Clinical and Preclinical Imaging of Hepatosplenic Schistosomiasis

Masi, Brice; Perles-Barbacaru, Teodora-Adriana; Bernard, Monique; Viola, Angèle

doi:10.1016/j.pt.2019.11.007

Cited by 29 publications

(31 citation statements)

References 99 publications

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“…Additionally, treated SchPAH patients have better survival rates compared to untreated SchPAH patients (89% and 69%, respectively, at 60 months) ( 74 ). A recent systematic review of the literature confirmed the better prognosis of SchPAH in relation to IPAH ( 11 ); however, similarly to the hemodynamic findings of this systematic review, the inclusion of several studies from just one center (potential sample overlap) might have influenced the systematic review findings. Additionally, this interpretation is confounded by the lack of effective non-invasive screening methods to uniformly diagnose PAH early in its course.…”

Section: Differences In Presentation and Prognosis Of Schpah Comparedmentioning

confidence: 50%

“…Hepatosplenic schistosomiasis (HSS) is characterized by hepatosplenomegaly, liver fibrosis, portal hypertension, and esophageal varices ( 11 ), and is generally thought to be a necessary precursor state on the path to development of pulmonary hypertension (PH) ( 12 ). The chronic form of hepatosplenic schistosomiasis follows a host immune system response to eggs generated by the paired flukes and deposited into the mesenteric and portal venous system.…”

Section: Introductionmentioning

confidence: 99%

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Schistosomiasis Pulmonary Arterial Hypertension

et al. 2020

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Pulmonary arterial hypertension (PAH) is a disease of the lung blood vessels that results in right heart failure. PAH is thought to occur in about 5% to 10% of patients with hepatosplenic schistosomiasis, particularly due to S. mansoni. The lung blood vessel injury may result from a combination of embolization of eggs through portocaval shunts into the lungs causing localized Type 2 inflammatory response and vessel remodeling, triggering of autonomous pathology that becomes independent of the antigen, and high cardiac output as seen in portopulmonary hypertension. The condition is likely underdiagnosed as there is little systematic screening, and risk factors for developing PAH are not known. Screening is done by echocardiography, and formal diagnosis requires invasive right heart catheterization. Patients with Schistosoma-associated PAH show reduced functional capacity and can be treated with pulmonary vasodilators, which improves symptoms and may improve survival. There are animal models of this disease that might help in understanding disease pathogenesis and identify novel targets to screen and treatment. Pathogenic mechanisms include Type 2 immunity and activation and signaling in the TGF-β pathway. There are still major uncertainties regarding Schistosoma-associated PAH development, course and treatment.

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Section: Differences In Presentation and Prognosis Of Schpah Comparedmentioning

confidence: 50%

Section: Introductionmentioning

confidence: 99%

Schistosomiasis Pulmonary Arterial Hypertension

et al. 2020

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“…This denoted greater amelioration of schistosomiasis-induced pathology which results from immune-mediated granulomatous responses against Schistosoma eggs trapped in tissues. These are likely to cause serious local and systemic pathological effects associated with granuloma formation and fibrosis [53]. The significant reduction in hepatic granuloma size could be attributed to the distribution of PZQ [13,54] and MFS [55,56] to the liver of mice.…”

Section: Discussionmentioning

confidence: 99%

Single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni

et al. 2020

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Background The control of schistosomiasis has been centered to date on a single drug, praziquantel, with shortcomings including treatment failure, reinfection, and emergence of drug resistance. Drug repurposing, combination therapy or nanotechnology were explored to improve antischistosomal treatment. The aim of the present study was to utilize a novel combination of the three strategies to improve the therapeutic profile of praziquantel. This was based on a fixed-dose nanocombination of praziquantel and miltefosine, an antischistosomal repurposing candidate, co-loaded at reduced doses into lipid nanocapsules, for single dose oral therapy. Methods Two nanocombinations were prepared to provide 250 mg praziquantel-20 mg miltefosine/kg (higher fixed-dose) or 125 mg praziquantel-10 mg miltefosine/kg (lower fixed-dose), respectively. Their antischistosomal efficacy in comparison with a non-treated control and their praziquantel or miltefosine singly loaded counterparts was assessed in murine schistosomiasis mansoni. A single oral dose of either formulation was administered on the initial day of infection, and on days 21 and 42 post-infection. Scanning electron microscopic, parasitological, and histopathological studies were used for assessment. Preclinical data were subjected to analysis of variance and Tukeyʼs post-hoc test for pairwise comparisons. Results Lipid nanocapsules (~ 58 nm) showed high entrapment efficiency of both drugs (> 97%). Compared to singly loaded praziquantel-lipid nanocapsules, the higher nanocombination dose showed a significant increase in antischistosomal efficacy in terms of statistically significant decrease in mean worm burden, particularly against invasive and juvenile worms, and amelioration of hepatic granulomas (P ≤ 0.05). In addition, scanning electron microscopy examination showed extensive dorsal tegumental damage with noticeable deposition of nanostructures. Conclusions The therapeutic profile of praziquantel could be improved by a novel multiple approach integrating drug repurposing, combination therapy and nanotechnology. Multistage activity and amelioration of liver pathology could be achieved by a new praziquantel-miltefosine fixed-dose nanocombination providing 250 mg praziquantel-20 mg miltefosine/kg. To the best of our knowledge, this is the first report of a fixed-dose nano-based combinatorial therapy for schistosomiasis mansoni. Further studies are needed to document the nanocombination safety and explore its prophylactic activity and potential to hinder the onset of resistance to the drug components.

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“…This denoted greater amelioration of schistosomiasis-induced pathology which results from immune-mediated granulomatous responses against Schistosoma eggs trapped in tissues. These are likely to cause serious local and systemic pathological effects associated with granuloma formation and brosis [53]. The signi cant reduction in hepatic granuloma size could be attributed to the distribution of PZQ [13,54] and MFS [55,56] to the liver of mice.…”

Section: Discussionmentioning

confidence: 99%

Single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni

Eissa

El‐Azzouni

El-Khordagui

et al. 2020

Preprint

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Background: The control of schistosomiasis has been centered to date on a single drug, praziquantel, with shortcomings including treatment failure, reinfection, and emergence of drug resistance. Drug repurposing, combination therapy or nanotechnology were explored to improve antischistosomal treatment. The aim of the present study was to utilize a novel combination of the three strategies to improve the therapeutic profile of praziquantel. This was based on a fixed-dose nanocombination of praziquantel and miltefosine, an antischistosomal repurposing candidate, co-loaded at reduced doses into lipid nanocapsules, for single dose oral therapy.Methods: Two nanocombinations were prepared to provide 250 mg praziquantel-20 mg miltefosine/kg (higher fixed-dose) or 125 mg praziquantel-10 mg miltefosine/kg (lower fixed-dose), respectively. Their antischistosomal efficacy in comparison with a non-treated control and their praziquantel or miltefosine singly loaded counterparts was assessed in murine schistosomiasis mansoni. A single oral dose of either formulation was administered on the initial day of infection, and on days 21 and 42 post-infection. Scanning electron microscopic, parasitological, and histopathological studies were used for assessment. Preclinical data were subjected to analysis of variance and Tukeyʼs post-hoc test for pairwise comparisons.Results: Lipid nanocapsules (~58 nm) showed high entrapment efficiency of both drugs (> 97%). Compared to singly loaded praziquantel-lipid nanocapsules, the higher nanocombination dose showed a significant increase in antischistosomal efficacy in terms of statistically significant decrease in mean worm burden, particularly against invasive and juvenile worms, and amelioration of hepatic granulomas (P ≤ 0.05). In addition, scanning electron microscopy examination showed extensive dorsal tegumental damage with noticeable deposition of nanostructures.Conclusions: The therapeutic profile of praziquantel could be improved by a novel multiple approach integrating drug repurposing, combination therapy and nanotechnology. Multistage activity and amelioration of liver pathology could be achieved by a new praziquantel-miltefosine fixed-dose nanocombination providing 250 mg praziquantel-20 mg miltefosine/kg. To the best of our knowledge, this is the first report of a fixed-dose nano-based combinatorial therapy for schistosomiasis mansoni. Further studies are needed to document the nanocombination safety and explore its prophylactic activity and potential to hinder the onset of resistance to the drug components.

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Clinical and Preclinical Imaging of Hepatosplenic Schistosomiasis

Cited by 29 publications

References 99 publications

Schistosomiasis Pulmonary Arterial Hypertension

Schistosomiasis Pulmonary Arterial Hypertension

Single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni

Single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni

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