Killing filarial nematode parasites: role of treatment options and host immune response

Kwarteng, Alexander; Ahuno, Samuel Terkper; Akoto, Freda Osei

doi:10.1186/s40249-016-0183-0

Cited by 36 publications

(34 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The primary burden of these is associated with Wuchereria bancrofti , which is transmitted via mosquito vector and is responsible for lymphatic filariasis (elephantitis) as well as Onchocerca volvulus , the causative agent of onchocerciasis, commonly referred to as river blindness, whose transmission is mediated by infected blackflies . Once infected, the adult worms reside in either the subcutaneous tissues or lymphatic system, where they produce microfilariae offspring . The primary treatment strategy for these infections has been through the use of antiparasitic drugs such as ivermectin ( 605 ), diethylcarbamazine ( 606 , MMV002816), and albendazole ( 320 ), which successfully kill microfilariae with little effect on the adult worms …”

Section: Filariasis and Wolbachiamentioning

confidence: 99%

Unpacking the Pathogen Box—An Open Source Tool for Fighting Neglected Tropical Disease

Veale

2019

ChemMedChem

View full text Add to dashboard Cite

The Pathogen Box is a 400‐strong collection of drug‐like compounds, selected for their potential against several of the world's most important neglected tropical diseases, including trypanosomiasis, leishmaniasis, cryptosporidiosis, toxoplasmosis, filariasis, schistosomiasis, dengue virus and trichuriasis, in addition to malaria and tuberculosis. This library represents an ensemble of numerous successful drug discovery programmes from around the globe, aimed at providing a powerful resource to stimulate open source drug discovery for diseases threatening the most vulnerable communities in the world. This review seeks to provide an in‐depth analysis of the literature pertaining to the compounds in the Pathogen Box, including structure–activity relationship highlights, mechanisms of action, related compounds with reported activity against different diseases, and, where appropriate, discussion on the known and putative targets of compounds, thereby providing context and increasing the accessibility of the Pathogen Box to the drug discovery community.

show abstract

Section: Filariasis and Wolbachiamentioning

confidence: 99%

Unpacking the Pathogen Box—An Open Source Tool for Fighting Neglected Tropical Disease

Veale

2019

ChemMedChem

View full text Add to dashboard Cite

show abstract

“…7), and limbs and hydrocele swelling (scrotal swelling or breast swelling) ( Fig. 8) and may develop to filarial abscesses [5,8,25,[28][29][30].…”

Section: Symptomsmentioning

confidence: 99%

“…These drugs work to dispose of the larval worm, to hold the reproduction of adult worm and kill it. Some studies showed the killing of adult worm with treatment by doxycycline [5,8,22,25,29,30,35,39,40].…”

Section: Treatment and Preventionmentioning

confidence: 99%

Lymphatic Filariasis: An Overview

Al-Tameemi

Kabakli

2019

Asian J Pharm Clin Res

View full text Add to dashboard Cite

Lymphatic filariasis (LF) is a tropical disease caused by infection with the parasitic filarial worms: Wuchereria bancrofti, Brugia malayi, and Brugia timori. The symptoms of this chronic disease appear in adults (in men more than in women) and include damage to the lymphatic system, arms, legs, and genitals, which cause significant pain, reducing productivity, and social problems. LF is a cause of continued disability, pain, disfigurement, and sexual disability in the world, so the knowledge of the disease and the infection control is very important. In addition to the importance of prevention, that includes giving medicine and using controlling ways of mosquitoes. Moreover, the prevention of disease is important, that includes giving medicine and using controlling ways of mosquitoes. However, although the efforts of health organizations to reduce the LF infections, there are still many challenges including the early diagnosis and control of infection among people.

show abstract

“…Lymphatic filariasis occurs in some 120 million people in developing countries, and regrettably, effective treatments for adult filaria infections are limited. Although a triple combination of ivermectin, diethylcarbamazine, and albendazole seems to be effective (18), development of new treatments to kill adults is still required (19,20). Cholinergic anthelmintics (levamisole, haloxon) are not regularly used for the treatment of B. malayi, but there are reports of their efficacy (21, 22) that have encouraged us to study their nAChRs as anthelmintic targets.…”

mentioning

confidence: 99%

Functional genomics in Brugia malayi reveal diverse muscle nAChRs and differences between cholinergic anthelmintics

Verma

Kashyap

Robertson

et al. 2017

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

View full text Add to dashboard Cite

Many techniques for studying functional genomics of important target sites of anthelmintics have been restricted to Caenorhabditis elegans because they have failed when applied to animal parasites. To overcome these limitations, we have focused our research on the human nematode parasite Brugia malayi, which causes elephantiasis. Here, we combine single-cell PCR, whole muscle cell patch clamp, motility phenotyping (Worminator), and dsRNA for RNAi for functional genomic studies that have revealed, in vivo, four different muscle nAChRs (M-, L-, P-, and N-). The cholinergic anthelmintics had different selectivities for these receptors. We show that motility and patch-clamp responses to levamisole and pyrantel, but not morantel or nicotine, require the unc-38 and/or unc-29 genes. Derquantel behaved as a competitive antagonist and distinguished M-nAChRs activated by morantel (K b 13.9 nM), P-nAChRs activated by pyrantel (K b 126 nM), and L-nAChRs activated by levamisole (K b 0.96 μM) and bephenium. Derquantel was a noncompetitive antagonist of nicotine, revealing N-type nAChRs. The presence of four diverse nAChRs on muscle is perhaps surprising and not predicted from the C. elegans model. The diverse nAChRs represent distinguishable drug targets with different functions: Knockdown of unc-38+unc-29 (L-and/or P-receptors) inhibited motility but knockdown of acr-16+acr-26 (M-and/or N-receptors) did not.T he neglected tropical diseases caused by nematode parasites affect some 2 billion people globally, and effective vaccines are not available. Although these parasites by themselves do not produce high mortality, they produce significant morbidity that affects worker productivity and increase susceptibility to AIDS and malaria, and they are strongly associated with poverty in endemic countries (1-4). There are only a limited number of classes of anthelmintic drugs that are used to treat these diseases, and there are concerns about the development of resistance (5). There is a pressing need to advance the study of anthelmintic drugs.Many useful studies on modes of action of anthelmintic drugs have been conducted on the model nematode, Caenorhabditis elegans, but this is not a parasite: It is separated evolutionarily by millions of years from parasitic nematodes and it does not possess "parasitism genes" (6). This separation increases the impetus for anthelmintic studies using real parasites, but until now many techniques developed in C. elegans have not have been tractable when applied to animal parasites (7).The neuromuscular systems of nematodes, which control motility and support feeding, growth, and reproduction, are governed by significant parts of their gene pools (8, 9). Their neuromuscular systems are unlike those of vertebrates because nematode muscles send processes to the motor neurons to form synapses, rather than the other way around. Membrane ion-channels, which regulate nematode neuromuscular systems, are target sites of major classes of anthelmintic drugs, including the cholinergic anthelmintics levamisole,...

show abstract

Killing filarial nematode parasites: role of treatment options and host immune response

Cited by 36 publications

References 42 publications

Unpacking the Pathogen Box—An Open Source Tool for Fighting Neglected Tropical Disease

Unpacking the Pathogen Box—An Open Source Tool for Fighting Neglected Tropical Disease

Lymphatic Filariasis: An Overview

Functional genomics in Brugia malayi reveal diverse muscle nAChRs and differences between cholinergic anthelmintics

Contact Info

Product

Resources

About