Diethylcarbamazine (DEC): immunopharmacological interactions of an anti-filarial drug

Maizels, Rick M.; Denham, D. A.

doi:10.1017/s0031182000075351

Cited by 134 publications

(98 citation statements)

References 73 publications

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“…[14][15][16] The effective microfilaricidal activity of AgNPs at relatively low concentration as reported in this study, with evidence of apoptotic induction in microfilariae, can project nanosilver as a potential drug adjuvant against lymphatic filariasis. Unlike DEC, which is effective against microfilariae only in vivo and not in vitro, 35 nanosilver promises greater therapeutic effectiveness. Remarkably, a recent report has demonstrated the therapeutic potential of AgNPs against leishmaniasis, another parasitic disease caused by Leishmania tropica.…”

Section: Resultsmentioning

confidence: 99%

Novel microfilaricidal activity of nanosilver

Singh¹,

Goswami²,

Sharma³

et al. 2012

IJN

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Purpose:The currently available drug repertoire against lymphatic filariasis, a major health hazard in the developing world, is inadequate and is fraught with serious limitations. Thus, the development of an effective antifilarial strategy has become a global research thrust mandated by the World Health Organization. Nanoparticles of silver endowed with antibacterial potency are known to induce apoptosis in eukaryotic cells. The present study was designed to investigate the possible microfilaricidal efficacy of silver nanoparticles and to establish the validity of apoptotic rationale in antifilarial drug designing. Methods: This report analyzed the effect of nanoparticles of silver as well as gold (size range: 10-15 nm) on the microfilariae of Brugia malayi obtained from the lavage of peritoneal cavities of infected jirds (Meriones unguiculatus). The study included a microfilarial motility assay, a trypan blue exclusion test, a poly(adenosine diphosphate-ribose) polymerase activity study, ethidium bromide/acridine orange differential staining, and transmission, as well as scanning electron microscopic evaluation of ultrastructural changes in microfilariae. Results: The study demonstrates that nanoparticles of silver, but not of gold, elicited significant loss in microfilarial motility. Differential staining of parasites with ethidium bromide and acridine orange, poly(adenosine diphosphate-ribose) polymerase activity in microfilarial lysate, and electron microscopic findings underscored apoptotic death of parasites attributable to nanosilver. In a trypan blue exclusion test, the 50% lethal dose of nanosilver was measured to be 101.2 µM, which was higher than the recorded complete inhibitory concentration value (50.6 µM), thus supporting nanosilver as a potential drug candidate against lymphatic filariasis. Conclusion:The present report provides the first ever conclusive proof in support of apoptosis as a novel stratagem in antifilarial drug designing and nanoscale silver as a valid lead in research on antifilarial therapeutics. The main embargo about the current drug diethylcarbamazine citrate is its empirical use without rationale. Effective microfilaricidal activity of nanosilver at relatively low concentrations as reported in this study, with evidence of the induction of apoptosis in microfilariae, projects nanosilver as a potential drug adjuvant against lymphatic filariasis. The much higher 50% lethal dose value of nanosilver compared to the complete inhibitory concentration value reported in this study argues in favor of a safe therapeutic window of this agent in its antifilarial efficacy.

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Section: Resultsmentioning

confidence: 99%

Novel microfilaricidal activity of nanosilver

Singh¹,

Goswami²,

Sharma³

et al. 2012

IJN

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“…Em alguns poucos casos, pode haver necessidade de se fazer uso de antitérmicos e analgégicos. No entanto, não há indicação para o uso de corticosteróides com a finalidade de minimizar ou de abolir tais reações 46 . As reações adversas localizadas estão associadas à morte dos vermes adultos e apresentam-se clinicamente como linfangite e adenite.…”

Section: Tratamento Quimioterápico Antifilarialunclassified

Recomendações para o tratamento da filariose bancroftiana, na infecção e na doença

Dreyer

Norões

2002

Rev. Soc. Bras. Med. Trop.

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Resumo As bases para se instituir o tratamento da filariose linfática são: prevenir, reverter ou diminuir a progressão da doença e interromper a transmissão do parasita. A escolha das medidas mais adequadas para o tratamento dos pacientes portadores de filariose linfática requer o conhecimento das diversas manifestações clínicas, assim como os seus diferentes mecanismos patogênicos. No passado, o tratamento da filariose era baseado somente na prescrição da droga antifilarial, porém, para os pacientes apresentando as manifestações agudas ou crônicas da doença, é imperativo que outras medidas sejam indicadas, incluindo higiene e dieta. Assim, essa nova visão multidisciplinar terapêutica é tão ou mais importante do que o início imediato da terapia antifilarial. Independentemente da manifestação clínica do paciente, três componentes estão agora indicados: 1) os cuidados clínicos e higiênico-dietéticos específicos para as diversas manifestações clínicas, 2) a educação e o suporte psicológico e finalmente 3) o tratamento quimioterápico com a dietilcarbamazina (DEC) ou a combinação de DEC e ivermectina. Os autores descrevem também as eficácias relativas macro e microfilaricidas da dietilcarbamazina e da ivermectina sozinhas ou em combinação usadas em programas de tratamento em massa para interrupção da transmissão e comentam sobre a introdução do uso da higiene em programas de saúde pública para a prevenção do linfedema. Palavras-chaves: Controle. Tratamento. Dietilcarbamazina. Ivermectina. Bancroftose. Elefantíase.Abstract The goals of treatment for lymphatic filariasis are: to prevent, reverse, or halt progression of disease; and to interrupt transmission of the parasite. Selecting the appropriate therapy for the patient with lymphatic filariasis requires knowledge of the various clinical features of filarial disease and their pathogenesis. In the past, treatment of lymphatic filariasis has focused primarily on antiparasitic chemotherapy; however, for many of the acute and chronic manifestations of lymphatic filariasis, it is now clear that supportive or other forms of clinical care are even more important than antiparasitic medication in order to prevent worsening of the disease. Regardless of the clinical manifestations of filarial disease in a particular patient, the following three components of treatment should, in general, be considered: supportive or disease-specific clinical care (including higiene and diet), patient education and counseling and finally, antiparasitic chemotherapy with diethylcarbamazine (DEC) and/or the combination of DEC with ivermectin. The authors also describe the proportional efficacy of diethylcarbamazine and ivermectin, alone or in combination, for use in mass treatment aiming at transmission interruption and the use of hygiene as a public health approach for lymphedema prevention. Key-words: Control. Treatment. Diethylcarbamazine. Ivermectin. Bancroftian filariasis. Elephantiasis. Nos últimos anos, a filariose linfática tem surgido como um problema crescente em saúde pública em vária...

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“…It is extremely effective against microfilariae of several parasites, capable of reducing the number of microfilariae in the circulation of an infected human by 60% within four minutes (32). It can also be used as a prophylactic against B. malayi in humans and has been shown to have activity against L3 larvae in cats (33,34). However, despite the remarkable efficacy of the drug in vivo, the means by which DEC eliminates B. malayi have not been established.…”

Section: Old Treatments Provide New Cluesmentioning

confidence: 99%

“…However, despite the remarkable efficacy of the drug in vivo, the means by which DEC eliminates B. malayi have not been established. When DEC is added to either microfilariae or L3 in vitro, worm viability is unaffected (34,35).…”

Section: Old Treatments Provide New Cluesmentioning

confidence: 99%

Investigating development of infective stage larvae of filarial nematodes

Smith

2000

Front Biosci

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Diethylcarbamazine (DEC): immunopharmacological interactions of an anti-filarial drug

Cited by 134 publications

References 73 publications

Novel microfilaricidal activity of nanosilver

Novel microfilaricidal activity of nanosilver

Recomendações para o tratamento da filariose bancroftiana, na infecção e na doença

Investigating development of infective stage larvae of filarial nematodes

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