Cryptosporidiosis - available

Control ToolsDisease details
Sources of informationRisks
ConclusionScore criteria
Prioritisation ModelGap Analysis

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

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.

Diagnostic kits validated by International, European or National Standards

None.

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

  • Direct immunofluorescence
  • ELISA
  • Immunochromatography

3. Nucleic acid recognition methods

  • PCR
  • Quantitative real time PCR

GAPS:

  • Need to evaluate the existing diagnostic assays for each specific diagnostic target: clinical, subclinical or epidemiological diagnosis.
  • Need to define the preferred diagnostic assay for each diagnostic target, in terms of additional info procured versus cost.
  • 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.
  • Examine duration of this type of response in symptomatic animal models and in infected people.

Commercial potential for diagnostic kits in Europe

Current diagnosis is based on identifying oocysts or cryptosporidium antigen in faeces samples. The currently available diagnostic kits are expensive and do not provide an improved detection rate compared to the older methods of staining oocysts.

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 dipsticks), but the cost is high. Furthermore, none of these assays allows the identification of the species/genotypes of the parasite.
 
GAPS:
  • Reduce cost of ELISA and/or dipsticks to make these tools available to veterinarians and farmers
  • Develop molecular-based platforms for routine detection, including species identification
  • Standardize assays for the detection of carriers
  • Develop ISO standards
  • 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.
  • Examine duration of this type of response in symptomatic animal models and in infected people
  • Develop multi-pathogen diagnostic tools

Vaccines availability

Commercial vaccines availability (globally)

No

Commercial vaccines authorised in Europe

No

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 in Europe

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

GAPS:

  • Alternative vaccination strategies have to be defined and evaluated in terms of feasibility and commercial potential.
  • The only feasible option is to vaccinate the dams and look at transfer of immue 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:

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

  • Understand host-parasite relationships at the molecular level to identify potential targets.
  • Understand the mechanism of action of protease inhibitors in HAART on Cryptosporidium.
  • Define delivery strategies.
  • Perform proper desk top study to evaluate cost-benefit analysis.
  • 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 new-born 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 is used in humans and has been found to be effective in normal and immunocompromised individuals. This is an orally administered nitrothiazole benzamide.

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:

  • Define efficacy guidelines for the evaluation of compounds against gastro-intestinal protozoa.
  • 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).
  • 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 in Europe

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

GAPS:

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

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:

  • Need for a cheap, reliable, on-site diagnosis.
  • 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:

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

  • Define the desired reduction in oocyst excretion, taking the need for adaptive immune development into account.
  • 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 are still to be defined. Identification of potential vaccine targets, and of a expression system.

GAPS:

  • Identify effective components (both antibody and cellular immune factors) of immune colostrums.
  • 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.
  • Study the composition of the colostrums and the subsequent transfer of these components to young livestock through immunological monitoring.

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.

GAP: 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).

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 timeframe.

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:

  • Study the life cycle in terms of molecular pathways to identify potential targets for treatment.
  • Study the pathogenicity in terms of life cycle in order to define the optimum time of treatment to achieve maximum efficacy.
  • 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 22 species have been identified: C. parvum, C. andersoni, C. ubiquitum, C. baileyi, C. meleagridis and C. galli have been reported to cause morbidity and outbreaks of disease in livestock. As well as the 22 recognized species, there are over 60 described genotypes and, as genotyping develops, it is likely that some of these will be re-categorised as species.

GAPS:

  • Standardized methods for the detection and characterization of Cryptosporidium at the genotype/subgenotype level.
  • Increase knowledge on the Cryptosporidium species infecting animals and/or humans.
  • 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).
  • Generate sequence data at the 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 animals is Cryptosporidium parvum whereas both C. parvum and C. hominis are important human pathogens. Other species of lesser importance in humans include C. felis, C. meleagridis, C. canis, and C. muris.

C. parvum has a very wide host range of animals and is responsible for half of the human cryptosporidiosis outbreaks. The other half of human outbreaks are caused by C.hominis, a relatively newly described species which is morphologically identical to, but genetically different from, C.parvum but for which there are no animal models. C.parvum is predominately a parasite of neonate animals.

GAPS:

  • Correlate pathogen and host characteristics with disease.
  • Identify the influence of temporal, geographic and climatic variations on clinical outcome.
  • Define oocysts excretion patterns in different animal hosts infected with different Cryptosporidium species.
  • 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 time periods (>6 months) in moist, cool environment. The oocysts are also very resistant to chlorine-based disinfectants.

GAPS:

  • Determine the survival of oocysts in different matrices (water, faeces, soil, etc).
  • Define the effects of environmental factors (temperature, UV scale, etc) on the viability of oocysts.
  • Develop in vitro methods to determine viability of oocysts.
  • Determine what oocyst viability assay should be used.
  • Identify novel, adequate oocysts inactivation measures.

Species involved

Animal infected/carrier/disease

A wide range of domestic and wild animals are affected. It is primarily in neonates especially in calves but also lambs, kids, foals and piglets.

GAPS:

  • Increase knowledge on the Cryptosporidium. species/genotypes infecting animals, including wildlife
  • Establish the host range of C. hominis (in both mono-and mixed infection).
  • Study the impact of host factors (including age and host immunological status) on infection level and pathogenicity caused by different species/genotypes, including mixed infections.
  • Identify asymptomatic carriers.

Human infected/disease

Cryptosporidium spp. are zoonotic agents with C.parvum and C.hominis being the most important in causing human infections.

GAPS:

  • Determine the long-term effects of infection
  • Determine risk groups more vulnerable to infection
  • Investigate the role of species other than C. parvum and C. hominis in human cryptosporidiosis
  • Develop tools to trace mixed infections at species and (sub)genotype level
  • 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 experimental infections)

Reservoir (animal, environmental)

Animals infected with Cryptosporidia act as a reservoir for infection in 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. Contamination of animal feed from rodents and other species is possible.

GAPS:

  • Determine the range of both host reservoirs and environmental reservoirs, and their likely risk of transmitting disease.
  • Determine the role of livestock movements.
  • Determine the role of social contacts.
  • 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 ingection (inhalation, mucosa) have been reported, but are considered as rare.

GAPS:

  • Determine the minimum infective dose for different Cryptosporidium species and genotypes using appropriate in vivo models
  • Determine the number of viable oocysts excreted by different infected hosts at different time-points during infection
  • Determine the significance of low level shedding by older animals on environmental contamination, and include genotyping studies

Pathogenic life cycle stages

Excystation occurs following ingestion of the oocysts with the release of the infective sporozoites. 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 with the development of 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:

  • Determine the molecular mechanisms involved in the invasion process
  • Identify mechanisms of pathogenicity using in vitro cell culture models
  • Determine how pathophysiological changes correlate with different Cryptosporidium species/genotypes
  • Study the invasion process and the host-pathogen interaction during parasite development in the gut, using proteonomic and genomic techniques. This may lead to the design of intervention strategies to reduce/prevent shedding by infected hosts.

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:
  • Identify pathological changes in the mucosa
  • Determine if chronic sequelae occur in animals
  • Study the role of co-infections in pathogenicity
  • Examine the correlation between strain variation and virulence
  • Determine immunological correlates of protection

Incubation period

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

GAPS:

  • Determine if the incubation period depends on the infective dose
  • Determine if the incubation period depends on the Cryptosporidium species/(sub)genotype
  • Determine if the incubation period depends on the infected host (immunological status, colostrum fed)

Mortality

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.

GAPS:

  • Determine if fatalities are associated with particular genotypes
  • 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.

GAPS:

  • Determine oocyst shedding profile (level of excretion and duration) in different animal hosts
  • Determine if, and to what extent, dead oocysts are shed during infection
  • Determine host correlates of protective immunity. Determine qualitative and quantitative nature of this response
  • 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:

  • Understand mechanisms/factors that regulate invasion
  • Understand host factors 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:

  • Develop better molecular tools for tracking the source of infection and identification of diffuse outbreaks
  • Determine the prevalence and distribution of zoonotic subtypes of C. parvum in different host species
  • Determine the prevalence and distribution of non-zoonotic subtypes of C. parvum that only cycle within humans
  • Determine the occurrence of C. hominis and other zoonotic genotypes in animals
  • 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?

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:

  • Availability of a therapy will contribute to an increased demand for diagnosis, in turn reducing under-reporting
  • Development of multi-pathogen diagnostic tools (both human and animal) where “neglected” diseases such as Cryptosporidium are automatically incorporated

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.

  • water contaminated with animal faeces where the water treatment is inadequate.
  • direct contact with farm animals
  • unhygienic handling of food

GAPS:

  • Determine the relative risk of different transmission routes
  • Understand the impact of the infection in risk groups, including transplant recipients and persons with congenital immunodeficiencies
  • 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

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 signs. Around 50% will also have fever, aching muscles, headache and fever. The clinical picture can last for 5-6 weeks in some cases. The disease can cause severe clinical signs in immunocompromised individuals with death resulting in some cases.

GAPS:

  • Determine chronic sequelae following infection
  • Determine the impact of paediatric cryptosporidiosis on parameters like height, weight and cognisance
  • Understand the impact of the interaction with other conditions such as malnutrition, pregnancy and immunosuppression
  • Examine duration and quality of immunity following exposure and disease

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.

Impact on animal welfare and biodiversity

Both disease and prevention/control measures related

None.

GAP: Investigate what risk factors (season, environment, climate) facilitate 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:

  • Further genotyping and sub-genotyping surveys related to farming and wildlife biosecurity.
  • Further disease and source tracking studies using dynamic and longitudinal study design (GIS).

Epizootic/endemic- if epidemic frequency of outbreaks

Endemic in most countries.

Seasonal cycle (seasonality)

Linked to the management practices in a country, and seasonal in relation to calving and lambing seasons.

GAPS:

  • Understand variability in disease patterns as related to calving and lambing season
  • Understand oocyst survival in relation to temporal, geographic and seasonal factors
  • Examine the importance of intake of colostrum on subsequent infection and disease
  • 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:

  • Understand the role of mechanical vectors (e.g., filth flies) in disease spread
  • Understand how different farm management practices influence disease spread
  • 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.

Seasonal cycle linked to climate

No.

Distribution of disease or vector linked to climate

No.

Outbreaks linked to extreme weather

No.

GAP: 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.

Sensitivity of disease or vectors to the effects of climate change (environmental changes/land use)

No.

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

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 facilities can all have an impact on the spread of disease. Disposal of waste, manure and faeces can lead to contamination of water courses that may be used for animals or humans.

GAPS:

  • 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.
  • Investigate different husbandry practices to minimise spread of infection and environmental contamination.
  • Determine best practise for treating waste on farms to kill or inactivate oocysts before they are released into the environment.

Occasional mode of transmission

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

GAP: Investigate airborne transmission of cryptosporidiosis.

Conditions that favour spread

Poor sanitation, faecal contamination of animal feed or water, and direct contact.

GAPS:

  • Determine the significance of climate changes
  • Determine the survival and viability of oocysts in different environmental matrices
  • Determine farm practises that may help prevent spread to the environment (i.e., how farm waste are treated)

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.

GAPS:

  • Understand mechanisms and effectors triggering a protective immune response
  • Understand mechanisms and effectors causing immune-mediated pathology
  • Develop apropriate in vitro and in vivo models
  • Examine duration of immunity following exposure and disease
  • 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 as a consequence 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:

  • Determine the best methods to treat farm waste in order to minimise contamination of the environment with viable oocysts
  • Determine barriers to uptake of these measures within the farming community
  • Develop and evaluate effective cleaning, disinfection and composting treatments that can be used at farm level.
  • Develop multi-barrier approaches for waste treatment – some can include solar insolation.

Mechanical and biological control

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

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

GAPS:

  • Further study the relative importance of risk factors in terms of infection spread, using longitudinal studies in stead of cross-sectional studies
  • Educate farmers about effective strategies to minimise disease spread, and determine any barriers to uptake of these measures
  • Define appropriate guidelines (at a Regional, National or European level) aimed at minimising/ controlling disease.
  • Examine quality of colostrum (with regard to specific immunological components that are active against Cryptosporidium)

Diagnostic tools

Detection of Cryptosporidium oocysts, specific antigens of Cryptosporidium and/or DNA detection from faeces or other suitable materials. Acid-fast staining methods, with or without faecal concentration, are most frequently used in clinical laboratories.

GAPS:

  • Develop molecular-based platform for rapid detection and species/(sub)genotype identification
  • Include cryptosporidiosis in the standard screening of neonates for diarrhoeal diseases
  • Develop cheap and reliable on-site diagnosis

Vaccines

None available.

GAPS:

  • Investigate the potential of adoptive transfer of protective immunity through colostrum from the dam.
  • Identify protective components of immunity within colostrums, including both humoral and cell-mediated immunity.
  • Identify Cryptosporidium antigens involved in host-pathogen interactions and evaluate these as targets for vaccine development.
  • Identify a proper in vivo model to test vaccine candidates.
  • Investigate vaccine delivery tools.
  • Determine the role of strain specific immunity.

Therapeutics

Halofuginone lactate is approved for use in new-born calves, but not in other animals. A number of additional compounds are known to reduce oocyst excretion and to control disease, but none are approved for use in animals.

GAPS:

  • Develop additional products with emphasis on safety (target animal, environment and person who gives the medicine).
  • Improve ease of use and decrease cost of existing drug while safeguarding efficacy.
  • Investigate plant products and their impact on the parasite and the host.

Biosecurity measures effective as a preventive measure

Easily spread to humans. Care should be taken by those working on farms especially during the calving and lambing periods.

GAPS:

  • Develop biosecurity measures based on social contacts, and other effective interventions.
  • Include Cryptosporidium in ‘on farm’ biosecurity, and, where possible, in wildlife management.
  • Develop educational material to advise on risks and how to minimise/avoid transmission.
  • 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:

  • Emphasize need for good management and hygiene practices.
  • Determine active component(s) in colostrum that is / are effective in limiting disease.
  • 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 for detecting antibodies which use various aqueous extracts of C. parvum oocysts.

GAPS:

  • Gather epidemiologic data from across Europe using passive surveillance, with focus on genotyping
  • Develop web-based, publicly available database
  • Investigate how long do antibodies / protection persist in infected individuals and livestock species
  • 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:

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

Disease notifiable to the OIE

No.

OIE disease card available

No.

OIE Terrestrial Animal Health Code (reference)

None.

OIE Terrestrial Manual (reference)

http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.09.04_CRYPTO.pdf 

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. DALY figures unknown but likely to have a major impact in the developing countries where young children may be malnourished and subject to concurrent infections.

GAPS:

  • Investigate recreational water (swimming pools) outbreaks
  • Determine 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.
  • Target specific practices / treatments that increase / reduce Cryptosporidium occurrence / infectivity, such as UV

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

Unknown.

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:

  • Determine the short and long-term impact of subclinical disease on productivity
  • 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.).
  • Examine the effects of husbandry and nutrition on impact of disease

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:

  • Determine costs of waterborne and foodborne outbreaks
  • Conduct a cost-benefit analysis of implementing effective prevention strategies

Indirect impact

Reduced production.

GAPS:

  • Increase and publicise better public health interventions.
  • Address social contacts and other aspects.

Trade implications

Impact on international trade/exports from the EU due to existing regulations

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

Impact on EU intra-community trade due to existing EU regulations

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

Impact on national trade due to existing regulations

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

Main perceived obstacles for effective prevention and control

  1. Endemic, world wide and a ubiquitous organism that cannot be eliminated.
  2. Occurs in neonates with the result that a a classic vaccine approach is unlikely to be effective unless given immediately after birth before the disease has developed.
  3. Very resistant oocysts present in high numbers in the environment
  4. Cryptosporidium species cannot be cultivated in vitro

Main perceived facilitators for effective prevention and control

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

GAPS:

  • Identify effective components (both antibody and cellular immune factors) of immune colostrums
  • 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
  • Study the composition of the colostrums and the subsequent transfer of these components to young livestock through immunological monitoring

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 water courses, wells and drinking water poses a major risk of infection to vulnerable children and those who are immunocompromised with infections such as HIV.

Conclusion

A widespread zoonoses 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.

Sources of information

Name of reviewers

Project Management Board.

Date of preliminary approval

22nd January 2011.

Date of final approval

26th April 2011.