Efficacy of Mefloquine Intermittent Preventive Treatment in Pregnancy Against Schistosoma haematobium Infection in Gabon: A Nested Randomized Controlled Assessor-Blinded Clinical Trial

Basra, Arti; Mombo-Ngoma, Ghyslain; Melser, Meskuere Capan; Diop, Daisy Akerey; Würbel, Heike; Mackanga, Jean-Rodolphe; Fürstenau, Moritz; Zoleko, Rella Manego; Adegnika, Ayôla Akim; González, Raquel; Menéndez, Clara; Kremsner, Peter G.; Ramharter, Michael

doi:10.1093/cid/cis976

Cited by 52 publications

(29 citation statements)

References 36 publications

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“…The activity of mefloquine on all the schistosome stages, the multiplicity of targets and the various damages observed on treated worms suggest a complex mode of action, involving both a heme-dependent pathway and a heme-independent mechanism [57][58][91][92]. In summary, the natural-derived drug mefloquine shows antischistosomal activity in animal models [57,[91][92] and clinical trials [93,94], which calls for further investigations in the treatment and control of schistosomiasis.…”

Section: Future Science Groupmentioning

confidence: 97%

Natural Products with Antischistosomal Activity

Moraes¹

2015

Future Med. Chem.

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In recent years, natural product groups have been gaining prominence as possible sources of new drugs for schistosomiasis. This review attempts to update the antischistosomal natural compounds, or natural product-derived compounds, from the mid-1980s. Some of the main metabolites obtained from plants (e.g., terpenes, alkaloids, phenolic compounds and peptides) with in vitro and/or in vivo antischistosomal properties are discussed. Less thoroughly, due to scarcity of data in the literature, molecules from animals (e.g., peptides) are also described. Special mention of the anthelmintic activity against different parasitic stages of schistosomes is made; the mechanism of action of most of the metabolites is discussed, and a number of bioassay procedures are listed.

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Section: Future Science Groupmentioning

confidence: 97%

Natural Products with Antischistosomal Activity

Moraes¹

2015

Future Med. Chem.

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“…In an exploratory trial in Côte d'Ivoire, a mefloquine-artesunate combination showed a moderate cure rate (61%) and high egg reduction rate (96%) in school-aged children infected with S. haematobium [19]. Recently, mefloquine, used as intermittent preventive therapy against malaria in pregnancy (IPT p ), showed high egg reduction rates in women with a concomitant S. haematobium infection [20]. However, combination therapy with mefloquine and praziquantel, which showed high worm burden reductions in laboratory animals [21], has not yet been studied in Schistosoma -infected patients.…”

Section: Introductionmentioning

confidence: 99%

Praziquantel, Mefloquine-Praziquantel, and Mefloquine-Artesunate-Praziquantel against Schistosoma haematobium: A Randomized, Exploratory, Open-Label Trial

Keiser

Silué

Adiossan³

et al. 2014

PLoS Negl Trop Dis

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BackgroundTreatment and morbidity control of schistosomiasis relies on a single drug, praziquantel. Hence, there is a pressing need to develop additional therapeutics against schistosomiasis. The antimalarial drug mefloquine shows antischistosomal activity in animal models and clinical trials, which calls for further investigations.MethodologyWe comparatively assessed the efficacy and tolerability of the following treatments against Schistosoma haematobium in school-aged children in Côte d'Ivoire: (i) praziquantel (40 mg/kg; standard treatment); (ii) mefloquine (25 mg/kg) combined with praziquantel (40 mg/kg); and (iii) mefloquine-artesunate (3× (100 mg artesunate +250 mg mefloquine)) combined with praziquantel (40 mg/kg) (treatments administered on subsequent days). Two urine samples were collected before, and on days 21–22 and 78–79 after the first dosing.Principal FindingsSixty-one children were present on all examination time points and had complete datasets. No difference in efficacy was observed between the three treatment groups on either follow-up. On the 21–22 day posttreatment follow-up, based on available case analysis, cure rates of 33% (95% confidence interval (CI) 11–55%), 29% (95% CI 8–50%), and 26% (95% CI 5–48%) were observed for praziquantel, mefloquine-artesunate-praziquantel, and mefloquine-praziquantel, respectively. The corresponding egg reduction rates were 94% and above. On the second follow-up, observed cure rates ranged from 19% (praziquantel) to 33% (mefloquine-artesunate-praziquantel), and egg reduction rates were above 90%. Praziquantel monotherapy was the best tolerated treatment. In the mefloquine-artesunate-praziquantel group, adverse events were reported by 91% of the participants, and in the mefloquine-praziquantel group, 95% experienced adverse events. With the exception of abdominal pain at moderate severity, adverse events were mild.Conclusions/SignificanceThe addition of mefloquine or mefloquine-artesunate does not increase the efficacy of praziquantel against chronic S. haematobium infection. Additional studies are necessary to elucidate the effect of the combinations against acute schistosomiasis.

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“…For example, the excellent antischistosomal activity of mefloquine (MQ, Figure 1) was demonstrated in S. haematobium , S. japonicum and S. mansoni rodent models [8]. The promising results obtained with MQ in laboratory studies were followed up in clinical trials in the past years [9, 10]. Over the last decade, there has been increasing interest in metal-based drugs and numerous metal complexes have been synthesized and evaluated as antimalarial agents [11].…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo antischistosomal activity of ferroquine derivatives

Keiser

Vargas

Rubbiani

et al. 2014

Parasites & Vectors

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BackgroundSchistosomiasis is a neglected tropical disease and drug-repurposing is a useful strategy to fill its exhausted drug development pipeline. The ferrocenyl analogue of chloroquine, ferroquine, is an antimalarial in late-stage drug development. The aim of the present work was to study the antischistosomal activity of ferroquine against Schistosoma mansoni adult worms and newly transformed schistosomula (NTS) in vitro and in vivo. Hydroxyl-ferroquine and ruthenoquine were included to study the potential role of reactive oxygen species in the antischistosomal activity. Chloroquine and mefloquine, the later described for its antischistosomal properties, served as comparators.FindingsAll metal complexes were shown to be moderately cytotoxic on human cervix HeLa cancer cells and human fetal lung fibroblasts MRC-5. 72 hours post-incubation NTS exposed to 33.3 µM ruthenoquine had died, while ferroquine and hydroxyl-ferroquine treated worms were strongly affected. No activity was observed treating NTS with chloroquine at 33.3 µM. Incubation of adult S. mansoni with 33.3 µM of the organometallic derivatives were highly affected in viability but were still alive 72 hours post-incubation. Mefloquine showed the highest activity against NTS and adult S. mansoni. Low total worm burden reductions of 0-36% were observed following oral administration of 200–800 mg/kg of the ferroquine derivatives to S. mansoni-infected mice.ConclusionsThe organometallic compounds evaluated in this study revealed moderate in vitro activity against both larval and adult stages of S. mansoni but low in vivo activity. No correlation can be drawn between the antimalarial and antischistosomal activity of chloroquine analogues and oxidative shock does not seem to play a role in the activity of these compounds against S. mansoni.

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Efficacy of Mefloquine Intermittent Preventive Treatment in Pregnancy Against Schistosoma haematobium Infection in Gabon: A Nested Randomized Controlled Assessor-Blinded Clinical Trial

Abstract: NCT01132248; ATMR2010020001429343.

Cited by 52 publications

References 36 publications

Natural Products with Antischistosomal Activity

Natural Products with Antischistosomal Activity

Praziquantel, Mefloquine-Praziquantel, and Mefloquine-Artesunate-Praziquantel against Schistosoma haematobium: A Randomized, Exploratory, Open-Label Trial

In vitro and in vivo antischistosomal activity of ferroquine derivatives

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