Prevention Of Cryptosporidiosis Research Articles

Anti-Cryptosporidial Drug-Discovery Challenges and Existing Therapeutic Avenues: A "One-Health" Concern.

Cryptosporidiosis is the leading cause of life-threatening diarrheal infection, especially in infants. Oocysts contaminate the environment, and also, being a zoonotic disease, cryptosporidiosis is a threat to One Health. Nitazoxanide is the only FDA-approved drug, effective only in immunocompetent adults, and is not safe for infants. The absence of mitochondria and apicoplast, the presence of an electron-dense band (ED band), hindrances in its genetic and phenotypic manipulations, and its unique position inside the host cell are some challenges to the anti-cryptosporidial drug-discovery process. However, many compounds, including herbal products, have shown efficacy against Cryptosporidium during in vitro and in vivo trials. Still, the "drug of choice" against this protozoan parasite, especially in immunocompromised individuals and infants, has not yet been explored. The One-Health approach addresses this issue, focusing on the intersection of animal, human, and environmental health. The objective of this review is to provide knowledge about novel anti-cryptosporidial drug targets, available treatment options with associated limitations, and possible future shifts toward natural products to treat cryptosporidiosis. The current review is organized to address the treatment and prevention of cryptosporidiosis. An anti-cryptosporidial drug that is effective in immunocompromised individuals and infants is a necessity of our time.

Cryptosporidium spp. in captive snakes from 26 provinces in China: Prevalence, molecular characterization, and symptoms.

Snakes are sometimes regarded as pets and are used in traditional Chinese medicine. Cryptosporidium spp. are frequently identified in snakes, representing an important pathogen and causing gastrointestinal diseases. Current data indicate that risk factors for infection and patterns of clinical symptom presentation may differ among Cryptosporidium spp. To better understand the infection status by Cryptosporidium spp., fecal samples were collected from 603 asymptomatic and 147 symptomatic snakes in 26 provinces of China. These samples came from Elaphe guttata, Elaphe obsoleta, Pituophis melanoleucus, Thamnophis sirtalis, Lampropeltis getulus, and Heterodon nasicus. The partial small subunit (SSU) rRNA gene was amplified using nested polymerase chain reaction (PCR) to investigate the infection rate of Cryptosporidium spp., and to assess evolutionary relationships and genetic characterization. A prevalence of 20% was recorded in asymptomatic snakes, with age identified as a significant risk factor. In contrast, 70% of symptomatic snakes were positive for Cryptosporidium spp., with Cryptosporidium serpentis and Cryptosporidium varanii (syn. C. saurophilum). Further analysis revealed a potential association between C. serpentis and regurgitation, and C. varanii and diarrhea, while neither species was linked to flatulence. To our knowledge, this is the first study to report Cryptosporidium spp. and associated clinical signs in symptomatic snakes in China. This study aims to enhance the understanding of Cryptosporidium infections, risk factors, and clinical manifestations in snakes, providing data crucial for the control and prevention of cryptosporidiosis.

Development of methods for prevention of cryptosporidiosis of calves

Cryptosporidiosis of calves, caused by the parasite Cryptosporidium parvum, is a dangerous disease for calves for up to one month. Sick animals suffer from debilitating diarrhea, intoxication, and dehydration, which can lead to death. Currently, effective preventive and curative measures have not been developed. Therefore, new strategies for preventing cryptosporidiosis in cattle are being sought. The study was conducted on the farm for raising young cattle in Holstein LTD agricultural firm “Lan” Sumy region in February 2021. The circulating microflora in the calf and the clinical condition of the animals were determined. The first experimental group of calves used the antimicrobial agent Trimeratinvet powder (water-soluble powder for oral administration). In the second experimental group, calves were fed the acidifier Kronocid L. As a control, healthy calves were used, which received a regular diet. Conducted a study of fecal masses of calves from birth to one month. The presence of Cryptosporidium spp. in fecal masses of calves was determined microscopically and by nested polymerase chain reaction. The count of microorganisms was performed after cultivation on elective media and determined the number of colony-forming units in CFU/cm3. The EXPERTISTM Rainbow diagnostic kit was used to diagnose Rotavirus and Coronavirus. Studies have shown that Cryptosporidium in calves under one month of age is the most common cause of diarrhea (42 %). Acidifier Kronocid L and Trimeratinvet inhibited the reproduction of cryptosporidia by stopping sporulation. Acidifier at a pH of 4.5 penetrated the oocyst's shell, causing cytoplasm compression. At 60 minutes of exposure, Kronocid L reduced the possibility of sporulation and destroyed 90 % of treated oocysts, which is 20 % more than the antimicrobial agent Trimeratinvet. In the experimental group using Trimeratinvet, the onset of chewing occurred later than eight days compared to the control group and with Kronocid L. Calves of the experimental groups had an average weight gain during the month with Trimeratinvet less by 20.8 % (P ≤ 0.05), with Kronocid L – by 14.3 % compared to healthy. Prospects for further research are to determine the effect of Cronocid L and other species of Cryptosporidium in adult cattle.

Diagnosis and control of cryptosporidiosis in farm animals.

Cryptosporidium is a pathogenic protozoan parasite infecting the gastrointestinal epithelium of human and animal hosts. In farm animals, cryptosporidiosis causes significant economic losses including deaths in newborn animals, retarded growth, increased labor involved and high cost of drugs. The detection of Cryptosporidium oocysts in fecal samples is traditionally dependent on examination of stained slides by light microscope or by advanced microscopical tools such as: electron microscopy and phase contrast microscopy. Immunological diagnosis using either antibody or antigen detection could offer high sensitivity and specificity. Examples for these tests are Enzyme Linked Immunosorbent Assay (ELISA), Immunochromatographic tests, Immunochromatographic lateral flow (ICLF), Immunofluorescence assays (IFA) and Flow cytometry coupled with cell sorting. Molecular methods could differentiate species and genotypes of Cryptosporidium and help in studying the epidemiological features of this parasite with rapid, simple and sensitive procedures. Nanotechnology-based platforms could improve the sensitivity and specificity of other detection methods like: ELISA, ICLF, IFA and polymerase chain reaction. As the available prophylactic and therapeutic drugs or natural products treatments are insufficient and no approved vaccines are available, the best approach to control this parasite is by following firm hygienic measures. Many vaccine attempts were performed using hyperimmune colostrum, live or attenuated vaccines, recombinant and Deoxyribonucleic acid vaccines. Also, Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 technology could help in Cryptosporidium genome editing to improve drug and vaccine discovery. Another approach that could be useful for assigning drug targets is metabolomics. Probiotics were also used successfully in the treatment of acute diarrhea and they proved a limiting effect on cryptosporidiosis in animal models. In addition, nanotherapy-based approaches could provide a good strategy for improving the potency of any type of drugs against Cryptosporidium and give good anti-cryptosporidial effects. In conclusion, accurate diagnosis using advanced techniques is the key to the control and prevention of cryptosporidiosis.

Prevalence and Molecular Characterization of Cryptosporidium serpentis in Captive Snakes in China.

Cryptosporidium species are the causative agent of cryptosporidiosis and common intracellular parasites that can infect a wide range of vertebrates, including snakes. In previous studies, Cryptosporidium species infections have been reported in snakes in Asia, Europe, and North America. However, limited information is available about the prevalence and molecular characterization of Cryptosporidium in captive snakes in China. Fecal specimens from 609 captive snakes were collected from Beijing (n = 227), Chengdu (n = 12), Dazhou (n = 359), and Ziyang (n = 11). The partial small-subunit (SSU) rRNA gene was amplified by nested polymerase chain reaction to determine the prevalence of Cryptosporidium, and a phylogenetic tree was constructed to assess evolutionary relationships and genetic characteristics. The overall prevalence of Cryptosporidium was 1.97% (12/609). BLAST and phylogenetic analysis of the small subunit ribosomal RNA (SSU rRNA) gene showed that the parasites belonged to Cryptosporidium serpentis. To the best of our knowledge, this is the first study to report the prevalence of Cryptosporidium in snakes of southwestern and northern China and provides preliminary data for the control and prevention of cryptosporidiosis in the investigated areas.

Seroprevalence of Cryptosporidium and risks of cryptosporidiosis in residents of Sothern Egypt: A cross-sectional study

Objective: To identify the serological epidemiology of Cryptosporidium infections and to follow up on the changes in the infection profile in Southern Egypt in order to establish a suitable scheme for control and prevention of cryptosporidiosis. Methods: A total of 1 912 (960 from human and 952 from animals) stool specimens and sera were screened for Cryptosporidium species using modified Ziehl Neelsen technique and a newly-developed enzyme-linked immunosorbent assay (ELISA). Environmental risk factors and socioeconomic data were surveyed by questionnaire between September 2016 and December 2017. Results: Totally, 20.83% of the human subjects were positive for Cryptosporidium infection tested by ELISA. The seropositivity was positively correlated with age. The prevalence of Cryptosporidium infections in females was significantly higher than in males (P Conclusions: The study observed that Cryptosporidium infections are common in the study area, with water sanitation, socioeconomic level; eating habits and hygienic status are considered the main risk factors for cryptosporidiosis. Therefore, environmental sanitation and health education will be useful in reducing the prevalence of infection.

A perspective on Cryptosporidium and Giardia, with an emphasis on bovines and recent epidemiological findings.

Cryptosporidium and Giardia are two common aetiological agents of infectious enteritis in humans and animals worldwide. These parasitic protists are usually transmitted by the faecal–oral route, following the ingestion of infective stages (oocysts or cysts). An essential component of the control of these parasitic infections, from a public health perspective, is an understanding of the sources and routes of transmission in different geographical regions. Bovines are considered potential sources of infection for humans, because species and genotypes of Cryptosporidium and Giardia infecting humans have also been isolated from cattle in molecular parasitological studies. However, species and genotypes of Cryptosporidium and Giardia of bovids, and the extent of zoonotic transmission in different geographical regions in the world, are still relatively poorly understood. The purpose of this article is to (1) provide a brief background on Cryptosporidium and Giardia, (2) review some key aspects of the molecular epidemiology of cryptosporidiosis and giardiasis in animals, with an emphasis on bovines, (3) summarize research of Cryptosporidium and Giardia from cattle and water buffaloes in parts of Australasia and Sri Lanka, considering public health aspects and (4) provide a perspective on future avenues of study. Recent studies reinforce that bovines harbour Cryptosporidium and Giardia that likely pose a human health risk and highlight the need for future investigations of the biology, population genetics and transmission dynamics of Cryptosporidium and Giardia in cattle, water buffaloes and other ruminants in different geographical regions, the fate and transport of infective stages following their release into the environment, as well as for improved strategies for the control and prevention of cryptosporidiosis and giardiasis, guided by molecular epidemiological studies.

Application of recombinant Cryptosporidium parvum P23 for isolation and prevention

Cryptosporidium parvum is a coccidian protozoan that causes diarrhea in immunocompromised humans and newborn animals. Billions of oocysts of C. parvum can be released from the infected calves and can contaminate the environment. The severity of the disease depends on the immunological status of the individual. Oocysts of Cryptosporidium are extremely resistant to many environmental stresses, and no effective disinfectant and curative agent against this organism is available. In our study, recombinant C. parvum P23 was prepared for application in the isolation and prevention of cryptosporidiosis. P23 is a glycoprotein that belongs to a family of protein of 23-27 kDa and is believed to be expressed in the different life stages of the parasite. Immunostaining analysis using the indirect fluorescent antibody test showed that P23 could be recognized on the surface of the oocysts. The antibody prepared in rabbit against P23 was bound to Sepharose 4B and used for the isolation of oocysts. The results showed that the prepared column was able to bind specifically only the oocysts. The effect of specific recombinant C. parvum IgY antibody against infection with C. parvum was examined in a mouse model. For this aim, purified egg yolk antibody prepared from immunized hens was used to analyze the protective effect of recombinant P23 specific antibody in immunosuppressed adult mice. The results showed more than 70% reduction in oocyst shedding after challenge with 1 × 10(4) oocysts. These results support previous studies of other investigators regarding the protective effect of P23 as an antigen against C. parvum infection and showed that it could be possible to design a passive immunization strategy against C. parvum based on the anti-P23 yolk antibody in animals and immunosuppressed humans.

Efficacy of halofuginone lactate in the prevention of cryptosporidiosis in dairy calves

To evaluate the efficacy of halofuginone lactate (Halocur; Intervet) when used prophylactically against cryptosporidiosis in dairy calves, 513 Holstein heifer calves were randomly distributed between two experimental groups. Those in...

Treatment and prevention of cryptosporidiosis: what options are there for a country like Zambia?

Cryptosporidiosis is a major infection of humans, leading to diarrhoea and growth failure in children, diarrhoea and malnutrition in immunocompromised adults, and is associated with increased mortality in all age groups. Using the country of Zambia as an example, I review the possible approaches to treatment and prevention in a tropical setting. The current optimal therapy for cryptosporidiosis is nitazoxanide which works well in HIV uninfected children, but treatment in patients with HIV infection remains remarkably difficult. No single drug has demonstrated efficacy in a randomised trial. No vaccine is available, so the best option for prevention for the moment is filtration and clean storage of drinking water. This would be expected to reduce cryptosporidiosis dramatically, but this needs to be demonstrated directly. Water filtration would have the added benefit of protection against many other pathogens, but the paucity of alternative approaches highlights the need for a better understanding of this important human pathogen.

Efficacy of halofuginone lactate for the treatment and prevention of cryptosporidiosis in goat kids: An extensive field trial

The effects of halofuginone lactate (100 μg/kg B.W.) for the treatment and prevention of cryptosporidiosis in goat kids was evaluated in 3 field trials. Trial 1 was to assess the efficacy of halofuginone on the treatment of kid diarrhoea caused by Cryptosporidium spp. Halofuginone given for 7 and for 3 consecutive days, respectively, was effective for the treatment of diarrhoea ( P < 0.05). Also, halofuginone administered for a 7-day treatment was significantly ( P < 0.05) more effective than a 3-day treatment in reducing the incidence of diarrhoea in the infected goat herds. In the second trial halofuginone given for 7 days reduced significantly ( P < 0.05) the diarrhoea incidence, the time of oocyst shedding and the mean intensity of shedding. In the third trial halofuginone was effective in reducing the death rate and preventing cryptosporidiosis. It was concluded, that halofuginone lactate at a dosage rate of 100 μg/kg for 7 days was effective in treatment and prevention of kid cryptosporidiosis.

Effect of halofuginone lactate on treatment and prevention of lamb cryptosporidiosis: an extensive field trial

This study aimed to investigate the effects of halofuginone lactate (100 mug/kg BW) on treatment and prevention of cryptosporidiosis in lambs. It consisted of three field trials. The first trial was designed to assess the efficacy of halofuginone in treating lamb diarrhoea caused by cryptosporidiosis, and in preventing the disease, using two schemes; halofuginone given for seven and for three consecutive days respectively. Halofuginone was effective in the treatment of diarrhoea caused by cryptosporidiosis (P < 0.01). In addition, halofuginone administered as a 7-day treatment was significantly (P < 0.05) more effective than a 3-day treatment in preventing diarrhoea in the infected flocks. The second trial was designed to evaluate the preventive effect of halofuginone, which was administered for 7 days in lambs infected with cryptosporidiosis, on diarrhoea incidence, oocyst shedding and body weight gain. Halofuginone significantly (P < 0.01) reduced the diarrhoea incidence, the time of oocyst shedding and the mean intensity of shedding, but did not affect body weight gain. The third trial was designed to examine the ability of halofuginone to reduce the death rate in flocks with cryptosporidiosis. Halofuginone treatment was effective in preventing and in reducing the death rate of cryptosporidiosis in these flocks.

Treatment of cryptosporidiosis in immunocompromised individuals: systematic review and meta-analysis.

Cryptosporidium is a common cause of gastroenteritis and is associated with severe life-threatening illness among immunocompromised individuals. This review aimed to assess the efficacy of interventions for the treatment and prevention of cryptosporidiosis among immunocompromised patients. A search of Medline, Embase and other electronic databases was carried out up to August 2005. Two reviewers independently extracted data and assessed study quality. The relative risk for each intervention was calculated. Seven trials involving 169 participants were included. Nitazoxanide and paramomycin were associated with a relative risk (RR) of reduction in the duration and frequency of diarrhoea of 0.83 [95% confidence interval (CI) 0.36, 1.94] and 0.74 (95% CI 0.42, 1.31), respectively, showing no evidence of effectiveness. Nitazoxanide led to significant evidence of oocyst clearance compared with placebo with a RR of 0.52 (95% CI 0.30, 0.91). The effect was not significant for HIV-seropositive participants (RR 0.71, 95% CI 0.36, 1.37). HIV-seronegative participants on nitazoxanide had a significantly higher relative risk of achieving parasitological clearance of 0.26 (95% CI 0.09, 0.80) based on a single study. No other intervention was associated with either a reduction in diarrhoea, mortality or a significant parasitological response. This review confirms the absence of evidence for effective agents in the management of cryptosporidiosis. The results indicate that nitaxozanide reduces load of parasites and may be useful in immunocompetent individuals. The absence of effective therapy highlights the importance of preventive interventions in this group of patients.

Prevention and treatment of cryptosporidiosis in immunocompromised patients

Cryptosporidiosis is a disease that causes diarrhoea lasting about one to two weeks, sometimes extending up to 2.5 months among the immunocompetent and becoming a more severe life-threatening illness among immunocompromised individuals. Cryptosporidium is a common cause of gastroenteritis. Cryptosporidiosis is common in HIV-infected individuals. The objective of the review was to assess the efficacy of interventions for the treatment and prevention of cryptosporidiosis among immunocompromised individuals. We searched the following databases for randomised controlled trials up to August 2005: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, AIDSLINE, AIDSearch, EMBASE, CINAHL, Current Contents, Geobase, and the Environmental Sciences and Pollution Management. Randomised controlled trials that compared the use of any intervention to treat or prevent cryptosporidiosis in immunocompromised persons were included. The outcome measures for treatment studies included symptomatic diarrhoea and oocyst clearance. Two reviewers independently assessed the trials for quality of randomisation, blinding, withdrawals, and adequacy of allocation concealment. The relative risk for each intervention was calculated using a random effects model. Seven trials involving 169 participants were included. There were 130 adults with AIDS enrolled in five studies. Evidence of significant heterogeneity was present. There was no evidence for a reduction in the duration or frequency of diarrhoea by nitazoxanide (RR 0.83 (95% CI 0.36-1.94)) and paramomycin (RR 0.74 (95% CI 0.42-1.31)) compared with placebo. Nitazoxanide led to a significant evidence of oocyst clearance compared with placebo among all children with a relative risk of 0.52 (95% CI 0.30-0.91). The effect was not significant for HIV-seropositive participants (RR 0.71 (95% CI 0.36-1.37)). HIV-seronegative participants on nitazoxanide had a significantly higher relative risk of achieving parasitological clearance of 0.26 (95% CI 0.09-0.80) based on a single study. The single study comparing spiramycin with placebo found no significant difference in reduction of the duration of hospitalisation (mean difference -0.40 days (95% CI -6.62-5.82)) or in mortality between the two arms of the trial (RR 0.43 (95% CI 0.04-4.35)). One study assessed the role of bovine dialyzable leukocyte extract, reporting a relative risk for decreased stool frequency of 0.19 (95% CI 0.03-1.19), while another compared bovine hyperimmune colostrum with placebo and found no evidence for improvement of stool volume (RR 3.00 (95% CI 0.61-14.86)) or in oocyst concentration per ml of stool (RR 0.27 (95% CI 0.02-3.74)). No studies were found that assessed prevention. This review confirms the absence of evidence for effective agents in the management of cryptosporidiosis. The results indicate that nitaxozanide reduces the load of parasites and may be useful in immunocompetent individuals. Due to the seriousness of the potential outcomes of cryptosporidiosis, the use of nitaxozanide should be considered in immunocompromised patients. The absence of effective therapy highlights the need to ensure that infection is avoided. Unfortunately, evidence for the effectiveness and cost-effectiveness of preventive interventions is also lacking.

Evaluation of the Efficacy of Halofuginone Lactate (Halocur®) as an Aid in the Prevention of Cryptosporidiosis in Ontario Dairy Calves

Cryptosporidium parvum is a common cause of diarrhea in calves less than one month of age. Prevalence of shedding of C. parvum and clinical disease is high on many dairy farms. Control of cryptosporidiosis is difficult. There are currently no approved products in North America for prevention of this disease. In Europe, halofuginone lactate (Halocur®) is marketed for the prevention of cryptosporidiosis by reducing and delaying excretion of C. parvum oocysts and in preventing diarrhea. The objective of this study was to evaluate the efficacy of halofuginone lactate as an aid in the prevention of cryptosporidiosis in dairy calves.

Effect of egg yolk antibody on experimental Cryptosporidiumparvum infection in scid mice

In this study the effect of chicken egg yolk antibody (IgY) against Cryptosporidium parvum infection was examined. IgY sample was prepared from eggs of chickens immunized with C. parvum oocyst antigens. In vitro, antibody-treated sporozoites showed reduced binding to Caco-2 cells and lost vitality. These phenomena were not observed with a control IgY sample prepared from eggs of non-immunized chickens. Scid mice orally administered with the antibody demonstrated partial reduction in oocyst shedding after challenge with 10 3 oocysts. IgY, however, could not eliminate the infection after 17 days of continuous treatment. The potentials of using specific IgY for treatment and prevention of cryptosporidiosis were discussed.

A review of the biology and epidemiology of cryptosporidiosis in humans and animals

The epidemiology of cryptosporidiosis, an infection caused by several genotypically and phenotypically diverse Cryptosporidium species, has been dynamically changing over the past decade from that of a rare, largely asymptomatic infection to an acute enteric disease of animals and humans. In this review, the current understanding of factors (biology and epidemiology) contributing to the emergence of cryptosporidiosis in animals, including parasite biology, genetic diversity, environmental spread, livestock production trends, presence of the parasite in livestock and companion animals, and potential risk of transmission from animals to humans is highlighted. Potential control measures and the role of veterinary and medical professionals in the prevention of cryptosporidiosis are also discussed.

Efficacy of halofuginone lactate in the prevention of cryptosporidiosis in suckling calves

The efficacy of halofuginone lactate in the prevention of cryptosporidiosis in suckling calves was evaluated in a multicentre, control versus placebo, randomised, double.blind clinical trial. Seventy-eight six- to 48- hour-old...

Knowledge of HIV infected individuals about prevention of cryptosporidiosis.

Knowledge of HIV infected individuals about prevention of cryptosporidiosis.