There has been an explosion of descriptions of new species of Cryptosporidium during the last two decades This has been accompanied by confusion regarding the criteria for species designation, largely because of the lack of distinct morphologic differences and strict host specificity among Cryptosporidium spp A review of the biologic species concept, the International Code of Zoological Nomenclature (ICZN), and current practices for Cryptosporidium species designation calls for the establishment of guidelines for naming Cryptosporidium species All reports of new Cryptosporidium species should include at least four basic components: oocyst morphology, natural host specificity, genetic characterizations, and compliance with the ICZN Altogether, 13 Cryptosporidium spp are currently recognized: C muris, C andersoni, C parvum, C hominis, C wrairi, C felis; and C cannis in mammals; C baileyi, C meleagridis, and C galli in birds; C serpentis and C saurophilum in reptiles; and C molnari in fish With the establishment of a framework for naming Cryptosporidium species and the availability of new taxonomic tools, there should be less confusion associated with the taxonomy of the genus Cryptosporidium The clarification of Cryptosporidium taxonomy is also useful for understanding the biology of Cryptosporidium spp, assessing the public health significance of Cryptosporidium spp in animals and the environment, characterizing transmission dynamics, and tracking infection and contamination sources

Cryptosporidium Taxonomy: Recent Advances and Implications for Public Health (Review)

Nitazoxanide: a first-in-class broad-spectrum antiviral agent.

Nitazoxanide is a new thiazolide antiparasitic agent that shows excellent in vitro activity against a wide variety of protozoa and helminths. It is given by the oral route with good bioavailability and is well tolerated, with primarily mild gastrointestinal side effects. At present, there are no documented drug-drug interactions. Nitazoxanide has been licensed for the treatment of Giardia intestinalis-induced diarrhea in patients >or=1 year of age and Cryptosporidum-induced diarrhea in children aged 1-11 years. At present, it is pending licensure for treatment of infection due to Cryptosporidium species in adults and for use in treating immunocompromised hosts. It represents an important addition to the antiparasitic arsenal.

Nitazoxanide: a new thiazolide antiparasitic agent.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(02)11401-2.pdf

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

A prospective randomized, double-blind, placebo-controlled study was conducted in 50 adults and 50 children from the Nile delta of Egypt, to evaluate the efficacy of nitazoxanide in treating diarrhea caused by Cryptosporidium parvum. Nitazoxanide was administered in 500-mg doses twice daily for 3 days in adults and adolescents, in 200-mg doses twice daily for 3 days in children aged 4-11 years, and in 100-mg doses twice daily for 3 days in children aged 1-3 years. At 7 days after initiation of therapy, diarrhea had resolved in 39 (80%) of the 49 patients in the nitazoxanide treatment group, compared with 20 (41%) of 49 in the placebo group (P<.0001). Diarrhea was resolved in most patients receiving nitazoxanide within 3 or 4 days of treatment initiation. Nitazoxanide treatment reduced the duration of both diarrhea (P<.0001) and oocyst shedding (P<.0001).

Treatment of Diarrhea Caused by Cryptosporidium parvum: A Prospective Randomized, Double-Blind, Placebo-Controlled Study of Nitazoxanide

The effects of nitazoxanide and its metabolites, tizoxanide and tizoxanide glucuronide, on the development of the asexual and sexual stages of Cryptosporidium parvum in differentiated human enterocytic HCT-8 cells were evaluated in a quantitative alkaline phosphatase immunoassay. Nitazoxanide, tizoxanide and tizoxanide glucuronide were inhibitory for up to 46 h when added after sporozoite invasion (MIC 50 1.2, 22.6 and 2.2 mg/L, respectively). Tizoxanide had only limited activity, but nitazoxanide and tizoxanide glucuronide strongly inhibited asexual and sexual stages, respectively.

/pdf/efficacy-of-nitazoxanide-tizoxanide-and-tizoxanide-2m40mmgfgo.pdf

Efficacy of nitazoxanide, tizoxanide and tizoxanide glucuronide against Cryptosporidium parvum development in sporozoite-infected HCT-8 enterocytic cells

Cryptosporidium parvum, Tyzzer, 1912 is identified as a common cause of diarrhoea in immunocompetent individuals. In immunocompromised, especially HIV-infected subjects, cryptosporidiosis causes severe chronic diarrhoea. In this study, nitazoxanide (NTZ) was compared for curative activity with sinefungin (SNF) and paromomycin (PRM) in immunosuppressed rats, a screening model for anticryptosporidial agents. NTZ at either 50 mg/kg/day, 100 mg/kg/day or 200 mg/kg/day resulted in seven days in a dose-dependent inhibition of oocyst shedding similar to that obtained with SNF (10 mg/kg/day) and PRM (100 mg/kg/day). Further discontinuation of SNF or PRM 100 mg/kg/day therapy resulted in early relapse of oocyst shedding which reached the pre-treatment levels in 2-4 days. In contrast, seven days after discontinuation of therapy, shedding inhibition was unchanged in NTZ-treated rats. Data prompt further assessment of the activity of NTZ on sequestered C. parvum.

/pdf/long-lasting-anticryptosporidial-activity-of-nitazoxanide-in-3v1l3ngvhe.pdf

Long-lasting anticryptosporidial activity of nitazoxanide in an immunosuppressed rat model.

Cryptosporidium oocysts in mussels (Mytilus edulis) from Normandy (France)

Contamination by water-born infectious diseases is closely linked to urban slums conditions such as overcrowding and high level of faecal pollution by animal and human excreta. In this environment, cryptosporidiosis is a major cause of acute diarrhoea in children and chronic persistent diarrhoea in AIDS patients, resulting in increased morbidity and mortality in both populations. The aims of this study conducted in Port-au-Prince, Haiti were to: (i) determine the frequency of Cryptosporidium infection in two populations of patients with diarrhoea, children and AIDS patients, and the existence of Cryptosporidium carriage in healthy adults living in close contact with them; (ii) identify by molecular genotyping the Cryptosporidium species involved; and (iii) evaluate the viability of Cryptosporidium oocysts isolated from human stools. From January 2000 to January 2001, 158 of 1529 diarrhoea stool samples collected from 93 patients with diarrhoea, 57 adults followed at Centres GHESKIO and 36 children admitted at the University Hospital in Port-au-Prince contained Cryptosporidium oocysts (10.3%). The majority of adult patients (98%) were HIV-infected whereas the majority of children (81%) tested negative for HIV. Cryptosporidium was documented in only 1/102 healthy persons living in contact with Cryptosporidium infected patients and infection was with the same genotype as that of the contact patient. Among the 69 Cryptosporidium isolates studied for genotyping, three species were identified: C. hominis (59%), C. parvum (38%) and C. felis (3%). The two C. felis cases are the first reported from AIDS patients in the Caribbean. Most of the children regardless of their HIV status were infected with C. hominis (72%), whereas AIDS patients were more likely to be infected by either human or animal genotypes. These data confirm that immunocompromised individuals are susceptible to a wide range of Cryptosporidium spp. Viability of Cryptosporidium oocysts were determined in an experimental mouse model for 17/18 specimen studied including in 12/13 C. hominis, 4/4 C. parvum and 1/1 C. felis. Infectivity in newborn mice was found to be dose-dependent and more effective with C. parvum than the other two genotypes. Cryptosporidiosis remains a frequent hazard for both AIDS patients and young children in Haiti because of poor hygiene, particularly contaminated water and overcrowded conditions associated with urban slums.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-3156.2006.01631.x

Cryptosporidiose humaine et espèces en cause en Haïti

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.

Xunde Li

Papers

Efficacy of nitazoxanide, tizoxanide and tizoxanide glucuronide against Cryptosporidium parvum development in sporozoite-infected HCT-8 enterocytic cells

Long-lasting anticryptosporidial activity of nitazoxanide in an immunosuppressed rat model.

Cryptosporidium oocysts in mussels (Mytilus edulis) from Normandy (France)

Cryptosporidiose humaine et espèces en cause en Haïti

Quantitative flow cytometric evaluation of maximal Cryptosporidium parvum oocyst infectivity in a neonate mouse model.