Phenotypic Evidence of Emerging Ivermectin Resistance in Onchocerca volvulus

Osei-Atweneboana, Mike Y.; Awadzi, K.; Attah, Simon K.; Boakye, Daniel; Gyapong, John; Prichard, Roger K.

doi:10.1371/journal.pntd.0000998

Cited by 273 publications

(242 citation statements)

References 24 publications

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“…These diseases affect more than 150 million individuals with over 1 billion people at risk for infection (10,11). No new classes of drugs directly targeting filariae with good efficacy and safety profiles have been developed in over 20 y, and suboptimal response/emerging resistance to currently used antifilarial drugs is apparent (12,13).…”

mentioning

confidence: 99%

Interdomain lateral gene transfer of an essential ferrochelatase gene in human parasitic nematodes

Novelli

Jiang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Lateral gene transfer events between bacteria and animals highlight an avenue for evolutionary genomic loss/gain of function. Herein, we report functional lateral gene transfer in animal parasitic nematodes. Members of the Nematoda are heme auxotrophs, lacking the ability to synthesize heme; however, the human filarial parasite Brugia malayi has acquired a bacterial gene encoding ferrochelatase (BmFeCH), the terminal step in heme biosynthesis. BmFeCH, encoded by a 9-exon gene, is a mitochondrial-targeted, functional ferrochelatase based on enzyme assays, complementation, and inhibitor studies. Homologs have been identified in several filariae and a nonfilarial nematode. RNAi and ex vivo inhibitor experiments indicate that BmFeCH is essential for viability, validating it as a potential target for filariasis control.

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mentioning

confidence: 99%

Interdomain lateral gene transfer of an essential ferrochelatase gene in human parasitic nematodes

Novelli

Jiang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Some macrofilaricidal effect might occur though, if ivermectin is combined with the broad-spectrum albendazole [50]. Despite ivermectin's remarkable effect against microfilariae, a suboptimal response has been recently reported in Asubende area of Ghana [51].…”

Section: Interrupting Transmission Of Lymphatic Filariasismentioning

confidence: 99%

Filarial hydrocele: a neglected condition of a neglected tropical disease

Otabil¹,

Tenkorang²

2015

J Infect Dev Ctries

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Filarial hydrocele is the most common chronic manifestation of lymphatic filariasis (LF) and poses a major public health burden to several filarial endemic countries. This review highlights the socio-economic impact of the disease, the role of the immune system in hydrocele development, current diagnostic approaches, and the control and management of filarial hydrocele. In the quest to facilitate the global effort to eliminate filarial hydrocele as a neglected tropical disease, a more comprehensive understanding of the mechanisms underlying the pathogenesis and development of the condition is important. In general, success has been achieved using annual treatment with ivermectin, but much remains to be done, particularly with late-stage infected individuals where surgery remains the only option. Studies have successfully demonstrated that inhibition of embryogenesis in adult female worms occurs after weeks of tetracycline treatment. Even more intriguing was the observation that the Wolbachia endosymbionts potently induce proinflammatory cytokines such as tumor necrosis factors (TNFs) and vascular endothelial growth factors (VEGFs), which are crucial for the development of filarial hydrocele. Furthermore, reports from human studies show that doxycycline treatment significantly ameliorates filarial hydrocele and markedly reverses early-stage filarial hydrocele. However, with the enormous challenges that face LF elimination such as global funding, logistics, civil wars, and drug resistance, a more relentless and collective approach from local governments as well as other stakeholders is needed to accelerate the fight against filarial hydrocele if the goal to eliminate it by 2020 is be to achieved.

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“…However, the insect has to blood-feed on a treated subject (i.e. patient compliance is a parameter to consider), and resistances to ivermectin have been already documented [88].…”

Section: Antimalarial Drug Delivery To Mosquitoesmentioning

confidence: 99%

Polyamidoamine Nanoparticles as Nanocarriers for the Drug Delivery to Malaria Parasite Stages in the Mosquito Vector

Urbán

Ranucci

Fernàndez‐Busquets

2015

Nanomedicine (Lond.)

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SummaryMalaria is arguably one of the main medical concerns worldwide because of the numbers of people affected, the severity of the disease and the complexity of the life cycle of its causative agent, the protist Plasmodium spp. With the advent of nanoscience, renewed hopes have appeared of finally obtaining the long sought-after magic bullet against malaria in the form of a nanovector for the targeted delivery of antimalarial compounds exclusively to Plasmodium-infected cells, thus increasing drug efficacy and minimizing the induction of resistance to newly developed therapeutic agents. Poly(amidoamine) (PAA)-derived nanovectors combine into a single chemical structure drug encapsulating capacity, antimalarial activity, low unspecific toxicity, specific targeting to Plasmodium, optimal in vivo activity, and affordable synthesis cost. After having shown their efficacy in targeting drugs to intraerythrocytic parasites, now PAAs face the challenge of spearheading a new generation of nanocarriers aiming at the malaria parasite stages in the mosquito vector.

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Phenotypic Evidence of Emerging Ivermectin Resistance in Onchocerca volvulus

Cited by 273 publications

References 24 publications

Interdomain lateral gene transfer of an essential ferrochelatase gene in human parasitic nematodes

Interdomain lateral gene transfer of an essential ferrochelatase gene in human parasitic nematodes

Filarial hydrocele: a neglected condition of a neglected tropical disease

Polyamidoamine Nanoparticles as Nanocarriers for the Drug Delivery to Malaria Parasite Stages in the Mosquito Vector

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