling in C. elegans) has been an explosion in information about the structural biology of Notch signaling; crystallographic determinations of structures, including structures of C. elegans components, have contributed much to the current understanding of molecular mechanism. Thus, here, we not only cover the genetics of Notch in C. elegans, focusing on conserved core components and modulators, we have also included structural information about these components, describing the key events occurring during ligand binding and transcriptional control of target genes. In addition to text, we include Tables listing core components and key modulators of the signaling pathway along with their orthologs in Drosophila and mammals, a Table listing validated target genes in various processes in C. elegans, and animated features to illustrate structural attributes.
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[
Infect Dis Poverty,
2019]
BACKGROUND: Onchocerciasis (river blindness), caused by the filarial worm species Onchocerca volvulus, is a serious vector-borne neglected tropical disease (NTD) of public health and socioeconomic concern. It is transmitted through the bite of black flies of the genus Simulium, and manifested in dermal and ocular lesions. Ninety-nine percent of the total global risk and burden of onchocerciasis is in Africa. This scoping review examines the key challenges related to the elimination of onchocerciasis by 2020-2025 in Africa, and proposes recommendations to overcome the challenges and accelerate disease elimination. To find relevant articles published in peer-reviewed journals, a search of PubMed and Google Scholar databases was carried out. MAIN TEXT: Rigorous regional interventions carried out to control and eliminate onchocerciasis in the past four decades in Africa have been effective in bringing the disease burden under control; it is currently not a public health problem in most endemic areas. Notably, transmission of the parasite is interrupted in some hyperendemic localities. Recently, there has been a policy shift from control to complete disease elimination by 2020 in selected countries and by 2025 in the majority of endemic African countries. The WHO has published guidelines for stopping mass drug administration (MDA) and verifying the interruption of transmission and elimination of human onchocerciasis. Therefore, countries have revised their plans, established a goal of disease elimination in line with an evidence based decision to stop MDA and verify elimination, and incorporated it into their NTDs national master plans. Nevertheless, challenges remain pertaining to the elimination of onchocerciasis in Africa. The challenge we review in this paper are: incomplete elimination mapping of all transmission zones, co-endemicity of onchocerciasis and loiasis, possible emergence of ivermectin resistance, uncoordinated cross-border elimination efforts, conflict and civil unrest, suboptimal program implementation, and technical and financial challenges. This paper also proposes recommendations to overcome the challenges and accelerate disease elimination. These are: a need for complete disease elimination mapping, a need for collaborative elimination activities between national programs, a need for a different drug distribution approach in conflict-affected areas, a need for routine monitoring and evaluation of MDA programs, a need for implementing alternative treatment strategies (ATSs) in areas with elimination anticipated beyond 2025, and a need for strong partnerships and continued funding. CONCLUSIONS: National programs need to regularly monitor and evaluate the performance and progress of their interventions, while envisaging the complete elimination of onchocerciasis from their territory. Factors hindering the targeted goal of interruption of parasite transmission need to be identified and remedial actions should be taken. If possible and appropriate, ATSs need to be implemented to accelerate disease elimination by 2025.
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[
Phytomedicine,
2017]
BACKGROUND: Biofilms contribute to the pathogenesis of many chronic and difficult-to eradicate infections whose treatment is complicated due to the intrinsic resistance to conventional antibiotics. As a consequence, there is an urgent need for strategies that can be used for the prevention and treatment of biofilm-associated infections. The combination therapy comprising an antimicrobial drug with a low molecular weight (MW) natural product and an antimicrobial drug (antifungal or antibacterial) appeared as a good alternative to eradicate biofilms. PURPOSE: The aims of this review were to perform a literature search on the different natural products that have showed the ability of potentiating the antibiofilm capacity of antimicrobial drugs, to analyze which are the antimicrobial drugs most used in combination, and to have a look on the microbial species most used to prepare biofilms. RESULTS: Seventeen papers, nine on combinations against antifungal biofilms and eight against antibacterial biofilms were collected. Within the text, the following topics have been developed: breaf history of the discovery of biofilms; stages in the development of a biofilm; the most used methodologies to assess antibiofilm-activity; the natural products with capacity of eradicating biofilms when acting alone; the combinations of low MW natural products with antibiotics or antifungal drugs as a strategy for eradicating microbial biofilms and a list of the low MW natural products that potentiate the inhibition capacity of antifungal and antibacterial drugs against biofilms. CONCLUSIONS AND PERSPECTIVES: Regarding combinations against antifungal biofilms, eight over the nine collected works were carried out with in vitro studies while only one was performed with in vivo assays by using Caenorhabditis elegans nematode. All studies use biofilms of the Candida genus. A 67% of the potentiators were monoterpenes and sesquiterpenes and six over the nine works used FCZ as the antifungal drug. The activity of AmpB and Caspo was enhanced in one and two works respectively. Regarding combinations against bacterial biofilms, in vitro studies were performed in all works by using several different methods of higher variety than the used against fungal biofilms. Biofilms of both the gram (+) and gram (-) bacteria were prepared, although biofilm of Staphylococcus spp. were the most used in the collected works. Among the discovered potentiators of antibacterial drugs, 75% were terpenes, including mono, di- and triterpenes, and, among the atibacterial drugs, several structurally diverse types were used in the combinations: aminoglycosides, -lactams, glucopeptides and fluoroquinolones. The potentiating capacity of natural products, mainly terpenes, on the antibiofilm effect of antimicrobial drugs opens a wide range of possibilities for the combination antimicrobial therapy. More in vivo studies on combinations of natural products with antimicrobial drugs acting against biofilms are highly required to cope the difficult to treat biofilm-associated infections.