Elimination of schistosomiasis: the tools required

Bergquist, Robert; Zhou, Xiao-Nong; Rollinson, David; Reinhard-Rupp, Jutta; Klohe, Katharina

doi:10.1186/s40249-017-0370-7

Cited by 93 publications

(78 citation statements)

References 44 publications

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Section: Introductionmentioning

confidence: 99%

“…Dependence on mass drug administration (MDA) alone with praziquantel (PZQ) for the past several decades has not yielded satisfactory results, and infection rates continue to be high despite global PZQ coverage in 2016 of 54%. 1,2,6,7 Furthermore, large-scale PZQ use may lead to drug resistance in the parasite. 4 An efficacious vaccine inducing prolonged protection would result in a substantial decrease in transmission of infection and morbidity, particularly if deployed concurrently with existing control measures.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sm‐p80‐based schistosomiasis vaccine: double‐blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission‐blocking efficacy

Zhang

Molehin

Rojo

et al. 2018

Annals of the New York Academy of Sciences

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Schistosomiasis is of public health importance to an estimated one billion people in 79 countries. A vaccine is urgently needed. Here, we report the results of four independent, double-blind studies of an Sm-p80-based vaccine in baboons. The vaccine exhibited potent prophylactic efficacy against transmission of Schistosoma mansoni infection and was associated with significantly less egg-induced pathology, compared with unvaccinated control animals. Specifically, the vaccine resulted in a 93.45% reduction of pathology-producing female worms and significantly resolved the major clinical manifestations of hepatic/intestinal schistosomiasis by reducing the tissue egg-load by 89.95%. A 35-fold decrease in fecal egg excretion in vaccinated animals, combined with an 81.51% reduction in hatching of eggs into the snail-infective stage (miracidia), demonstrates the parasite transmission-blocking potential of the vaccine. Substantially higher Sm-p80 expression in female worms and Sm-p80-specific antibodies in vaccinated baboons appear to play an important role in vaccine-mediated protection. Preliminary analyses of RNA sequencing revealed distinct molecular signatures of vaccine-induced effects in baboon immune effector cells. This study provides comprehensive evidence for the effectiveness of an Sm-p80-based vaccine for schistosomiasis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sm‐p80‐based schistosomiasis vaccine: double‐blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission‐blocking efficacy

Zhang

Molehin

Rojo

et al. 2018

Annals of the New York Academy of Sciences

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“…Schistosomiasis represents aw orldwidet hreat for humans and animals. Lowered PZQ sensitivity in treatedp atients has been observed, provoking the fear of future resistance, [10,11,27,28] therefore alternative medications are needed. An ew approach originating from potential inhibitors of human AR revealed promising anti-schistosomal compounds.…”

Section: Discussionmentioning

confidence: 99%

Development of Biarylalkyl Carboxylic Acid Amides with Improved Anti‐schistosomal Activity

et al. 2019

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The parasitic disease schistosomiasis is the cause of more than 200 000 human deaths per year. Although the disease is treatable, there is one major shortcoming: praziquantel has been the only drug used to combat these parasites since 1977. The risk of the emergence of resistant schistosomes is known to be increasing, as a reduced sensitivity of these parasites toward praziquantel has been observed. We developed a new class of substances, which are derived from inhibitors of human aldose reductase, and which showed promising activity against Schistosoma mansoni couples in vitro. Further optimisation of the compounds led to an increase in anti‐schistosomal activity with observed phenotypes such as reduced egg production, vitality, and motility as well as tegumental damage and gut dilatation. Here, we performed structure–activity relationship studies on the carboxylic acid moiety of biarylalkyl carboxylic acids. Out of 82 carboxylic acid amides, we identified 10 compounds that are active against S. mansoni at 25 μm. The best five compounds showed an anti‐schistosomal activity up to 10 μm and induced severe phenotypes. Cytotoxicity tests in human cell lines showed that two derivatives had no cytotoxicity at 50 or 100 μm. These compounds are promising candidates for further optimisation toward the new anti‐schistosomal agents.

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“…[10,11] The use of as ingle drug, however,c onstitutes as election pressure that might favor resistance development. [12,13] Oxamniquinep receded PZQ and represents ap ossible alternative, but it is only active against S. mansoni and is currently unavailable. [14,15] Therefore, it is generally acknowledged that new drugs are required to fight schistosomiasis and related parasite-induced infectious diseases.…”

Section: Schistosomiasismentioning

confidence: 99%

“…[88] (9)and their major metabolites 10. [56,66,67] B) Chemical structureso fmiracil A(11), oxamniquine ( 13), and (S)-oxamniquine. [89,90] C) Oxamniquine (13)a nd its mechanism of action.…”

Section: Oxamniquinementioning

confidence: 99%

Chemotherapy for Fighting Schistosomiasis: Past, Present and Future

et al. 2018

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Chemotherapy based on repeated doses of praziquantel remains the most effective control strategy against schistosomiasis, a neglected tropical disease caused by platyhelminths of the genus Schistosoma spp. Its long-term use, however, raises serious concerns about drug resistance against praziquantel. Therefore, it is generally acknowledged that alternative treatment options are urgently needed. This Review summarizes data on relinquished drugs as well as recent advances in the area of antischistosomal compounds from a medicinal chemistry point of view. Furthermore, insights into the structure-activity relationships of each class of compounds are presented including in vitro and in vivo data, if available. Although many compounds have demonstrated good antischistosomal activity in vitro, they offer little promise to replace praziquantel. Nevertheless, the race to develop novel antischistosomal agents is ongoing.

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Elimination of schistosomiasis: the tools required

Cited by 93 publications

References 44 publications

Sm‐p80‐based schistosomiasis vaccine: double‐blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission‐blocking efficacy

Sm‐p80‐based schistosomiasis vaccine: double‐blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission‐blocking efficacy

Development of Biarylalkyl Carboxylic Acid Amides with Improved Anti‐schistosomal Activity

Chemotherapy for Fighting Schistosomiasis: Past, Present and Future

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