Treatment of cryptosporidiosis

Pantenburg, Birte; Cabada, Miguel M.; White, A. Clinton

doi:10.1586/eri.09.24

Cited by 34 publications

(28 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In immunocompromised individuals, such as people receiving immunosuppressive drugs and acquired immunodeficiency syndrome (AIDS) patients with low CD4 lymphocyte counts, cryptosporidiosis is often chronic, leading to important weight loss and cachexia. Currently, very few drugs are active against Cryptosporidium and none is curative: the only antiparasitic drug proven to be effective in immunocompetent adults and children is nitazoxanide, and none has proven effective in severely immunocompromised patients [2].…”

Section: Introductionmentioning

confidence: 99%

Laboratory-based surveillance for Cryptosporidium in France, 2006–2009

et al. 2010

View full text Add to dashboard Cite

In 2002, the French Food Safety Agency drew attention to the lack of information on the prevalence of human cryptosporidiosis in the country. Two years later, the ANOFEL Cryptosporidium National Network (ACNN) was set up to provide public health authorities with data on the incidence and epidemiology of human cryptosporidiosis in France. Constituted on a voluntary basis, ACNN includes 38 hospital parasitology laboratories (mainly in university hospitals). Each laboratory is engaged to notify new cases of confirmed human cryptosporidiosis, store specimens (e.g. stools, duodenal aspirates or biopsies) and related clinical and epidemiological data, using datasheet forms. From January 2006 to December 2009, 407 cryptosporidiosis cases were notified in France and 364 specimens were collected. Of the notified cases, 74 were children under four years of age, accounting for 18.2%. HIV-infected and immunocompetent patients represented 38.6% (n=157) and 28% (n=114) of cases, respectively. A marked seasonal pattern was observed each year, with increased number of cases in mid to late summer and the beginning of autumn. Genotyping of 345 isolates from 310 patients identified C. parvum in 168 (54.2%) cases, C. hominis in 113 (36.4%) and other species in 29 (9.4%), including C. felis (n=15), C. meleagridis (n=4), C. canis (n=4), Cryptosporidium chipmunk genotype (n=1), Cryptosporidium rabbit genotype (n=1) and new Cryptosporidium genotypes (n=4). These data represent the first multisite report of laboratory-confirmed cases of cryptosporidiosis in France.

show abstract

Section: Introductionmentioning

confidence: 99%

Laboratory-based surveillance for Cryptosporidium in France, 2006–2009

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Recently, cryptosporidiosis has also been recognized as a serious cause of morbidity in young children in Africa and South Asia, being among the top three diarrhea-causing agents (3). Complicating this situation, there are few effective therapies for cryptosporidiosis, and the one FDA-approved drug, nitazoxanide, is not effective in immunocompromised patients or malnourished children (4).…”

mentioning

confidence: 99%

“…The genome of C. parvum is highly streamlined (7), lacking many metabolic pathways while containing a large number of transporters involved in nutrient uptake (8). As a result of its unique metabolism, and perhaps its unusual intracellular niche, few drugs that are effective against related parasites act on C. parvum or C. hominis (4). Therefore, there is a need to define new targets and to identify compounds that effectively inhibit parasite growth.…”

mentioning

confidence: 99%

Inhibition of Calcium-Dependent Protein Kinase 1 (CDPK1) In Vitro by Pyrazolopyrimidine Derivatives Does Not Correlate with Sensitivity of Cryptosporidium parvum Growth in Cell Culture

Kuhlenschmidt

Rutaganira

Long

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

cCryptosporidiosis is a serious diarrheal disease in immunocompromised patients and malnourished children, and treatment is complicated by a lack of adequate drugs. Recent studies suggest that the natural occurrence of a small gatekeeper residue in serine threonine calcium-dependent protein kinase 1 (CDPK1) of Cryptosporidium parvum might be exploited to target this enzyme and block parasite growth. Here were explored the potency with which a series of pyrazolopyrimidine analogs, which are selective for small gatekeeper kinases, inhibit C. parvum CDPK1 and block C. parvum growth in tissue culture in vitro. Although these compounds potently inhibited kinase activity in vitro, most had no effect on parasite growth. Moreover, among those that were active against parasite growth, there was a very poor correlation with their 50% inhibitory concentrations against the enzyme. Active compounds also had no effect on cell invasion, unlike the situation in Toxoplasma gondii, where these compounds block CDPK1, prevent microneme secretion, and disrupt cell invasion. These findings suggest that CPDK1 is not essential for C. parvum host cell invasion or growth and therefore that it is not the optimal target for therapeutic intervention. Nonetheless, several inhibitors with low micromolar 50% effective concentrations were identified, and these may affect other essential targets in C. parvum that are worthy of further exploration.

show abstract

“…Immunocompetent individuals usually recover spontaneously, but supportive therapy, including fluid and electrolyte replacement, should be provided (Pantenburg et al 2009). Antiparasitic drugs, like nitazoxanide (a nitrothiazole benzamide) and paromomycin (an oligosaccharide aminoglycoside related to kanamycin), are the mainstay drugs for treatment and currently used, as the first-line treatment, for Cryptosporidiosis (Garcia 2001;Pantenburg et al 2009). Nitazoxanide is US FDA approved for the treatment for Cryptosporidiosis and Giardiasis in immunocompetent individuals.…”

Section: Treatmentmentioning

confidence: 99%

“…In immunocompromised patients, treatment for longer durations may be required. Treatment with paromomycin has shown significantly decreased parasite shedding in stool and improved diarrheal symptoms (Pantenburg et al 2009). Dosage is 500 mg, thrice daily, for 7-14 days, often followed by a maintenance therapy with 500 mg twice daily.…”

Section: Treatmentmentioning

confidence: 99%

Human Cryptosporidiosis and Drinking Water: Looking Beyond HIV

Ghoshal

Dey

2013

Water and Health

View full text Add to dashboard Cite

Cryptosporidium is an obligate intracellular apicomplexan parasite, responsible for significant morbidity and mortality in both humans and animals. It causes protracted and life-threatening diarrhea in HIV-infected individuals, along with some extra-intestinal symptoms. It also causes infection in other immunocompromised hosts like organ transplant recipients, patients with hematological malignancies, though there are fewer reports on this issue. Cryptosporidial infection is transmitted through feco-oral route by contaminated food and water. Oocyst of Cryptosporidium species is highly resistant to common water disinfection procedures, which has led to waterborne Cryptosporidium outbreaks, in both large and small communities. UV radiation, flocculation, sedimentation, and filtration are efficient against water contamination by cryptosporidial oocysts. Diagnosis of the parasite is based mainly on acid-fast staining, fluorescent stains like auramine-carbolfuchsin stain, ELISA of specific antigens, as well as antibodies, and polymerase chain reaction. The principle defense mechanism against Cryptosporidium sp. is cell-mediated immunity, particularly macrophage activation by CD4 ? T cells-derived cytokines. Th1 response assists in developing resistance to infection, whereas activation of Th2 cells results in increased parasite survival and exacerbation of lesions, due to macrophage suppressive action of Th2 cytokines, or during recovery stages of the infection. Immune restoration is very important for treatment. Nitazoxanide and Paramomycin are the mainstay of therapy, however complete elimination of the parasite is difficult.

show abstract

Treatment of cryptosporidiosis

Cited by 34 publications

References 55 publications

Laboratory-based surveillance for Cryptosporidium in France, 2006–2009

Laboratory-based surveillance for Cryptosporidium in France, 2006–2009

Inhibition of Calcium-Dependent Protein Kinase 1 (CDPK1) In Vitro by Pyrazolopyrimidine Derivatives Does Not Correlate with Sensitivity of Cryptosporidium parvum Growth in Cell Culture

Human Cryptosporidiosis and Drinking Water: Looking Beyond HIV

Contact Info

Product

Resources

About