Genetic analysis of decreased praziquantel sensitivity in a laboratory strain of Schistosoma mansoni

Pica‐Mattoccia, Livia; Doenhoff, Michael J.; Valle, Cristiana; Basso, Annalisa; Troiani, Anna-Rita; Liberti, Piero; Festucci, Alfredo; Гуиди, Алессандра; Cioli, Donato

doi:10.1016/j.actatropica.2009.01.012

Cited by 77 publications

(65 citation statements)

References 21 publications

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“…PZQ sensitivity of the latter was assessed using both in vivo and in vitro methods and the results from both approaches lead to the conclusion that hybrid schistosomes of the F 1 generation have a drug sensitivity intermediate between those of the two parental strains. This outcome is thus suggestive of a pattern of partial dominance for the trait under study (Pica-Mattoccia et al 2009). …”

Section: R E S I S T a N C E T O P Z Q I N S M A N S O N Imentioning

confidence: 99%

Praziquantel: its use in control of schistosomiasis in sub-Saharan Africa and current research needs

et al. 2009

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S U M M A R YTreatment with praziquantel (PZQ) has become virtually the sole basis of schistosomiasis control in sub-Saharan Africa and elsewhere, and the drug is reviewed here in the context of the increasing rate that it is being used for this purpose. Attention is drawn to our relative lack of knowledge about the mechanisms of action of PZQ at the molecular level, the need for more work to be done on schistosome isolates that have been collected recently from endemic areas rather than those maintained in laboratory conditions for long periods, and our reliance for experimental work mainly on Schistosoma mansoni, little work having been done on S. haematobium. There is no evidence that resistance to PZQ has been induced in African schistosomes as a result of its large-scale use on that continent to date, but there is also no assurance that PZQ and/ or schistosomes are in any way unique and that resistant organisms will not be selected as a result of widespread drug usage. The failure of PZQ to produce complete cures in populations given a routine treatment should therefore solicit considerable concern. With few alternatives to PZQ currently available and/or on the horizon, methods to monitor drug-susceptibility in African schistosomes need to be devised and used to help ensure that this drug remains effective for as long a time as possible.

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Section: R E S I S T a N C E T O P Z Q I N S M A N S O N Imentioning

confidence: 99%

Praziquantel: its use in control of schistosomiasis in sub-Saharan Africa and current research needs

et al. 2009

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“…There is also some evidence, albeit controversial, that resistance to PZQ may be emerging in Africa, where there has been heavy exposure to the drug and where, worryingly, there are reports of S. mansoni and S. haematobium infections that are not responsive (80). There is laboratory evidence that schistosomes subjected to repeated in vivo PZQ treatments for several generations have reduced drug sensitivity (156) and that drug-tolerant schistosome worms have altered tegumental architecture and increased Pglycoprotein levels (143), which could limit the effectiveness of the drug. So far, however, patients in many communities have undergone multiple courses of treatment over a period of 10 years or more without a demonstrable loss of efficacy.…”

Section: Vol 23 2010 Schistosomiasis and The Three Gorges Dam 451mentioning

confidence: 99%

Schistosomiasis in the People's Republic of China: the Era of the Three Gorges Dam

et al. 2010

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SUMMARY The potential impact of the Three Gorges Dam (TGD) on schistosomiasis transmission in China has invoked considerable global concern. The TGD will result in changes in the water level and silt deposition downstream, favoring the reproduction of Oncomelania snails. Combined with blockages of the Yangtze River's tributaries, these changes will increase the schistosomiasis transmission season within the marshlands along the middle and lower reaches of the Yangtze River. The changing schistosome transmission dynamics necessitate a comprehensive strategy to control schistosomiasis. This review discusses aspects of the epidemiology and transmission of Schistosoma japonicum in China and considers the pathology, clinical outcomes, diagnosis, treatment, immunobiology, and genetics of schistosomiasis japonica together with an overview of current progress in vaccine development, all of which will have an impact on future control efforts. The use of synchronous praziquantel (PZQ) chemotherapy for humans and domestic animals is only temporarily effective, as schistosome reinfection occurs rapidly. Drug delivery requires a substantial infrastructure to regularly cover all parts of an area of endemicity. This makes chemotherapy expensive and, as compliance is often low, a less than satisfactory control option. There is increasing disquiet about the possibility that PZQ-resistant schistosomes will develop. Consequently, as mathematical modeling predicts, vaccine strategies represent an essential component in the future control of schistosomiasis in China. With the inclusion of focal mollusciciding, improvements in sanitation, and health education into the control scenario, China's target of reducing the level of schistosome infection to less than 1% by 2015 may be achievable.

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“…Furthermore, the appearance of drug-resistant strains of Schistosoma is a constant concern for public health authorities (16)(17)(18). Hence, the massive use of PZQ in zones of endemicity with the possibility of the emergence of drug-resistant Schistosoma, combined with the lack of any other effective antischistosomal drug, requires new effective schistosomicidal compounds to be developed and further studies to be carried out with a view to developing alternative therapies that could either replace or complement the use of PZQ for treatment of S. mansoni infection (4,13).…”

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confidence: 99%

Evaluation of the Anti-Schistosoma mansoni Activity of Thiosemicarbazones and Thiazoles

Santiago

Oliveira

Filho

et al. 2014

Antimicrob Agents Chemother

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f Schistosomiasis is a chronic and debilitating disease caused by a trematode of the genus Schistosoma and affects over 207 million people. Chemotherapy is the only immediate recourse for minimizing the prevalence of this disease and involves predominately the administration of a single drug, praziquantel (PZQ). Although PZQ has proven efficacy, there is a recognized need to develop new drugs as schistosomicides since studies have shown that repeated use of this drug in areas of endemicity may cause a temporary reduction in susceptibility in isolates of Schistosoma mansoni. Hydrazones, thiosemicarbazones, phthalimides, and thiazoles are thus regarded as privileged structures used for a broad spectrum of activities and are potential candidates for sources of new drug prototypes. The present study determined the in vitro schistosomicidal activity of 10 molecules containing these structures. During the assays, parameters such motility and mortality, oviposition, morphological changes in the tegument, cytotoxicity, and immunomodulatory activity caused by these compounds were evaluated. The results showed that compounds formed of thiazole and phthalimide led to higher mortality of worms, with a significant decline in motility, inhibition of pairing and oviposition, and a mortality rate of 100% starting from 144 h of exposure. These compounds also stimulated the production of nitric oxide and tumor necrosis factor alpha (TNF-␣), thereby demonstrating the presence of immunomodulatory activity. The phthalyl thiazole LpQM-45 caused significant ultrastructural alterations, with destruction of the tegument in both male and female worms. According to the present study, phthalyl thiazole compounds possess antischistosomal activities and should form the basis for future experimental and clinical trials.

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Genetic analysis of decreased praziquantel sensitivity in a laboratory strain of Schistosoma mansoni

Cited by 77 publications

References 21 publications

Praziquantel: its use in control of schistosomiasis in sub-Saharan Africa and current research needs

Praziquantel: its use in control of schistosomiasis in sub-Saharan Africa and current research needs

Schistosomiasis in the People's Republic of China: the Era of the Three Gorges Dam

Evaluation of the Anti-Schistosoma mansoni Activity of Thiosemicarbazones and Thiazoles

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