Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomised controlled trial

Amadi, Beatrice; Mwiya, Mwiya; Musuku, John; Watuka, Angela; Sianongo, Sandie; Ayoub, Ayman; Kelly, Paul

doi:10.1016/s0140-6736(02)11401-2

Cited by 378 publications

(244 citation statements)

References 22 publications

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“…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). Clinical and parasitological cures were recorded following a three-day course of treatment in adults, adolescents and children (1-11 years of age).…”

Section: Roxithromycinmentioning

confidence: 99%

Drug treatment and novel drug target againstCryptosporidium

Gargala

2008

Parasite

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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.

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Section: Roxithromycinmentioning

confidence: 99%

Drug treatment and novel drug target againstCryptosporidium

Gargala

2008

Parasite

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“…In malnourished children, a survival advantage was shown with nitazoxanide treatment, but the response rate was poor [7,8]. Furthermore, randomized trials show no benefit with nitazoxanide treatment in patients with AIDS [8,17]. More-effective parasite-specific drugs are clearly needed for treating cryptosporidiosis.…”

mentioning

confidence: 99%

Novel Bumped Kinase Inhibitors Are Safe and Effective Therapeutics in the Calf Clinical Model for Cryptosporidiosis

et al. 2016

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Cryptosporidiosis, caused by the apicomplexan parasite Cryptosporidium parvum, is a diarrheal disease that has produced a large global burden in mortality and morbidity in humans and livestock. There are currently no consistently effective parasite-specific pharmaceuticals available for this disease. Bumped kinase inhibitors (BKIs) specific for parasite calcium-dependent protein kinases (CDPKs) have been shown to reduce infection in several parasites having medical and veterinary importance, including Toxoplasma gondii, Plasmodium falciparum, and C. parvum. In the present study, BKIs were screened for efficacy against C. parvum infection in the neonatal mouse model. Three BKIs were then selected for safety and clinical efficacy evaluation in the calf model for cryptosporidiosis. Significant BKI treatment effects were observed for virtually all clinical and parasitological scoring parameters, including diarrhea severity, oocyst shedding, and overall health. These results provide proof of concept for BKIs as therapeutic drug leads in an animal model for human cryptosporidiosis.

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“…2 Antibiotic therapy for DC is not effective without an appropriate immune restoration. 23 In HSCT recipients, a combination of antimicrobial therapy and tapering of immunosuppressive drugs is necessary to restore immune response and to eradicate the protozoa.…”

Section: Discussionmentioning

confidence: 99%

Diagnosis and treatment of digestive cryptosporidiosis in allogeneic haematopoietic stem cell transplant recipients: a prospective single centre study

Legrand¹,

Grenouillet

Larosa³

et al. 2010

Bone Marrow Transplant

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Digestive cryptosporidiosis (DC) can mimic GVHD after allogeneic haematopoietic stem cell transplantation (HSCT), thus requiring a reduction of immunosuppressive drugs and a specific therapy, whereas GVHD requires an intensification of immunosuppression. We systematically searched for cryptosporidiosis by light microscopy, immunochromatography and PCR in HSCT recipients who presented with at least one episode of diarrhoea. Of 115 consecutive patients allografted between July 2006 and November 2008, we analysed stools in 52 of 56 patients meeting these criteria. We identified Cryptosporidium parvum in 5 of the 52 patients (9.6%) at a median of 503 days (range 20-790) after HSCT. In those five patients, the median CD4 þ cell and B lymphocyte counts were 60/mm 3 (0-234) and 0/mm 3 (0-96), respectively. Two patients died of invasive fungal infections. In the other three patients, diarrhoea disappeared after a median of 5 weeks following onset of bitherapy with azithromycine and nitazoxanide; they were still alive 433, 380 and 1179 days after the DC diagnosis. DC is probably under diagnosed after HSCT because it is difficult to detect during the asymptomatic phase. Early bitherapy and reduction of immunosuppression seem efficacious. In our series, DC has a seasonal pattern and is promoted by profound T lymphopenia.

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Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomised controlled trial

Cited by 378 publications

References 22 publications

Drug treatment and novel drug target againstCryptosporidium

Drug treatment and novel drug target againstCryptosporidium

Novel Bumped Kinase Inhibitors Are Safe and Effective Therapeutics in the Calf Clinical Model for Cryptosporidiosis

Diagnosis and treatment of digestive cryptosporidiosis in allogeneic haematopoietic stem cell transplant recipients: a prospective single centre study

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