Diseases

Cryptosporidiosis

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Control Tools

  • Diagnostics availability

  • Commercial diagnostic kits available worldwide

    A variety of antibody based commercial detection kits are available all of which rely on the identification of oocysts from concentrated or unconcentrated faeces samples.

    These include immunofluorescent, ELISA and immunochromatography based kits. Quantitative real time PCR kits are also available.

  • Commercial diagnostic kits available in Europe

    See Section above "Commercial diagnostic kits available worldwide"

  • Diagnostic kits validated by International, European or National Standards

    No.

  • Diagnostic method(s) described by International, European or National standards

    Routine methods are described in the OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. These involve:

    1. Demonstration of Cryptosporidium oocysts in faeces

    2. Immunological methods to demonstrate Cryptosporidium-specific antigen in faecal samples

    a) Direct immunofluorescence microscopy

    b) ELISA

    c) Immunochromatography

    3. Nucleic acid recognition methods

    a) PCR

    b) Quantitative real time PCR

    GAPS:

    1. Need to evaluate the existing diagnostic assays for each specific diagnostic target: clinical, subclinical or epidemiological diagnosis

    2. Need to define the preferred diagnostic assay for each diagnostic target, in terms of additional info procured versus cost

    3. Investigate the efficacy of using cell-mediated immune based assays using specific Cryptosporidium antigens and induction of interferon gamma as a diagnostic test in people

    4. Examine duration of this type of response in symptomatic animal models and in infected people

  • Commercial potential for diagnostic kits worldwide

    Current diagnosis is based on identifying oocysts, antigens, or DNA in faeces samples. PCR kits are numerous and are more sensitive than other methods.

  • DIVA tests required and/or available

    No.

  • Opportunities for new developments

    Microscopy is still the most commonly used diagnostic assay and is validated for clinical diagnosis. Commercial kits are available (ELISA and immunochromographic lateral flow assays), but the cost is high.

    Furthermore, none of these assays allows the identification of the species/genotypes of the parasite.

    GAPS:

    1. Further reduce cost of ELISA and/or immunochromographic lateral flow assays in cassette and/or dipstick format to make these tools available to veterinarians and farmers

    2. Develop molecular-based platforms for routine detection, including species identification

    3. Improve and standardize assays for the detection of carriers

    4. Develop ISO standards

    5. Investigate the efficacy of using cell-mediated immune based assays using specific Cryptosporidium antigens and induction of interferon gamma as a diagnostic test in people

    6. Examine duration of this type of response in symptomatic animal models and in infected people

    7. Develop multi-pathogen diagnostic tools

  • Vaccines availability

  • Commercial vaccines availability (globally)

    None.

  • Commercial vaccines authorised in Europe

    None.

  • Marker vaccines available worldwide

    No.

  • Marker vaccines authorised in Europe

    No.

  • Effectiveness of vaccines / Main shortcomings of current vaccines

    None.

    GAP: Define evaluation criteria for vaccines (level of reduction in oocyst excretion, (sub)clinical benefit

  • Commercial potential for vaccines

    As the disease affects young, often unweaned, animals the classic vaccination strategy (multiple challenges) cannot be applied.

    GAPS:

    1. Alternative vaccination strategies have to be defined and evaluated in terms of feasibility and commercial potential

    2. The only feasible option is to vaccinate the dams and look at transfer of immune colostrum to the neonates

  • Regulatory and/or policy challenges to approval

    Use of genetically modified vaccines might be problematic in some countries. The field trials may need specific regulation regarding the release of GMOs into the environment.

    GAP: Identify potential vaccine candidates, the appropriate expression system and route of vaccination, taking regulatory constraints into account

  • Commercial feasibility (e.g manufacturing)

    Possible provided there is a market: given the high prevalence, clinical relevance in a high number of animal species and the public health importance, there is a potential market.

    GAPS:

    1. Perform proper desk top study to evaluate cost-benefit analysis

    2. Since livestock is a major source of infection for other animals and people, an effective vaccine to reduce shedding would be of immense benefit. Models may be developed to look at how much of a reduction in shedding is required in order to have an impact on transmission and environmental contamination

  • Opportunity for barrier protection

    No.

  • Opportunity for new developments

    Develop vaccines against C. parvum in ruminants for use in the dams to generate high levels of antibody in the colostrum which will provide passive immunity in young animals in the first few weeks of life.

    GAPS:

    1. Understand host-parasite relationships at the molecular level to identify potential targets

    2. Understand the mechanism of action of protease inhibitors in HAART on Cryptosporidium

    3. Define delivery strategies

    4. Perform proper desk top study to evaluate cost-benefit analysis

    5. Perform market studies in order to evaluate the cost-effectiveness of vaccines

  • Pharmaceutical availability

  • Current therapy (curative and preventive)

    Halofuginone lactate is approved for use in newborn calves. A number of additional compounds are known to reduce oocyst excretion and to control disease, but are not approved for use in animals. Nitazoxanide, an orally administered nitrothiazole benzamide, is used in humans and has been found to be effective mainly in immunocompetent individuals.

    Paromomycin is effective in high doses for the treatment of cryptosporidiosis in animal models. This drug is a non- absorbable aminoglycoside which is normally indicated for the treatment of intestinal amoebiasis.

    There may be some potential for development of these compounds in animals although the question of parasite resistance remains a potential problem.

    GAPS:

    1. Define efficacy guidelines for the evaluation of compounds against gastro-intestinal protozoa

    2. Evaluate alternative treatment programs (lower dosage, alternate day treatments) with existing compounds (halofuginone, paromomycin) in order to reduce potential side effects in terms of toxicity (environmental, user, animal)

    3. Evaluate combination of treatment and additional environmental measures

  • Future therapy

    Improved antiparasitic therapy for use as a prophylactic as well as curative drug. Use of pharmaceuticals to reduce oocysts production.

  • Commercial potential for pharmaceuticals

    Good potential as the disease is widespread, and of public health importance.

    GAPS:

    1. Perform proper desk top study to evaluate cost-benefit analysis

    2. Perform studies to evaluate the impact of preventive animal treatment on outbreak-related costs

  • Regulatory and/or policy challenges to approval

    None.

  • Commercial feasibility (e.g manufacturing)

    Depends on demand and price.

    GAP: Perform proper desk top study to evaluate costs vs. benefits.

  • Opportunities for new developments

    As there is only a single approved compound, there is a need for alternative treatments, with emphasis on safety.

  • New developments for diagnostic tests

  • Requirements for diagnostics development

    There are several diagnostic assays available, yet a reliable and cheap on-site diagnosis and a high throughput PCR assay are still lacking.

    GAPS:

    1. Need for a cheap, reliable, on-site diagnosis

    2. Need for a high throughput PCR assay, able to differentiate between different species/(sub)genotypes

  • Time to develop new or improved diagnostics

    In general, the development of tests is much faster and less expensive than developing vaccines. From development through validation to commercial availability will be time consuming and can take years.

  • Cost of developing new or improved diagnostics and their validation

    The development and validation of new tests is time consuming and labour intensive which is costly. Costs cannot be specified as they will depend on the nature of the test and the cost of producing reagents and supplying reading or processing machines if necessary Once validated there will need to be a commercial company willing to market the test.

    GAPS:

    1. Need to evaluate the existing diagnostic assays for each specific diagnostic target: clinical, subclinical or epidemiological diagnosis.

    2. Need to define the preferred diagnostic assay for each diagnostic target, in terms of additional info procured versus cost

  • Research requirements for new or improved diagnostics

    Whole genome sequencing of relevant species and genotypes will greatly enhance fundamental and applied research including development of vaccines, diagnostics, and genotyping tools.

  • Technology to determine virus freedom in animals

    Not applicable.

  • New developments for vaccines

  • Requirements for vaccines development / main characteristics for improved vaccines

    The vaccine should probably be a colostral vaccine, able to achieve (close to) 100% reduction in disease development, and also able to achieve a high reduction in oocyst excretion.

    GAPS:

    1.Define the desired reduction in oocyst excretion, taking the need for adaptive immune development into account.

    2. An effective vaccine to reduce shedding would be of immense benefit. Models may be developed to look at how much of a reduction in shedding is required in order to have an impact on transmission and environmental contamination

  • Time to develop new or improved vaccines

    Depending on when a candidate vaccine could be identified the timescale will be 5-10 years. This will involve development, clinical trials and licensing. Potential vaccines need to be identified and subjected to initial trials and depending on the outcome will depend the time to commercial availability.

  • Cost of developing new or improved vaccines and their validation

    Expensive with the need to develop and undertake all the relevant tests to provide data to enable the product to be authorised. Field trial will be difficult as will evaluating the results.

  • Research requirements for new or improved vaccines

    The optimal administration route and time is still undefined. Identification of potential vaccine targets, and of an expression system.

    GAPS:

    1. Identify effective components (both antibody and cellular immune factors) of immune colostrums

    2. Study the effect of particular antigenic components of the parasite on the stimulation of effective immune factors in the dams than cam be transferred in the colostrums

    3. Study the composition of the colostrums and the subsequent transfer of these components to young livestock through immunological monitoring

    4. Develop an in vivo model allowing the evaluation of a colostral vaccine.

  • New developments for pharmaceuticals

  • Requirements for pharmaceuticals development

    At present, there are no data on the working mechanism of the available compounds. The limited insight in the microorganism itself impedes the development of other compounds.

    GAPS:

    1. Study the molecular targets and working mechanism for the different active compounds, in order to better understand and manipulate safety (environmental, animals and person who gives treatment)

    2. Develop an in vitro screening model to screen the activity of large compound libraries

  • Time to develop new or improved pharmaceuticals

    Time to develop would depend on the product and the trials necessary to validate the efficacy and safety. Commercial production would then take further time. Five to 10 years seems a realistic time frame.

  • Cost of developing new or improved pharmaceuticals and their validation

    Expensive but difficult to assess as it will depend on the product and the trials necessary to validate and license.

  • Research requirements for new or improved pharmaceuticals

    As the working mechanisms are not known, it is unclear at what stage of the life cycle the compounds are effective.

    GAPS:

    1. Study the life cycle in terms of molecular pathways to identify potential targets for treatment

    2. Study the pathogenicity in terms of life cycle in order to define the optimum time of treatment to achieve maximum efficacy

    3. Whole genome sequencing of relevant species and genotypes to help future research on vaccines, diagnostics, and genotyping tools

Disease details

  • Description and characteristics

  • Pathogen

    Cryptosporidiosis is caused by protozoan parasites belonging to the genus Cryptosporidium. Currently 31 species have been recognized as valid. Among these, C. parvum, C. andersoni, C. ubiquitum, C. baileyi, C. meleagridis and C. galli have been reported to cause morbidity and/or outbreaks of disease in mammalian and avian livestock. Apart from the recognized species, there are over 60 described genotypes and it is likely that some of these will be re-categorised as species. C. parvum is the main zoonotic pathogen.

    GAPS:

    1. Improve and standardize methods for the detection and characterization of Cryptosporidium at the species level and develop and standardize a multi-locus genotyping scheme for C. parvum

    2. Use improved sampling and testing methods to obtain better occurrence and prevalence data across all host ages

    3. Increase knowledge of the Cryptosporidium species infecting animals and/or humans and the relationships between them

    4. Understand, based on a combination of morphologic, biologic and genetic data, the risk for animal and public health posed by different Cryptosporidium species (to include infectivity, pathogenesis and shedding profiles)

    5. Generate sequence data at the whole genome level

  • Variability of the disease

    Many species of Cryptosporidium exist which can infect humans and a wide range of animals. The most common species causing disease in animals is Cryptosporidium parvum whereas both C. parvum and C. hominis are important human pathogens. Other species of lesser importance in humans include C. canis, C. cuniculus, C. felis, C. meleagridis, C. ubiquitum,and C. viatorum.

    C. parvum has a very wide host range of animals and is responsible for severe infection in neonatal ruminants. Human outbreaks are caused by both C. parvum and C.hominis.

    GAPS:

    1. Correlate pathogen and host characteristics with detailed disease progression and outcome

    2. Identify the influence of temporal, geographic, socio-economic and climatic variations on prevalence and clinical outcome

    3. Define oocyst excretion patterns in different animal hosts infected with different Cryptosporidium species and implications for transmission

    4. Define the influence of mixed Cryptosporidium infections in the outcome of disease

  • Stability of the agent/pathogen in the environment

    The oocysts are protected by an outer shell which allows them to survive outside the body for long periods (>6 months) in moist, cool environments. The oocysts are also very resistant to chlorine-based disinfectants at concentrations normally used. Currently, only disinfectants based on phenols (Neopredisan, Bi-oo-cyst) or NH4 (Killcox, OO-Cide) seem to be effective against Cryptosporidium oocysts.

    GAPS:

    1. Determine whether/when an oocyst viability assay can be used as a surrogate, and which is appropriate

    2. Determine the survival of oocysts in different matrices (water, faeces, soil, biofilms, food and feedstuffs etc)

    3. Define the effects of environmental factors (temperature, UV scale, predation by other microorganisms etc) and food/feed processing and preservation techniques on the survival of oocysts

    4. Identify novel, adequate oocyst inactivation measures

  • Species involved

  • Animal infected/carrier/disease

    A wide range of domestic and wild animals are affected by cryptosporidiosis, but overt disease is primarily observed in calves, lambs, kids, foals, piglets, reptiles and some avian species.

    Older animals may be infected asymptomatically, thus acting as carriers.

    GAPS:

    1. Increase knowledge on the Cryptosporidium species/genotypes infecting animals, including wildlife

    2. Establish the host range of C. hominis (in both mono-and mixed infection) and potential for transmission

    3. Study the impact of host factors (including genetics, physiology, diet and supplements, age and host immunological status) on infection level and pathogenicity caused by different species/genotypes, including mixed infections

    4. Identify asymptomatic carriers through improved sampling and testing

  • Human infected/disease

    C. parvum and C. hominis are the most important species causing human infections, but other species, most of which have zoonotic potential, have been reported.

    GAPS:

    1. Determine the long-term health effects of infection

    2 .Determine risk groups more vulnerable to infection and develop intervention strategies

    3. Develop and standardise sensitive diagnostic tests for early detection of infection in vulnerable patients

    4. Investigate the role of species other than C. parvum and C. hominis in human cryptosporidiosis

    5. Develop tools to trace mixed infections at species and (sub)genotype level

    6. Develop immunological tools to monitor humoral and CMI responses following exposure and the duration of these responses

  • Vector cyclical/non-cyclical

    None.

    GAPS:

    • Understand the role of mechanical vectors (e.g. filth flies)
    • Understand the role of shellfish in the transmission of cryptosporidiosis (to include recommended depuration times as a result of infectivity studies)

  • Reservoir (animal, environment)

    Animals infected with Cryptosporidium spp. act as reservoirs for infection in other animals and humans. Wild animals are also infected but little is known about their potential role in the epidemiology of infection and whether they play a role in transmitting infection to domestic animals or humans. Contamination of animal feed from rodents and other host species is possible.

    GAPS:

    1. Determine the range of both host reservoirs and environmental reservoirs, and their likely risk of transmitting disease

    2. Determine the role of livestock movements

    3. Determine the role of social contacts

    4. Determine interventions and biosecurity measures to reduce transmission via reservoir

  • Description of infection & disease in natural hosts

  • Transmissibility

    Oral ingestion of oocysts, which are fully infective upon excretion in the faeces. Other routes of infection (aspiration, inhalation, mucosa) have been reported, but are considered as rare.

    GAPS:

    1. Determine the minimum infective dose for different Cryptosporidium species and genotypes using appropriate in vivo and statistical models

    2. Determine the number and proportion of viable oocysts excreted by different infected hosts at different time-points during infection

    3. Determine the significance of low level shedding by older animals on transmission and environmental contamination, and include genotyping studies

    4. Determine the importance of other routes of infection

  • Pathogenic life cycle stages

    Following ingestion of the oocysts, excystation occurs and infective sporozoites are released. These undergo asexual multiplication in the epithelial cells of the gastrointestinal tract or other tissues followed by sexual multiplication (gametogony) producing male and female gametes. Following gamete fusion in the infected host, oocysts develop and sporulate generating 4 sporozoites. This means the oocysts are fully infective upon excretion in the faeces. Two types of oocysts are produced, the thick walled are excreted in the faeces whilst the thin walled are involved in auto-reinfection.

    GAPS:

    1. Determine the molecular mechanisms involved in the invasion process

    2. Identify mechanisms of pathogenicity using in vitro cell culture models and continuous culture

    3. Determine how host physiology and pathophysiological changes correlate with different Cryptosporidium species/genotypes

    4. Study the invasion process and the host-pathogen interaction during parasite development in the gut, using proteomic and genomic techniques. This may lead to the design of intervention strategies to reduce/prevent shedding by infected hosts

    5. Determine the role of gut microbiota in the mechanisms of pathogenesis

    6. Develop a cryptosporidiosis small animal laboratory model for the study of pathogenicity

  • Signs/Morbidity

    Cryptosporidiosis is primarily a problem in neonates especially young ruminants up to the age of 4 weeks. Clinical disease is rare in older animals due to the development of immunity. Severe watery diarrhoea, weight loss and loss of appetite are the main clinical signs, which may persist for several days. Some infected animals will not develop clinical signs but will excrete the organism in their faeces. Cryptosporidiosis is commonly associated with other infections, such as rotavirus, which results in more severe disease. Piglets and foals can also be infected but disease is seen over a wider age range and it does not seem to be such an important pathogen in these species.

    GAPS:

    1. Identify pathological changes in the mucosa

    2. Determine if chronic sequelae occur in animals and the significance for food production

    3. Study the role of co-infections in pathogenicity

    4. Examine the correlation between strain variation and virulence

    5. Determine immunological correlates of protection

    6. Investigate the economic impact of infection on for livestock farmers and small-scale husbandry

  • Incubation period

    Incubation period is short, albeit it varies with host species. In general, it is between 2-10 days.

    GAPS:

    1. Determine if the incubation period depends on the infective dose

    2. Determine if the incubation period depends on the Cryptosporidium species/(sub)genotype

    3. Determine if the incubation period depends on the infected host (immunological status, colostrum fed)

  • Mortality

    In animals, generally low unless associated with concurrent infection with rotavirus or coronavirus, inadequate intake of colostrum, high stocking density, failure to ensure adequate rehydration and energy intake or the impact of adverse weather conditions.

    In humans, cryptosporidiosis is the second cause of diarrhoea-associated mortality in very young, malnourished children in developing countries.

    GAPS:

    1. Determine if fatalities are associated with particular genotypes, or host-related factors

    2. Examine the role of co-infections in controlled conditions

  • Shedding kinetic patterns

    Large numbers of infective, fully sporulated oocysts are excreted in the faeces for 3 to 12 days in the case of calves. Weaned and adult animals do not appear to exhibit clinical signs but can excrete a low number of oocysts per gram thus totalling a significant daily output.

    GAPS:

    1. Determine oocyst shedding profile (level of excretion and duration) in different animal hosts using sensitive sampling and testing methods

    2. Determine if, and to what extent, dead oocysts are shed during infection

    3 .Determine host correlates of protective immunity. Determine qualitative and quantitative nature of this response

    4. Determine genotype of oocysts shed by older cattle to rule out the presence of species pathogenic to humans

  • Mechanism of pathogenicity

    Damage to the host epithelial cells mainly in the gastrointestinal tract where villous atrophy occurs in the small intestine.

    GAPS:

    1. Understand mechanisms/factors that regulate invasion

    2. Understand host factors, including gut microbiota, contributing to pathogenesis

  • Zoonotic potential

  • Reported incidence in humans

    Considered to be relatively common in children where it usually causes self-limiting diarrhoea. Can affect any age group. A higher incidence is reported in immunocompromised individuals.

    GAPS:

    1. Develop better molecular tools for tracking the source of infection and identification of diffuse outbreaks

    2. Determine the prevalence and distribution of zoonotic subtypes of C. parvum in different host species

    3. Determine the prevalence and distribution of non-zoonotic subtypes of C. parvum that only cycle within humans

    4. Determine the occurrence of C. hominis in animals and whether there is onward transmission

    5. Determine development of species and strain specific immunity in humans. Use suitable animal models to examine long lasting immunity against particular species/genotypes. Can hosts be re-infected with the same antigenic type?

  • Risk of occurence in humans, populations at risk, specific risk factors

    The most common route of transmission is person to person. Animal-to-human transmission occurs in a number of ways all of which are related to faecal contamination and ingestion of the oocysts.

    1. water contaminated with human or animal faeces, sewage and effluent where the water treatment is inadequate.

    2. direct contact with farm animals

    3. unhygienic handling of food

    4. baby swimmer

    GAPS:

    1. Determine the relative risk of different transmission routes

    2. Understand the prevalence and impact of the infection in risk groups, including transplant recipients and persons with congenital immunodeficiency’s

    3. Develop better epidemiological questionnaires Involve social scientists. Set up knowledge exchange projects and educational programmes to help prevent transmission of Cryptosporidium from animals to people as well as between people

  • Symptoms described in humans

    Cryptosporidiosis is most common in children aged between 1 and 5 years. Watery diarrhoea, abdominal cramps, vomiting and loss of appetite are the predominant presenting symptoms. Around 50% will also have low-grade fever, aching muscles, and headache. The clinical picture can last for 5-6 weeks in some cases. The disease can cause severe clinical signs symptoms in immunocompromised individuals and in immunocompetent young children in developing countries with death resulting in some cases.

    GAPS:

    1. Determine more precisely the acute symptoms. Do some cases have vomiting and not diarrhoea? Is vomit a risk for onward transmission?

    2. Determine chronic sequelae following infection

    3. Determine the impact of paediatric infection and cryptosporidiosis on parameters like height, weight and cognisance

    4. Understand the impact of the interaction with other conditions such as malnutrition, pregnancy and immunosuppression, and treatments such as biologics for rheumatoid conditions

    5. Examine duration and quality of immunity following exposure and disease

  • Estimated level of under-reporting in humans

    Probably high, although difficult to quantify as it depends on the person visiting a doctor and faeces samples being examined for confirmation.

    GAPS:

    1. Re-evaluate under-ascertainment with up to date information. This could be done in silico

    2. Availability of a therapy will contribute to an increased demand for diagnosis, in turn reducing under-ascertainment and under-reporting

    3. Notifiable status could reduce under-reporting

    4. Development of multi-pathogen diagnostic tools (both human and animal) where “neglected” diseases such as cryptosporidiosis are included

  • Likelihood of spread in humans

    High in poor hygiene environments. Possible in good hygiene environments through faecal accidents. Spread of the disease occurs easily to other persons in contact in places such as families, schools, day care centres, hospitals and other types of institution.

    GAP: How much secondary spread is there? In which setting / households is this more likely? What preventive measures should be put in place?

  • Impact on animal welfare and biodiversity

  • Both disease and prevention/control measures related

    None.

    GAP: Investigate what risk factors (season, environment, climate) facilitate or decrease transmission between wildlife and other populations (human and production animals)

  • Endangered wild species affected or not (estimation for Europe / worldwide)

    No.

    GAP: Investigate whether endangered wild species are affected or not, with special focus on neonates and immunocompromised animals

  • Slaughter necessity according to EU rules or other regions

    No.

  • Geographical distribution and spread

  • Current occurence/distribution

    Worldwide.

    GAPS:

    1. Further genotyping and sub-genotyping surveys related to farming and wildlife biosecurity

    2. Further disease and source tracking studies. using dynamic and longitudinal study design (GIS)

  • Epizootic/endemic- if epidemic frequency of outbreaks

    Endemic in most countries.

    GAP: Can the cycle of infection/transmission be broken?

  • Seasonality

    Linked to the management practices in a country, and seasonal in relation to calving and lambing seasons and in people to seasonal recreational activities and drinking water quality.

    GAPS:

    1. Understand variability in disease patterns as related to calving and lambing seasons

    2. Understand oocyst survival and transport in relation to temporal, geographic and seasonal factors

    3. Understand whether farm ecological health (such as density of dung beetles) can contribute to oocyst degradation and reduction in transmission

    4. Examine the importance of intake and uptake of colostrum on subsequent infection and disease

    5. Examine the effect of biosecurity measures/practices on farms such as quarantine of new stock and housing of birthing animals and young stock

  • Speed of spatial spread during an outbreak

    Rapid and easily spread from animal to animal.

    GAPS:

    1. Understand the role of mechanical vectors (e.g., filth flies) in disease spread

    2. Understand how different farm management practices influence disease spread

    3. Examine the effect of biosecurity measures/practices on farms such as quarantine of new stock and housing of birthing animals and young stock

  • Transboundary potential of the disease

    Spread by domestic and wild animals.

    GAP: Understand the role of wild animals in maintaining a reservoir of infection.

  • Route of Transmission

  • Usual mode of transmission (introduction, means of spread)

    The source of infection is the oral ingestion of infective oocysts excreted by infected animals. Husbandry practices in relation to housing, feeding, lambing and calving patterns and facilities can all have an impact on the spread of disease. Disposal of waste, manure and faeces can lead to contamination of watercourses that may be used for animals or humans.

    GAPS:

    1. Determine the relative importance of the different infections sources, including potential vectors and environment/food, for each population/host species in different management, climate, management settings

    2. Investigate different husbandry practices to minimise spread of infection and environmental contamination

    3. Determine best practise for treating waste on farms to kill or inactivate oocysts

  • Occasional mode of transmission

    Inhalation is reported to occur. There is evidence for transmission from clinically normal dams to suckling calves or lambs, but the precise mechanism remains unknown.

    GAPS:

    1. Investigate airborne transmission of cryptosporidiosis

    2. Investigate faecal oral route with improved sampling and detection from dams

    3. Investigate contamination of udders and milk ducts

  • Conditions that favour spread

    Poor sanitation, faecal contamination of animal feed or water, and direct contact. Stress and buying in animals, overcrowding, lengthy lambing or calving seasons with opportunity for older animals to infection new-borns.

    GAPS:

    1. Determine the significance of climate changes

    2. Determine the survival and viability of oocysts in different environmental matrices

  • Detection and Immune response to infection

  • Mechanism of host response

    Infection results in both humoral and cell mediated immunity. Local antibody production in the gastrointestinal tract also occurs. Parasite specific antibodies are produced but are not protective.

    GAPS:

    1. Understand mechanisms and effectors triggering a protective immune response

    2. Understand mechanisms and effectors causing immune-mediated pathology

    3. Develop apropriate in vitro and in vivo models

    4. Examine duration of immunity following exposure and disease

    5. Examine the specificity of the immune response to the infecting isolate/strain, and establish if cross-protection occurs with different strains

  • Immunological basis of diagnosis

    As the disease generally occurs in the neonate, serum antibodies are not present and therefore serological assays are not helpful. Immunodiagnostic assays for copro-antigens are commercially available.

    GAP: Investigate the usefulness of a CMI assay based on induction of interferon gamma in response to specific antigens

  • Main means of prevention, detection and control

  • Sanitary measures

    Cryptosporidiosis is difficult to control due to the number of infective oocysts that contaminate the environment, and due to the high number excreted by infected animals. Control by reducing the potential for ingesting infected oocysts is the only effective measure to limit spread of the disease. In any event, as infected animals and humans will continue to contaminate the environment, the complete elimination of these sources is virtually impossible.

    GAPS:

    1. Determine the best methods to treat farm waste in order to minimise contamination of the environment with viable oocysts

    2. Determine barriers to uptake of these measures within the farming community

    3. Develop and evaluate effective cleaning, disinfection and composting treatments that can be used at farm level

    4. Develop multi-barrier approaches for waste treatment – some can include solar insolation.

    5. Determine methods for vegetable production that limit contamination and consequent foodborne transmission

  • Mechanical and biological control

    A number of control measures can be used, the most important are listed below:

    • Calving and lambing in a clean environment
    • Increasing the bedding to reduce contamination
    • Feed adequate amounts of colostrums
    • Isolate affected animals
    • All in all-out management systems
    • Preventing faecal contamination of feed and water troughs
    • Clean and disinfect all buildings with products that kill oocysts
    • Disposal of faeces and manure with care to avoid contamination of water.

    GAPS:

    1. Further study the relative importance of risk factors in terms of infection spread, using longitudinal studies instead of cross-sectional studies

    2. Educate farmers and other decision makers about effective strategies to minimise disease spread, and determine any barriers to uptake of these measures

    3. Define appropriate guidelines (at a Regional, National or European level) aimed at minimising/ controlling disease

    4. Examine quality of colostrum (with regard to specific immunological components that are active against Cryptosporidium) and ensure uptake of these components is enabled

  • Diagnostic tools

    Detection of Cryptosporidium oocysts, specific antigens or nucleic acids present in faeces or other matrices. Acid-fast staining methods, with or without faecal concentration, are most frequently used in clinical laboratories but are not sensitive and liable to mis-interpretation.

    GAPS:

    1. Develop molecular-based platform for rapid detection and species/(sub)genotype identification

    2. Include cryptosporidiosis in the standard testing of neonates for diarrhoeal diseases

    3. Develop cheap and reliable on-site diagnosis

    4. Develop sensitive methods for diagnosing early infection, monitoring oocyst shedding accurately

    5. Develop the knowledge of medical doctors about cryptosporidiosis for enhancing diagnostic of human cryptosporidiosis

  • Vaccines

    None available.

    GAPS:

    1. Investigate the potential of adoptive transfer of protective immunity through colostrum from the dam.

    2. Identify protective components of immunity within colostrums, including both humoral and cell-mediated immunity

    3. Identify Cryptosporidium antigens involved in host-pathogen interactions and evaluate these as targets for vaccine development

    4. Identify a proper in vivo model to test vaccine candidates

    5. Investigate vaccine delivery tools and the use of adjuvants

    6. Determine the role of strain specific immunity

  • Therapeutics

    Halofuginone lactate is approved for use in newborn calves, but not in other animals, for the prevention and reduction of diarrhea due to C. parvum. A number of additional compounds are known to reduce oocyst excretion and to control disease, but are either not approved for use in animals or at not approved at the effective dose regimen.

    GAPS:

    1. Develop additional products with emphasis on safety target animal, environment and person who gives the medicine

    2. Improve ease of use and decrease cost of existing drug while safeguarding efficacy

    3. Investigate plant products and their impact on the parasite and the host

    4. Investigate protective potential of prebiotics/probiotics

  • Biosecurity measures effective as a preventive measure

    Easily spread to humans. Those working on farms, especially during the calving and lambing periods, and those visiting petting farms should take care.GAPS:

    1. Develop biosecurity measures based on social contacts, and other effective interventions

    2. Include Cryptosporidium in ‘on farm’ biosecurity, and, where possible, in wildlife management

    3. Develop educational material to advise on risks and how to minimise/avoid transmission

    4. Set up knowledge/exchange events to look at potential barriers to uptake of appropriate biosecurity and other advice to help reduce transmission

  • Border/trade/movement control sufficient for control

    None.

  • Prevention tools

    Good management and hygiene is critical for preventing outbreaks of cryptosporidiosis. No vaccines are available nor are there approved treatments. Use of colostrum.

    GAPS:

    1. Emphasize need for good management and hygiene practices

    2. Determine active component(s) in colostrum that is / are effective in limiting disease

    3. Investigate the effect of active component(s) or plant extracts to pooled colostrum sources

  • Surveillance

    Passive surveillance resulting from samples submitted to diagnostic laboratories. In addition, seroepidemiological surveys of exposure can be undertaken mostly using ELISA based methods.

    GAPS:

    1. Gather epidemiologic data from across Europe using passive surveillance, with focus on genotyping

    2. Develop web-based, publicly available database

    3. Investigate how long do antibodies / protection persist in infected individuals and livestock species

    4. Determine the nature of strain-specific antigens, and develop serologic (or other immunological tests) tests that allow their specific detection

  • Past experiences on success (and failures) of prevention, control, eradication in regions outside Europe

    Good hygiene can be effective, albeit treatment and isolation of clinically affected animals is warranted. Eradication of the parasite is unlikely.

    GAPS:

    1. Perform field studies in order to evaluate treatment and/or management/environmental measures, under different management/climate conditions

    2. Do specific monitoring studies in water catchment areas near study farms where measures are being implemented to reduce/prevent Cryptosporidium from contaminating the environment.

  • Costs of above measures

    Variable.

  • Disease information from the WOAH

  • Disease notifiable to the WOAH

    Cryptosporidiosis is not an OIE listed disease. OIE does not require reporting of Cryptosporidiosis and consequently no information is available.

  • WOAH disease card available

    No.

  • WOAH Terrestrial Animal Health Code

    None.

  • Socio-economic impact

  • Zoonosis: impact on affected individuals and/or aggregated DALY figures

    Cryptosporidiosis has been recognized as one of the most common causes of waterborne gastrointestinal disease (recreational water and drinking water) in humans.

    Cryptosporidiosis is likely to have a major impact in developing countries where young children may be malnourished and subject to concurrent infections.

    GAPS:

    1. Continue to investigate recreational water (swimming pools) outbreaks

    2. Improve codes of practice for community drinking water, private supplies for those that have paying guests, and for swimming pools in both public and private sectors

    3. Target specific practices / secondary disinfection treatments that increase / reduce Cryptosporidium occurrence / infectivity, such as UV

  • Zoonosis: cost of treatment and control of the disease in humans

    Unknown.

    GAP: Needs economic impact studies

  • Direct impact (a) on production

    Morbidity with reduced growth rate in young animals. The impact of subclinical disease on productivity is not known. In situations with poor husbandry a higher mortality would be expected.

    GAPS:

    1. Determine the short and long-term impact of subclinical disease on productivity

    2. Determine costs for C. parvum and other species / genotypes known to be pathogenic and to cause outbreaks in livestock, farmed animals and wildlife (e.g. C. andersoni, etc.)

    3. Examine the effects of husbandry and nutrition on impact of disease

    4. Undertake economic impact assessments for dairy and beef cattle, sheep and goat farming in different areas, farming scales and husbandry

  • Direct impact (b) cost of private and public control measures

    Cost of treatment and management of outbreaks. No cost to the public control measures as generally no control measures are in place.

    GAPS:

    1. Better determine costs of waterborne and foodborne outbreaks

    2. Conduct a cost-benefit analysis of implementing effective prevention strategies

  • Indirect impact

    Reduced production, impact on reputation.

    GAPS:

    1. Increase and publicise better public health interventions

    2. Address social contacts and other aspects

  • Trade implications

  • Impact on international trade/exports from the EU

    None. There are no international standards for trade laid down by the OIE.

  • Impact on EU intra-community trade

    None. There are no EU standards related to trade in animals.

  • Impact on national trade

    None. There is no control programme nor restriction on movements.

  • Main perceived obstacles for effective prevention and control

    Endemic, worldwide and a ubiquitous organism that cannot be eliminated:

    • Occurs in neonates with the result that a classic vaccine approach is unlikely to be effective unless given immediately after birth before the disease has developed
    • Very resistant oocysts present in high numbers in the environment but with low infectious dose
    • Cryptosporidium species cannot be cultivated in vitro

  • Main perceived facilitators for effective prevention and control

    • Availability of vaccines and therapeutics
    • Use of prophylactic therapeutics in the first few weeks of life
    • Vaccines for the dams which stimulate colostral antibodies

    GAPS:

    1. Identify effective components (both antibody and cellular immune factors) of immune colostrums

    2. Study the effect of particular antigenic components of the parasite on the stimulation of effective immune factors in the dams than cam be transferred in the colostrums

    3. Study the composition of the colostrums and the subsequent transfer of these components to young livestock through immunological monitoring

  • Links to climate

    Seasonal cycle linked to climate

    No.

    GAP: Likely – climate change could be important

  • Distribution of disease or vector linked to climate

    No.

  • Outbreaks linked to extreme weather

    No.

    GAPS:

    1. Understand how climate changes, including flooding, droughts, increased/decreased snow melt, can compromise water treatment and sewage treatment plants and help spread farm waste into the environment

    2. Impact of human behaviours

  • Sensitivity of disease or vectors to the effects of global climate change (climate/environment/land use)

    No.

    GAP: Understand how exposure to increased solar irradiation and UV affects parasite survival

Risk

  • Cryptosporidiosis remains a significant public health threat. The infection is the 4th most important cause of gastrointestinal infection in developed countries (UK) and is on the increase. Can be a serious problem in developing countries where the contamination of watercourses, wells and drinking water poses a major risk of infection to vulnerable children and those who are immunocompromised with infections such as HIV.

Main critical gaps

Conclusion

  • A widespread zoonosis of major importance in the developing world. The discovery of new genes, biochemical pathways and protective antigens through mining of the Cryptosporidium genomes will help to develop novel therapies and/or vaccines for cryptosporidiosis.

    The development of vaccines to provide passive immunity to young animals would contribute to the reduction of the level of oocysts in the environment. Future controls could result form passive immunity derived from vaccinated dams and appropriate application of therapies such as nitazoxanide.

    The recent development of a method for the genetic manipulation of the parasite will allow robust testing of the biological role of potential vaccine candidates.

Sources of information

  • Expert group composition

    Expert group members are included where permission has been given

    Simone M Cacciò, Istituto Superiore di Sanità / EU Reference Laboratory for Parasites, Italy - [Leader]

    Rachel M. Chalmers, Cryptosporidium reference Unit, Public Health Wales, UK

    Loic Favennec, Université de Rouen Normandie / CNR laboratory expert Cryptosporidiosis, CHU de Rouen, France

    Thomas Geurden, Zoetis

  • Date of submission by expert group

    21st of November 2017.

  • Name of reviewers

    Project Management Board