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Jeanfrancois Rossignol - One of the best experts on this subject based on the ideXlab platform.
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activity of halogeno thiazolides against cryptosporidium parvum in experimentally infected immunosuppressed gerbils meriones unguiculatus
Antimicrobial Agents and Chemotherapy, 2013Co-Authors: Gilles Gargala, Laurent Favennec, Arnaud Francois, Jeanfrancois RossignolAbstract:Nitazoxanide and three halogeno-thiazolides, RM-4850, RM-4865, and RM-5038, were tested against Cryptosporidium parvum in experimentally infected immunosuppressed Mongolian gerbils. Daily 400-mg/kg doses of the four test drugs for 5 to 8 consecutive days produced similar reductions of oocyst shedding. Using early-infected gerbils, a shorter 4-day treatment with RM-5038 reduced oocyst shedding by 95%, compared to 47% for Nitazoxanide (P = 0.02), suggesting that RM-5038 is more effective than Nitazoxanide under the experimental conditions used.
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Nitazoxanide for the empiric treatment of pediatric infectious diarrhea
Transactions of The Royal Society of Tropical Medicine and Hygiene, 2012Co-Authors: Jeanfrancois Rossignol, Nicolas Lopezchegne, Luis Martin Julcamoro, Maria E Carrion, Matthew BardinAbstract:Summary We conducted a double-blind, placebo-controlled clinical trial to demonstrate the efficacy of Nitazoxanide suspension for the treatment of presumed infectious diarrhea in children. Eligible patients must have had diarrheal illness lasting 3–29 days. Patients were randomized to receive either Nitazoxanide or placebo twice daily for three days. The primary endpoint was time from first dose to resolution of symptoms. One hundred children mean age 3.3 years were enrolled. The median time to resolution of symptoms for Nitazoxanide treated patients was 23 hours (IQR 4–48 hours) vs 103.5 hours (IQR 63– >168 hours) for placebo (p Giardia lamblia (n = 32, p 0.001) and those with no identified enteropathogen (n = 38, p = 0.008), when compared to placebo. The study medication was well tolerated. Overall, Nitazoxanide was effective at reducing the duration of diarrheal illness associated with multiple etiologies, including patients with no identified enteropathogen. These results suggest Nitazoxanide may be a viable therapeutic option for the empiric treatment of diarrheal illness in children where the etiology is unknown or presumed to be of infectious origin. Clinical trial registry number NCT01326338 .
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evaluation of new thiazolide thiadiazolide derivatives reveals nitro group independent efficacy against in vitro development of cryptosporidium parvum
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Gilles Gargala, Laetitia Le Goff, Jean Jacques Ballet, Laurent Favennec, Andrew V Stachulski, Jeanfrancois RossignolAbstract:Thirty-nine new thiazolide/thiadiazolide compounds were compared with the nitrothiazole Nitazoxanide for activity against Cryptosporidium parvum development in HCT-8 cells. Twenty-seven agents exerted ≥90% inhibition. Agents with a lower 50% inhibitory concentration (IC50) than Nitazoxanide were either NO2 or halogen 5 substituted on the thiazole moiety. Other 5 substitutions such as methyl, C3H7, C6H11, H, SO2CH3, and SCH3 negatively impacted activity. Five-substituted deacetylated analogues exhibited higher IC50s than their acetylated counterparts. Halogeno-thiazolide/thiadiazolides may provide valuable nitro-free alternatives to Nitazoxanide.
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cryptosporidium and giardia treatment options and prospects for new drugs
Experimental Parasitology, 2010Co-Authors: Jeanfrancois RossignolAbstract:Cryptosporidium species and Giardia intestinalis are the most common enteric protozoan pathogens affecting humans worldwide. In recent years, Nitazoxanide has been licensed in the United States for the treatment of cryptosporidiosis in non-immunodeficient children and adults, becoming the first drug approved for treating this disease. There is a need for a highly effective treatment for cryptosporidiosis in immunodeficient patients, but the quest for such a drug has proven to be elusive. While not effective against Cryptosporidium, nitroimidazoles such as metronidazole or tinidazole are effective treatments for giardiasis and can be administered as a single dose. Albendazole and Nitazoxanide are effective against giardiasis but require multiple doses. Nitazoxanide is the first new drug developed for treating giardiasis in more than 20years. New potentially promising drug targets in Cryptosporidium and Giardia have been identified, but there appears to be little activity toward clinical development of new drugs.
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effect of Nitazoxanide in diarrhea and enteritis caused by cryptosporidium species
Clinical Gastroenterology and Hepatology, 2006Co-Authors: Jeanfrancois Rossignol, Samir M Kabil, Yehia El Gohary, Azza M YounisAbstract:Background & Aims: The aim of this study was to evaluate the efficacy of Nitazoxanide for the treatment of diarrhea and enteritis caused by Cryptosporidium species in patients 12 years of age and older. Methods: A multicenter, randomized, double-blind, placebo-controlled study was conducted in 90 outpatients 12 years of age and older from the Nile Delta region of Egypt. Patients were randomized to receive either one 500 mg tablet or one matching placebo tablet, or 25 mL of Nitazoxanide oral suspension (500 mg Nitazoxanide), each given twice daily for 3 days. Clinical and microbiologic response rates were evaluated 4 days after completion of treatment. Results: Twenty-seven (96%) of the 28 patients receiving Nitazoxanide tablets responded clinically compared with 11 (41%) of 27 patients who received placebo (P < .0001). Twenty-six (93%) of the 28 patients who received Nitazoxanide were free of Cryptosporidium oocysts in each of 2 posttreatment stool samples compared with only 10 (37%) of 27 patients who received placebo (P < .0001). Response rates in patients receiving the tablets and the suspension were comparable (clinical response rate for suspension, 27 of 31 [87%]; microbiologic response rate for suspension, 28 of 31 [90%]). Conclusions: These findings show that a 3-day course of Nitazoxanide is effective in treating diarrhea and enteritis caused by Cryptosporidium in nonimmunodeficient patients 12 years of age and older.
Norbert Müller - One of the best experts on this subject based on the ideXlab platform.
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nitroreductase glnr1 increases susceptibility of giardia lamblia and escherichia coli to nitro drugs
Journal of Antimicrobial Chemotherapy, 2011Co-Authors: Dorothea Nillius, J Muller, Norbert MüllerAbstract:OBJECTIVES: The protozoan parasite Giardia lamblia causes the intestinal disease giardiasis, which may lead to acute and chronic diarrhoea in humans and various animal species. For treatment of this disease, several drugs such as the benzimidazole albendazole, the nitroimidazole metronidazole and the nitrothiazolide Nitazoxanide are currently in use. Previously, a G. lamblia nitroreductase 1 (GlNR1) was identified as a Nitazoxanide-binding protein. The aim of the present project was to elucidate the role of this enzyme in the mode of action of the nitro drugs Nitazoxanide and metronidazole. METHODS: Recombinant GlNR1 was overexpressed in both G. lamblia and Escherichia coli (strain BL21). The susceptibility of the transfected bacterial and giardial cell lines to Nitazoxanide and metronidazole was analysed. RESULTS: G. lamblia trophozoites overexpressing GlNR1 had a higher susceptibility to both nitro drugs. E. coli were fully resistant to Nitazoxanide under both aerobic and semi-aerobic growth conditions. When grown semi-aerobically, bacteria overexpressing GlNR1 became susceptible to Nitazoxanide. CONCLUSIONS: These findings suggest that GlNR1 activates nitro drugs via reduction yielding a cytotoxic product.
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Identification of differentially expressed genes in a Giardia lamblia WB C6 clone resistant to Nitazoxanide and metronidazole
The Journal of antimicrobial chemotherapy, 2008Co-Authors: Joachim Müller, Andrew Hemphill, Serej D. Ley, Ingrid Felger, Norbert MüllerAbstract:OBJECTIVES The characterization of differential gene expression in Giardia lamblia WB C6 strain C4 resistant to metronidazole and Nitazoxanide using microarray technology and quantitative real-time PCR. METHODS In a previous study, we created and characterized the G. lamblia WB C6 clone C4 resistant to Nitazoxanide and metronidazole. In this study, using a microarray-based approach, we have identified open-reading frames (ORFs) that were differentially expressed in C4 when compared with its wild-type WB C6. Using quantitative real-time PCR, we have validated the expression patterns of some of those ORFs, focusing on chaperones such as heat-shock proteins in wild-type and C4 trophozoites. In order to induce an antigenic shift, trophozoites of both strains were subjected to a cycle of en- and excystation. Expression of selected genes and resistance to Nitazoxanide and metronidazole were investigated after this cycle. RESULTS Forty of a total of 9115 ORFs were found to be up-regulated and 46 to be down-regulated in C4 when compared with wild-type. After a cycle of en- and excystation, resistance of C4 to Nitazoxanide and metronidazole was lost. Resistance formation and en-/excystation were correlated with changes in expression of ORFs encoding for major surface antigens such as the variant surface protein TSA417 or AS7 ('antigenic shift'). Moreover, expression patterns of the cytosolic heat-shock protein HSP70 B2, HSP40, and of the previously identified Nitazoxanide-binding proteins nitroreductase and protein disulphide isomerase PDI4 were correlated with resistance and loss of resistance after en-/excystation. C4 trophozoites had a higher thermotolerance level than wild-type trophozoites. After en-/excystation, this tolerance was lost. CONCLUSIONS These results suggest that resistance formation in Giardia to Nitazoxanide and metronidazole is correlated with altered expression of genes involved in stress response such as heat-shock proteins.
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in vitro efficacies of Nitazoxanide and other thiazolides against neospora caninum tachyzoites reveal antiparasitic activity independent of the nitro group
Antimicrobial Agents and Chemotherapy, 2005Co-Authors: Marco Esposito, Rebecca Stettler, Shelley L Moores, Chandrakala Pidathala, Neil G Berry, Norbert Müller, Andrew V Stachulski, Jeanfrancois Rossignol, Andrew HemphillAbstract:The thiazolide Nitazoxanide [2-acetolyloxy-N-(5-nitro-2-thiazolyl)benzamide] (NTZ) exhibits a broad spectrum of activities against a wide variety of intestinal and tissue-dwelling helminths, protozoa, and enteric bacteria infecting animals and humans. The drug has been postulated to act via reduction of its nitro group by nitroreductases, including pyruvate ferredoxin oxidoreductase. In this study, we investigated the efficacies of Nitazoxanide and a number of other thiazolides against Neospora caninum tachyzoites in vitro. We employed real-time-PCR-based monitoring of tachyzoite adhesion, invasion, and intracellular proliferation, as well as electron microscopic visualization of the effects imposed by Nitazoxanide. In addition, we investigated several modified versions of this drug. These modifications included on one hand the replacement of the nitro group on the thiazole ring with a bromide, thus removing the most reactive group, and on the other hand the differential positioning of methyl groups on the salicylate ring. We show that the thiazole-associated nitro group is not necessarily required for the action of the drug and that methylation of the salicylate ring can result in complete abrogation of the antiparasitic activity, depending on the positioning of the methyl group. These findings indicate that other mechanisms besides the proposed mode of action involving the pyruvate ferredoxin oxidoreductase enzyme could be responsible for the wide spectrum of antiparasitic activity of NTZ and that modifications in the benzene ring could be important in these alternative mechanisms.
Andrew Hemphill - One of the best experts on this subject based on the ideXlab platform.
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Identification of differentially expressed genes in a Giardia lamblia WB C6 clone resistant to Nitazoxanide and metronidazole
The Journal of antimicrobial chemotherapy, 2008Co-Authors: Joachim Müller, Andrew Hemphill, Serej D. Ley, Ingrid Felger, Norbert MüllerAbstract:OBJECTIVES The characterization of differential gene expression in Giardia lamblia WB C6 strain C4 resistant to metronidazole and Nitazoxanide using microarray technology and quantitative real-time PCR. METHODS In a previous study, we created and characterized the G. lamblia WB C6 clone C4 resistant to Nitazoxanide and metronidazole. In this study, using a microarray-based approach, we have identified open-reading frames (ORFs) that were differentially expressed in C4 when compared with its wild-type WB C6. Using quantitative real-time PCR, we have validated the expression patterns of some of those ORFs, focusing on chaperones such as heat-shock proteins in wild-type and C4 trophozoites. In order to induce an antigenic shift, trophozoites of both strains were subjected to a cycle of en- and excystation. Expression of selected genes and resistance to Nitazoxanide and metronidazole were investigated after this cycle. RESULTS Forty of a total of 9115 ORFs were found to be up-regulated and 46 to be down-regulated in C4 when compared with wild-type. After a cycle of en- and excystation, resistance of C4 to Nitazoxanide and metronidazole was lost. Resistance formation and en-/excystation were correlated with changes in expression of ORFs encoding for major surface antigens such as the variant surface protein TSA417 or AS7 ('antigenic shift'). Moreover, expression patterns of the cytosolic heat-shock protein HSP70 B2, HSP40, and of the previously identified Nitazoxanide-binding proteins nitroreductase and protein disulphide isomerase PDI4 were correlated with resistance and loss of resistance after en-/excystation. C4 trophozoites had a higher thermotolerance level than wild-type trophozoites. After en-/excystation, this tolerance was lost. CONCLUSIONS These results suggest that resistance formation in Giardia to Nitazoxanide and metronidazole is correlated with altered expression of genes involved in stress response such as heat-shock proteins.
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Nitazoxanide a broad spectrum thiazolide anti infective agent for the treatment of gastrointestinal infections
Expert Opinion on Pharmacotherapy, 2006Co-Authors: Andrew Hemphill, Joachim Mueller, Marco EspositoAbstract:Colonisation of the gastrointestinal tract by anaerobic bacteria, protozoa, trematodes, cestodes and/or nematodes and other infectious pathogens, including viruses, represents a major cause of morbidity and mortality in Africa, South America and southeast Asia, as well as other parts of the world. Nitazoxanide is a member of the thiazolide class of drugs with a documented broad spectrum of activity against parasites and anaerobic bacteria. Moreover, the drug has recently been reported to have a profound activity against hepatitis C virus infection. In addition, Nitazoxanide exhibits anti-inflammatory properties, which have prompted clinical investigations for its use in Crohn's disease. Studies with Nitazoxanide derivatives have determined that there must be significantly different mechanisms of action acting on intracellular versus extracellular pathogens. An impressive number of clinical studies have shown that the drug has an excellent bioavailability in the gastrointestinal tract, is fast acting and highly effective against gastrointestinal bacteria, protozoa and helminthes. A recent Phase II study has demonstrated viral response (hepatitis C) to monotherapy, with a low toxicity and an excellent safety profile over 24 weeks of treatment. Pre-clinical studies have indicated that there is a potential for application of this drug against other diseases, not primarily affecting the liver or the gastrointestinal tract.
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in vitro efficacies of Nitazoxanide and other thiazolides against neospora caninum tachyzoites reveal antiparasitic activity independent of the nitro group
Antimicrobial Agents and Chemotherapy, 2005Co-Authors: Marco Esposito, Rebecca Stettler, Shelley L Moores, Chandrakala Pidathala, Neil G Berry, Norbert Müller, Andrew V Stachulski, Jeanfrancois Rossignol, Andrew HemphillAbstract:The thiazolide Nitazoxanide [2-acetolyloxy-N-(5-nitro-2-thiazolyl)benzamide] (NTZ) exhibits a broad spectrum of activities against a wide variety of intestinal and tissue-dwelling helminths, protozoa, and enteric bacteria infecting animals and humans. The drug has been postulated to act via reduction of its nitro group by nitroreductases, including pyruvate ferredoxin oxidoreductase. In this study, we investigated the efficacies of Nitazoxanide and a number of other thiazolides against Neospora caninum tachyzoites in vitro. We employed real-time-PCR-based monitoring of tachyzoite adhesion, invasion, and intracellular proliferation, as well as electron microscopic visualization of the effects imposed by Nitazoxanide. In addition, we investigated several modified versions of this drug. These modifications included on one hand the replacement of the nitro group on the thiazole ring with a bromide, thus removing the most reactive group, and on the other hand the differential positioning of methyl groups on the salicylate ring. We show that the thiazole-associated nitro group is not necessarily required for the action of the drug and that methylation of the salicylate ring can result in complete abrogation of the antiparasitic activity, depending on the positioning of the methyl group. These findings indicate that other mechanisms besides the proposed mode of action involving the pyruvate ferredoxin oxidoreductase enzyme could be responsible for the wide spectrum of antiparasitic activity of NTZ and that modifications in the benzene ring could be important in these alternative mechanisms.
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in vitro effects of Nitazoxanide on echinococcus granulosus protoscoleces and metacestodes
Journal of Antimicrobial Chemotherapy, 2004Co-Authors: Mirjam Walker, Jeanfrancois Rossignol, Paul R Torgerson, Andrew HemphillAbstract:Objectives: Infection of humans and domestic ruminants with the larval stage (metacestode) of Echinococcus granulosus results in cystic echinococcosis (CE). The metacestode causes a space-occupying lesion in visceral organs, most commonly in the liver. Benzimidazole carbamate derivatives, such as mebendazole and albendazole, are currently used for chemotherapeutic treatment of CE. In human patients, benzimidazoles have to be applied in high doses for extended periods of time, and adverse side effects are frequently observed. In order to evaluate alternative treatment options, the in vitro efficacy of Nitazoxanide, a broad-spectrum drug used against intestinal parasites and bacteria, was investigated. Methods: Freshly isolated E. granulosus protoscoleces were subjected to Nitazoxanide treatment (1, 5 and 10mg/mL), and the effects on parasite viability were monitored by Trypan Blue staining and scanning electron microscopy. Protoscolex cultures were maintained further, until metacestode development took place. Metacestodes were then subjected to Nitazoxanide treatment (10mg/mL), and corresponding effects were visualized by scanning and transmission electron microscopy. Results: Dose-dependent protoscolex death within a few days of Nitazoxanide treatment was observed. Subsequent in vitro culture of drug-treated protoscoleces confirmed the non-viability of parasites, while further cultivation of non-treated protoscoleces for a period of at least 3 months resulted in stage conversion and the formation of small metacestodes 3‐4 mm in diameter. Nitazoxanide had a deleterious effect on these metacestodes, which was comparable to that of albendazole. Conclusions: Our study indicates a potential for Nitazoxanide as an alternative treatment option against CE.
Laurent Favennec - One of the best experts on this subject based on the ideXlab platform.
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activity of halogeno thiazolides against cryptosporidium parvum in experimentally infected immunosuppressed gerbils meriones unguiculatus
Antimicrobial Agents and Chemotherapy, 2013Co-Authors: Gilles Gargala, Laurent Favennec, Arnaud Francois, Jeanfrancois RossignolAbstract:Nitazoxanide and three halogeno-thiazolides, RM-4850, RM-4865, and RM-5038, were tested against Cryptosporidium parvum in experimentally infected immunosuppressed Mongolian gerbils. Daily 400-mg/kg doses of the four test drugs for 5 to 8 consecutive days produced similar reductions of oocyst shedding. Using early-infected gerbils, a shorter 4-day treatment with RM-5038 reduced oocyst shedding by 95%, compared to 47% for Nitazoxanide (P = 0.02), suggesting that RM-5038 is more effective than Nitazoxanide under the experimental conditions used.
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evaluation of new thiazolide thiadiazolide derivatives reveals nitro group independent efficacy against in vitro development of cryptosporidium parvum
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Gilles Gargala, Laetitia Le Goff, Jean Jacques Ballet, Laurent Favennec, Andrew V Stachulski, Jeanfrancois RossignolAbstract:Thirty-nine new thiazolide/thiadiazolide compounds were compared with the nitrothiazole Nitazoxanide for activity against Cryptosporidium parvum development in HCT-8 cells. Twenty-seven agents exerted ≥90% inhibition. Agents with a lower 50% inhibitory concentration (IC50) than Nitazoxanide were either NO2 or halogen 5 substituted on the thiazole moiety. Other 5 substitutions such as methyl, C3H7, C6H11, H, SO2CH3, and SCH3 negatively impacted activity. Five-substituted deacetylated analogues exhibited higher IC50s than their acetylated counterparts. Halogeno-thiazolide/thiadiazolides may provide valuable nitro-free alternatives to Nitazoxanide.
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in vitro efficacy of nitro and halogeno thiazolide thiadiazolide derivatives against sarcocystis neurona
Veterinary Parasitology, 2009Co-Authors: Gilles Gargala, Laetitia Le Goff, Jean Jacques Ballet, Laurent Favennec, Andrew V Stachulski, J.-f. RossignolAbstract:Sarcocystis neurona is an obligate intracellular parasite that causes equine protozoal myeloencephalitis (EPM). The aim of this work was to document inhibitory activities of Nitazoxanide (NTZ, [2-acetolyloxy-N-(5-nitro 2-thiazolyl) benzamide]) and new thiazolides/thiadiazolides on S. neurona in vitro development, and investigate their structure-activity relationships. S. neurona was grown in bovine turbinate cell cultures. At concentrations varying from 1.0 to 5.0mg/L, Nitazoxanide and 21 of 32 second generation thiazolide/thiadiazolide agents exerted a > or =95% maximum inhibition on S. neurona development. Most active agents were either NO(2) or halogen substituted in position 5 of their thiazole moiety. In contrast, other 5-substitutions such as hydrogen, methyl, SO(2)CH(3), and CH(3) negatively impacted activity. Compared with derivatives with an acetylated benzene moiety, deacetylated compounds which most probably represent primary metabolites exhibited similar inhibitory activities. Present data provide the first evidence of in vitro inhibitory activities of Nitazoxanide and new thiazolides/thiadiazolides on S. neurona development. Active halogeno-thiazolide/thiadiazolides may provide a valuable nitro-free alternative to Nitazoxanide for EPM treatment depending on further evaluation of their in vivo activities.
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Efficacy of Nitazoxanide and paromomycin in biliary tract cryptosporidiosis in an immunosuppressed gerbil model
The Journal of antimicrobial chemotherapy, 2005Co-Authors: A. Baishanbo, Gilles Gargala, Jean Jacques Ballet, C. Duclos, A. Francois, J.-f. Rossignol, Laurent FavennecAbstract:Objectives: To evaluate the efficacy of Nitazoxanide and paromomycin in biliary tract cryptosporidiosis in an immunosuppressed Mongolian gerbil (Meriones unguiculatus) model. Methods: Gerbils (1-month-old) were dexamethasone-immunosuppressed for 10 days and challenged orally with 10 5 Cryptosporidium parvum oocysts. From day 0 to day 12 post-infection, one group (n = 14) was treated with 200 mg/kg/day Nitazoxanide and another (n = 15) with 100 mg/kg/day paromomycin. Infection and efficacy of Nitazoxanide and paromomycin were assessed by measuring oocyst shedding in faeces, biliary tract and ileum histological examination. Results: In Nitazoxanide-treated and paromomycin-treated groups as compared with untreated animals (P 0.05). Parasites were present in histological sections of the ileal mucosa of 16/16 infected untreated animals versus 3/14 and 6/15 in the Nitazoxanide-treated and the paromomycin-treated groups, respectively (P< 0.05). In addition, gall bladder infection was less frequent in Nitazoxanide-treated (2/14, P< 0.01) and paromomycin-treated (5/15, P= 0.07) animals than in untreated controls (9/16). No histological alteration of biliary mucosa was observed in both treated and untreated infected gerbils. Conclusions: Present data support the efficacy of Nitazoxanide and, to a lesser extent, paromomycin on biliary C. parvum infection in gerbils, and prompt further investigation of the potential clinical benefits of Nitazoxanide in treating human biliary cryptosporidiosis.
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double blind randomized placebo controlled study of Nitazoxanide in the treatment of fascioliasis in adults and children from northern peru
Alimentary Pharmacology & Therapeutics, 2003Co-Authors: Laurent Favennec, Gilles Gargala, A Ayoub, Jave J Ortiz, Lopez N Chegne, J.-f. RossignolAbstract:Summary Background : Human fascioliasis is a significant world-wide health problem, and massive or repeated infections by Fasciola hepatica can lead to considerable morbidity. Aim : To evaluate the safety and efficacy of Nitazoxanide, when compared with placebo, in the treatment of fascioliasis in adults and children from northern Peru. Methods : A double-blind, placebo-controlled study was carried out in 50 adults and 50 children infected with F. hepatica. The diagnosis of infection was based on the presence of F. hepatica eggs in one stool sample obtained before inclusion in the study. Patients were randomized to receive treatment with either a 7-day course of Nitazoxanide (100 mg b.d., age range 2–3 years; 200 mg b.d., age range 4–11 years; 500 mg b.d., age > 12 years) or matching placebo. Three post-treatment stool examinations were carried out between 30 and 90 days after initiation of treatment. Results : The parasite was eliminated in 18 of 30 (60%) adults completing the study who received Nitazoxanide vs. one of eight adults in the placebo group (P = 0.042), and similarly in 14 of 35 (40%) children completing the treatment vs. none of eight in the placebo group (P = 0.038). Only mild, transient adverse events were reported. Conclusions : A 7-day course of Nitazoxanide was effective in adults and children in the treatment of F. hepatica, when compared with placebo.
J.-f. Rossignol - One of the best experts on this subject based on the ideXlab platform.
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in vitro efficacy of nitro and halogeno thiazolide thiadiazolide derivatives against sarcocystis neurona
Veterinary Parasitology, 2009Co-Authors: Gilles Gargala, Laetitia Le Goff, Jean Jacques Ballet, Laurent Favennec, Andrew V Stachulski, J.-f. RossignolAbstract:Sarcocystis neurona is an obligate intracellular parasite that causes equine protozoal myeloencephalitis (EPM). The aim of this work was to document inhibitory activities of Nitazoxanide (NTZ, [2-acetolyloxy-N-(5-nitro 2-thiazolyl) benzamide]) and new thiazolides/thiadiazolides on S. neurona in vitro development, and investigate their structure-activity relationships. S. neurona was grown in bovine turbinate cell cultures. At concentrations varying from 1.0 to 5.0mg/L, Nitazoxanide and 21 of 32 second generation thiazolide/thiadiazolide agents exerted a > or =95% maximum inhibition on S. neurona development. Most active agents were either NO(2) or halogen substituted in position 5 of their thiazole moiety. In contrast, other 5-substitutions such as hydrogen, methyl, SO(2)CH(3), and CH(3) negatively impacted activity. Compared with derivatives with an acetylated benzene moiety, deacetylated compounds which most probably represent primary metabolites exhibited similar inhibitory activities. Present data provide the first evidence of in vitro inhibitory activities of Nitazoxanide and new thiazolides/thiadiazolides on S. neurona development. Active halogeno-thiazolide/thiadiazolides may provide a valuable nitro-free alternative to Nitazoxanide for EPM treatment depending on further evaluation of their in vivo activities.
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Nitazoxanide in the treatment of viral gastroenteritis a randomized double blind placebo controlled clinical trial
Alimentary Pharmacology & Therapeutics, 2006Co-Authors: J.-f. Rossignol, Y M ElgoharyAbstract:Summary Background Enteric viruses including noroviruses and rotavirus are leading causes of diarrhoeal disease and gastroenteritis worldwide, and there is no effective treatment. Aim To evaluate Nitazoxanide, a thiazolide anti-infective agent, in treating viral gastroenteritis in adults and adolescents. Methods 50 out-patients at least 12 years of age (mean 33.5 years) presenting with diarrhoea and stool-positive by enzyme-linked immunosorbent assay for norovirus, rotavirus or adenovirus were enrolled in a double-blind, placebo-controlled clinical trial. Patients were randomly assigned either Nitazoxanide 500 mg or placebo twice daily for 3 days. The primary end point was time from first dose to resolution of symptoms. Analysis was modified intent-to-treat for 45 patients, excluding five patients with other identified enteropathogens at baseline. Results The median time from first dose to resolution of symptoms was 1.5 days (IQR: 0.5–2.5) for Nitazoxanide-treated patients and 2.5 days (IQR: 1.5–4.5) for the placebo group. Significant reductions in time to resolution of symptoms were observed for all patients analysed (P < 0.0001) and for subsets of patients with rotavirus (P = 0.0052) and norovirus (P = 0.0295). The number of patients with adenovirus (n = 5) was too small to draw any conclusion. No significant adverse events were reported. Conclusions Nitazoxanide may play an important role in managing viral gastroenteritis in adults.
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Nitazoxanide in the treatment of acquired immune deficiency syndrome related cryptosporidiosis results of the united states compassionate use program in 365 patients
Alimentary Pharmacology & Therapeutics, 2006Co-Authors: J.-f. RossignolAbstract:Summary Background Cryptosporidiosis in patients with acquired immune deficiency syndrome is a serious, life-threatening disease. Aim A large compassionate use clinical trial was conducted in the USA to make Nitazoxanide available to patients with acquired immune deficiency syndrome-related cryptosporidiosis and to collect data related to safety and effectiveness of the drug in this population. Methods Patients at least 3 years of age with acquired immune deficiency syndrome, diarrhoea (≥4 stools/day for >2 weeks) and Cryptosporidium-positive stools received 500–1500 mg of Nitazoxanide twice daily. Patients were evaluated at weeks 1, 2, 4 and monthly thereafter for drug safety and effectiveness including the stool examinations, review of symptoms and patient diaries. Data analysis for clinical and parasitological response was intention-to-treat. Results Three hundred and sixty-five patients were enrolled at 165 study centres throughout the USA. The duration of treatment ranged from 1 to 1528 days (median 62 days). Among the 357 patients included in the intent-to-treat analysis, 209 (59%) achieved a sustained clinical response while on treatment. Clinical responses were closely associated with Cryptosporidium-negative stools (P < 0.0001). No safety issues were identified at doses up to 3000 mg/day or for long durations of treatment. Conclusions Nitazoxanide can be considered useful therapy for treatment of with acquired immune deficiency syndrome-related cryptosporidiosis.
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Efficacy of Nitazoxanide and paromomycin in biliary tract cryptosporidiosis in an immunosuppressed gerbil model
The Journal of antimicrobial chemotherapy, 2005Co-Authors: A. Baishanbo, Gilles Gargala, Jean Jacques Ballet, C. Duclos, A. Francois, J.-f. Rossignol, Laurent FavennecAbstract:Objectives: To evaluate the efficacy of Nitazoxanide and paromomycin in biliary tract cryptosporidiosis in an immunosuppressed Mongolian gerbil (Meriones unguiculatus) model. Methods: Gerbils (1-month-old) were dexamethasone-immunosuppressed for 10 days and challenged orally with 10 5 Cryptosporidium parvum oocysts. From day 0 to day 12 post-infection, one group (n = 14) was treated with 200 mg/kg/day Nitazoxanide and another (n = 15) with 100 mg/kg/day paromomycin. Infection and efficacy of Nitazoxanide and paromomycin were assessed by measuring oocyst shedding in faeces, biliary tract and ileum histological examination. Results: In Nitazoxanide-treated and paromomycin-treated groups as compared with untreated animals (P 0.05). Parasites were present in histological sections of the ileal mucosa of 16/16 infected untreated animals versus 3/14 and 6/15 in the Nitazoxanide-treated and the paromomycin-treated groups, respectively (P< 0.05). In addition, gall bladder infection was less frequent in Nitazoxanide-treated (2/14, P< 0.01) and paromomycin-treated (5/15, P= 0.07) animals than in untreated controls (9/16). No histological alteration of biliary mucosa was observed in both treated and untreated infected gerbils. Conclusions: Present data support the efficacy of Nitazoxanide and, to a lesser extent, paromomycin on biliary C. parvum infection in gerbils, and prompt further investigation of the potential clinical benefits of Nitazoxanide in treating human biliary cryptosporidiosis.
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double blind randomized placebo controlled study of Nitazoxanide in the treatment of fascioliasis in adults and children from northern peru
Alimentary Pharmacology & Therapeutics, 2003Co-Authors: Laurent Favennec, Gilles Gargala, A Ayoub, Jave J Ortiz, Lopez N Chegne, J.-f. RossignolAbstract:Summary Background : Human fascioliasis is a significant world-wide health problem, and massive or repeated infections by Fasciola hepatica can lead to considerable morbidity. Aim : To evaluate the safety and efficacy of Nitazoxanide, when compared with placebo, in the treatment of fascioliasis in adults and children from northern Peru. Methods : A double-blind, placebo-controlled study was carried out in 50 adults and 50 children infected with F. hepatica. The diagnosis of infection was based on the presence of F. hepatica eggs in one stool sample obtained before inclusion in the study. Patients were randomized to receive treatment with either a 7-day course of Nitazoxanide (100 mg b.d., age range 2–3 years; 200 mg b.d., age range 4–11 years; 500 mg b.d., age > 12 years) or matching placebo. Three post-treatment stool examinations were carried out between 30 and 90 days after initiation of treatment. Results : The parasite was eliminated in 18 of 30 (60%) adults completing the study who received Nitazoxanide vs. one of eight adults in the placebo group (P = 0.042), and similarly in 14 of 35 (40%) children completing the treatment vs. none of eight in the placebo group (P = 0.038). Only mild, transient adverse events were reported. Conclusions : A 7-day course of Nitazoxanide was effective in adults and children in the treatment of F. hepatica, when compared with placebo.