Diseases

Small Ruminant Lentiviruses

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Control Tools

  • Diagnostics availability

  • Commercial diagnostic kits available worldwide

    Many different assays are available commercially for Agar Gel Immunodiffusion (AGID) and ELISA. These include competitive and indirect ELISAs using purified virus, recombinant proteins/glycoproteins and synthetic peptides. In very limited circumstances OIE Terrestrial Manual indicates the use of indirect fluorescent antibody test (IFAT) for individual animal freedom from infection prior to movement and to define prevalence of infection – surveillance. There is a commercial Elisa kit ( as well as some PCR kits capable of serologically distinguishing the different genotypes.

    Available tests can be consulted here (Diagnostics for Animals).

    GAPS :

    There are few commercially available PCR tests to diagnose infection or to differentiate between MVV and CAEV biotypes.

    The question is are the commercially available molecular kits sensitive enough and capable of identifying most of the circulating genotypes? Are there suitable for a correct diagnosis? Do they differentiate between biotypes?

  • Commercial diagnostic kits available in Europe

    Many serological tests are available. There are also PCR kits. Tests can be consulted here (Diagnostics for Animals).

    GAPS :

    Most tests have been validated against a consensus serological quasi-gold standard therefore only relative diagnostic sensitivity and specificity are reported, not true/absolute diagnostic Se/Sp.

    Large variation between reported Se/Sp of the available kits.

    Different commercial ELISAs lead in some cases to contradictory results, based on the context in which they were used and on the circulating genotypes.

    Additionally, some ELISA tests fail to detect animals with low antibody titers.

    RT-PCR for A-E genotypes. Are commercial kits capable of identifying all known genotypes?

  • Diagnostic kits validated by International, European or National Standards

    Elitest MVV/CAEV ELISA validated to OIE standards (Saman et all, 1996).

    There are no SRLV tests currently on the OIE List of Diagnostic tests, however the Terrestrial Code identifies test methodologies (see below).

    In several EU countries commercial ELISA tests are used in voluntary control programmes, however, often no batch controls are performed. Most kits are validated and batches certified before distribution.

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

    OIE – AGID, ELISA EU - no diagnostic methods described

    National - VMRD OPP/CAEV ELISA is USDA approved.

  • Commercial potential for diagnostic kits in Europe

    The European market is well served by the available serological kits, subject to limitations with Se/Sp, in part depending on the locally circulating strains.

    The potential market for PCR kits is not clear but is likely to be small. Limitations of PCR are due to sequence variation, low amount of provirus during latency and low titres of virus in clinically relevant samples.

    GAPS :

    Further studies should be carried out to develop a molecular test capable to overcome the limitations due to poor sensitivity and specificity.

    The difference in performance offered by the different commercial kits (see Echeverria et al 2020 and Ramirez et al 2021) could suggest that updating serological tests by including antigen mixes is highly needed.

  • DIVA tests required and/or available

    No vaccines are available, so DIVA tests not required.

  • Opportunities for new developments

    More sensitive serological tests, e.g. multiplex serology. Comparative evaluation of kits against a ‘true infection’ standard.

    GAPS :

    Whether there is a market for PCR tests depends on the specificity and sensitivity of different PCRs. However, those available tend to perform poorly compared to serology. They will be useful in analysing animals which remain negative in serology to determine their true infection status. Some animals have delayed seroconversion so PCR tests could be considered in control schemes and for lambs less than 1 year old. Molecular tests can be used in association with Elisa in eradication programmes for excluding infected subjects that may result negative in serological tests.

    Multiplex serology tests are now available commercially. Further work needed to establish their sensitivity and specificity especially in relation to currently available tests.

  • Vaccines availability

  • Commercial vaccines availability (globally)

    None available. Production of an SRLV vaccine will be very challenging given the difficulties of producing effective vaccines against the related Human Immunodeficiency Virus.

  • Commercial vaccines authorised in Europe

    N/A.

  • Marker vaccines available worldwide

    N/A.

  • Marker vaccines authorised in Europe

    N/A.

  • Effectiveness of vaccines / Main shortcomings of current vaccines

    N/A.

  • Commercial potential for vaccines in Europe

    Potentially a large market if an efficacious and cost effective vaccine could be produced, however, the costs would have to be very low to generate any interest as even in those countries which do have MVV/CAEV most commercial producers pay little attention to it.

    GAPS :

    In most countries there is no particular attention to SRLV infections. Up to now, there have been sporadic control plans mostly limited to goats and the B genotype circulation in areas characterized by particular food productions.Wedo not believe at present there is a great interest in the use of a vaccine, even if inexpensive.

    Also, if used as part of an eradication programme a companion DIVA test would be needed.

    Spain have an ongoing research project evaluating a viral vector encoding MVV genes. In vitro viral vector restricts SRLV infection (see de Pablo et al 2020).

  • Regulatory and/or policy challenges to approval

    If nucleic acid-based vaccine approaches were successful, regulatory policy changes may be required for use in the field.

  • Commercial feasibility (e.g manufacturing)

    Commercial production of protein, viral vector, or nucleic acid-based vaccines should be perfectly feasible.

  • Opportunity for barrier protection

    N/A.

  • Opportunity for new developments

    If a ‘breakthrough’ was made on developing lentivirus vaccines in other species, e,g humans, then perhaps these could benefit the development of SRLV vaccines. mRNA vaccine strategies, for example, are currently being investigated for HIV. In Spain their approach is based on Sendai virus vectors which is also being explored in HIV.

  • Pharmaceutical availability

  • Current therapy (curative and preventive)

    No curative or preventative therapies available. Palliative treatments only for high value animals, perhaps to allow recovery of high genetic value from pedigree female sheep/goats.

    GAPS :

    A challenging gap to fill as the pathologies in SRLV would require complex biological and anti-inflammatory products which would not have a large market to the economics of sheep/goat production.

    Furthermore, such products would not be able to remove the virus from the host due to latency, and would need to be administered continuously.

  • Future therapy

    Effective anti-lentiviral drugs are available in Man to combat HIV but these would probably be too expensive for use in small ruminants and would require too frequent administration.

    GAP :

    A cost effective efficacious one-shot drug to eliminate SRLV infection or prevent it causing clinical problems in a market where sheep/goat economics do not favour species-specific drugs.

  • Commercial potential for pharmaceuticals in Europe

    Limited.

  • Regulatory and/or policy challenges to approval

    N/A.

  • Commercial feasibility (e.g manufacturing)

    N/A.

  • Opportunities for new developments

    A cost effective efficacious one-shot drug to eliminate SRLV infection or prevent it causing clinical problems is an opportunity. However, the market and sheep/goat economics do not favour development of species-specific drugs.

  • New developments for diagnostic tests

  • Requirements for diagnostics development

    More sensitive and specific serological tests. Further work on studies of serology, our recent work has shown considerable differences in sensitivity between commercial ELISA kits.

    Strain specific diagnostic tests in the final phase of an eradication program would be useful and tests adjustable to locally circulating strains.

    More sensitive PCR able to cope with variations between SRLV.

    Test for likely disease progression to enable ‘risk based’ culling as part of management.

    Test to differentiate A, B, C, D and E genotypes.

    GAPS :

    Better knowledge of antigenicity / cross reactivity of viral proteins between different genotypes.Multiplex serology tests.Multiplex PCR, or other types of molecular tests.

    More scientific knowledge of antibodies against different viral proteins, and potential differences depending on homologous (genotype A in sheep and genotype B in goats) and heterologous infections (genotype A in goats and genotype B in sheep).

  • Time to develop new or improved diagnostics

    First there would need to be a commercial imperative. If there was a viable market, then development could take 1-2 years.

  • Cost of developing new or improved diagnostics and their validation

    Starting from scratch will be expensive but companies that already have diagnostics could modify their antigens and their presentation to better detect early infection and to differentiate between biotypes. However, whether it is necessary to differentiate biotypes in eradication programmes is not clear, it may be that the same control techniques will be equally effective with all biotypes.

    GAP :

    It is extremely important to increase the test sensitivity and improve detectability of an immune response induced by several circulating genotypes.

  • Research requirements for new or improved diagnostics

    A-E genotype-specific epitopes and RNA sequences.

    GAPS :

    Multiplex serology could be developed further. Recent work with a multiplex ELISA (in Norway and Netherlands shows improved sensitivity.

    Characterization of immune responses after cross species transmission could be important to determine any differences which may be relevant to the choice of diagnostics.

  • Technology to determine virus freedom in animals

    Combination of ELISA, multiplex ELISA and PCR diagnostics.

    GAP :

    Immunoblotting could play a role as confirmatory test to declare the herd free of infection. Immunoblotting should also be implemented with different strains.

  • New developments for vaccines

  • Requirements for vaccines development / main characteristics for improved vaccines

    See previous comments, none anticipated at present. Need to overcome antigenic variation in target antigens and ideally determine the mechanism of immunity.

    Most vaccine approaches have been tried: inactivated virus; attenuated virus; recombinant viral protein subunits; viral vectors (Vaccinia); plasmid DNA with and without boosts. Several studies have shown partial protection with respect to virus load and lesions against homologous challenge and some against heterologous challenge. A promising approach is mucosal vaccination with plasmid DNA vectors.

    GAPS :

    There is a need to establish a reliable method of vaccination (type, route, dose, boost, immunomodulators, etc) to show high levels of protection against homologous challenge in the first instance and heterologous challenge ultimately.

    There will be a need to overcome antigenic variation in target antigens and ideally determine the mechanism of immunity.

  • Time to develop new or improved vaccines

    Since SRLV are slow viruses, vaccine studies need to be extended to determine long term efficacy. Timescales of up to 4 years have been used in previous studies for example.

  • Cost of developing new or improved vaccines and their validation

    It is difficult to estimate these costs. The lab costs for a typical 3 year project would be € 0.5 M? The experimental animal costs over a 2-4 year vaccine trial would be € 0.5 M? Field trials over a 2-4 year period would be € 1 M? Actual costs could be well in excess of this if problems are encountered.

  • New developments for pharmaceuticals

  • Requirements for pharmaceuticals development

    See previous comments, none anticipated at present.

    GAP :

    Not much is known about the role of the innate response in preventing infection. In flocks we have studied about 5-10% animals remain persistently seronegative despite presumed exposure to circulating virus. It would be useful to know whether these animals are genuinely resistant and, if so, it’s mechanism eg IFN, tetherin, which could lead to potential preventative therapeutics.

  • Time to develop new or improved pharmaceuticals

    N/A.

  • Cost of developing new or improved pharmaceuticals and their validation

    N/A.

  • Research requirements for new or improved pharmaceuticals

    Plasmid DNA vaccination efficiency can be significantly increased using electroporation for example.

    An mRNA vaccine approach may provide an increase in the efficiency of vaccination over what has been achieved with plasmid DNA vaccines so far for SRLV.

    Given the efficacy achieved with mRNA COVID 19 vaccines, a similar approach to vaccinating against SRLV may be worth pursuing. The COVID vaccines are administered into muscle tissue but provide protection against SARS CoV 2 which is a mucosal pathogen just like SRLV.

    GAP :

    It’s not clear whether there are companies interested in developing the mRNA technology used for COVID, even for SRLV, especially knowing that the economic return is uncertain.

Disease details

  • Description and characteristics

  • Pathogen

    Lentivirus in the family Retroviridae, subfamily Orthoretrovirinae, genus Lentivirus, species Visna-maedi virus (sheep) and Caprine Arthritis Encephalitis Virus (goats), collectively known as Small Ruminant Lenti Viruses (SRLV).

    The SRLV virus particle is approximately 90-120 nm in diameter, is enveloped (formed from a membrane bilayer of host cell-derived phospholipids in which viral-encoded glycoproteins (gp46 and gp135) are embedded. The core is a protein case composed of p25 (capsid), p17 (matrix) and p14 (nucleocapsid) proteins. The core contains the viral RNA and enzymes necessary for viral replication. The viral genome comprises two linear molecules of single-stranded RNA from which double stranded DNA is formed by the viral reverse transcriptase (RT). This forms a pro-virus which is then integrated into the host cell DNA. The genome contains genes coding for structural proteins/glycoproteins. The gag gene codes for p25CA (capsid), p17MA (matrix), p14NC (nucleocapsid). The env gene codes for gp135SU (surface unit) which recognises the mannose as a putative receptor, or one of them and gp46TM (transmembrane) which mediates fusion with the cell membrane to insert viral RNA into the cytoplasm.

    The pol gene codes for regulatory proteins and those involved in viral replication and integration – p10PR (protease), p68RT (reverse transcriptase), p14DU (dUTPase) and p35IN (integrase). Accessory regulatory genes are located within pol and env and code for vif (virion infectivity factor), rev (regulator of viral expression) and vpr-like (similar to vpr in other lentiviruses) proteins which may, by analogy with vpr, be involved in controlling the efficiency of replication in macrophage target cells.

    Most diagnostic serology using synthetic antigens use the envelope (gp135SU and/or gp46TM antigens or peptides derived from them, or p25CA. gp46TM is less variable than gp135SU and contains a peptide which is highly conserved across all SRLV strains.

    GAPS :

    Identify and understand the mechanisms involved in cell binding, entry and initiation of infection, genome replication, assembly and packaging, control of differential protein expression levels in target cells/organs, release and transmission of SRLV at the molecular, cellular and whole organism level.

    Genetic heterogeneity amongst field strains of SRLV remains to be fully characterized, which is important as this genetic variation in turn translates into virus strains and genetic sequences with different biological properties such as virulence.

    Identification of the receptor(s)/co-receptor(s) for SRLV, these have not yet been identified definitively.

  • Variability of the disease

    SRLV have a wide pathogenic variability, which is partially virus strain dependent and partially host dependent. The antibody response generated during infection is not protective.

    A, B, C, D and E genotypes – geographical? Associated with variations in pathogenicity? Highly mutable gp135 envelope gene and limited to infrequent variation elsewhere in the genome.

    Host range includes sheep, goats, mouflon and some cervids. Fallow deer and Red deer may control virus infection event by means of innate responses.

    Vaccination with AlOH-based vaccines may amplify viral infection since SRLV are highly replicative in post-vaccine granulomas.

    GAPS :

    We cannot exclude the presence of other genotypes. The geographical distribution of different genotypes is reported in the Review: Small Ruminant Lentiviruses: Genetic Variability, Tropism and Diagnosis. Hugo Ramírez et al. (Table 1) and in the OIE 2009 v.1.4.

    The genotype E has been characterized in Italy as a low pathogenic caprine lentivirus.

    Which factors are responsible for a difference in disease outcome upon infection of sheep and goats with a specific strain?

    Colitti et al 2019 Plos One have explored an alternative strategy to isolate and characterize genetic sequences from SRLV infected animals. By means of splenic biopsies and NGS a wider genotype distribution within animals was detected and correspondence to classical techniques is low. No new genotypes have been described but new subgroups (B3-B5 and some A22-25).

    Genotypes A and B are worldwide distributed whereas genotypes C and E seem to be restricted to Norway and Italy, respectively.

    Genotype D seems to be a genotype A with a divergent pol gene.

    Phylogeny is based on gag and pol (not env) and variability is patent.

  • Stability of the agent/pathogen in the environment

    Low stability, susceptible to low pH, most detergents and desiccation. Survival times in the environment are short and not significant in transmission.

  • Species involved

  • Animal infected/carrier/disease

    Sheep, goat (domestic and wild species).

    GAPS :

    Wild ungulates were proved to be susceptible to SRLVs in many regions and various diseases affecting new hosts have already been identified in wildlife.(Fatal Caprine arthritis encephalitis virus-like infection in 4 Rocky Mountain goats (Oreamnos americanus).Patton KM, Bildfell RJ, Anderson ML, Cebra CK, Valentine BA. J Vet Diagn Invest. 2012 Mar; 24(2):392-6.) / Seroprevalence, clinical incidence, and molecular and epidemiological characterisation of small ruminant lentivirus in the indigenous Passirian goat in northern Italy. Gufler H, Moroni P, Casu S, Pisoni G. Arch Virol. 2008; 153(8):1581-5.

    The successful experimental and natural infections of wild small ruminants, such as ibex (Capra ibex) and mouflon (Ovis gmelinii) with SRLVs provide proof that these wild ruminants are susceptible to CAEV infection.

  • Human infected/disease

    None proven.

  • Vector cyclical/non-cyclical

    Iatrogenic via needles and equipment not proven, no known insect vectors.

  • Reservoir (animal, environment)

    SRLV cause latent infections, so infected animals remain lifelong carriers. Asymptomatic infected individuals.No proven environmental reservoir.

    GAP :

    Wildlife and livestock may represent major reservoirs of SRLVs from which cross-species infection may occur.

  • Description of infection & disease in natural hosts

  • Transmissibility

    Close prolonged contact with transfer of free virus/cells via respiratory and oral (milk, colostrum) routes. Horizontal transmission from animal to animal is more important than vertical transmission via germplasm or in utero.

  • Pathogenic life cycle stages

    Initial infection leads to local viral replication in respiratory tract, followed by infection of monocytes and stem cells in bone marrow leading to lifelong infection. Infection leads to antibody production, then follows a variable period of latency/dormancy which may last months to several years. In some animals clinical disease ensues which is progressive due to repeated cycles of latency and reaction and the associated immune responses lead to pathological lesions. Infection can lead to death or culling.

    GAP :

    Information on what controls the rate of progression. For example, host and viral factors, triggers such as intercurrent disease.

  • Signs/Morbidity

    Pneumonia – common in sheep, adults >2 years old, shortness of breath, dyspnoea at rest, abdominal breathing, neck extension, flared nostrils and mouth breathing, increased respiratory rate, exercise intolerance, anorexia, loss of condition, cachexia. Secondary bacterial infections may occur.Mastitis – usually subclinical but becomes clinical, chronic, diffuse, bilateral, non-painful, enlarged mammary lymph nodes. Leads eventually to decreased milk production, difficulty raising lambs/kids.Encephalomyelitis – rare in sheep, more common in goats especially the young. Animals usually over 2 years but can be earlier in goats and some breeds of sheep (eg Assaf). Loss of condition, demyelination, ataxia, hypermetria, recumbent but alert. Limb paresis and paralysis, often the hind limbs and initially more prominent on one side, lack of proprioception leading to standing on dorsal aspect of foot, foot dragging and scuffing of toes.Arthritis – frequent in goats but also occurs in sheep. Affects animals from 2-3 years old, swelling of joints, especially the carpo-metacarpal and tarsal with occasional involvement of atlantal bursa and nuchal ligament.

  • Incubation period

    Variable, months to years, often no clinical symptoms during a commercial or ordinary lifespan.

  • Mortality

    Variable, increases as disease progresses at flock/herd level but may take several years before economically important. Can be high in intensive, housed management systems, much lower or negligible in extensively managed systems.

  • Shedding kinetic patterns

    Research needed.

    GAP :

    Results could be used to identify periods or factors which increase or decrease shedding to help management of infection.

  • Mechanism of pathogenicity

    Dysregulation of immune and inflammatory responses leading to lymphoid accumulation in key target organs, and organ-specific lesions such as smooth muscle hyperplasia and fibrosis in lung, glandular ablation and fibrosis in mammary gland, proliferation of synovial membrane tissues in joints, demyelination in CNS.

    GAPS :

    Knowledge on which mechanisms are responsible for differences in virulence and pathogenesis between strains? Which mechanisms are responsible for the different disease outcome after infection of sheep and goat with the same strain.

    Relationship with other concomitant pathogens. Some research has been done regarding Brucella ovis and Ovine Pulmonary Adenocarcinoma.

  • Zoonotic potential

  • Reported incidence in humans

    No proven infection of humans. Has been associated with arthritis in humans in Mexico but not proven.

    GAP :

    This subject may be worth looking at again when new diagnostic tests including all genotypes will be available, especially in similar pathologies eg rheumatoid, lymphocytic interstitial pneumonia.

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

    N/A.

  • Symptoms described in humans

    N/A.

  • Estimated level of under-reporting in humans

    N/A.

  • Likelihood of spread in humans

    N/A.

  • Impact on animal welfare and biodiversity

  • Both disease and prevention/control measures related

    High impact disease in heavily infected flocks, low impact in extensive situations.

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

    Not known.

    GAP :

    A possible gap to study. What is the situation in wild ruminants across Europe? Mouflons? Wild goats?There are few publications. But if we accept that wild animals can be a reservoir for the “virus”, in some regions/areas, it can be dangerous.

  • Slaughter necessity according to EU rules or other regions

    Group B disease, slaughter required by national authorities in country-specific eradication campaigns.

  • Geographical distribution and spread

  • Current occurence/distribution

    De Miguel et al., (2021) performed a worldwide review of the prevalence of SRLV and concluded that Europe is the continent with the most information on the prevalence of the infection as well as with the highest SRLV prevalence at the individual level. Flock prevalence depends directly on the individual prevalence.

  • Epizootic/endemic- if epidemic frequency of outbreaks

    Not epizootic.

  • Seasonality

    No seasonal cycle. Highest transmission during lambing period (vertical transmission) and moments when animals are in close contact, whenever this may be during the year e.g. winter/lambing housing, overnight housing in hot countries with shepherded management during day, natural association of some breeds.

  • Speed of spatial spread during an outbreak

    Variable, may be dependent on other intercurrent diseases e.g. Ovine Pulmonary Adenocarcinoma (OPA).

    GAP :

    Only limited data available on spread within flocks, and on the efficiency of horizontal transmission.

  • Transboundary potential of the disease

    High as routine tests used have sub-optimal sensitivity (AGID, ELISA) and irregularly appliedHigh, in case of uncontrolled export. Control programmes necessary to certify SRLV negative flocks.

    GAP :

    Lack of guidelines for biosecurity and farm management, control plans, effective diagnostic approaches.

  • Route of Transmission

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

    Horizontal transmission via respiratory route when animals are in close contact, vertical transmission via milk/colostrum, iatrogenic.

    GAP :

    Role of semen in transmission has not been fully studied.

  • Occasional mode of transmission

    N.A.

  • Conditions that favour spread

    Close contact, (apparently) not using individual needles for routine procedures like vaccination.

    GAP :

    Difficult to give a scientific explanation, this is an area for further study.

  • Detection and Immune response to infection

  • Mechanism of host response

    Humoral immune response: Antibodies. Cell mediated immune response, incompletely understood.

    GAP :

    Incomplete knowledge of humoral and cell mediated immune responses upon SRLV infection in sheep and goats.

  • Immunological basis of diagnosis

    Antibodies detected by AGID and ELISA tests. No tests for cell mediated immunity.

    GAP :

    Serological tests with improved sensitivity are needed.

  • Main means of prevention, detection and control

  • Sanitary measures

    Limited spread by mechanisms where sanitary measures would be effective.

  • Mechanical and biological control

    N/A.

  • Diagnostic tools

    AGID, ELISA, Multiplex ELISA, PCR, histopathology.

    GAP :

    Immunoblotting for antibody could be explored as an additional technique.

  • Vaccines

    N/A. Not likely to be produced.

  • Therapeutics

    N/A. Not effective or cost effective.

  • Biosecurity measures effective as a preventive measure

    Main means of control, prevent infection getting into flock by accreditation schemes to identify low risk flocks and per- post-movement testing.Remove newborn from dam before colostrum intake.

  • Border/trade/movement control sufficient for control

    Limited checks in some countries, often at level of individual animal rather than flock of origin, low sensitivity tests used.There are several local and national control programs leading to certified SRLV free herds.

  • Prevention tools

    Management, diagnostics.

    GAP :

    Knowledge needed on biosecurity measures, Control programmes, low cost effective management interventions.

  • Surveillance

    Limited.

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

    1. Norway – eradication programme for CAEV, CLA and Paratuberculosis in Norwegian dairy goat herds. Serological and milk testing allied with snatching kids prior to suckling colostrum and rearing separately. Program started in 2010 and completed in 2018 with monitoring of bulk milk samples to monitor for infection since then. Has led to a 40% increase in milk production from some previously heavily infected herds.

    2. Minnesota Ovine Progressive Pneumonia (OPP) Eradication Program – eradication program for OPP in flocks in mid-west and other parts of USA. Targeted testing of young and replacement animals. A number of flocks have gone OPP free.

    3. Eradication program in Italy (Tyrol) (Nardelli et al, 2020) and Switzerland.

  • Disease information from the WOAH

  • Disease notifiable to the WOAH

    MVV/CAEV used to be a List B disease.

    Currently, regarding importation of and goats for breeding, OIE recommend that:

    Veterinary Authorities of importing countries should require the presentation of an international veterinary certificate attesting that:

    1. the animals showed no clinical sign of maedi-visna on the day of shipment;
    2. animals over one year of age were subjected to a diagnostic test for maedi-visna with negative results during the 30 days prior to shipment;
    3. maedi-visna was neither clinically nor serologically diagnosed in the sheep and goats present in the flocks of origin during the past three years, and also that no sheep or goat from a flock of inferior health status was introduced into these flocks during that period.

    GAPS :

    Regarding 1-3

    1. Clinical signs are an insensitive indicator of infection
    2. The diagnostic test isn’t specified, as sensitivity of tests vary this means that insensitive tests eg AGID, could be used.
    3. This would encourage authorities not to look for SRLV and the part on flocks or origin and inferior health status would be very difficult to define and police.

    Taken together these represent gaps in the ability to prevent SRLV moving between countries.

  • WOAH disease card available

    No.

  • Socio-economic impact

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

    N/A.

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

    N/A.

  • Direct impact (a) on production

    Lower milk production, lower reproduction rate, decreased birth weight, decreased growth, increased mortality.

    GAP :

    Variable, limited data available, constrained by tests used. A significant gap as lack of this knowledge makes it difficult to persuade farmers to take control actions.

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

    Diagnostics for individual flocks.Accreditation schemes.Impact on animal welfare and need for veterinary intervention.

  • Indirect impact

    N/A.

  • Trade implications

  • Impact on international trade/exports from the EU

    Currently variable rules on trade within and between countries. It would make sense to only trade of animals from certified negative flocks.

    GAP :

    This is a significant gap as infection can easily be transmitted within and between countries.

  • Impact on EU intra-community trade

    Currently variable rules on trade within and between countries. It would make sense to only import/export of certified negative animals.

    GAP :

    This is a significant gap as infection can easily be transmitted within and between countries.

  • Impact on national trade

    In Belgium, owners of certified negative flocks can only introduce new animals from other certified negative flocks. Few limitations in other countries, or tests used don’t have the sensitivity to prevent spread of infection.

    GAP :

    This is a significant gap as infection can easily be transmitted within and between countries.

  • Links to climate

  • Seasonal cycle linked to climate

    Not to climate per se but to management as it is affected by climate eg winter housing.

  • Distribution of disease or vector linked to climate

    No evidence for this.

    GAP :

    This is a gap area which should be looked at given the importance of climate change.

  • Outbreaks linked to extreme weather

    No evidence. If it were to occur there’s likely to be a significant lag phase due to the slow nature of the development of pathology, unless secondary bacterial infection intervenes.

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

    No insect vectors known.

    GAP :

    The potential importance of biting flies should be looked at using molecular techniques.

  • Main perceived obstacles for effective prevention and control

    Current tests have suboptimal sensitivity, problems with suboptimal specificity of diagnostic tests, leading to false positive and false negative results and participants dropping out of control programs, no therapeutics or vaccines.

    Lack or pressure from farmers who do not believe the infection causes significant production problems due to long incubation period and considerable amount of animals that remain asymptomatic.

    Not zoonotic so receiving low attention from governmental control programmes.

    GAP :

    Increased knowledge needed on evaluation of production and economic losses in different production systems, breeds and geographical areas.

  • Main perceived facilitators for effective prevention and control

    Better diagnostic tests more widely used. Effective therapeutics and vaccines would be useful but are unlikely to be developed, or even achievable.

Risk

  • Impact on production economics and animal welfareThreat for rare breeds.

Main critical gaps

  • SRLV importance - In most countries there is no particular attention to SRLV infections. Up to now, there have been sporadic control plans mostly limited to goats and the B genotype circulation in areas characterized by particular food productions. There is variable, limited data available on the effect on production and this is constrained by the sensitivity of the tests used. This is a significant gap as lack of this knowledge makes it difficult to persuade farmers to take control actions when the disease has a long incubation period and a considerable proportion of infected animals that remain asymptomatic. Increased knowledge needed on evaluation of production and economic losses in different production systems, breeds and geography

    Diagnostic serology - The mainstay of SRLV control is the use of serological diagnostic techniques. Most serology tests have been validated against a consensus serological quasi-gold standard therefore only relative diagnostic sensitivity and specificity are reported, not true/absolute diagnostic Se/Sp. Large variation between reported Se/Sp of the available kits. This difference could suggest that updating serological tests by including antigen mixes is highly needed. Different commercial ELISAs lead in some cases to contradictory results, based on the context in which they were used and on the circulating genotypes, and some ELISA tests fail to detect animals with low antibody titres. Multiplex serology tests are now available commercially . Further work is needed to establish its sensitivity and specificity especially in relation to currently available tests. Recent work with a multiplex ELISA improved sensitivity. Better knowledge of antigenicity / cross reactivity of viral proteins between different genotypes is needed. More scientific knowledge of antibodies against different viral proteins, and potential differences depending on homologous (genotype A in sheep and genotype B in goats) and heterologous infections (genotype A in goats and genotype B in sheep). Characterization of immune responses after cross species transmission could be important to determine any differences which may be relevant to the choice of diagnostics. Immunoblotting could play a role as confirmatory test to declare the herd free of infection.

    Diagnostic PCR - Are the commercially available molecular kits sensitive enough and capable of identifying most of the circulating genotypes? Are there suitable for a correct diagnosis given the low amounts of viral DNA/RNA present in target tissues? Do they differentiate between biotypes? PCR will be useful in analysing animals which remain negative in serology to determine their true infection status. Some animals have delayed seroconversion so PCR tests could be considered in control schemes and for lambs less than 1 year old.

    Innate immune response - Not much is known about the role of the innate response in preventing infection. In flocks we have studied about 5-10% animals remain persistently seronegative despite presumed exposure to circulating virus. It would be useful to know whether these animals are genuinely resistant and, if so, it’s mechanism e.g. IFN, tetherin, which could lead to potential preventative therapeutics.

    Cell biology - We need to identify and understand the mechanisms involved in cell binding, entry and initiation of infection, genome replication, assembly and packaging, control of ifferential protein expression levels in target cells/organs, release and transmission of SRLV at the molecular, cellular and whole organism level. Identification of the receptor(s)/co-receptor(s) for SRLV, these have not yet been identified definitively.

    Pathogenesis - Information is needed on what controls the rate of disease progression. For example, host and viral factors, triggers such as intercurrent disease. Research is needed on shedding kinetics. Results could be used to identify periods or factors which increase or decrease shedding to help management of infection. Knowledge needed on which mechanisms are responsible for differences in virulence and pathogenesis between strains. Which mechanisms are responsible for the different disease outcome after infection of sheep and goat with the same strain?

    Interactions with other pathogens - Relationship with other concomitant pathogens has not been fully studied. Some research has been done regarding Brucella ovis and Ovine Pulmonary Adenocarcinoma.

    Human infection - Zoonotic infection has not been reported and for this reason some governments are not interested in SRLV. This subject may be worth looking at again as new diagnostic tests, including all genotypes, will be available. We need especially to study human diseases with similar pathologies eg rheumatoid, lymphocytic interstitial pneumonia.

    Genetic heterogeneity amongst field strains of SRLV - This remains to be fully characterized, which is important as this genetic variation in turn translates into virus strains and genetic sequences with different biological properties such as virulence. There may well be more genotypes yet to be discovered. The geographical distribution of different genotypes is reported in the literature. Which factors are responsible for a difference in disease outcome upon infection of sheep and goats with a specific strain?

    Transmission - The role of semen in transmission has not been fully studied, nor has the potential importance of biting flies. The former is important regarding advanced breeding technologies and the latter in relation to climate change and distributions of potential vectors. These should be looked at using molecular techniques. The conditions that favour spread have not been fully studied yet knowledge in this area would inform biosecurity measures, control programmes and the management techniques to reduce spread and impact in a cost effective way.

    Vaccines - There is a need to establish a reliable method of vaccination (type, route, dose, boost, immunomodulators, etc) to show high levels of protection against homologous challenge in the first instance and heterologous challenge ultimately. There will be a need to overcome antigenic variation in target antigens and ideally determine the mechanism of immunity. However, we do not believe there is a great interest in the use of a vaccine, even if inexpensive, at present.

    Wild ungulates - Wild ungulates are susceptible to SRLVs in many regions and various diseases affecting new hosts have already been identified in wildlife. Wildlife and livestock may represent major reservoirs of SRLVs from which cross-species infection may occur. Further studies are needed to determine the epidemiological risk of infection from and of wildlife. Implication for endangered species may also require more attention.

    Climate change - This is a gap area which should be looked at given the importance of climate change.

Conclusion

  • Significant gaps still exist in our knowledge of the biology, immunology and epidemiology of SRLV, and, crucially, their effects on livestock production and welfare. These are inhibiting action being taken to effectively control the diseases they cause.

    Serological diagnosis is the best choice for SRLV detection in livestock. It has been widely applied in control programmes. However, serological methods may fail at detecting the whole infected population due to virus antigenic diversity or to delayed seroconversion. It is necessary performed an update of existing serological methods to new variants and challenging the development and evaluation of new molecular methods.

    A combination of serological and molecular tests could be applied, but despite this at present we still do not have good performance of either serology or PCR techniques. There is some promise from new multiplex serological techniques to improve sensitivity.

    It is unlikely that there will be significant progress on vaccines and therapeutics given the scientific challenges faced and the economics of the marketplace. However, developments in these areas should be monitored for potential application to SRLV.

Sources of information

  • Expert group composition

    Neil J. Watt, MV Diagnostics Ltd, United Kingdom – [Leader]

    Gordon D. Harkiss, University of Edinburgh and MV Diagnostics Ltd, United Kingdom

    Lluis Lujan, University of Zaragoza, Spain

    Ramses Reina, University of Navarra, Spain

    Jaroslaw Kaba, University of Warsaw, Poland

    Nick de Regge, Sciensano, Belgium

    Monica Giammarioli – IZS Umbria e Marche “Togo Rosati”, Italy

    William Heuston, University of Minnesota, USA

  • Date of submission by expert group

    8 December 2021