Praziquantel Resistance in the Zoonotic Cestode Dipylidium caninum

Chelladurai, Jeba Jesudoss; Kifleyohannes, Tsegabirhan; Scott, Janelle  Rose; Brewer, Matthew T.

doi:10.4269/ajtmh.18-0533

Cited by 51 publications

(51 citation statements)

References 27 publications

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“…PZQ shows excellent efficacy against various species of worm; however, drug resistance and low susceptibility of parasites have been recently observed [ 10 , 11 ]. PZQ resistance has been reported in various species of worms, including S. mansoni [ 12 , 13 ], S. japonicum [ 14 ], S. hematobium [ 15 ] and other cestode species [ 16 , 17 ]. For blood flukes, PZQ is effective only on adult and cercarial stage worms, while juvenile stage schistosomulae can retain viability after chemotherapy and progress to adulthood [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of Praziquantel on Schistosoma mekongi Proteome and Phosphoproteome

et al. 2020

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Schistosoma mekongi causes schistosomiasis in southeast Asia, against which praziquantel (PZQ) is the only treatment option. PZQ resistance has been reported, thus increasing the requirement to understand mechanism of PZQ. Herein, this study aimed to assess differences in proteome and phosphoproteome of S. mekongi after PZQ treatment for elucidating its action. Furthermore, key kinases related to PZQ effects were predicted to identify alternative targets for novel drug development. Proteomes of S. mekongi were profiled after PZQ treatment at half maximal inhibitory concentration and compared with untreated worms. A total of 144 proteins were differentially expressed after treatment. In parallel, immunohistochemistry indicated a reduction of phosphorylation, with 43 phosphoproteins showing reduced phosphorylation, as identified by phosphoproteomic approach. Pathway analysis of mass spectrometric data showed that calcium homeostasis, worm antigen, and oxidative stress pathways were influenced by PZQ treatment. Interestingly, two novel mechanisms related to protein folding and proteolysis through endoplasmic reticulum-associated degradation pathways were indicated as a parasiticidal mechanism of PZQ. According to kinase–substrate predictions with bioinformatic tools, Src kinase was highlighted as the major kinase related to the alteration of phosphorylation by PZQ. Interfering with these pathways or applying Src kinase inhibitors could be alternative approaches for further antischistosomal drug development.

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Section: Introductionmentioning

confidence: 99%

Effect of Praziquantel on Schistosoma mekongi Proteome and Phosphoproteome

et al. 2020

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“…The urgency to look for new antischistosomal and anticestodal compounds is supported by the recent alarming identification of PZQ resistance of the zoonotic cestode Dipylidium caninum , which infects dogs, cats, and humans (Chelladurai et al 2018 . Thus, clinical resistance was detected in dogs against PZQ and the structurally related epsiprantel.…”

Section: Discussionmentioning

confidence: 99%

“…The urgency for new antischistosomal and anticestodal drugs is seen by the recent alarming appearance of PZQ-resistant zoonotic Dipylidium caninum , infecting dogs, cats, and humans (Chelladurai et al 2018 . During the time course from 2016 to 2018, cases of clinical resistance in dogs with this cestode against PZQ and the structurally related epsiprantel have been reported.…”

Section: Pzq Resistancementioning

confidence: 99%

Activation of transient receptor potential channel Sm.(Schistosoma mansoni)TRPMPZQ by PZQ, enhanced Ca++ influx, spastic paralysis, and tegumental disrupture—the deadly cascade in parasitic schistosomes, other trematodes, and cestodes

Harder

2020

Parasitol Res

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After almost 50 years of praziquantel (PZQ) research, Park and Marchant (Trends Parasitol 36:182–194, 2020 ) described the Ca ++ -permeable transient receptor potential (TRP) channel Sm.TRPM PZQ in Schistosoma mansoni as target of PZQ. Here we describe the deadly cascade in schistosomes which is induced by the (R)-PZQ enantiomer that includes contemporaneous stereoselective activation of Sm.TRPM PZQ -mediated Ca ++ influx, disturbed Ca ++ homeostasis, Ca ++ -dependent spastic paralysis, and Ca ++ - and PZQ-dependent disruption of parasitic teguments. Under normal conditions, there is a reversible balance between bilayer, isotropic, and HII phases in biological membranes (Jouhet 2013 ). In vitro, we could observe an irreversible but not stereoselective transition to the HII phase in liposomes consisting of phosphatidylethanolamine (PE) and phosphatidylserine (PS), two naturally occurring phospholipids in schistosomes, by the concerted action of Ca ++ and PZQ (Harder 2013 ). HII structures are a prerequisite for induction of fusion processes (Jouhet 2013 ), which, indeed, become visible as blebs, vacuolation processes, and large balloon-like surface exudates in a large variety of PZQ-sensitive parasitic flukes and cestodes after PZQ treatment. These tegument damages are irreversible. As homologs of Sm.TRPM PZQ are also present in the other trematodes S. japonicum , S. haematobium , or Clonorchis sinensis and cestodes Taenia solium , Echinococcus multilocularis , or Hymenolepis microstoma (Park and Marchant, Trends Parasitol 36:182–194, 2020 ), it is suggested that a similar deadly cascade will be operating generally in PZQ-sensitive parasites.

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“…Praziquantel resistance in unresolving Dipylidium infection in dogs has been recently reported. ese dogs were later successfully treated with nitroscanate or a compounded pyrantel/ praziquantel/oxantel product [15]. Importantly, prevention of human cases should include primarily prompt parasitic treatment of the pets and flea control in their indoor and outdoor environments along with appropriate disposal of their feces, discouraging children to play in areas soiled with pets' feces, and good hand hygiene after playing with animals or outdoors.…”

Section: Discussionmentioning

confidence: 99%

Presumptive Dipylidium caninum Infection in a Toddler

Chong

Hammoud

Chang

2020

Case Reports in Pediatrics

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We report a female toddler who presented repetitively with a chief complaint of motile white worms seen in her diapers. Symptoms of perianal itching and visualization of visible motile worms persisted for 6 months despite being treated with multiple courses of albendazole causing a lot of frustration and distress to the caregivers. The characteristics of the worms by inspection along with the presence of 3 pet dogs are consistent with Dipylidium caninum.

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Praziquantel Resistance in the Zoonotic Cestode Dipylidium caninum

Cited by 51 publications

References 27 publications

Effect of Praziquantel on Schistosoma mekongi Proteome and Phosphoproteome

Effect of Praziquantel on Schistosoma mekongi Proteome and Phosphoproteome

Activation of transient receptor potential channel Sm.(Schistosoma mansoni)TRPMPZQ by PZQ, enhanced Ca++ influx, spastic paralysis, and tegumental disrupture—the deadly cascade in parasitic schistosomes, other trematodes, and cestodes

Presumptive Dipylidium caninum Infection in a Toddler

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