Study of Schistosoma mansoni isolates from patients with failure of treatment with oxamniquine

Conceição, Maria José; Argento, Carlos Alberto; Corrêa, Acyr

doi:10.1590/s0074-02762000000300013

Cited by 17 publications

(4 citation statements)

References 30 publications

(27 reference statements)

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“…Then, worms were washed in a 1:1 ratio of PBSTx and pre-hybridization solution for 10 min at room temperature. Male parasites (5)(6) were placed into 48-well-sized baskets (Intavis Bioanalytical Instruments) and incubated in pre-hybridization solution (50% deionized formamide, 5× SSC, and 1.2% H 2 O 2 ) for 2 h at 52 • C. The worms were then incubated in 300 µL of hybridization solution (prehybridization solution with 10% dextran sulfate) and 150 ng/mL of Riboprobe generated for SULT RNA overnight at 52 • C (Supplemental Table S3). The worms were then washed twice, for 30 min each, in wash hybridization buffer, 2× SSC + 0.1% Triton-X, and lastly with 0.2× SSC + 0.1% Triton-X.…”

Section: Whole Worm In Situ Hybridizationmentioning

confidence: 99%

“…Because of this species specificity, OXA was the drug of choice in Brazil [ 3 ], where only S. mansoni is present. However, resistance has developed in the field [ 4 , 5 , 6 , 7 ] and was selected for use in the laboratory [ 8 , 9 ]. Praziquantel (PZQ) was developed around the same time as OXA but had the advantage of treating infections caused by all three schistosome species.…”

Section: Introductionmentioning

confidence: 99%

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Schistosome Sulfotransferases: Mode of Action, Expression and Localization

Guzman¹,

Rugel²,

Alwan³

et al. 2022

Pharmaceutics

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Oxamniquine (OXA) is a prodrug activated by a sulfotransferase (SULT) that was only active against Schistosoma mansoni. We have reengineered OXA to be effective against S. haematobium and S. japonicum. Three derivatives stand out, CIDD-0066790, CIDD-0072229, and CIDD-0149830 as they kill all three major human schistosome species. However, questions remain. Is the OXA mode of action conserved in derivatives? RNA-interference experiments demonstrate that knockdown of the SmSULT, ShSULT, and SjSULT results in resistance to CIDD-0066790. Confirming that the OXA-derivative mode of action is conserved. Next is the level of expression of the schistosome SULTs in each species, as well as changes in SULT expression throughout development in S. mansoni. Using multiple tools, our data show that SmSULT has higher expression compared to ShSULT and SjSULT. Third, is the localization of SULT in the adult, multicellular eucaryotic schistosome species. We utilized fluorescence in situ hybridization and uptake of radiolabeled OXA to determine that multiple cell types throughout the adult schistosome worm express SULT. Thus, we hypothesize the ability of many cells to express the sulfotransferase accounts for the ability of the OXA derivatives to kill adult worms. Our studies demonstrate that the OXA derivatives are able to kill all three human schistosome species and thus will be a useful complement to PZQ.

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Section: Whole Worm In Situ Hybridizationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Schistosome Sulfotransferases: Mode of Action, Expression and Localization

Guzman¹,

Rugel²,

Alwan³

et al. 2022

Pharmaceutics

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show abstract

“…In the other cases, surgical indications were due to gastrointestinal hemorrhage resultant from esophageal varices rupture, hypersplenism, abdominal pain and discomfort, and hypogonadism (Conceição et al 2002). Treatment with oxamniquine showed no response in 10.3% of patients, and treatment failure was experimentally confirmed (Katz et al 1973, Conceição et al 2000. Regarding praziquantel, it was presented a patient that underwent to three successive treatments and was still eliminating eggs of S. mansoni .…”

Section: Specific Treatment With Oxamniquine or Praziquantel And Thementioning

confidence: 99%

Epidemiology of Schistosomiasis Mansoni in Brazil

Conceição¹,

Coura²

2012

Schistosomiasis

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“…An important aspect to be considered in the control program context is the emergent problem of resistance or tolerance of parasites to the main drugs used in schistosomiasis chemotherapy (Dias & Gonçalves 1992, Cioli 1993, Araújo et al 1996, Conceição et al 2000, Liang et al 2001. Due to those aspects, the combat against vector, associated to other control measures, is again emphasized.…”

mentioning

confidence: 99%