Review

Authors: William Checkley, A Clinton White, Devan Jaganath...

Cryptosporidium spp are well recognised as causes of diarrhoeal disease during waterborne epidemics and in immunocompromised hosts. Studies have also drawn attention to an underestimated global burden and suggest major gaps in optimum diagnosis, treatment, and immunisation. Cryptosporidiosis is increasingly identified as an important cause of morbidity and mortality worldwide. Studies in low-resource settings and high-income countries have confirmed the importance of cryptosporidium as a cause of diarrhoea and childhood malnutrition. Diagnostic tests for cryptosporidium infection are suboptimum, necessitating specialised tests that are often insensitive. Antigen-detection and PCR improve sensitivity, and multiplexed antigen detection and molecular assays are underused. Therapy has some effect in healthy hosts and no proven efficacy in patients with AIDS. Use of cryptosporidium genomes has helped to identify promising therapeutic targets, and drugs are in development, but methods to assess the efficacy in vitro and in animals are not well standardised. Partial immunity after exposure suggests the potential for successful vaccines, and several are in development; however, surrogates of protection are not well defined. Improved methods for propagation and genetic manipulation of the organism would be significant advances.

Topics: Antiprotozoal Agents; Cryptosporidiosis; Diagnostic Tests, Routine; Diarrhea; Global Health; Humans; Protozoan Vaccines

PubMed: 25278220
DOI: 10.1016/S1473-3099(14)70772-8

Review

Authors: Alexis R Gibson, Boris Striepen

The apicomplexan parasite Cryptosporidium parvum is the second leading cause of death in children due to diarrheal disease worldwide. Gibson and Striepen offer insights into the fascinating biology of this poorly understood parasite, and describe new strategies aimed at defeating it.

Topics: Cryptosporidiosis; Cryptosporidium; Humans

PubMed: 29510102
DOI: 10.1016/j.cub.2017.11.070

Review

Authors: S M Cacciò, R M Chalmers

Cryptosporidium has emerged as a significant cause of diarrhoeal disease worldwide, with severe health consequences for very young, malnourished children living in endemic areas and for individuals with highly impaired T-cell functions. In Europe, as elsewhere, the burden of disease has been difficult to measure as a result of the lack of appropriate, standardized surveillance and monitoring systems. The recent occurrence of large water- and foodborne outbreaks in several EU countries, as well as the results of many surveys of human and animal cryptosporidiosis, indicate that this parasite is widespread. Specific subtypes of the zoonotic Cryptosporidium parvum and the anthroponotic C. hominis are responsible for the majority of human cases in Europe. No treatment is currently available to clear the infection, but recent progress in genetic engineering of the parasite, coupled with advances in genomics, have opened important avenues for future research. Here we explore the possible reasons for underascertainment of cryptosporidiosis and the importance of accurate diagnosis in clinical management, the epidemiology of human cryptosporidiosis and key messages from recent outbreaks to highlight important interventions and emerging public health issues.

Topics: Cryptosporidiosis; Cryptosporidium; Disease Outbreaks; Europe; Genotype; Humans; Prevalence

PubMed: 27172805
DOI: 10.1016/j.cmi.2016.04.021

Review

Authors: Sarah Thomson, Carly A Hamilton, Jayne C Hope...

Gastrointestinal disease caused by the apicomplexan parasite Cryptosporidium parvum is one of the most important diseases of young ruminant livestock, particularly neonatal calves. Infected animals may suffer from profuse watery diarrhoea, dehydration and in severe cases death can occur. At present, effective therapeutic and preventative measures are not available and a better understanding of the host-pathogen interactions is required. Cryptosporidium parvum is also an important zoonotic pathogen causing severe disease in people, with young children being particularly vulnerable. Our knowledge of the immune responses induced by Cryptosporidium parasites in clinically relevant hosts is very limited. This review discusses the impact of bovine cryptosporidiosis and describes how a thorough understanding of the host-pathogen interactions may help to identify novel prevention and control strategies.

Topics: Animals; Cattle; Cattle Diseases; Cryptosporidiosis; Cryptosporidium parvum; Host-Parasite Interactions

PubMed: 28800747
DOI: 10.1186/s13567-017-0447-0

Review

Authors: W L Current, L S Garcia

Before 1982, only eight case reports of human cryptosporidiosis and fewer than 30 papers on Cryptosporidium spp. appeared in the biomedical literature. At that time, cryptosporidiosis was thought to be an infrequent infection in animals and rarely an opportunistic infection in humans. The concept of Cryptosporidium spp. as pathogens has changed dramatically within the past 8 years because of improved diagnostic techniques, increased awareness within the biomedical community, and the development of basic research programs in numerous laboratories. Presently, greater than 1,000 publications including over 400 case reports in the biomedical literature address Cryptosporidium spp. and cryptosporidiosis. Cryptosporidium parvum is now thought to be one of the three most common enteropathogens causing diarrheal illness in humans worldwide, especially in developing countries. It is likely that cryptosporidiosis was previously included in the 25 to 35% of diarrheal illness with unknown etiology. Because of the severity and length of diarrheal illness and because no effective therapy has been identified, cryptosporidiosis is one of the most ominous infections associated with AIDS. The role of C. parvum as an enteropathogen is well established; documentation of its role as a cause of hepatobiliary and respiratory diseases is now appearing in the literature. Our present understanding of the natural history, epidemiology, biology, and immunology of Cryptosporidium spp. as well as the clinical features, pathogenicity, and treatment of cryptosporidiosis are reviewed here.

Topics: Animals; Cryptosporidiosis; Cryptosporidium; Humans

PubMed: 1889046
DOI: 10.1128/CMR.4.3.325

Authors: Lisa J Funkhouser-Jones, Rui Xu, Georgia Wilke...

Cryptosporidiosis is a leading cause of life-threatening diarrhea in young children in resource-poor settings. To explore microbial influences on susceptibility, we screened 85 microbiota-associated metabolites for their effects on Cryptosporidium parvum growth in vitro. We identify eight inhibitory metabolites in three main classes: secondary bile salts/acids, a vitamin B precursor, and indoles. Growth restriction of C. parvum by indoles does not depend on the host aryl hydrocarbon receptor (AhR) pathway. Instead, treatment impairs host mitochondrial function and reduces total cellular ATP, as well as directly reducing the membrane potential in the parasite mitosome, a degenerate mitochondria. Oral administration of indoles, or reconstitution of the gut microbiota with indole-producing bacteria, delays life cycle progression of the parasite in vitro and reduces the severity of C. parvum infection in mice. Collectively, these findings indicate that microbiota metabolites impair mitochondrial function and contribute to colonization resistance to Cryptosporidium infection.

Topics: Animals; Mice; Cryptosporidium parvum; Cryptosporidiosis; Cryptosporidium; Microbiota; Mitochondria; Indoles

PubMed: 37384526
DOI: 10.1016/j.celrep.2023.112680

Authors: Ian H Gilbert, Sumiti Vinayak, Boris Striepen...

Topics: Humans; Cryptosporidiosis; Neglected Diseases

PubMed: 37541693
DOI: 10.1136/bmjgh-2023-012540

Review

Authors: Anne-Charlotte Lenière, Alexis Vlandas, Jérôme Follet...

Despite several decades of research on therapeutics, cryptosporidiosis remains a major concern for human and animal health. Even though this field of research to assess antiparasitic drug activity is highly active and competitive, only one molecule is authorized to be used in humans. However, this molecule was not efficacious in immunocompromised people and the lack of animal therapeutics remains a cause of concern. Indeed, the therapeutic arsenal needs to be developed for both humans and animals. Our work aims to clarify research strategies that historically were diffuse and poorly directed. This paper reviews in vitro and in vivo methodologies to assess the activity of future therapeutic compounds by screening drug libraries or through drug repurposing. It focuses on High Throughput Screening methodologies (HTS) and discusses the lack of knowledge of target mechanisms. In addition, an overview of several specific metabolic pathways and enzymatic activities used as targets against Cryptosporidium is provided. These metabolic processes include glycolytic pathways, fatty acid production, kinase activities, tRNA elaboration, nucleotide synthesis, gene expression and mRNA maturation. As a conclusion, we highlight emerging future strategies for screening natural compounds and assessing drug resistance issues.

Topics: Cryptosporidiosis; Drug Discovery; Humans; Animals; High-Throughput Screening Assays; Cryptosporidium; Antiprotozoal Agents; Drug Repositioning; Drug Resistance; Antiparasitic Agents

PubMed: 38669849
DOI: 10.1016/j.ijpddr.2024.100542

Review

Authors: AbdelRahman Zueter

BACKGROUND

Cryptosporidium is a waterborne intestinal parasite that causes diarrhoea in low and middle-income countries worldwide. Reports from Mediterranean countries have documented the prevalence of cryptosporidiosis in children at various ages, also among cancer patients, and in cases of chronic kidney disease, haemodialysis, and organ transplant. Untill now, modified-acid staining preceded by stool concentration preparation remains the leading screening diagnostic test for the infection. In Jordan, few studies for cryptosporidiosis have been performed during the last 3 decades.

AIMS

This paper reviewed the status of cryptosporidiosis in Jordan and tracked recent updates for this emerging protozoal infection among different population groups.

METHODS

In this study, an online search was conducted on Google Scholar and PubMed databases using the keywords: Jordan, cryptosporidiosis and Cryptosporidium to inspect studies done on this parasite in Jordan.

RESULTS

Only 9 articles were identified from 1994 to 2019. These were analysed in terms of population group, demography, clinical history and the diagnostic tools used.

CONCLUSION

Cryptosporidiosis is still neglected in Jordan as indicated by the low number of studies over the last 3 decades and the prevalence is diverse depending on the diagnostic test used and socioeconomic status.

Topics: Child; Cryptosporidiosis; Cryptosporidium; Diarrhea; Feces; Humans; Jordan; Prevalence

PubMed: 33355397
DOI: 10.26719/emhj.20.065

Authors: Nicolás Hernández-Gallo, Luis J Hernández-Flórez, Jesús A Cortés-Vecino...

Cryptosporidiosis is a diarrheal disease (zoonotic) caused by the parasite Cryptosporidium, which infects the intestine. It occurs in humans and in different pets, farm and wild animals. Its role is underestimated and little is known about its epidemiology, due to the low interest it draws and the limited availability of diagnostic methods. The population health, both human and animal, is related to a close interaction of three factors: the environment, pathogens, and population, which determines the state of health and disease; some of the diseases considered as emerging, that appeared in the last years. The approach, known as "One Health", is a growing global strategy being adopted by a diversity of organizations and policy makers in response to the need for integrated approaches. This approach may be relevant to a wide range of global development goals. There is more and more talk about holistic health. It seems that we are more aware that health is not reduced to something purely biological, but affects the whole person. It is not only seeing the patient globally, it is starting from the complexity of the human being and the whole world crossed by vulnerability and interacting with the totality of the subjects.

Topics: Animals; Cryptosporidiosis; Global Health; Humans; One Health

PubMed: 30183897
DOI: 10.15446/rsap.V20n1.69959