Praziquantel

Andrews, P. R.; Thomas, H.; Pohlke, R.; Seubert, J.

doi:10.1002/med.2610030204

Cited by 374 publications

(324 citation statements)

References 91 publications

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“…1 In a number of regions, including much of Egypt, PZQ has been copiously used, and the impact of the drug on schistosome infections has been significant. 2,3 In the laboratory, exposure of schistosomes to subcurative doses of PZQ over generations resulted in drugresistant schistosomes, 4 demonstrating the possibility of resistance arising in the field.…”

mentioning

confidence: 99%

Resistance to praziquantel: direct evidence from Schistosoma mansoni isolated from Egyptian villagers.

Ismail¹,

Botros²,

Metwally³

et al. 1999

Am J Trop Med Hyg

431

270

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Abstract. Recent evidence suggest that resistance to praziquantel (PZQ) may be developing. This would not be surprising in countries like Egypt where the drug has been used aggressively for more that 10 years. The classic phenotype of drug resistance is a significant increase in the 50% effective dose value of isolates retrieved from patients not responding to the drug. In a previous publication, we reported that such phenotypes have been isolated from humans infected with Schistosoma mansoni. Since the action of PZQ may be dependent upon the drug and host factors, most notably the immune system, we analyzed the quantitative effects of PZQ on single worms that differed in their response to PZQ when maintained in mice. Our hypothesis was that the in vitro action of the drug would correlate with it in vivo action. We confirmed this hypothesis and conclude that the in vitro action of the drug is related to its in vivo action. Knowing this relationship will assist in our ability to detect or survey for the PZQ resistant phenotype in human populations.Praziquantel (PZQ) is used for the treatment of infections caused by Schistosoma spp. 1 In a number of regions, including much of Egypt, PZQ has been copiously used, and the impact of the drug on schistosome infections has been significant. 2,3 In the laboratory, exposure of schistosomes to subcurative doses of PZQ over generations resulted in drugresistant schistosomes, 4 demonstrating the possibility of resistance arising in the field. Indeed, reports of resistance in the field have recently appeared. 5 However, the reality of these reports is difficult to establish because it is often difficult to distinguish between host factors and parasite factors when patients are not cured of schistosomiasis with normally effective doses. First, since the host immune system plays an active role in the process of killing PZQ-damaged worms, 6 normal parasites might survive treatment in immunocompromised hosts. In vivo studies can also be confounded by the fact that PZQ is less effective in killing immature parasites, 7 such that a wide range of host factors inhibiting development of the parasites can cause an apparent decrease in drug efficacy. Variability of host PZQ metabolism can also cause variability of efficacy. 8 In an effort to minimize the variability of these host factors, parasites isolated from patients not cured by antischistosomal drugs have been used to establish experimental infections in less-variable laboratory animal hosts. 9 If infections produced by these isolates are not cured by normal doses of PZQ, it suggests that the decreased responsiveness of the isolates is due to worm factors rather than host factors. However, this type of assessment is a rather toilsome process.Despite the dependence of PZQ on the host immune system for killing the parasites in vivo, PZQ has dramatic, measurable effects on schistosomes in vitro. The three hallmark effects are contraction of the worm musculature, 10 an influx of calcium into the worm, 11 and disruption of the tegument...

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mentioning

confidence: 99%

Resistance to praziquantel: direct evidence from Schistosoma mansoni isolated from Egyptian villagers.

Ismail¹,

Botros²,

Metwally³

et al. 1999

Am J Trop Med Hyg

431

270

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“…Massive chemotherapy with OX or PZQ (Cline et al 1982, Andrews et al 1983, Cioli et al 1993 has been one of the most important measures in the control of schistosomiasis in endemic areas. While resistance to OX is well docummented, such has not been the case for PZQ.…”

mentioning

confidence: 99%

The immunopathology of human schistosomiasis-III: immunoglobulin isotype profiles and response to praziquantel

Ramirez

Ceballos

Noya

et al. 1996

Mem. Inst. Oswaldo Cruz

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“…A 779-nucleotide transcript was identified that includes a 438-nucleotide open reading frame encoding a putative 146-amino acid protein. 3 The transcript also featured a polyadenylation signal (AATAAA) 22 nucleotides upstream of a poly(A) ϩ tail.…”

Section: Resultsmentioning

confidence: 99%

“…To examine for the presence of introns, the S. mansoni gene was amplified from a genomic DNA template isolated from adult S. mansoni worms. The primers used in this PCR, NPFgenF2 and NPFA2R, were based on sequence obtained through 3Ј-and 3 The S. japonicum NPF cDNA has GenBank TM accession number AY533028. 4 The smNPF cDNA has GenBank TM accession number AY299474.…”

Section: Resultsmentioning

confidence: 99%

Structure and Bioactivity of Neuropeptide F from the Human Parasites Schistosoma mansoni and Schistosoma japonicum

Humphries

Kimber

Barton

et al. 2004

Journal of Biological Chemistry

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The blood flukes Schistosoma mansoni and Schistosoma japonicum inflict immense suffering as agents of human schistosomiasis. Previous investigations have found the nervous systems of these worms contain abundant immunoreactivity to antisera targeting invertebrate neuropeptide Fs (NPFs) as well as structurally similar neuropeptides of the mammalian neuropeptide Y (NPY) family. Here, cDNAs encoding NPF in these worms were identified, and the mature neuropeptides from the two species differed by only a single amino acid. Both neuropeptides feature the characteristics common among NPFs; they are 36 amino acids long with a carboxyl-terminal Gly-Arg-X-Arg-Phe-amide and Tyr residues at positions 10 and 17 from the carboxyl terminus. Synthetic S. mansoni NPF potently inhibits the forskolin-stimulated accumulation of cAMP in worm homogenates, with significant effects at 10 ؊11 M. This is the first demonstration of an endogenous inhibition of cAMP by an NPF, and because this is the predominant pathway associated with vertebrate NPY family peptides, it demonstrates a conservation of downstream signaling pathways used by NPFs and NPY peptides.Blood fluke parasites of the genus Schistosoma are the most important metazoan parasites of humans and are the etiological agents of schistosomiasis (bilharzia), which afflicts over 200 million people. Schistosomiasis ranks second, behind only malaria, in terms of its overall negative socio-economic and public health impact on the tropical and subtropical world, and it remains among the top five disease priorities of the World Health Organization (WHO) 1 (1). Control of the disease rests almost solely on chemotherapy using the anthelmintic praziquantel (2-4). Most disturbingly, the long term utility of praziquantel has been brought into question because of growing reports of infections not responding to the recommended dosage (5-8) and worms with decreased sensitivity (9, 10). WHO has accordingly identified research into the basic biology of schistosomes as a priority, with the hope of identifying targets for the next generation of antischistosomal drugs (1).Schistosomes belong to the class Trematoda of the phylum Platyhelminthes (flatworms) and, as such, are among the simplest extant animals to display brain development with the concomitant distinction between central and peripheral neuronal elements. One distinct feature of platyhelminths and other early diverging phyla is a prominent peptidergic component within their nervous systems. One family of neuropeptides abundant among these early animals is the neuropeptide F (NPF) family (11-14). NPFs are 36 -40-amino acid peptides featuring a carboxyl-terminal Gly-Arg-X-Arg-Phe-amide (GRXRF-NH 2 ) motif and tyrosine residues at positions 10 and 17 relative to the carboxyl terminus.These characteristics are common to those of vertebrate NPY family peptides, 36 amino acid neuropeptides with RXR(F/Y)-NH 2 carboxyl termini, Tyr residues at positions 10 and 17 relative to the carboxyl termini, and prolines in a PXXPXXP motif near the amino ter...

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Praziquantel

Cited by 374 publications

References 91 publications

Resistance to praziquantel: direct evidence from Schistosoma mansoni isolated from Egyptian villagers.

Resistance to praziquantel: direct evidence from Schistosoma mansoni isolated from Egyptian villagers.

The immunopathology of human schistosomiasis-III: immunoglobulin isotype profiles and response to praziquantel

Structure and Bioactivity of Neuropeptide F from the Human Parasites Schistosoma mansoni and Schistosoma japonicum

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