Control Tools

• Diagnostics availability

• Commercial diagnostic kits available worldwide

  Yes, diagnostic tests are available for animals and humans.Serological tests: In addition to numerous in-house tests, commercial tests are available to detect infection in humans and animals (often limited to pigs and small ruminants; few tests allow testing of a broader range of species but diagnostic characteristics are often not well defined). In the human sector and also in animals so called “avidity” tests, or tests applying immunoglobulin type specific secondary antibodies/conjugates are able to differentiate acute from chronic infection.DNA detection tests: In addition to multiple in-house tests, commercial DNA detection tests are marketed, but in the veterinary sector only few.Antigen detection: Detection of parasitic antigens in histological sections may aid diagnosis. Monoclonal antibodies as well as polyclonal sera are available in a number of laboratories and some are made commercially available.

  List of commercially available kits (Diagnostics for Animals)

  Gaps :

  • There is a need to develop sufficiently validated tests that can be applied to a larger spectrum of animal species. Actual tests for livestock are validated for pigs and small ruminants.
  • There is a need to develop tests able to better predict viable infections in livestock animals, especially in large ruminants and horses (i.e. tests that could be applied prior to or at slaughter of livestock).
  • Sensitive and specific rapid assays or point-of-care assays to determine patent T. gondii infections in cats (i.e. T. gondii oocyst shedding in cats).
  • From the epidemiological point of view there is a need to develop specific tests to differentiate oocyst-mediated infections from infections by bradyzoites or tachyzoites.

• Commercial diagnostic kits available in Europe

  See “Commercial diagnostic kits available worldwide”.

• Diagnostic kits validated by International, European or National Standards

  No such standards for livestock are available.

  Gap :

  The establishment of such standards is desirable.

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

  Serology, DNA detection: Routine serological methods (IFAT, ELISA, MAT), procedures to extract oocysts DNA and PCRs are described in the OIE Manual of Diagnostic Tests and Vaccines (Chapter 2.9.9.).National licensing for commercial diagnostic tests (serological diagnosis in animals, DNA detection in animals) is implemented in Germany and Spain. In other European countries, e.g. UK and Switzerland, this is not the case. However, national reference laboratories for the diagnosis of T. gondii in livestock exist in several European countries and are coordinated by the European Union Reference Laboratory for Parasites (EURLP, located at Istituto Superiore di Sanità (ISS) in Rome, Italy) and by the European Commission Health & Consumers Directorate General (Directorate G - Veterinary and International affairs DDG2.G4 - Food, Alert System and Training).

  Gap :

  The establishment of international or European standards is desirable.

• Commercial potential for diagnostic kits in Europe

  In small ruminants, toxoplasmosis causes serious economic losses and small ruminants are regarded as epidemiologically important intermediate hosts in parts of Europe and worldwide. Pigs are regarded as important sources of human infection in Europe and worldwide. Bovines and bovine meat are under discussion to represent an additional important source for human infection. Equine meat has been shown to represent a source of human infection. Depending on farm management, poultry is infected with T. gondii often; the relative importance of poultry for human infection is under discussion.Specific and sensitive diagnostic kits covering livestock and game in which toxoplasmosis may represents an economic problem (i.e. small ruminants, pigs, deer) have a commercial potential, as well as tests which predict viable infection in meat-producing livestock and game, particularly venison. To a largely unknown extend, T. gondii oocysts, which are temporarily shed by cats, cause infection by contaminating environment, vegetables or fruits.

  Gaps :

  • While well characterized serological diagnostic kits are available for small ruminants and pigs, sufficiently validated tests for cattle and horses are not available. In cattle and equids, the concordance between serological reactions to T. gondii antigens and the existence of viable infection seems to be low.
  • As game animals may represent an important source of infection for humans, sufficiently validated serological tests covering game animals are also needed. Diagnostic kits, applicable and validated for a wide range of livestock and game animals may have economic potential.
  • Sensitive and specific diagnostic kits or tools to detect T. gondii oocysts in environmental samples (water, soil, other environmental samples), shellfish, vegetables and fruits are necessary.
  • Sensitive and specific rapid assays or point-of-care assays to determine patent T. gondii infections in cats (i.e. T. gondii oocyst shedding in cats) are necessary, too.

• DIVA tests required and/or available

  Vaccination is practiced in a few regions of the world. Target species of this vaccine is sheep and the aim is to protect foetuses from trans-placental infection. Because prevalence in sheep and goats is usually high and persistently infected sheep are unlikely to pass their infection to offspring or otherwise involved in disease transmission, there is a limited need for a DIVA test.

  Gap :

  No DIVA strategy established for the only existing vaccine.

• Opportunities for new developments

  1. Serological diagnostic kits with improved sensitivity and specificity for livestock animals in which toxoplasmosis has economic importance (small ruminants, pigs).
  2. Diagnostic kits for a multiplexed detection of abortifacients in small ruminants (including T. gondii as one of the important causes) or pigs as an important source of human infection seems to be an interesting opportunity, too.
  3. Specific and sensitive diagnostic kits for DNA detection.

  Gaps :

  • Serological diagnostic kits to multiplex with serological diagnostic tests for other infective diseases of livestock.
  • Tests applicable to meat juice for applications to slaughtered livestock and meat samples.
  • Specific and sensitive diagnostic kits for DNA detection.

• Vaccines availability

• Commercial vaccines availability (globally)

  TOXOVAX® MSD Animal Health (http://www.noahcompendium.co.uk/?id=-456185): A live vaccine, i.e. live organisms of an attenuated strain of Toxoplasma gondii (Strain 48). Commercially and seasonally available in a few regions of the world, we are aware of marketing in New Zealand, UK, Ireland, Spain, France and Norway. In countries that are not registered-licensed, Toxovax can be imported by therapeutic gap after the approval of the drug agency of each country.

  Gaps :

  • The commercial availability of further vaccines, including non-live vaccines, is necessary as for the existing vaccines there are occasionally major problems in terms of availability (probably due to problems in production or transportation).
  • New vaccines, both transmission blocking vaccines for cats and vaccines for intermediate hosts should have a longer shelf life.

• Commercial vaccines authorised in Europe

  TOXOVAX® MSD Animal Health is licenced in UK, Ireland, France, Spain and Norway.

  Gap :

  The commercial availability of authorized vaccines, including non-live vaccines in EU is desirable.

• Marker vaccines available worldwide

  No marker vaccine available.

  Gap :

  Not applicable.

• Marker vaccines authorised in Europe

  No marker vaccine available.

  Gap :

  Not applicable.

• Effectiveness of vaccines / Main shortcomings of current vaccines

  TOXOVAX® MSD Animal Health:1. Live vaccine poses risk to pregnant animals: Vaccination in general no later than 3 weeks prior to mating and not applicable to pregnant sheep. A basic vaccination should be given as a single dose at least 4 weeks prior to mating. Lambs destined for breeding purposes may be vaccinated from 4-5 months of age. Shearlings and older ewes should be vaccinated during the 4-month period prior to mating. A re-vaccination is advised after 2 years (as a single dose at least 3 weeks prior to mating)2. Shelf life of the concentrate for sale is only 10 days, after dilution only 2 hours. As TOXOVAX® has a shelf life of only 10 days it is manufactured upon order. Thus establishing an improved web-based ordering and supply system is particularly important. Transportation strictly requires cooling.3. Potentially infective for user: Not to be handled by pregnant women.

  Gap :

  Not applicable.

• Commercial potential for vaccines in Europe

  1. There is a potential for more user-friendly vaccines against toxoplasmosis in livestock species, in which toxoplasmosis is of economic importance there is commercial potential. 2. There is also the potential to produce a vaccine to increase food safety by preventing food animals to establish tissue cysts, following vaccination.3. A transmission blocking vaccine for young cats could considerably reduce the oocyst contamination in the environment and could probably be commercialised with other well accepted cat vaccines.

  Gap :

  The protective efficiency (depending on the aim of vaccination, e.g. protection of lambs from vertical transmission) of various vaccine candidates (i.e. components of parasitic organelles and surface proteins) and various vaccination strategies (including the selection of appropriate adjuvant) need to be studied in detail. Appropriate experimental animal and infection models need to be established.

• Regulatory and/or policy challenges to approval

  1. TOXOVAX® MSD Animal Health:This vaccine was first recorded in the 1980s. We assume that each country in which it is used made a local extension of the vaccine record (However, we are unable to gain detailed information of licensing in individual countries). Therefore, it is assumed that any country that wants to market / register the product has to do an extension of the initial TOXOVAX® registration.2. Novel vaccines: For companies it will be important to discuss with the authorities the required endpoints sufficiently in advance.

  Gap :

  Not applicable.

• Commercial feasibility (e.g manufacturing)

  1. Commercial feasibility of manufacturing live vaccines is low. In contrast, vaccines with inactivated T. gondii or subunit vaccines have a higher commercial feasibility as industry has experience in producing such vaccines.2. The more the manufacturing process can be up-scaled and standardized, the better the feasibility. Thus, one should also consider recombinant antigens or alternative technologies not requiring the cultivation of the whole parasite.

  Gap :

  Not applicable.

• Opportunity for barrier protection

  Not applicable.

  Gap :

  Not applicable.

• Opportunity for new developments

  Toxoplasma vaccines that are not based on live parasitic stages (e.g. vector subunit vaccines, DNA vaccines) represent opportunities for new developments.

  Gap :

  Not applicable.

• Pharmaceutical availability

• Current therapy (curative and preventive)

  In livestock animals only symptomatic treatment is available, aimed at reducing clinical symptoms during acute infection (e.g. fever). In case of companion animals (e.g. dogs or cats suffering from toxoplasmosis) there are further options. In the human sector mainly Macrolide antibiotics (Spiramycin) or Folate inhibitors (Sulfamethazine Pyrimethamine sulphate) are applied, especially during pregnancy to avoid transplacental transmission of T. gondii and congenital toxoplasmosis.

  Gap :

  There is a lack of registered drugs for the treatment of toxoplasmosis in livestock.

• Future therapy

  Macrolide antibiotics (Spiramycin), Polyether ionophore antibiotics (Monensin, peroral application, possible side effects in young animals, poisoning?), Folate inhibitors (Sulfamethazine Pyrimethamine sulphate, reduces abortion?), Quinolones (Decoquinate, peroral application possible) and Triazinones (e.g. Toltrazuril, peroral treatment possible, possibly act also against tissue cysts of T. gondii) are pharmaceutical experimentally tested and represent potential options. However, as time of infection is generally unknown and in a natural situation it is unknown which animal of a flock or herd becomes exposed, a long term and general treatment of a flock or herd seems to be the only option to efficiently prevent toxoplasmosis in livestock. Due to problems with residues of pharmaceuticals and the potentially high costs if applied to larger parts of a flock or herd, the practical use of pharmaceuticals needs discussion.

  Gap :

  Thiazolides, diamidines, artemisinines (artemiside, artemisone), Naphthoquinones, Anticancer drugs (Miltefosine, Organometallic ruthenium complexes), Endochin-like quinolones and Calcium-dependent protein kinase inhibitors are potentially interesting compounds.

• Commercial potential for pharmaceuticals in Europe

  A low commercial potential is assumed, due to difficulties in applicability, high costs and because of problems with residues.

  Gap :

  A new drug that is able to kill tissue cysts would represent a break through, as it would allow to eliminate latent infection (depending on costs, safety and withholding period).

• Regulatory and/or policy challenges to approval

  For companies it will be important to discuss with the authorities the required endpoints sufficiently in advance.

  Gap :

  Not applicable.

• Commercial feasibility (e.g manufacturing)

  Once licensed, drugs against toxoplasmosis in livestock are commercially feasible.

  Gap :

  Not applicable.

• Opportunities for new developments

  1. Since drugs against toxoplasmosis in livestock may also provide options for the development of new drugs for the human sector there are opportunities for new developments.2. However, in the veterinary sector a new compound can only be marketed as a commercially viable product, if it shows a clear advantage for the farmer. If the treatment regime for prevention of abortion is too complex (e.g. several treatments during pregnancy) or costs are high, it will be very difficult to gain a reasonable market.

  Gap :

  Thiazolides, diamidines, artemisinines (artemiside, artemisone), Naphthoquinones, Anticancer drugs (Miltefosine, Organometallic ruthenium complexes), Endochin-like quinolones and Calcium-dependent protein kinase inhibitors are potentially interesting compounds, which need to be evaluated in-vitro and in model hosts first.

• New developments for diagnostic tests

• Requirements for diagnostics development

  1. From the epidemiological perspective, there is a need to develop specific tests to differentiate oocyst-mediated infections from infections by bradyzoites or tachyzoites. However, such tests are not going to be widely applied. 2. There is a need to develop tests able to predict viable infections in livestock animals/food that do not depend on bioassay.3. Development of multiplex-serological tests (i.e. a test to be multiplexed with tests for other pathogens, e.g. applicable to meat juice or serum at or prior to slaughter).4. Next generation sequencing (NGS)-based tests and test protocols with a high analytic sensitivity and specificity to determine the T. gondii genotypes/subtypes in infected hosts, because genotype may determine virulence for animals and humans.5. There is a need for diagnostic tests that can accurately and reliably diagnose infection in wild species, important reservoirs of infection.6. Diagnostic (multiplex) tests to determine the causes of ovine abortions or abortion in small ruminants.7. Efficient diagnostic methods for the detection of oocysts in environmental and other samples (including shellfish vegetables, fruits), which is e.g. Immuno-Magnetic Separation (IMS) based.8. A rapid test to detect patency in cats (used by the cat owner)

  Gaps :

  • Although a number of diagnostic candidates to differentiate oocyst-mediated infection from other infections (tissue cyst, tachyzoite) have been reported, the validity of the respective antigens are under discussion and findings/reports not generally accepted. Research is necessary to identify further potentially suitable diagnostic candidates and to validate those for which a diagnostic potential was claimed.
  • Current serological diagnostic tools rely mainly on total lysate or on particular surface and dense granule related antigen. Research is necessary to identify further diagnostic antigens and their potential to be recognised during viable infection.
  • Tools need to be developed to specifically purify and enrich parasitic molecules (e.g. proteins, peptides, messenger RNA, DNA) suitable to facilitate diagnosis.
  • Slaughter-house analysis may allow to diagnose a previous infection of animals against zoonotic pathogens (including T. gondii).
  • Further assays allowing multiplexing (such as Luminex bead-based assays) need to be established and marketed.
  • Research is needed on sensitive and specific recombinant antigens and conditions of their applicability in tests.
  • Research is needed to establish suitable polymorphic sites in the genome of Toxoplasma to better differentiate strains.
  • Development of monoclonal antibodies that can be used for Immuno-Magnetic Separation (IMS) development for T. gondii oocysts.
  • Identification of better markers for virulence, leading to molecular tests to determine virulence without the need for assays in mice.

• Time to develop new or improved diagnostics

  From the development of a new test, through validation to commercial availability it may take years.

  Gap :

  Not applicable.

• Cost of developing new or improved diagnostics and their validation

  Development and validation of a new test is time consuming and labour intensive, i.e. costly. However, it is hard to estimate costs as they will depend on the type of the test (including also production of specific reagents or equipment to run the test).

  Gap :

  Not applicable.

• Research requirements for new or improved diagnostics

  Sufficient funding and interdisciplinary exchange are important drivers and requirements to establish new and improved diagnostics. Industrial cooperation might help to bring new tools into the market.

  Gap :

  Not applicable.

• Technology to determine virus freedom in animals

  A technology to confirm freedom of T. gondii infection is difficult or even impossible to establish. Currently, as an approximation, sero-negativity is used. However, under specific conditions and in some host species, infection has been identified also in case of serologically negative animals.

  Gap :

  Research on serological and other tools (e.g. DNA detection) to increase sensitivity of diagnosis at the same or even better level of specificity.

• New developments for vaccines

• Requirements for vaccines development / main characteristics for improved vaccines

  1. A vaccine should be applicable to livestock in which toxoplasmosis plays an economic role (small ruminants, possibly pigs)

  2. (i) It should be applicable to livestock to reduce the tissue cysts burden (having in mind the zoonotic aspect of livestock infections); (ii) To prevent oocyst mediated infection in humans and animals, a vaccine that could block oocyst shedding (transmission blocking) in cats is required.3. A vaccine needs to be highly efficient and safe (e.g. complete prevention from infection, i.e. no tissue cyst formation and no reduced fertility at the same time)4. No live vaccine and no infection risk for user5. Not specific for particular T. gondii lineages / applicable on several continents 6. Less important but nevertheless desirable: A vaccine providing the possibility to discriminate between infected vs. vaccinated animals

  Gap :

  Many reports on approaches to establish new anti-Toxoplasma vaccines are in literature – most of the vaccine candidates are tested in mouse models. It is necessary to translate the findings into commercially available products, i.e. Toxoplasma vaccines should be evaluated in relevant host species.

• Time to develop new or improved vaccines

  From the development of a new vaccine, through validation (safety, efficiency) to commercial availability it may take years (up to 10 years, or even more).

  Gap :

  Not applicable.

• Cost of developing new or improved vaccines and their validation

  Development and validation of a new vaccine is time consuming and labour intensive, i.e. costly. However, it is hard to estimate costs, as they depend on the type of the vaccine.

  Gap :

  Not applicable.

• Research requirements for new or improved vaccines

  Sufficient funding, interdisciplinary exchange and industrial collaboration are important drivers and requirements to establish new and improved vaccines.

  Gap :

  Not applicable.

• New developments for pharmaceuticals

• Requirements for pharmaceuticals development

  A Target Product Profile is necessary which defines the expectations:1. A new drug should be applicable to livestock in which toxoplasmosis plays an economic role (small ruminants, pigs?)2. It needs to be applicable to livestock to reduce the tissue cysts burden (having in mind the zoonotic aspect of livestock infections)3. It needs to be highly efficient, efficient against the relevant parasitic stage4. There should be knowledge on mode of action.5. Way of administration should be as convenient as possible (oral, injectable)?6. No side effects, safety7. No residues problematic, acceptable withholding periods

• Time to develop new or improved pharmaceuticals

  From the development of a new pharmaceutical or even the new claim for an existing pharmaceutical, through validation (safety, efficiency) to commercial availability it may take years (up to 10 years, or even more).

  Gap :

  Not applicable.

• Cost of developing new or improved pharmaceuticals and their validation

  Development and validation of a new pharmaceutical is time consuming and labour intensive, i.e. costly. However, it is hard to estimate costs.

  Gap :

  Not applicable.

• Research requirements for new or improved pharmaceuticals

  Sufficient funding, interdisciplinary exchange and industrial collaboration are important drivers and requirements to establish new and improved pharmaceuticals.

  Gap :

  Not applicable.

Disease details

• Description and characteristics

• Pathogen

  T. gondii is ubiquitous world-wide and virtually all warm blooded animals are able to serve as intermediate hosts. T. gondii has a clonal population structure with clonal types I, II and III prevailing in Europe and North America. Type II (ToxoDB#1, #3) is the dominating clonal type in Europe. In North America additional genotypes are observed, including a type X (synonym haplotype 12, or ToxoDB#4, #5) prevailing in North American wildlife. In South America the T. gondii population structure is very heterogeneous with an often limited clonality. In Asia, especially in China and South East Asia further genotypes are present (Chinese I and in addition clonal type I, the latter which is rare in Europe and almost absent in North America is one of the dominating genotypes in China). In Africa there are other genotypes than in Europe but some are similar to those in South America (Africa 1 – BrI). However, especially in Northern Africa clonal type II and III - also occurring in Europe - seem to prevail. Australia seems to mirror very much the European situation (i.e. clonal types I, II, III).

  Gap :

  The extent of genetic diversity within the clonal types in Europe and North America is unknown.Only a portion of the virulence determinants are known, mostly those specific for laboratory mice. Little is known of the genetic base of differences in virulence to other intermediate hosts including humans.

• Variability of the disease

  1. Genotypes and host range: Little is known on variation of T. gondii virulence in humans. Reports from South America suggest that virulence of local South American T. gondii is much higher than virulence of T. gondii in Europe or North America. This higher virulence is characterized by more severe and more frequent cases of ocular toxoplasmosis as well as the possibility of superinfection and severe acquired toxoplasmosis in immunocompetent individuals.2. Species variability: For mice (especially laboratory mice) there is large variation in virulence, often correlated to the T. gondii genotype. However, mouse virulence is an unreliable measure for virulence in other host species. The interplay of the hosts immune system and the parasites immune-modulating activities, largely determines the outcome of infection.3. Spatial variability: In general, the prevalence of infection seem to be higher in temperate areas of the world.4. Temporal variability: European data suggest that there is seasonal variation in both the number of cats shedding oocysts, the prevalence in pigs and the incidence of human infection.

  Gaps :

  • There are huge gaps in scientific knowledge to understand differences of T. gondii in virulence for humans.
  • While there is an abundance of knowledge on virulence determinants in laboratory mice there is little known in other host species, including the main livestock species.
  • There are huge gaps of knowledge to understand temporal variability (e.g. seasonality, differences between years).
  • Spatial variability is not understood at all.

• Stability of the agent/pathogen in the environment

  T. gondii oocysts have a very high stability in the environment. Under optimal conditions, oocysts are able to survive for about 4 years. Essential parameters seem to be presence of water/humidity, cold but not water-freezing temperatures and enough oxygen.

  Gap :

  Knowledge on further details on the resistance of oocysts in the environment (e.g. various freezing-thawing cycles, details on draught resistance, molecules facilitating environmental resistance) is necessary to at least partially understand spatial and temporal variability. Knowledge on key molecules facilitating this resistance may provide a rational for the development of better disinfectants.

• Species involved

• Animal infected/carrier/disease

  Virtually all warm-blooded animals can serve as intermediate hosts, i.e. may represent reservoir hosts. Among livestock, small ruminants and pigs represent animal species in which the disease/toxoplasmosis may play an important role. Chickens and possibly other poultry represent important reservoir hosts, because if reared free-range they are susceptible to infection but resistant to disease. Because these birds are ground-feeding, oocysts are the most likely source of infection.Other species that may serve as reservoir animals are game animals such as deer or wild boars.

  Gap :

  The role of many animal species in the life cycle of T. gondii needs to be elucidated. In particular, among the main livestock species, the role of cattle and equids in the T. gondii life cycle is not sufficiently determined.

• Human infected/disease

  Humans can become infected prenatally or acquire the infection postnatally. Prenatal infection may have severe consequences, including abortion or congenital toxoplasmosis (including hydrocephalus, neuro-motoric disorders, seizures, ocular toxoplasmosis). When postnatally acquired, infection usually goes un-noticed. However, depending on the parasitic genotype and on the immune-status of the individual, also postnatally acquired infection may have severe consequences including ocular toxoplasmosis even in immunocompetent individuals or T. gondii encephalitis in immunocompromised individuals (e.g. in transplant patients).

  Gap :

  The relative importance of oocysts, tissue cysts and possibly also tachyzoites in sources of infection in humans need to be studied.

• Vector cyclical/non-cyclical

  The role of mechanical/noncyclical vectors, harbouring oocysts has been shown. The relative importance of these vectors regarding transmission to livestock is largely unknown. In the marine environment organisms filtering water (shell-fish) represent an important source of infection for marine mammals and presumably also humans, if shell-fish is consumed not sufficiently inactivated.

  Gap :

  Relative importance of non-cyclical vectors is generally un-known. One exception is the role of shell-fish in case of Californian sea-otters.In addition, there is limited knowledge whether depuration times for shellfish might be able to sufficient clear oocyst contaminants before human consumption.

• Reservoir (animal, environment)

  Virtually all warm blooded animals can serve as intermediate hosts. Contaminated water and land (e.g. pastures, farmland) including infected small mammals or birds represent likely reservoirs.

  Gaps :

  • Relative importance of intermediate hosts, contaminated water and land needs to be explored in detail. Only preliminary data exist e.g. on the spatial distribution of T. gondii in villages and the surrounding area of villages.
  • There is a need for sensitive and specific detection methods to efficiently examine water or soil are required for such analyses.
  • Information on an existing and the level of contamination or infection in intermediate hosts could provide valuable information for veterinarians and farmers and may represent base line data for decisions on biosecurity measures.
  • To the best of our knowledge, almost no studies on contaminated water and environment exist for cities. In a Brazilian study, T. gondii oocysts were isolated in 23% of school playgrounds.

• Description of infection & disease in natural hosts

• Transmissibility

  Definitive hosts (exclusively cats and their wild relatives, felids) are shedding temporarily oocysts into the environment after infection. Virtually all warm-blooded animals are able to serve as intermediate hosts. Oral uptake of oocysts (e.g. in herbivorous livestock) causes acute (characterized by tachyzoite multiplication) and eventually chronic infection (establishment of bradyzoites and tissue cyst development). During acute infection, parasites may be transmitted transplacentally and infect foetuses (prenatal infection). Chronic infection is characterized by tissue cysts predominantly in muscles and neural tissues of infected intermediate hosts. Felids and also carnivorous or omnivorous intermediate hosts may become infected after oral ingestion of infective intermediate host tissues. Infected intermediate hosts may shed also tachyzoites with milk and infection after oral uptake of infective milk is possible. In humans, solid organ transplantation, stem cell transplantation and probably blood transfusion are regarded as cause of infection.

  Gaps :

  • Gaps of knowledge exist regarding the existence and the conditions of repeated transmission in chronically infected intermediate hosts (including livestock and natural intermediate hosts).
  • Gaps exist regarding the relative importance of young versus old felids in terms of their competence to serve as definitive hosts.
  • It is necessary to clarify if some host species are able to completely clear the infection, e.g. cattle or horses.

• Pathogenic life cycle stages

  The tachyzoite, the rapidly multiplying parasitic stage represents the most pathogenic life cycle stage. Tachyzoite multiplication causes cell death and parasitic stages interfere in multiple ways with the host and the host cell immune system. This interference with the immune system is involved in pathogenesis.

  Gap :

  Virulence mechanisms of tachyzoites need to be studied in more detail and for a broader spectrum of livestock species.

• Signs/Morbidity

  Abortion (predominantly in small ruminants but also in pigs), stillbirth, weak progeny, unspecific clinical signs (fever, in-appetence, loss of weight) and morbidity can be very high in particular flocks of sheep or goats, also in pigs but rarely in other livestock. Definitive hosts, like cats, usually do not show clinical signs (rarely diarrhoea).

  Gaps :

  • There are knowledge gaps regarding the parasites genotype and the frequency and severity of clinical signs and morbidity. In addition, as yet unknown epigenetic differences between or within strains could be responsible for differences in virulence.
  • Further, individual host genetics (independent of species genetics) plays a role, which needs to be studied in more detail. Knowledge on this is available only for a few species.

• Incubation period

  Few days until unspecific clinical signs appear; days/weeks until there is abortion or stillbirth.

  Gap :

  It is not well known whether incubation periods may differ according to the route of infection (oocyst, tissue cyst or tachyzoite).

• Mortality

  Mortality is usually low, but in sheep and goat flocks abortion storms may occur affecting a large proportion of the pregnant animals. In China, a few severe outbreaks of toxoplasmosis in pigs have been recorded.

  Gap :

  Little is known on differences between various T. gondii genotypes which may affect mortality in a given intermediate host species. Again, in addition to parasites genetic background also epigenetic patterns may play a role. Further, host genetics (independent of species genetics) is of importance.

• Shedding kinetic patterns

  1. Oocysts: Only cats (including wild felids) shed oocysts starting as early as 2-3 days post infection and ending usually a few days up to a few weeks later. Re-shedding is possible but some cats can become immune.2. Tachyzoites in milk: Tachyzoites can be shed via milk (e.g. goat milk, but also sheep and cattle) during acute infection but was also shown during chronic infection. The drinking of unpasteurized goat's milk was found to be a risk factor in an epidemiological survey in humans.3. Tachyzoites in semen: This was shown in sheep and goats.

  Gaps :

  • Oocysts: Gaps of knowledge are related to the parameters affecting the period, the intensity and the duration of oocyst shedding in cats.Why do some cats shed oocysts although they had a previous exposure to T. gondii?
  • Milk, semen other body fluid: Relative epidemiological importance of shedding via milk, semen or other body fluids needs to be studies in more detail, taking into account also the parasites genotype.

• Mechanism of pathogenicity

  Mechanisms of pathogenicity in “classical congenital toxoplasmosis” in small ruminants are well-known, however mechanisms underlying early abortion are unknown.

  Gaps :

  • Mechanisms of early abortion cases in small ruminants.
  • Is there a similar situation in humans? Are early abortion cases present in women?

• Zoonotic potential

• Reported incidence in humans

  1. Incidence of infection (examples): In Austria the incidence rates based on intra- and intergravid seroconversions in women aged 15–44 years at three-year intervals ranged between 1.03 to 0.19% with a clear overall tendency to decrease (similar in Switzerland). In Germany incidence was estimated much higher at 1.1% of adults and 1.3% of women aged 18–49 to seroconvert each year (incidence of infection). During 2008-2012 there were 1824 cases of toxoplasmosis reported in England and Wales. The majority of cases were in immunocompetent people and the most common disease symptoms were lymphadenopathy.2. Incidence of congenital toxoplasmosis: During 2008-2012 there were 33 congenital toxoplasmosis cases and 28 people suffered a foetal loss or stillbirth in England and Wales. According to the EU summary of Foodborne diseases (FBDs, Table 57) for 2017, 40 cases of congenital toxoplasmosis were reported in the EU by 19 member states (MS). Seven MS (Bulgaria, Czech Republic, Germany, Poland, Slovenia, Spain and the United Kingdom) reported at least one confirmed congenital toxoplasmosis case and 12 MS reported zero cases. The EU notification rate was 1.31 per 100,000 live birth. (https://www.ecdc.europa.eu/sites/portal/files/documents/zoonoese-food-borne-outbreaks-surveillance-2017-updated.pdf)

  Gaps :

  • Infection incidence data is unknown for many countries and is needed at least for women in childbearing age.
  • Data on incidence of congenital toxoplasmosis is very fragmented across Europe and world-wide. Often such data are not reliable, as reporting systems are not efficient or simply not existing.
  • Incidence of postnatal acquired toxoplasmosis: For most countries there are no data on the incidence of postnatally acquired toxoplasmosis.

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

  A number of risk factor studies are available, providing some evidence on factors related to infection risk. To sum a few of the most import ones up:1. Kapperud et al. 1996: Factors identified: 1) eating raw or undercooked minced meat products (odds ratio (OR) = 4.1, p = 0.007); 2) eating unwashed raw vegetables or fruits (OR = 2.4, p = 0.03); 3) eating raw or undercooked mutton (OR = 11.4, p = 0.005); 4) eating raw or undercooked pork (OR = 3.4, p = 0.03); 5) cleaning the cat litter box (OR = 5.5, p = 0.02);and 6) washing the kitchen knives infrequently after preparation of raw meat, prior to handling another food item (OR = 7.3, p = 0.04).2. Cook et al. 2000: Risk factors most strongly predictive of acute infection in pregnant women were 1. eating undercooked lamb, beef, or game, 2. contact with soil, and 3. travel outside Europe and the United States and Canada. Contact with cats was not a risk factor. Between 30% and 63% of infections in different centres were attributed to consumption of undercooked or cured meat products and 6% to 17% to soil contact.3. Jones et al. 2009: Factors identified: 1. eating raw ground beef (adjusted odds ratio [aOR]= 6.67; 95% confidence limits [CLs], 2.09, 21.24; attributable risk [AR], 7%); 2. eating rare lamb (aOR=8.39; 95% CLs, 3.68, 19.16; AR, 20%); 3. eating locally produced cured, dried, or smoked meat (aOR, 1.97; 95% CLs, 1.18, 3.28; AR, 22%); 4. working with meat (aOR=3.15; 95% CLs, 1.09, 9.10; AR, 5%); 5. drinking unpasteurized goat's milk (aOR=5.09; 95% CLs, 1.45, 17.80; AR, 4%); and 6. having 3 or more kittens (aOR=27.89; 95% CLs, 5.72, 135.86; AR, 10%). 7. Eating raw oysters, clams, or mussels (aOR=2.22; 95% CLs, 1.07, 4.61; AR, 16%) was significant in a separate model among persons asked this question.4. Wilking et al. 2016: 1. Male gender, 2. keeping cats and 3. BMI ≥30 were independent risk factors for seropositivity, while being 4. vegetarian and 5. high socio-economic status were negatively associated.

  Immunosuppression may cause toxoplasmosis due to reactivation of a pre-existing or a recent infection. In case of a transplantation or blood transfusion a transmission from the donor to the recipient is possible and not unlikely.

  Gap :

  All the risk factor studies are retrospective. Findings are only associations but not clearly confirm a causal relation. There are no prospective studies (such studies are difficult to perform and expensive). Further risk factor studies in other regions than Europe and North America are important, because the existence or the relative importance of risk factors may vary between geographical regions, countries and continents.

• Symptoms described in humans

  Congenital/prenatal toxoplasmosis can develop when a woman experiences primary infection with T. gondii during pregnancy. Clinical surveys demonstrate that up to 20% of such maternal infections result in transplacental transmission, and that in 27% of the infected neonates specific symptoms develop.Gestational age of the foetus at infection is associated with the probability of transmission. If the infected foetus survives infection, predominantly retino-choroiditis, calcifications, hydrocephalus, psycho-motoric and neurological disabilities can develop short after birth or later in life.In humans, most postnatal infections remain without clinical symptoms or manifest with mild flu-like symptoms; however, severe forms can occur. These include acute and reactivated infections in immunocompromised individuals (which may cause e.g. cerebral toxoplasmosis) or ocular toxoplasmosis causing visual impairment. T. gondii from South America with an unusual genetic composition have been linked to ocular toxoplasmosis even if the infected humans were immunocompetent.

  Gap :

  In many European countries the incidences for the various forms of toxoplasmosis (human, animals) are largely unknown. For some countries there are robust figures for congenital human toxoplasmosis. In many countries no incidence data on postnatal/acquired toxoplasmosis (including data on ocular toxoplasmosis) are available.

• Estimated level of under-reporting in humans

  In many countries worldwide, there is no reporting at all.1. Depending on the country and the reporting system / reporting regulations / structure of health system it has to be assumed that most of the human congenital toxoplasmosis cases go un-reported. In many countries postnatal T. gondii infections are not reported at all. Seroprevalence data e.g. in Germany suggest a massive underreporting (about 6-20 cases of congenital toxoplasmosis per year reported, about 300-400 cases of congenital toxoplasmosis are expected based on the experiences of countries in which T. gondii testing during pregnancy is mandatory). In postnatal infection, which usually goes un-noticed or with non-specific symptoms, underreporting is even worse.2. For postnatally acquired toxoplasmosis, the availability of data is very limited, too. For UK it was estimated, based on prevalence figures, that 350,000 people become infected with T. gondii each year but only 10-20% have a symptomatic toxoplasmosis.

  Gap :

  Gaps of knowledge are precise data on incidence of postnatal as well as congenital infection. Only in countries, in which pregnant women are screened for T. gondii-infection, incidence rates are available. Most likely, there is a huge difference in incidence rates, depending on region/country/continent.

• Likelihood of spread in humans

  1. Congenital/transplacental transmission: Clinical surveys demonstrate that up to 20% of maternal infections during pregnancy result in transplacental transmission, and that in 27% of the infected neonates specific symptoms develop. Gestational age of the foetus at infection is associated with the probability of transmission. The later during pregnancy the higher the likelihood of transmission.2. Transmission after solid organ transplant or stem cells: In case of solid organ transplantation, especially in case of heart/heart-lung transplantations the risk was regarded high in case of a positive donor and a negative recipient. In case of hematologous stem cell transplantation the risk seems to be low (Derouin, F., Pelloux, H., Parasitology, E.S.G.o.C., 2008. Prevention of toxoplasmosis in transplant patients. Clinical microbiology and infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases 14, 1089-1101).

  Gap :

  One of the un-answered questions is how the genotype of the parasite and in addition parasites epigenetic factors have an effect on the transmission in humans. In addition, little is known on the effect of the host genetic background.

• Impact on animal welfare and biodiversity

• Both disease and prevention/control measures related

  1. Disease related: Effects on highly susceptible species but free-living in their natural environment (including New world monkeys, Suricates, Pallas’s cats and Sand cats) are not reported. In California, toxoplasmosis represents a fatal disease in Sea otters, an endangered species. T. gondii infection has also been suggested as a possible cause of death for other sea mammals.2. Control measures related: Not known.

  Gaps :

  • The effect of T. gondii on endangered wild species needs to be elucidated in their natural environment (preferably in those species known to be highly susceptible for toxoplasmosis).
  • It is not known what effect wild cat conservation/re-introductions has on environmental contamination with oocysts.

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

  In general, the impact on endangered wild species is not clear. It is well known that certain animal species (including New world monkeys, Suricates, Pallas’s cats and Sand cats) are highly susceptible to toxoplasmosis, probably because there was no co-evolution between these animal species and the parasite. Thus, these animals’ immune system is not able to adequately respond on a T. gondii infection. However, to which extent these animal species are exposed to T. gondii in their natural environment is unknown.

  Gap :

  No estimates on the effect of T. gondii on endangered wild species in their natural environment are available.

• Slaughter necessity according to EU rules or other regions

  No regulations in place, worldwide.

• Geographical distribution and spread

• Current occurence/distribution

  T. gondii and toxoplasmosis occur world-wide. In humans, prevalence data for many countries are lacking; in those were prevalence data are available the quality of data is not always good. There seems to be a tendency that those countries with a sometimes very cold (e.g. Scandinavian countries, Canada), or a very hot climate (e.g. Saharan, Sub-Saharan countries, Australia) have lower prevalence in humans, while those countries with a warm and humid climate (e.g. Brazil, South-East Asian countries) have very high prevalence in humans. However, the heterogeneity of prevalence in Europe with a temperate climate is most likely related to other factors, such as eating habits and the prevailing type of livestock. Examples: The habit to consume raw pork might be responsible for high prevalence in Germany while in many (but not all) neighbouring countries, prevalence is low.

  Gap :

  Livestock infection is influenced by many factors, including climatic or other factors related to geography. More studies are needed to explore the effect of climate/weather/temperature/rain and other geographic parameters on prevalence in livestock.Other effects such as eating habits, water supply safety and other risk based activities need to be assessed on a country by country basis.

• Epizootic/endemic- if epidemic frequency of outbreaks

  There is a number of epidemic outbreaks in humans, related to water contaminations, in literature. Epidemics are also known from livestock, for example, sheep flocks. However, in comparison to other parasitic infections, i.e. cryptosporidiosis the reports on out-breaks are rare. Toxoplasma gondii is endemic in most countries with a low yearly clinical incidence in humans.

  Gap :

  Actually, we have no reliable tools to find out the proportion of oocyst-derived infections and tissue-cysts or tachyzoite mediated infections in humans. This is also true for omnivorous livestock species.Tools to reliably differentiate different routes of infection need to be established.

• Seasonality

  Seasonality was observed in Europe in human cases of toxoplasmosis in several countries. Seasonality was further observed in the proportions of cats shedding T. gondii oocysts in their faeces. There are indications that there is also seasonality in prevalence of infection in pigs reared in Europe with highest prevalence in winter. Studies in cats predominantly from Germany identified summer and autumn as season in which proportions of cats shedding oocysts were highest. It was discussed whether seasonality in cats can cause seasonality in other host species but with a time lag due to incubation time and time of infection to progress.

  Gap :

  Further research is needed to look for similar patterns in other countries/ on other continents and on parameters able to explain these observations.Seasonality in human infections needs to be investigated as this may give an indication of sources of infection.

• Speed of spatial spread during an outbreak

  Nothing is known on that.

  Gap :

  Most likely, a spatial spreading is noticed if contamination (by oocysts) affects water, widely disturbed into a country and coming from a single source. However, this is hypothetical and needs to be explored. The long delay between infection and the development of symptoms, if any, makes this challenging.

• Transboundary potential of the disease

  The transboundary potential is high due to animal transportation and trade with meat. However, as T. gondii infections are endemic in most countries, the transboundary potential is of limited importance in the epidemiology of the disease.There is a significant risk to human health if unusual and more virulent isolates from South America would be introduced into Europe and if these isolates would be able to spread, e.g. via oocysts shed by cats.

  Gap :

  Gaps of knowledge exist on the extent foreign genotypes could enter countries/continents. Case reports from France suggest a possible relevance of this route of entry into a foreign country which may have severe consequences in the infected humans.

• Route of Transmission

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

  1. In livestock, the usual routes are oral uptake of oocysts in case of herbivorous animals and the oral uptake of infective tissue cysts in not sufficiently treated meat or meat products or other body tissues than meat.Vertical transmission is most likely less important in livestock. However, vertical transmission is the route a foetus becomes infected and disease and losses occur (see Section “Occasional mode of transmission).2. In humans all routes are important.

  Gap :

  Relative importance of different routes of transmission needs further investigation.

• Occasional mode of transmission

  1. In several animal species (including small ruminants and rodents) vertical transmission represents an important route of transmission, too. Vertical transmission is able to maintain the parasite in the prey populations.Occasionally milk may contain tachyzoites and milk represents a possible route of transmission.Further possibility represents the transmission via semen or transmission of oocysts in fresh produce.2. In humans vertical transmission cases congenital toxoplasmosis. Case reports suggested, that ingestion of raw milk from infected small ruminants represents a putative route of infection for humans.

  Gap :

  Relative importance of different routes of transmission needs to be assessed. Are these alternative routes of epidemiological importance?

• Conditions that favour spread

  Poor hygiene, insufficiently treated meat or meat products.

  Gap :

  Conditions that favour spread need further investigation.

• Detection and Immune response to infection

• Mechanism of host response

  Cellular immune-response is regarded as the dominating part of the immune system to control T. gondii infection.

  Gaps :

  • Experimental data show that also antibodies against the parasite are beneficial to control infection. To which extent is unknown and may vary between hosts.
  • The immunological components controlling the development of T. gondii in the intestine of the definitive host and affects oocysts development in non-naïve cats is unknown.
  • Immune evasion by the cysts is also an area of interest.

• Immunological basis of diagnosis

  Animals and humans usually develop specific antibodies against T. gondii. But there are exceptions:1. In humans, there are conditions under which antibody development is impaired, e.g. in immunosuppressed individuals and in some individuals that were congenitally infected. Under these conditions, diagnostic tests based on antibody detection may test false negative. There is a need for alternative diagnostic tools in these situations.2. In several animal species, i.e. particular rodents, cattle and horses, the predictive values of T. gondii specific antibodies is limited, at least with the existing serological tests.

  Gaps :

  • In the human sector there are conditions in which levels of antibodies are affected by the immunological status of patients. In these patients, other means of diagnosis are better than serodiagnosis. However, the panel of such diagnostic tools need to be expanded.
  • In humans, the serological diagnosis of an acute infection is still challenging. In addition to IgM/IgA detection or avidity testing further tools are necessary.
  • The diagnosis of ocular toxoplasmosis is also still challenging. A comparison of levels of intraocular antibodies and serum antibodies needs better standardization.
  • In certain livestock species, the presence of specific antibodies is hard to determine, but the reasons for this are largely unknown.
  • Another problem (mainly in livestock) represent cross-reactions between T. gondii and Hammondia hammondi, which most likely causes false positives in a largely unknown extent in several livestock species and possibly also in humans.

• Main means of prevention, detection and control

• Sanitary measures

  T. gondii oocysts can survive for a long time in the environment and are highly resistant to chemical disinfection.

  Gap :

  The development of effective disinfection measures for killing oocysts in feed, water and the farm environment.

• Mechanical and biological control

  1. Control of T. gondii infection of farm animals by reduction of environmental oocyst load through feline population control is likely an important measure. However, this is fraught with ethical concerns and requires coordinated efforts in monitoring of feral cat colonies. Neutering cats is an ethical way to control feral cat populations but neutering cats from wild felid populations is challenging.2. Rodent control has been shown to be one of the components to prevent introduction and spread of T. gondii infections on pig farms. However, the “biological control” of rodents by using felids is not advised as the presence as well as the number of cats on farms was shown as risk factors in several studies.3. Other options include the storage of animal feeds in places to which cats do not have access and can’t defecate into.

  Gaps :

  The effectiveness of various control options needs to be assed in epidemiological studies (e.g. cohort studies).

• Diagnostic tools

  It has been proposed to use antibody tests to monitor T. gondii infection in pigs going for slaughter. The aim of this was to identify pig farms with a large proportion of seropositive animals. Based on the serological findings, i.e, the proportion of seropositivity, measures on farms should be taken to prevent future infections. To the best of our knowledge no published programs exists in which diagnostic tools were used to prevent and control T. gondii in livestock.

  Gap :

  There is currently no effective diagnostic tool to determine the viability of T. gondii in meat from infected animals. Thus, the development of effective and rapid diagnostic tools to assess the risk of food-borne T. gondii is needed.

• Vaccines

  A live vaccine for sheep is available but only marketed in a few countries due to limitations in production and logistics of transport. To the best of our knowledge, no other vaccines are commercialized and used for prevention.

  Gaps :

  • Development of vaccination strategies to include especially young cats and prevent oocyst shedding.
  • Development of vaccines to make food safer by vaccinating food animals before they become infected.

• Therapeutics

  No therapeutic treatments in livestock recommended and no drug licenced. In the human sector therapeutics exist but new developments with less side effects are desirable.

  Gap :

  Identification of potentially new therapeutics.

• Biosecurity measures effective as a preventive measure

  Risk factor studies in livestock suggest that in part of the livestock species and related to production system (e.g. in pigs and poultry) biosecurity methods are likely to provide protection. The proposed measures are rodent control, avoiding contaminations of stored feed and to ensure a high water quality. Further, the access or number of cats having access to barns, pastures and other farmland should be limited as much as possible.

  Gap :

  Intervention studies, i.e. prospective studies are necessary to confirm the validity of (biosecurity) recommendations and to identify the most important measures.

• Border/trade/movement control sufficient for control

  Border/trade/movement control appears of little value due to the widespread distribution of T. gondii infection. Border/trade/movement control might be of value to prevent introduction of foreign genotypes of Toxoplasma especially for virulent South American genotypes into the EU.

  Gap :

  Research necessary on the extent to which foreign T. gondii genotypes are introduced into Europe or other parts of the world.

• Prevention tools

  Possible prevention tools could be:

  1. Prevent or reduce transmission by cats/by oocysts: (i) Reduction of cat numbers. (ii) Prevent infection of cats or other felids (several options: e.g. no feeding of non-inactivated materials; rodent control; vaccination of cats against oocysts-shedding).2. Prevent or reduce introduction and transmission of infection by intermediate host into flock or herd (including prey animals of cats, like rodents and birds; by including positive replacement; by improving biosafety measures, farm management).3. Prevent or reduce the probability of transmission from infective meat to humans (several options: inactivation of parasite; excluding meat from serologically positive animals to generate meat or meat-products, which are used to prepare not sufficiently inactivated meals or meat products.4. Information and education of consumers. 5. Vaccination of food animals at a young age to stop them to form tissue cysts if they become infected subsequently.6. Depending the conditions, freezing of meat may inactivate T. gondii tissue cysts. Existing data suggest that e.g. a -8 °C freezing of 20 g samples for about three days is able to inactivate tissue cysts (as determined by bioassay in mice).

  Gaps :

  • Research is necessary to develop efficient control programs to intervene on-farm infection of livestock by e.g. improving biosecurity protocols, hygienic measures or farm management.
  • Research is necessary to provide vaccines preventing infected cats from shedding T. gondii oocysts by faeces.
  • Research is necessary to provide vaccines preventing food animals to from tissue cysts.
  • Research is necessary on methods to inactivate T. gondii in cat litter or bind the faeces so they do not disperse in the environment.
  • To help prevent water-mediated infections with oocysts, future studies could focus on optimal methods to filter T. gondii in municipal water. Public water supplies that could be contaminated by T. gondii or other parasites should be filtered as part of the treatment process sufficiently to eliminate Cryptosporidium spp. (diameter 3–5 µm), which should also eliminate T. gondii oocysts (diameter 10–12 µm).
  • Another area for further study is the possible impact of recreational water use and inadvertent swallowing of water on acquisition of T. gondii infection.
  • The risk of surface water for washing fresh produce such as salad leaves and vegetables needs to be investigated.
  • If freezing of meat should be a way of inactivation, further studies are necessary to clearly define conditions/parameters (temperature, time, de-freezing time, etc,) under which freezing is a reliable method. Further, it needs to be clarified whether different strains or genotypes of parasites have a similar susceptibility to the freezing conditions.
  • Exploration of other possible ways to inactivate T. gondii in meat or meat-products.

• Surveillance

  In some but not all European countries it is mandatory to notify authorities on toxoplasmosis in humans and/or animals. There is no surveillance in most European counties.

  Gaps :

  • Underreporting (if there is reporting at all) in many European countries is an important issue. In addition, surveillance data needs to be analysed in appropriate ways.
  • To have a better base of data, well–designed surveillance programs need to be implemented.

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

  No such experiences on a regional prevention, control or eradication is reported.1. Vaccination in sheep in UK and New Zealand is on a voluntary base and to the best of our knowledge there are no robust estimates on the economic benefit these vaccinations had. 2. In the past there were serious outbreaks of toxoplasmosis in the US caused by contamination of drinking water by T. gondii oocysts. A more severe situation existed/exists for Cryptosporidium spp. oocysts which also may contaminate water. Based on an Interim Enhanced Surface Water Treatment Rule, promulgated on December 16, 1998 (USEPA, 1998), which applies to water utilities using surface water, or groundwater under the direct influence of surface water, and serving more than 10,000 people and was designed to establish physical removal efficiencies and to minimize Cryptosporidium levels in finished water. It was estimated that the likelihood of endemic illness from Cryptosporidium will decrease by 110,000 to 463,000 cases annually due to the establishment of physical removal. Unfortunately, nothing is known on the potential effects of these measures on human cases of toxoplasmosis caused via oocysts in water.

  Gap :

  Research on potential intervention and control strategies is necessary.

• Costs of above measures

  No estimates of cost available.

• Disease information from the WOAH

• Disease notifiable to the WOAH

  No.

• WOAH disease card available

  No.

• WOAH Terrestrial Animal Health Code

  No.

• WOAH Terrestrial Manual

  http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.09.09_TOXO.pdf

• Socio-economic impact

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

  Congenital toxoplasmosis:

  Globally: the burden of congenital toxoplasmosis was estimated at 1.20 million DALYs. High burdens were seen in South America and in some Middle Eastern and low income countries.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699792/ (Global)

  Individual countries:https://www.ncbi.nlm.nih.gov/pubmed/19430666 (The Netherlands)https://www.ncbi.nlm.nih.gov/pubmed/22541392 (The Netherlands)https://www.ncbi.nlm.nih.gov/pubmed/28605518 (Belgium)https://www.ncbi.nlm.nih.gov/pubmed/28558051 (Denmark)https://www.ncbi.nlm.nih.gov/pubmed/22980013 (USA, QALY)

  Acquired toxoplasmosis:https://www.ncbi.nlm.nih.gov/pubmed/22541392 (The Netherlands)https://www.ncbi.nlm.nih.gov/pubmed/22980013 (USA, QALY)

  Gap :

  Estimates are desirable for further countries but not available.

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

  No estimates available.

  Gap :

  Estimates are desirable and not available. To have estimates is hard to achieve.

• Direct impact (a) on production

  Limited information is available for the small ruminants sector in a few countries including UK, Uruguay and possibly New Zealand (non-peer reviewed data).In the UK, Toxoplasma is the second most diagnosed cause of ovine abortion. Estimates from the past say that 1-2% of all sheep pregnancies are lost each year due to Toxoplasma infection. In Spain, infection by T. gondii is the 2nd-3rd important cause of abortion in small ruminants.

  Gap :

  Estimates are desirable for almost all livestock species, but are not available.

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

  No estimates available.

  Gap :

  Estimates are desirable and not available.

• Indirect impact

  No estimates available.

  Gap :

  Estimates are desirable and not available.

• Trade implications

• Impact on international trade/exports from the EU

  No regulations exist.

• Impact on EU intra-community trade

  No regulations exist.

• Impact on national trade

  No regulations exist.

• Main perceived obstacles for effective prevention and control

  To prevent infection via meat producing livestock animals: Facilitators for effective prevention and control are farmers, meat producing companies/slaughterhouses as well as veterinary and public health authorities and also physicians (especially gynaecologists). In addition, public education may lead to better understanding how to limit human exposure. Political commitment is necessary to push developments in the different sectors.To prevent/limit/reduce infections via the excretions of cats: Facilitators are cat owners and physicians (gynaecologists) but if cat vaccines or treatment would be effective options, vaccine and pharmaceutical industry represent further facilitators.As T. gondii infections of cats (oocyst shedding by cats) usually goes unnoticed and usually does not affect cats health it appears unlikely that e.g. cat owners would vaccinate or treat cats on a voluntary base. Again, also political commitment and that of public health authorities is necessary to push developments into this direction.As feral cats also represent a source of environmental oocysts contaminations, political commitment and that of public health authorities is necessary to initiate measures to either reduce feral cat populations or (if applicable) vaccinate or treat such populations.

• Links to climate

  Seasonal cycle linked to climate

  In Europe prevalence in cats (France), incidences in humans (Czech Republic) and proportions of cats shedding T. gondii oocysts (Germany) could be modelled by using North Atlantic Oscillation Index (NAO) as a parameter. A high NAO winter index suggests mild winters while a low NAO winter index suggests a strong and cold winter. Seasonal cycle linked to climate are likely but need to be explored further.

  Gap :

  The existence of a seasonal cycle linked to climate is likely but needs to be confirmed independently.This may also vary for different countries.

• Distribution of disease or vector linked to climate

  1. Disease linked to climate: As mentioned above, there seems to be a tendency that those countries with a sometimes very cold (e.g. Scandinavian countries, Canada), or a very hot climate (e.g. Saharan, Sub-Saharan countries, Australia) have lower prevalence in humans, while those countries with a warm and humid climate (e.g. Brazil, South-East Asian countries) have very high prevalence in humans. Breeding seasons of cats may also affect environmental contamination.2. Vectors linked to climate: Although mechanical vectors or infected intermediate hosts play a role in lifecycle it is largely unknown whether there is a significant effect of climate on the abundance of mechanical vectors or certain (wild) intermediate hosts.

  Gap :

  The effect of climate on both disease and vector or intermediate host driven transmission need to be explored.More specifically, three different effects can be identified and should be evaluated: (1) pathogen survival will be affected by environmental changes; (2) because of increased precipitation, sporulated oocysts may be more easily spread throughout the environment; and (3) climate change will influence the ecology of (transport or reservoir) hosts.

• Outbreaks linked to extreme weather

  Outbreaks associated with the contamination of reservoirs supplying water, such as those described for the Greater Victoria area of British Columbia, Canada, in Santa Isabel do Ivai, Brazil, or in Coimbatore, India, involved a large number of patients. The epidemics were preceded by peaks of heavy rainfall and turbidity in the implicated reservoirs. Smaller epidemics were described after the drinking of raw surface water in remote tropical areas. In Colombia, a correlation was found between the mean amount of rainfall and the incidence of congenital toxoplasmosis.

  Gaps :

  • There is growing evidence that T. gondii infections in Californian marine intermediate hosts are likely attributable to ingestion of oocysts that were transported to the ocean by overland watersheds.
  • It needs to be further studied whether this also applies to overland run-off and discharge systems of land, including villages and cities. Further it needs to be assessed whether in sweet water there are filtering and concentration by biotic (e.g. by invertebrates like bivalves or snails) and abiotic processes.
  • There is a potential need to test drinking water for T. gondii oocysts.

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

  Statistical modelling for Europe suggested that climate change (warming) may cause a substantial increase in the prevalence of T. gondii infection in humans over the next decades.

  Gap :

  We are far from understanding the potential effects of climate change (warming) on T. gondii incidence in animals and humans.

Risk

• Toxoplasmosis is an important zoonosis in many countries of the world, especially in low-income countries, e.g. countries in South America and South East Asia. There are other countries in the world, in which consumer habits in combination with a wide distribution of T. gondii in livestock and the felid population is responsible for an increased zoonotic potential of T. gondii in humans (e.g. France, Germany).

Conclusion

• Basic diagnostic tests to diagnose infection are available, although not standardized and often not sufficiently validated for this purpose. Diagnostic tests for specific applications (e.g. better prediction of viable infection) are under development.

  A live vaccine is available, but it is not widely marketed due to restrictions regarding shelf life. The development and marketing of more user-friendly vaccines is desirable. Such vaccines could have different scopes: (i) prevention of parasitaemia and transplacental transmission, (ii) reduction of tissue cysts in meat producing animals, (iii) reduction of oocyst shedding in cats.

Sources of information

• Expert group composition

  Gereon Schares, Friedrich-Loeffler-Institute, Germany – [Leader]

  Laura Kramer, Università di Parma, Italy

  Peter Deplazes, University of Zurich, Switzerland

  Luis Ortega-Mora, University Complutense of Madrid, Spain

  Frank Katzer, Moredun Research Institute, UK

  Anja Heckeroth, MSD, Germany/US

  Heinz Sager, Elanco, Switzerland/US

  Jorge Gutierrez, MSD, Spain/US

• Reviewed by

  Project Management Board

• Date of submission by expert group

  23 April 2019