A review of the genetic determinants of praziquantel resistance in Schistosoma mansoni: Is praziquantel and intestinal schistosomiasis a perfect match?

Summers, Shannan; Bhattacharyya, Tapan; Allan, Fiona; Stothard, J. Russell; Edielu, Andrew; Webster, Bonnie L.; Miles, Michael A.; Bustinduy, Amaya L.

doi:10.3389/fitd.2022.933097

Cited by 20 publications

(13 citation statements)

References 176 publications

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“…Diagnostic methods that are not adequately specific for FGS diagnosis may lead to over-treatment with praziquantel and may overlook the diagnosis and treatment of STIs and cervical cancer. Although there is little evidence of praziquantel resistance in humans 8 , indiscriminate treatment may theoretically increase the risk of the development of praziquantel resistance 9 . Since cervicovaginal visualization is widely promoted 10 for FGS screening and diagnosis, we aimed to further evaluate the agreement of human expert reviewers for the diagnosis of visual-FGS.…”

Section: Introductionmentioning

confidence: 99%

Visual diagnosis of female genital schistosomiasis in Zambian women from hand-held colposcopy: agreement of expert image review

Sturt¹,

Bristowe²,

Webb³

et al. 2023

Wellcome Open Res

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Female genital schistosomiasis (FGS) can occur in S. haematobium infection and is caused by parasite egg deposition in the genital tract. Confirming a diagnosis of FGS is challenging due to the lack of a diagnostic reference standard. A 2010 expert-led consensus meeting proposed visual inspection of the cervicovaginal mucosa as an adequate reference standard for FGS diagnosis. The agreement of expert human reviewers for visual-FGS has not been previously described. Methods: In two Zambian communities, non-menstruating, non-pregnant, sexually-active women aged 18-31 years participating in the HPTN 071 (PopART) Population-Cohort were enrolled in a cross-sectional study. Self-collected genital swabs and a urine specimen were collected at a home visit; trained midwives performed CVL and hand-held colposcopy at a clinic visit. S. haematobium eggs and circulating anodic antigen (CAA) were detected from urine. Two expert reviewers independently diagnosed visual-FGS as the presence of sandy patches, rubbery papules or abnormal blood vessels in digital cervicovaginal images obtained by hand-held colposcopy. PCR-FGS was defined as Schistosoma DNA detected by real-time PCR in any genital specimen (CVL or genital swab). Results: Of 527 women with cervicovaginal colposcopic images, 468/527 (88.8%) were deemed interpretable by Reviewer 1 and 417/527 (79.1%) by Reviewer 2. Visual-FGS was detected in 35.3% (165/468) of participants by expert review of colposcopic images by Reviewer 1 and in 63.6% (265/417) by Reviewer 2. Cohen’s kappa statistic for agreement between the two expert reviewers was 0.16, corresponding to "slight" agreement. The reviewers made concordant diagnoses in 38.7% (204/527) participants (100 negative, 104 positive) and discordant diagnoses in 31.8% (168/527) participants. Conclusions: The unexpectedly low level of correlation between expert reviewers highlights the imperfect nature of visual diagnosis for FGS based on cervicovaginal images obtained with a hand-held colposcope. This finding is a call to action for improved point-of-care diagnostics for female genital schistosomiasis

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Section: Introductionmentioning

confidence: 99%

Visual diagnosis of female genital schistosomiasis in Zambian women from hand-held colposcopy: agreement of expert image review

Sturt¹,

Bristowe²,

Webb³

et al. 2023

Wellcome Open Res

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“…On the contrary, the CR in the present study was lower than previous reports from Ethiopia [ 47 ] and Tanzania [ 24 ]. Variations in the study population, baseline infection intensity, and diagnostic methods as well as parasite, host, and drug associated factors might contribute for the difference in CR [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of prazequantel for the treatment of Schistosoma mansoni infection across different transmission settings in Amhara Regional State, northwest Ethiopia

Alemu,

Amor,

Nibret

et al. 2024

PLoS ONE

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Background Schistosoma mansoni and S. haematobium infections have been public health problems in Ethiopia, S. mansoni being more prevalent. To reduce the burden of schistosomiasis, a national school-based prazequantel (PZQ) mass drug administration (MDA) program has been implemented since November 2015. Nevertheless, S. mansoni infection is still a major public health problem throughout the country. Reduced efficacy of PZQ is reported by a few studies in Ethiopia, but adequate data in different geographical settings is lacking. Hence, this study aimed to assess the efficacy and safety of PZQ for the treatment of S. mansoni infection across different transmission settings in Amhara Regional State, northwest Ethiopia. Methods A school-based single-arm prospective cohort study was conducted from February to June, 2023 among 130 S. mansoni-infected school-aged children (SAC). Forty-two, 37, and 51 S. mansoni-infected SAC were recruited from purposely selected schools located in low, moderate, and high transmission districts, respectively. School-aged children who were tested positive both by Kato Katz (KK) using stool samples and by the point of care circulating cathodic antigen (POC-CCA) test using urine samples at baseline were treated with a standard dose of PZQ and followed for 21 days for the occurrence of adverse events. After three weeks post-treatment, stool and urine samples were re-tested using KK and POC-CCA. Then the cure rate (CR), egg reduction rate (ERR), and treatment-associated adverse events were determined. The data were analyzed using SPSS version 21. Results Out of the total 130 study participants, 110 completed the follow-up. The CR and ERR of PZQ treatment were 88.2% (95%CI: 82.7–93.6) and 93.5% (95%CI: 85.4–98.5), respectively, by KK. The CR of PZQ based on the POC-CCA test was 70.9% (95%CI: 62.7–79.1) and 75.5% (95%CI: 67.3–83.6) depending on whether the interpretation of ‘trace’ results was made as positive or negative, respectively. After treatment on the 21st day, 78 and 83 participants tested negative both by KK and POC-CCA, with respective interpretations of ‘trace’ POC-CCA test results as positive or negative. The CR in low, moderate and high transmission settings was 91.7%, 91.2% and 82.5%, respectively (p = 0.377) when evaluated by KK. The CR among SAC with a light infection at baseline (95.7%) by KK was higher than that of moderate (81.5%) and heavy (64.3%) infections (χ2 = 12.53, p = 0.002). Twenty-six (23.6%) participants manifested at least one adverse event. Eleven (10.0%), eight (7.3%), six (5.5%), and three (2.7%) participants complained about abdominal pain, nausea, headache, and anorexia, respectively. All adverse events were mild, needing no intervention. Occurrence of adverse events was slightly higher in high endemic areas (32.5%) than moderate (23.5%) and low endemic areas (p = 0.279). Conclusions A single dose of 40 mg/kg PZQ was efficacious and safe for the treatment of S. mansoni infection when it was evaluated by the KK test, but a lower efficacy was recorded when it was evaluated by the POC-CCA test. However, the POC-CCA test’s specificity, clearance time of CCA from urine after treatment, and interpretation of weakly reactive (trace) test results need further research.

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“…With major morbidities like irreversible hepatic fibrosis and enormous splenomegaly inflicted by schistosomiasis, and the continuous threat of developing praziquantel (Pzq) resistance in endemic areas [22], there is an urge to assess how Clq may affect NLRP3 inflammasome activation and macrophage‐related pro‐inflammatory/anti‐inflammatory enzymes paradigm (e.g., i‐Nos/Arginase‐1) in experimental schistosomiasis mansoni, as well as the parasitic load and hepato‐splenic insults.…”

Section: Introductionmentioning

confidence: 99%

Potential i‐Nos/Arg‐1 Switch with NLRP3 and Parasitic Load Down Regulation in Experimental Schistosoma mansoni Infection via Chloroquine Repurposing

Hasby Saad,

El‐Saadi,

Ali

et al. 2024

Parasite Immunology

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In previous studies, the inhibitory effect of chloroquine on NLRP3 inflammasome and heme production was documented. This may be employed as a double‐bladed sword in schistosomiasis (anti‐inflammatory and parasiticidal). In this study, chloroquine's impact on schistosomiasis mansoni was investigated. The parasitic load (worm/egg counts and reproductive capacity index [RCI]), i‐Nos/Arg‐1 expression, splenomegaly, hepatic insult and NLRP3‐immunohistochemical expression were assessed in infected mice after receiving early and late repeated doses of chloroquine alone or dually with praziquantel. By early treatment, the least RCI was reported in dually treated mice (41.48 ± 28.58) with a significant reduction in worm/egg counts (3.50 ± 1.29/2550 ± 479.58), compared with either drug alone. A marked reduction in the splenic index was achieved by prolonged chloroquine administration (alone: 43.15 ± 5.67, dually: 36.03 ± 5.27), with significantly less fibrosis (15 ± 3.37, 14.25 ± 2.22) than after praziquantel alone (20.5 ± 2.65). Regarding inflammation, despite the praziquantel‐induced significant decrease in NLRP3 expression, the inhibitory effect was marked after dual and chloroquine administration (liver: 3.13 ± 1.21/3.45 ± 1.23, spleen: 5.7 ± 1.6/4.63 ± 2.41). i‐Nos RNA peaked with early/late chloroquine administration (liver: 68.53 ± 1.8/57.78 ± 7.14, spleen: 63.22 ± 2.06/62.5 ± 3.05). High i‐Nos echoed with a parasiticidal and hepatoprotective effect and may indicate macrophage‐1 polarisation. On the flip side, the chloroquine‐induced low Arg‐1 seemed to abate immune tolerance and probably macrophage‐2 polarisation. Collectively, chloroquine synergised the praziquantel‐schistosomicidal effect and minimised tissue inflammation, splenomegaly and hepatic fibrosis.

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A review of the genetic determinants of praziquantel resistance in Schistosoma mansoni: Is praziquantel and intestinal schistosomiasis a perfect match?

Cited by 20 publications

References 176 publications

Visual diagnosis of female genital schistosomiasis in Zambian women from hand-held colposcopy: agreement of expert image review

Visual diagnosis of female genital schistosomiasis in Zambian women from hand-held colposcopy: agreement of expert image review

Efficacy and safety of prazequantel for the treatment of Schistosoma mansoni infection across different transmission settings in Amhara Regional State, northwest Ethiopia

Potential i‐Nos/Arg‐1 Switch with NLRP3 and Parasitic Load Down Regulation in Experimental Schistosoma mansoni Infection via Chloroquine Repurposing

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