Gilles Gargala

Successful Treatment of Metronidazole- and Albendazole-Resistant Giardiasis with Nitazoxanide in a Patient with Acquired Immunodeficiency Syndrome

A case of metronidazole- and albendazole-resistant giardiasis in a patient with the acquired immunodeficiency syndrome was successfully treated with nitazoxanide (1.5 g twice a day for 30 days). Animal studies and in vitro assays showed that the isolate was resistant to both metronidazole and albendazole and susceptible to nitazoxanide.

Randomized clinical study of nitazoxanide compared to metronidazole in the treatment of symptomatic giardiasis in children from Northern Peru.

Enteric infection by Giardia intestinalis is a common cause of diarrhoea world‐wide and a significant cause of morbidity in children.

Comparative clinical studies of nitazoxanide, albendazole and praziquantel in the treatment of ascariasis, trichuriasis and hymenolepiasis in children from Peru

Three randomized clinical studies were conducted in 2000 to evaluate the efficacy of nitazoxanide paediatric suspension compared to albendazole in the treatment of ascariasis and trichuriasis and praziquantel in the treatment of hymenolepiasis in children from Cajamarca, Peru. Nitazoxanide was administered at a dose of 100 mg (age 1-3 years) or 200 mg (age 4-11 years) twice daily for 3 days, albendazole as a 400-mg single dose and praziquantel as a 25-mg/kg single dose. Post-treatment parasitological examinations were carried out on 3 faecal samples, each collected on a different day between 21 and 30 days following initiation of treatment. Nitazoxanide cured 89% (25/28), 89% (16/18) and 82% (32/39) of the cases of ascariasis, trichuriasis and hymenolepiasis respectively compared with 91% (32/35), 58% (11/19) and 96% (47/49) for the comparator drugs. Each of the drugs produced egg reduction rates in excess of 98%. There were no significant adverse events or abnormalities in haematology or clinical chemistry values or urinalysis.

Double-blind, randomized, placebo-controlled study of nitazoxanide in the treatment of fascioliasis in adults and children from northern Peru

Background : Human fascioliasis is a significant world‐wide health problem, and massive or repeated infections by Fasciola hepatica can lead to considerable morbidity.

Infectivity of Cryptosporidium hominis and Cryptosporidium parvum genotype 2 isolates in immunosuppressed Mongolian gerbils.

ABSTRACT One-month-old dexamethasone-immunosuppressed Mongolian gerbils were challenged with 1 oocyst to 2 × 105 oocysts from two isolates genotyped as Cryptosporidium hominis and C. parvum (genotype 2), respectively. A similar dose-dependent gut infection was obtained, and the initial genotype maintained for 21 to 22 days. The data suggest that immunosuppressed gerbils provide a reliable rodent model of persistent C. hominis infection.

First description of azole-resistant Aspergillus fumigatus due to TR46/Y121F/T289A mutation in France

ABSTRACT Azole resistance in Aspergillus fumigatus is an emerging public health concern. Recently, a novel fungicide-driven mutation in the cyp51A gene and its promoter, TR46/Y121F/T289A, leading to high-level resistance to voriconazole has been identified in The Netherlands, Belgium, Germany, Denmark, Tanzania, and India in both clinical and environmental samples. Here we report the first description of A. fumigatus carrying this mutation in France, in a cystic fibrosis patient, underlining the need for extensive monitoring of Aspergillus resistance.

Limitations of tpi and bg genes sub-genotyping for characterization of human Giardia duodenalis isolates

The intestinal protozoan Giardia duodenalis includes 2 genetically distinct assemblages, A and B, which are responsible for human infections. Little is known so far on the genotypes of G. duodenalis human isolates in France. The present characterization of 19 French clinical isolates was aimed at determining their genotype patterns and associations with clinical symptoms, and in vivo metronidazole resistance, respectively. Based on both triose-phosphate isomerase (tpi) and β-giardin (bg) gene sequences, twelve isolates were identified as assemblage A, and 7 as assemblage B for the 2 gene loci. Sub-genotyping heterogeneities were observed in 15/19 isolates attributed to either A or B assemblage. They include frequent mismatches and intra-assemblage discordances and mixed positions, which were found more frequently in tpi than in bg sequences, and in assemblage B than in assemblage A sequences. No association was found between sub-genotypes, clinical symptoms and metronidazole sensitivity. Present data underline the need for improvements in the standardization of G. duodenalis multilocus genotyping approach for further molecular epidemiologic studies of giardiasis.

Inhibitory Activities of Epidermal Growth Factor Receptor Tyrosine Kinase-Targeted Dihydroxyisoflavone and Trihydroxydeoxybenzoin Derivatives on Sarcocystis neurona, Neospora caninum, and Cryptosporidium parvum Development

ABSTRACT Several gene sequences of parasitic protozoa belonging to protein kinase gene families and epidermal growth factor (EGF)-like peptides, which act via binding to receptor tyrosine kinases of the EGF receptor (EGFR) family, appear to mediate host-protozoan interactions. As a clue to EGFR protein tyrosine kinase (PTK) mediation and a novel approach for identifying anticoccidial agents, activities against Sarcocystis neurona, Neospora caninum, and Cryptosporidium parvum grown in BM and HCT-8 cell cultures of 52 EGFR PTK inhibitor isoflavone analogs (dihydroxyisoflavone and trihydroxydeoxybenzoine derivatives) were investigated. Their cytotoxicities against host cells were either absent, mild, or moderate by a nitroblue tetrazolium test. At concentrations ranging from 5 to 10 μg/ml, 20 and 5 analogs, including RM-6427 and RM-6428, exhibited an in vitro inhibitory effect of ≥95% against at least one parasite or against all three, respectively. In immunosuppressed Cryptosporidium parvum-infected Mongolian gerbils orally treated with either 200 or 400 mg of agent RM-6427/kg of body weight/day for 8 days, fecal microscopic oocyst shedding was abolished in 6/10 animals (P of <0.001 versus untreated controls) and mean shedding was reduced by 90.5% (P of <0.0001) and 92.0% (P of <0.0001), respectively, higher levels of inhibition than after nitazoxanide (200 mg/kg/day for 8 days) or paromomycin (100 mg/kg/day for 8 days) treatment (55.0%, P of <0.001, and 17.5%, P of >0.05, respectively). After RM-6427 therapy (200 mg/kg/day for 8 days), the reduction in the ratio of animals with intracellular parasites was nearly significant in ileum (P = 0.067) and more marked in the biliary tract (P < 0.0013) than after nitazoxanide or paromomycin treatment (0.05 < P < 0.004). RM-6428 treatment at a regimen of 400 mg/kg/day for 12 days inhibited oocyst shedding, measured using flow cytometry from day 4 (P < 0.05) to day 12 (P < 0.02) of therapy, when 2/15 animals had no shedding (P < 0.0001) and 11/15 were free of gut and/or biliary tract parasites (P < 0.01). No mucosal alteration was microscopically observed for treated or untreated infected gerbils. To our knowledge, this report is the first to suggest that the isoflavone class of agents has the potential for anticoccidial therapy.

Evaluation of New Thiazolide/Thiadiazolide Derivatives Reveals Nitro Group-Independent Efficacy against In Vitro Development of Cryptosporidium parvum

ABSTRACT 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.

Quantitative Flow Cytometric Evaluation of Maximal Cryptosporidium parvum Oocyst Infectivity in a Neonate Mouse Model

ABSTRACT The importance of waterborne transmission of Cryptosporidium parvum to humans has been highlighted by recent outbreaks of cryptosporidiosis. The first step in a survey of contaminated water currently consists of counting C. parvum oocysts. Data suggest that an accurate risk evaluation should include a determination of viability and infectivity of counted oocysts in water. In this study, oocyst infectivity was addressed by using a suckling mouse model. Four-day-old NMRI (Naval Medical Research Institute) mice were inoculated per os with 1 to 1,000 oocysts in saline. Seven days later, the number of oocysts present in the entire small intestine was counted by flow cytometry using a fluorescent, oocyst-specific monoclonal antibody. The number of intestinal oocysts was directly related to the number of inoculated oocysts. For each dose group, infectivity of oocysts, expressed as the percentage of infected animals, was 100% for challenge doses between 25 and 1,000 oocysts and about 70% for doses ranging from 1 to 10 oocysts/animal. Immunofluorescent flow cytometry was useful in enhancing the detection sensitivity in the highly susceptible NMRI suckling mouse model and so was determined to be suitable for the evaluation of maximal infectivity risk.