Efficacy of nitazoxanide and paromomycin in biliary tract cryptosporidiosis in an immunosuppressed gerbil model

Baishanbo, A.; Gargala, Gilles; Duclos, C.; Audigier, François; Rossignol, Jean‐François; Ballet, Jean-Jacques; Favennec, L

doi:10.1093/jac/dki456

Cited by 43 publications

(21 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TZ had only limited activity, but NTZ and TZglu strongly inhibited asexual and sexual stages, respectively (Gargala, 2000). NTZ was shown to be more effective than paromomycin on biliary tract cryptosporidiosis in immunosuppressed gerbils (Baishanbo, 2006). The efficacy of NTZ in treating cryptosporidiosis in immunocompetent patients was well established by three double blind placebo-controlled clinical studies carried out in more than 140 immunocompetent adults and 150 immunocompetent children from Egypt and Zambia (Rossignol, 2001(Rossignol, , 2006Amadi, 2002).…”

Section: Roxithromycinmentioning

confidence: 99%

“…In 2006, Stachulski et al synthesized 52 EGFR-PTK inhibitor isoflavone analogs such as dihydroxyisoflavone and trihydroxydeoxybenzoine derivatives. For identifying anticoccidial agents among these new agents, Gargala et al (2006) studied the activities of EGF receptor inhibitors against Sarcocystis neurona, Neospora caninum, and C. parvum grown in cell cultures. Agents induced a maximum development inhibition (MI) of more than 95 % for at least one parasite.…”

Section: Isoflavone Derivativesmentioning

confidence: 99%

See 1 more Smart Citation

Drug treatment and novel drug target againstCryptosporidium

Gargala

2008

Parasite

Self Cite

View full text Add to dashboard Cite

Summary :Cryptosporidiosis emergence triggered the screening of many compounds for potential anti-cryptosporidial activity in which the majority were ineffective. The outbreak of cryptosporidiosis which occurred in Milwaukee in 1993 was not only the first significant emergence of Cryptosporidium spp. as a major human pathogen but also a huge waterborne outbreak thickening thousands of people from a major city in North America. Since then, outbreaks of cryptosporidiosis are regularly occurring throughout the world. New drugs against this parasite became consequently urgently needed. Among the most commonly used treatments against cryptosporidiosis are paromomycin, and azithromycin, which are partially effective. Nitazoxanide (NTZ)'s effectiveness was demonstrated in vitro, and in vivo using several animal models and finally in clinical trials. It significantly shortened the duration of diarrhea and decreased mortality in adults and in malnourished children. NTZ is not effective without an appropriate immune response. In AIDS patients, combination therapy restoring immunity along with antimicrobial treatment of Cryptosporidium infection is necessary. Recent investigations focused on the potential of molecular-based immunotherapy against this parasite. Others tested the effects of probiotic bacteria, but were unable to demonstrate eradication of C. parvum. New synthetic isoflavone derivatives demonstrated excellent activity against C. parvum in vitro and in a gerbil model of infection. Newly synthesized nitroor non nitro-thiazolide compounds, derived from NTZ, have been recently shown to be at least as effective as NTZ against C. parvum in vitro development and are promising new therapeutic agents.

show abstract

Section: Roxithromycinmentioning

confidence: 99%

Section: Isoflavone Derivativesmentioning

confidence: 99%

Drug treatment and novel drug target againstCryptosporidium

Gargala

2008

Parasite

Self Cite

View full text Add to dashboard Cite

show abstract

“…This drug exhibits a broad spectrum of activities against intestinal and tissue-dwelling helminths, protozoa and enteric bacteria infecting humans and animals (Hemphill et al 2006). Several data obtained from laboratory animals (mice, rats, gerbils and piglets) experimentally infected with Cryptosporidium sp have indicated a partial prophylactic or curative efficacy of nitazoxanide when administered between 50 and 250 mg/kg BW (Blagburn et al 1998;Theodos et al 1998;Li et al 2003;Baishanbo et al 2006). Similarly, nitazoxanide has been recently approved by the FDA for treatment of diarrhoea caused by Cryptosporidium parvum in human (Bobak 2006).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of nitazoxanide against experimental cryptosporidiosis in goat neonates

et al. 2007

View full text Add to dashboard Cite

Preliminary results obtained in mice, rats and piglets experimentally infected with Cryptosporidium sp have indicated a partial prophylactic or curative efficacy of nitazoxanide when administered between 50 and 250 mg/kg BW. In this study, the efficacy of nitazoxanide was evaluated in goat neonates experimentally infected with Cryptosporidium sp oocysts. Forty-seven 2- to 4-day-old kids were experimentally infected once on day 0 with 10(6) Cryptosporidium oocysts isolated from a dead kid, and allocated to three groups. Group 1 acted as control untreated group, group 2 received nitazoxanide for 8 days from day -1 to day 6 at a daily dose rate of 200 mg/kg BW, group 3 received nitazoxanide for 7 days from day 2 to day 8 at 100 mg/kg BW. Individual oocyst shedding was monitored by daily examination of faecal smears stained by carbol fuchsin and scored semi-quantitatively (zero to four). The other criteria included for nitazoxanide evaluation were weight gain and mortality. In the control group, oocyst shedding that started 3 days post-inoculation (PI) was maximal 6-7 days PI (mean scores ranging from 1.69 to 1.94) and became undetectable from day 16 PI. In group 2, oocyst shedding started 1 day later, peaked 9-11 days PI (1.33 to 1.5) and vanished day 18 PI. In group 3, results were similar to those of group 1 except for the mean scores ranging from 1.0 to 1.58. No significant difference was seen for weight gains between groups. Five kids died in group 1 as well as in group 3, whereas seven kids died in group 2. An acute toxicity of nitazoxanide was suspected as soon as the first 2 days of treatment.

show abstract

“…In high-risk patient groups, such as infants and the elderly or people suffering from severe malnutrition, advanced human immunodeficiency virus/AIDS, or having undergone immunosuppressive therapy, cryptosporidiosis can be chronic, leading to severe dehydration and/or malabsorption (34). Although there has been progress with the development of drugs, such as paromomycin (10,44,56) and nitazoxanide (8,65), currently there is limited accessibility to efficacious treatment in many countries (9,13,29,43,86). As a result, chronic cryptosporidiosis can be fatal and substantially affects the health of human communities, particularly in developing countries (39,45).…”

mentioning

confidence: 99%

Classification ofCryptosporidiumSpecies from Patients with Sporadic Cryptosporidiosis by Use of Sequence-Based Multilocus Analysis following Mutation Scanning

et al. 2008

View full text Add to dashboard Cite

In the present study, we analyzed genetic variation in Cryptosporidium species from humans (n ‫؍‬ 62) with clinical cryptosporidiosis in South Australia. Sequence variation was assessed in regions within the small subunit of nuclear rRNA (p-SSU), the 70-kDa heat shock protein (p-hsp70), and the 60-kDa glycoprotein (p-gp60) genes by employing single-strand conformation polymorphism analysis and sequencing. Based on the analyses of p-SSU and p-hsp70, Cryptosporidium hominis (n ‫؍‬ 38) and Cryptosporidium parvum (n ‫؍‬ 24) were identified. The analysis of p-gp60 revealed eight distinct subgenotypes, classified as C. hominis IaA17R1 (n ‫؍‬ 3), IbA9G3R2 (n ‫؍‬ 14), IbA10G2R2 (n ‫؍‬ 20), and IfA12G1R1 (n ‫؍‬ 1), as well as C. parvum IIaA18G3R1 (n ‫؍‬ 15), IIaA20G3R1 (n ‫؍‬ 6), IIaA22G4R1 (n ‫؍‬ 2), and IIcA5G3R2 (n ‫؍‬ 1). Subgenotypes IaA17R1 and IIaA22G4R1 are new. Of the six other subgenotypes, IbA10G2R2, IIaA18G3R1, IIaA20G3R1, and IIcA5G3R2 were reported previously from the state of Victoria. This is the fourth record in Australia of C. parvum subgenotype IIaA18G3R1 from humans, which, to date, has been isolated only from cattle in other countries. This subgenotype might be a significant contributor to sporadic human cryptosporidiosis and may indicate a greater zoonotic contribution to the infection of humans in the area of study. Comparative analyses revealed, for the first time, the differences in the genetic makeup of Cryptosporidium populations between two relatively close, major metropolitan cities.

show abstract

Efficacy of nitazoxanide and paromomycin in biliary tract cryptosporidiosis in an immunosuppressed gerbil model

Abstract: 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.

Cited by 43 publications

References 17 publications

Drug treatment and novel drug target againstCryptosporidium

Drug treatment and novel drug target againstCryptosporidium

Efficacy of nitazoxanide against experimental cryptosporidiosis in goat neonates

Classification ofCryptosporidiumSpecies from Patients with Sporadic Cryptosporidiosis by Use of Sequence-Based Multilocus Analysis following Mutation Scanning

Contact Info

Product

Resources

About