Factors controlling the effect of praziquantel on liver fibrosis in<i>Schistosoma mansoni</i>-infected patients

Rahoud, Siddig A.; Mergani, Adil; Khamis, Ammar H.; Saeed, Osman K.; Mohamed-Ali, Qurashi; Dessein, Alain; Elwali, Nasr Eldin

doi:10.1111/j.1574-695x.2009.00640.x

Cited by 15 publications

(10 citation statements)

References 30 publications

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“…Another research in Ethiopia also revealed the reversibility of schistosomal periportal fibrosis after praziquantel therapy (Berhe et al 2008). Rahoud et al (2010) reported that in Sudanese patients infected with S. mansoni, 39 months after treatment with praziquantel, ultrasound evaluation showed the periportal fibrosis was regressed in 35.6% of patients, the disease progressed to higher grades in 13.6% of patients, and there were no changes in the others. The study indicated that regression, progression, and stabilization of periportal fibrosis after praziquantel therapy was controlled by gender, age, grade of fibrosis, and possibly inherited factors.…”

Section: Discussionmentioning

confidence: 96%

Effect of praziquantel prolonged administration on granuloma formation around Schistosoma japonicum eggs in lung of sensitized mice

Huang

et al. 2011

Parasitol Res

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Schistosomiasis remains a major public health problem and it is an immune disease. The schistosome egg is the primary parasite factor responsible for the overt disease. The eggs release the soluble antigen, which induces intensive tissue reaction, a granulomatous reaction to the eggs. If granuloma formation could be suppressed, overt disease might not develop. Praziquantel is an effective antischistosomal drug especially for adult worms. However, whether praziquantel has a suppressing effect on granuloma formation around schistosome eggs directly remains unclear. The purpose of the present study was to investigate the effect of praziquantel, especially administered persistently, on granuloma formation around Schistosoma japonicum eggs in the lung of sensitized mice. Thirty-six mice were divided into three groups averagely. Group A was a control group. First, the mice were injected with schistosomal eggs hypodermically in abdomen, and 10 days later injected with schistosomal eggs intravenously via a tail vein. Group B was a praziquantel short administration group. In addition to the injections of schistosomal eggs as the same of Group A, the mice were administered with praziquantel in a daily dose of 300 mg/kg for 3 days, from 1 day before the intravenous injection of the eggs. Group C was a praziquantel prolonged administration group. In addition to the injections of schistosomal eggs as the same of Group A, the mice were administered with praziquantel in a daily dose of 150 mg/kg for 5 days weekly until the mice were sacrificed. Three mice of each group were sacrificed on days 7, 14, 28, and 56, respectively after the intravenous injection of the eggs, and the lung tissues were fixed with formalin and the slices were HE stained. The granulomas containing eggs in their centers were selected, and 25-30 granulomas from the animals of each group were measured at each time period. The mean areas of egg granulomas of each group were calculated, and the neutrophilic granulocytes, eosinocytes, lymphocytes, fibroblasts, and macrophages within the egg granulomas were counted. The mean numbers of them of each group were calculated. All the data of each group were analyzed and compared statistically. On day 56 after the intravenous injection of the eggs, the mean area of schistosomal egg granulomas in group B was (227.4 ± 728.0) × 10(3) μm(2), less than that of [(297.9 ± 153.3) × 10(3) μm(2)] in group A, and the suppression rate was 23.7% (P < 0.05). On days 7, 14, 28, and 56, the mean areas of schistosomal egg granulomas in group C were (575.8 ± 155.6) × 10(3) μm(2), (310.5 ± 854.0) × 10(3) μm(2), (267.7 ± 513.3) × 10(3) μm(2), and (214.9 ± 446.4) × 10(3) μm(2), respectively, significantly less than those of [(692.7 ± 232.6) × 10(3) μm(2), (439.4 ± 165.0) × 10(3) μm(2), (385.7 ± 129.3) × 10(3) μm(2), and (297.9 ± 153.3) × 10(3) μm(2)] in group A. The suppression rates were 16.9%, 29.3%, 30.6%, and 27.9%, respectively (P values <0.05). On day 56, the mean numbers of neutrophilic granulocytes were 11.4 ± 5.0 in group A and 5...

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Section: Discussionmentioning

confidence: 96%

Effect of praziquantel prolonged administration on granuloma formation around Schistosoma japonicum eggs in lung of sensitized mice

Huang

et al. 2011

Parasitol Res

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“…With respect to organ damage, many studies have tried to analyze the efficacy of varying concentrations of PZQ on organ injury [25,26]. However, little is known of its effect to the liver and kidney as a result of repeated and higher doses for treating S. haematobium among sub-Saharan subjects.…”

Section: Discussionmentioning

confidence: 99%

Three monthly doses of 60 mg/kg praziquantel for Schistosoma haematobium infection is a safe and effective treatment regimen

et al. 2020

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Background: Praziquantel (PZQ) is the standard treatment for Schistosomiasis in sub-Saharan Africa. However, there is evidence suggesting praziquantel treatment failure in Schistosome infections with associated potential renal impairment. The objective of this study was to determine the effect of three monthly doses of 60 mg/kg/day PZQ on schistosome egg count, liver and renal function during the treatment of urinary schistosomiasis in Ghana. Methods: A nested case-control study was designed from a cohort screened for schistosomiasis; 28 schistosomiasis positive cases by microscopy matched with 53 healthy controls by age and gender. The study population was urban dwellers from the Asokwa sub-metropolitan area, Kumasi in Ghana. Participants were within the age range of 6 to 30 years. We assessed Schistosoma haematobium egg counts in urine and its associated impact on liver and renal function at baseline, treatment and post-treatment phases using serum. Results: Of the 28 cases and 53 controls, 78.6% and 81.1% were males respectively. Globulin levels before treatment was higher in cases [36.7 (32.8, 40.1) vrs 30.5 (22.4, 33.8), p = 0.005] at pre-treatment but not at post-treatment [35.8 (31.2, 39.1) vrs 37.4 (29.7, 43.0), p = 0.767]. Estimated cure rate was 42.9, 46.4 and 96.4% after first, second and third dose respectively. Schistosome egg counts dropped significantly (p = 0.001) from before second dose to post-treatment. Similarly, levels of alanine aminotransferase (p = 0.001), aspartate aminotransferase (p = 0.028) and gamma glutamyl transferase (p = 0.001) significantly declined towards post-treatment. Estimated glomerular filtration rate significantly improved from before second dose to post-treatment using both the Chronic Kidney Disease Epidemiology Program (p = 0.001) and 4-variable Modification of Diet in Renal Disease (p = 0.002) equations. Conclusion: Treatment of urinary Schistosoma hematobium infections with a repeated high monthly dose of 60 mg/kg of praziquantel for 3 months is safe and effective.

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“…investigated the effect of PZQ treatment (using either R or S enantiomers) on multi-donor hepatocytes seeded and co-cultivated with Kupffer cells, liver endothelial cells and hepatic stellate cells until aggregation into 3D microtissue for 48h 37,38 . Microtissues kept in culture were treated with TGF-β for 7 days and PZQ enantiomers were added during these 7 days of treatment (at day 2 and day 5) at various concentrations (10,33 or 100 µM, as shown in Fig. 2A).…”

Section: Effects Of Pzq Enantiomers In a 3d Human Microtissue Hepaticmentioning

confidence: 99%

Investigating the antifibrotic effect of the antiparasitic drug Praziquantel in in vitro and in vivo preclinical models

Nono

Mpotje

et al. 2020

Sci Rep

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Tissue fibrosis underlies the majority of human mortality to date with close to half of all reported deaths having a fibrotic etiology. The progression of fibrosis is very complex and reputed irreversible once established. Although some preventive options are being reported, therapeutic options are still scarce and in very high demand, given the rise of diseases linked to fibroproliferative disorders. Our work explored four platforms, complementarily, in order to screen preventive and therapeutic potentials of the antiparasitic drug Praziquantel as a possible antifibrotic. We applied the mouse CCl 4driven liver fibrosis model, the mouse chronic schistosomiasis liver fibrosis model, as well as novel 2D and 3D human cell-based co-culture of human hepatocytes, KCs (Kupffer cells), LECs (Liver Endothelial Cells), HSCs (Hepatic Stellate Cells) and/or myofibroblasts to mimic in vivo fibrotic responses and dynamics. Praziquantel showed some effect on fibrosis marker when preventively administered before severe establishment of fibrosis. However, it failed to potently reverse already established fibrosis. Together, we provided a novel sophisticated multi-assay screening platform to test preventive and therapeutic antifibrotic candidates. We further demonstrated a direct preventive potential of Praziquantel against the onset of fibrosis and the confirmation of its lack of therapeutic potential in reversing already established fibrosis. Discovered close to 50 years ago, Praziquantel (PZQ), a tetracyclic tetrahydroisoquinoline derivative administered as a racemate is the main drug therapy for combating flatworm parasites including tapeworms and schistosomes 1,2. In vitro and in vivo, the antischistosomal activity of PZQ enantiomers resides primarily in the (R)-enantiomer 3,4. The drug induces rapid paralysis of adult flatworm musculature and tegumental damage that facilitate the immunological removal of the worm from the host 5,6. As a result, the morbid manifestations of tissue-dwelling flatworm larvae were reported to be considerably, and even at times fully, controlled by PZQ treatment 7-25. One crippling and life-threatening sequelae resulting from Schistosoma eggs trapped in tissue is fibrosis 26,27. Fibrosis manifests as the uncontrolled formation of extracellular matrix in injured organ that progressively replaces the tissue parenchyma and drives pathology. Reduction of tissue fibrosis following PZQ treatment of flatworm-driven infections and injuries has been reported to be a direct consequence of the antiparasitic effect of the drug 28. The still poorly defined mode of action of the drug 5,6,29-32 has made definitive claims on its scope of action difficult. In fact, a recent report claiming PZQ-associated reduction of pathological

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Factors controlling the effect of praziquantel on liver fibrosis inSchistosoma mansoni-infected patients

Cited by 15 publications

References 30 publications

Effect of praziquantel prolonged administration on granuloma formation around Schistosoma japonicum eggs in lung of sensitized mice

Effect of praziquantel prolonged administration on granuloma formation around Schistosoma japonicum eggs in lung of sensitized mice

Three monthly doses of 60 mg/kg praziquantel for Schistosoma haematobium infection is a safe and effective treatment regimen

Investigating the antifibrotic effect of the antiparasitic drug Praziquantel in in vitro and in vivo preclinical models

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