Diseases

Orthopox

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  • Diagnostics availability

  • Commercial diagnostic kits available worldwide

    No universal diagnostic test in use. When available, diagnosis is mainly performed at academic institutions or in public health reference laboratories.

    GAP: Rapid (validated), point-of-care tests are not available.

  • Commercial diagnostic kits available in Europe

    No universal diagnostic test in use. When available, diagnosis is mainly performed at academic institutions or in public health reference laboratories.

    GAP: Rapid (validated), point-of-care tests are not available.

  • Diagnostic kits validated by International, European or National Standards

    None.

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

    None.

  • Commercial potential for diagnostic kits in Europe

    Recently, possibly due to the increase in severe outbreaks of disease, labs across Europe, the US, Japan, India and South Africa have shown an interest in the parapox-viruses. In most instances this has been to confirm diagnosis of disease outbreaks, thereby reducing the incidence of misdiagnosis. At present there are no routine diagnostic tests in use for poxviruses and this can lead to misdiagnosis with other pathogens causing vesicular disease in ruminants. Practical problems emerged during the 2001 pan-asiatic type O FMD outbreak in the UK because of the difficulty of diagnosing FMD in sheep and cattle. Nowadays this can be again a cause of concern due to the recent spread of Bluetongue virus in Northern Europe and vaccinia-like outbreaks in cattle in several countries.

    GAP: These zoonotic infections share clinical manifestations and exposure risks with other, potentially life-threatening zoonoses (e.g., cutaneous anthrax) and are likely under-recognized because of a lack of clinical suspicion and widely available diagnostics.

  • DIVA tests required and/or available

    None available / Low requirement.

  • Opportunities for new developments

    As with parapox-viruses, point-of-care diagnostic assays would be of considerable value for routine screening of animals (and people) having vesicular-pustular lesions. This would enable to quickly determine an appropriate level of suspicion for orthopox-virus infection. It would encourage rapid implementation of sanitary measures to prevent ongoing transmission of virus. This type of intervention is particularly important because vaccines and therapies are not readily available. Rule-out of other lesion causing agents (anthrax, foot-and-mouth disease) is also of great importance.

    GAPS:

    Specificity and sensitivity needs to be maximised against the library of virus strains from across Europe

    Differential diagnosis will also require an understanding of variation present among other agents causing vesicular disease and how they differ genetically and biologically.

  • Vaccines availability

  • Commercial vaccines availability (globally)

    Live fully virulent virus applied by scarification of the axilla. Currently, several orf vaccines are licensed:  Scabivax (Schering-Plough), Vaxall Orf Vaccine (Fort Dodge) and ECTIVAC, prepared by “Pasteur”-Bucharest. Tissue culture licenced in a minority of countries.

    ACAM2000 (Acambis, USA) and MVA are vaccines licensed in the US for prevention of smallpox in immune-competent and immune-compromised persons, respectively.

    During the smallpox era, lack of adherence to appropriate hygienic measures among recent vaccines led to instances of anthropozoonotic transmission of VV from dairy workers to cattle (and back) causing focal outbreaks of disease.  These outbreaks were documented in Europe, Asia, North Africa and North and South America.

    GAPS:

    Vaccines for prevention of Orthopox-virus infection in animals are currently unavailable and none are under development (that we know of).

  • Commercial vaccines authorised in Europe

    Vaccinia virus Lister was approved by the World Health Organization for use in smallpox eradication and is currently licensed in the UK (Lister Elstree, Bavarian Nordic).

    GAP: Vaccines for prevention of Orthodox-virus infection in animals are currently unavailable and none are under development.

  • Marker vaccines available worldwide

    None.

  • Marker vaccines authorised in Europe

    None.

  • Effectiveness of vaccines / Main shortcomings of current vaccines

    In humans, vaccination against smallpox is considered to provide not sterilizing, immunity against infection with VV/BPXV and MPXV.

    GAPS:

    It is undetermined if vaccination against smallpox extends protection from infection with CPXV

    The duration of immunity conferred by smallpox vaccination is unknown and highly debated.

  • Commercial potential for vaccines in Europe

    Vaccines would be of greatest value in the event of an outbreak and or following an introduction event of OPXV.

  • Regulatory and/or policy challenges to approval

    Second and third generation vaccines currently licensed or in clinical trial have improved safety profiles and are likely to be of greater acceptability than vaccines used during smallpox eradication.

  • Commercial feasibility (e.g manufacturing)

    National/Federal support underpins vaccine procurement and stockpiling in the United States.

  • Opportunity for barrier protection

    Barrier protection would be advocated.

  • Opportunity for new developments

    The lack of commercially available products for prevention and control of Orthopox-virus infections suggests that highly-targeted opportunities exist in this arena, particular for overseas markets in highly affected regions.

    Vaccines against orthopox-virus-associated zoonoses should provide durable cross-protection against infection with multiple species of orthopoxvirus and should pose little to no risk of transmission between humans (giving special consideration to persons with immune-compromising conditions).

    GAPS:

    ·         Determine how the virus avoids the immune response

    ·         Determine how an effective vaccine can be achieved:

    o    Identification of virulence genes to facilitate the selection of virus components that are capable of inducing immune reactions without being blocked by counteracting viral proteins

    o    Determine which genes encode produce protective antigens able to stimulate protective immune responses. best at stimulating immune activities

    ·       Continued studies on the use of poxviruses as expression vectors to improve vaccine development and possibly gene therapy by exploiting their potential as immunomodulators.

  • Pharmaceutical availability

  • Current therapy (curative and preventive)

    There are no approved veterinary treatments for poxvirus-related infections.

    In the United States, people experiencing severe adverse effects of VV infection following smallpox vaccination, can be treated intravenously with vaccinia hyper-immuneglobulin (IV-VIG) available from the US Centers for Disease Control and Prevention.  IV-VIG is licensed for the treatment of eczema vaccinatum, generalized vaccinia, pregressive vaccinia and other serious abberant infections (excluding keratitis and encephalitis).  Cidofovir (VISTIDE®) has shown a significant level of anti-orthopoxvirus activity in cell-based in vitro and animal model studies and may be used— along with Probenecid— in ‘off-label’ treatment of humans orthopoxvirus infections or, where possible, as an investigational therapy. VISTIDE® has been licensed for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS and may be available in hospital pharmacies, however, due to significant toxicity, this drug must be administered along with Probenecid to protect against renal damage.
  • Future therapy

    Several promising compounds, developed under the auspices of bioterrorism preparedness, are currently under. investigation. There has been little consideration thus far of their potential application to the prevention and treatment of neglected poxvirus-associated zoonoses.

  • Commercial potential for pharmaceuticals in Europe

    Pharmaceuticals would be of greatest value in the event of an outbreak and or following an introduction event.

  • Regulatory and/or policy challenges to approval

    The acceptability of using antivirals in food animals is unknown, but use of these compounds for humans, companion and other high value animals (zoo animals) could be explored.

  • Commercial feasibility (e.g manufacturing)

  • Opportunities for new developments

  • New developments for diagnostic tests

  • Requirements for diagnostics development

    Diagnostic tests for poxvirus-associated zoonoses should be developed such that rapid screening can be performed in the field by clinicians (veterinarians and physicians) to readily distinguish poxvirus-associated illnesses from other sources of infection.

    GAPS:

    Antigen or nucleic acid-based rapid detection assays would likely be preferable and of greater utility than screening tests designed to detect orthopoxvirus antibodies in serum.  The former could be run using lesion material as clinical diagnostic specimens.  Confirmatory testing could be performed at designated reference facilities having appropriate bio-containment capacity. Ideally, reference laboratories would include facilities specializing in human and in veterinary medical diagnosis.  Confirmatory testing should encompass identification of the viral agent to species level (e.g. vaccinia virus vs. monkeypox virus) which is typically accomplished through nucleic acid-based analysis (i.e., PCR, DNA sequencing).

  • Time to develop new or improved diagnostics

    Short term. Assay validation will likely require collaboration with reference facilities.
  • Cost of developing new or improved diagnostics and their validation

    Limited.

  • Research requirements for new or improved diagnostics

    Limited.

    GAPS:

    • A better understanding should be obtained with respect to the identity and distribution of zoonotic reservoirs for OPX-associated zoonotic agents; this will enhance understanding of the genetic variability of species of concern;
    • In keeping with point 2 above, a better understanding of protein and nucleic acid level differences between OPX viruses and within OPX species will allow for the development of rapid diagnostic tests that can distinguish between agents and identify viruses to strain type; understanding the precise clinical profiles of the different infections along with risk factors for human and animal infection would support development of clinical algorithms to identify suspected cases and to guide appropriate application of any diagnostic testing.
  • Technology to determine virus freedom in animals

    This technology does not exist and would be difficult to develop (CDC).

  • New developments for vaccines

  • Requirements for vaccines development / main characteristics for improved vaccines

    Vaccines should provide durable cross-protection against infection with multiple species of orthopoxvirus and should pose little to no risk of transmission between humans (giving special consideration to persons with immune-compromising conditions).

  • Time to develop new or improved vaccines

    Long term (5 years with full market authorization).

  • Cost of developing new or improved vaccines and their validation

    Unknown/ variable.  Will depend on the approach selected.

  • Research requirements for new or improved vaccines

    See Section “Vaccines availability – Opportunities for new developments”.

  • New developments for pharmaceuticals

  • Requirements for pharmaceuticals development

    Testing of anti-virals / excipients / delivery mechanisms.

    GAP:

    • efficacy after development of symptoms,  
    • low toxicity, 
    • low potential for development of resistance.
  • Time to develop new or improved pharmaceuticals

    2-3 years.

  • Cost of developing new or improved pharmaceuticals and their validation

    Unknown.

  • Research requirements for new or improved pharmaceuticals

    Robust animal infection model.

Disease details

  • Description and characteristics

  • Pathogen

    Family Poxviridae, subfamily Chordopoxvirinae.

    The genus Parapoxvirus (PPV) includes three members, bovine papular stomatitis virus (BPSV), pseudocowpox virus (PCPV) and orf virus (OV). The parapoxvirus of Red deer (PVNZ) has been recently reported outside New Zealand in Italy and Germany.

    The genus Orthopoxvirus (OPXV) includes three virus species of significant consequence to human and animal health: vaccinia virus/buffalopox virus (VV/BPXV), cowpox virus (CPXV), and monkeypox virus (MPXV).

    GAPS:

  • Little is known about prevalence
  • Inadequate disease recognition
  • Outmoded countermeasures
  • Few barriers to importation
  • Variability of the disease

    There are multiple zoonotic pathogens within the genus Orthopoxvirus.  These engender a high degree of serologic cross reactivity and may confer some degree of immunologic protection following infection. Within certain “species” , most notably cowpox, there is a significant amount of diversity which may contribute to different disease severity/disease manifestations.

    GAPS:

  • Virus reservoirs (particularly rodent)
  • Range of permissive hosts
  • Genetic variation within “species” and effect on disease presentation
  • Stability of the agent/pathogen in the environment

    Scabs contain millions of virus particles which, when they dry up and drop off the animal, will contaminate the environment for years. Very stable in dry environments.

    GAP: Stability of live virus under ambient conditions in nature is largely unknown.

  • Species involved

  • Animal infected/carrier/disease

    Zoonotic OPXV are:

    • VV/BPXVs scabby lesions and ulcers - bovids/ sylvan and peri-domestic rodents, and rodents/humans. An outbreak of VV was recently described in horses in Brazil. Cowpox (CPXV) Pustular rash and fever - historically associated with dairy cattle, but occurs naturally in sylvan rodents (voles, wood mice, gerbils) with some spill-over into in peri-domestic pests (rats). Occasionally observed in housecats, exotic felids, elephants, rhinoceros, horses and okapis. Foxes are also suspected to be susceptible. Cattle (now rare), humans, domestic felines /zoo animals/rodents.
    • Monkeypox (MPXV) - smallpox-like illness with disseminated pustular rash and fever. -primates/ rodents, squirrels and marsupials. 

    GAPS:

    • Range of permissive hosts for interspecies recombination
    • Virus reservoirs (particularly rodent)
    • Sylvatic transmission cycles and principal opportunities/risks for spill-over

  • Human infected/disease

    Yes, from benign and self-limiting to severe (hospitalisation).

    The number of reported complicated cases in immune-suppressed patients is increasing as well as cases linked to religious slaughtering and cases of human to human transmission.

    VV/BPXVs, CPXV infections can be life-threatening in people who are immune-compromised.

    A fatal case of CPXV occurred in Germany in 1990.

    MPXV infections in people result in the development of a smallpox-like illness with fever, prostration and disseminated pustular rash. Human infections with Congo Basin variants of MPXV are fatal up to 15% of the time.

    GAP:

    Nothing is known about risk factors associated with severe disease. 

    The number of reports on complicated orf virus infections, after religious slaughtering, seems to suggest that predisposing factors related to the ethnic background may contribute to the condition.

    Under-reported because it is seen as occupational hazard that normally is self-limiting

    Proportion of population at risk for sever adverse consequences from Orthopoxvirus infection, owing to immune compromise, exfoliative skin conditions, pregnancy, etc.

  • Vector cyclical/non-cyclical

    None.

  • Reservoir (animal, environment)

    VV are known to be capable of infecting several species of sylvan and peri-domestic rodents, which are thought to be important for maintaining local foci of infection. Eurasian CPXVs have historically been associated with dairy cattle, but occur naturally in sylvan rodents (voles, wood mice, gerbils) with some spill-over into in peri-domestic pests (rats). CPXV infections have occasionally also been observed in housecats, exotic felids, elephants, rhinoceros, horses and okapis. Foxes are also suspected to be susceptible. Similarly, MPXV is thought to be maintained naturally in one or more species of African rodent (possibly pouched rats or African dormice), but has the capacity to infect and cause illness in a broad range of taxa including primates, squirrels and marsupials.

    GAPS:

    • A better understanding of the identity and distribution of reservoirs for poxvirus associated zoonotic agents.
    • Sylvatic transmission cycles and principal opportunities/risks for spill-over.
    • Subclinical infections either caused by OPXV or PPVs have been recently reported in cattle, horse and red deer. Subclinically infected animals may play the role of reservoirs.
    • For OPXV: Virus reservoirs (particularly rodents) and range of permissive hosts/transmitting hosts.
  • Description of infection & disease in natural hosts

  • Transmissibility

    Highly transmissible (almost 100% morbidity on affected farms). VV/BPXV and CPXVs are transmissible by direct contact with infectious material, either cutaneous lesions or fomites contaminated with scab material or lesion exudate. The viruses establish infections in new hosts through breaks in the skin or across mucous membranes (particularly of the eye).  In certain cases, respiratory transmission is also likely.

    MPXV can be transmitted via direct physical contact (as above) but also via inhalation of infectious materials or respiratory droplets. Infectious respiratory droplets are a particular concern in that person-to-person transmission of virus can occur if hygienic measures are not enacted, especially during the first three days after symptom onset, when ill persons are febrile but lacking in evident signs of rash. Viable virus has also been recovered from the urine and faeces of animals infected with MPXV in laboratory settings.

    GAPS:

    Circumstances surrounding interspecies transmission of Orthopoxviruses remain largely unknown.

    Orthopoxviruses are not thought to be transmissible through contaminated milk products, but definitive evidence is lacking.

  • Pathogenic life cycle stages

    VV/BPXV and CPXV are epitheliotropic, infecting damaged skin and replicating in regenerating epidermal keratinocytes., Lesions are localised and progress from erythema to pustule and scab causing painful oral sores in nursing young or cutaneous infections in dairy workers (typically on the hands or arms). Lesions on individual animals can persist for several weeks; animal mortality is rare, but has been reported. In other cases, such as taterapox, no visible lesions were observed in the species attributed as the host.  Rodents and primates experimentally infected with MPXV typically demonstrate fever, weight loss, diminished activity and disseminated rash, often with signs of pneumonia, blepharoconjunctivitis, and/or anal sores. Manifestation of illness and mortality proportion are dependent on virus dose, route of infection, age and size of the animal etc. Infectious MPXV virions are shed from excretions and secretions of infected animals. 

    GAPS:

    Several aspects of virus genotype-associated pathology remain undefined and are currently understudied.

  • Signs/Morbidity

    Clinically, VV/BPXV and CPXV infections of domestic bovines manifest similarly, causing lesions and nodules on the teats of milk-producing animals which release infectious virions. Primary lesions can be severe and proliferative, but generally resolve within 6 weeks. Reinfections are less severe and resolve more rapidly than primary ones, usually within 2 weeks. Virus is shed with scab material, and there is no evidence of systemic spread. Severe outbreaks of orf can occur where lesions are extensive and proliferative and do not  spontaneously regress. 

    Clinically, VV/BPXV and CPXV infections of domestic bovines manifest similarly, causing lesions and nodules on the teats of milk-producing animals which release infectious virions that can cause painful oral sores in nursing young. Potential for misdiagnosis with other pathogens causing vesicular disease in ruminants.

    Rodents and primates experimentally infected with MPXV typically demonstrate fever, weight loss, diminished activity and disseminated rash, often with signs of pneumonia, blepharoconjunctivitis, and/or anal sores. Manifestation of illness and mortality proportion are dependent on virus dose, route of infection, age and size of the animal etc. Infectious MPXV virions are shed from excretions and secretions of infected animals.

    GAPS:

    • Prevalence not known in EU member states
    • Possibility of mis-diagnosis with other pathogens causing vesicular disease in ruminants.
  • Incubation period

    VV/CPXV: 5-8 days; 

    MPXV: 6-10 days.

    GAPS:

    • The influence of virus strain, host type and condition and mode of infection on incubation is under study for OPXV.
  • Mortality

    The mortality rate in humans for MPXV (Congo basin genetic type) can be as high as 15% and the virus is highly lethal in many animal species.

    GAPS:

    The influence of virus strain, host type and condition and mode of infection on morbidity/mortality is under study for OPXV.

  • Shedding kinetic patterns

    Virus is principally shed during the symptomatic phases of illness. All scab that is shed into the environment is loaded with fully infectious virus. Viral DNA can be recovered weeks after symptom defervescence in animals experimentally infected in the laboratory and in rare instances live virus has been recovered from animals > 1 month after initial infection.

    GAPS:

    Shedding patterns have not been defined for all of the permissive hosts for these promiscuous viruses.

    The shedding caused by subclinically infected animals acting as reservoirs need to be further investigated.

  • Mechanism of pathogenicity

    GAP: Much is inferred from studies of vaccinia virus or ectromelia, but actual studies in reservoir, transmitting or “end” hosts have been limited.

  • Zoonotic potential

  • Reported incidence in humans

    Multiple reports by CDC for OV, VACV, MPXV.  In late 2008-early 2009 an outbreak of pet-associated CPXV occurred in the EU resulting in >30 human cases in France, Germany and the Netherlands (ECDC report 11/02/2009).

    Monkeypox virus is communicable in humans.

    An increasing number of complicated cases after religious slaughtering is being reported.

    GAPS:

    Lack of epidemiological investigations.

    The incidence in humans is frequently unknown because the diseases are not notifiable.

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

    Recent human Orthopoxvirus infections in the EU have been in pet owners, zoo workers and veterinarians. Infections have either direct contact with infected rats, or contact with other animals (elephant, cat) that had presumably became infected following contact with a rat or other small rodent harbouring CPXV.

    Those currently most at risk for infection with VV/BPXVs are individuals engaged in traditional, non-mechanized, dairy production in Brazil and south Asia. Milkers contract infection from manual contact with affected animals and often play a role in transmitting the virus to other animals in the herd.

    Decreasing cross-protection achieved by VV vaccination

    GAPS:

    Currently both OPXV and PPV infections are an occupational risk of veterinarians and exotic animal handlers, but as OPXV gains further inroads into the peridomestic rat population, the range of people at risk for infection is likely to increase.

    OPXV are not thought to be transmissible through contaminated milk products, but definitive evidence is lacking.

    Many risk factors are unknown. It might be reasonable to investigate population specific contribution of the HLA haplotype leading to complications after infection with ZPs.

  • Symptoms described in humans

    These OPX viruses cause painful lesions, typically on the hands and forearms of people at occupational risk; systemic flu-like symptoms (fever, myalgia, fatigue) also occur. People with compromised immune systems or with concurrent exfoliative skin conditions such as eczema are at risk for severe complications from infection, including death. 

    A fatal human case of CPXV occurred in Germany in 1990.

    MPXV infections in people result in the development of a smallpox-like illness with fever, prostration and disseminated pustular rash. Human infections with Congo Basin variants of MPXV are fatal up to 15% of the time.

    GAPS:

    These zoonotic infections share clinical manifestations and exposure risks with other, potentially life-threatening zoonoses (e.g., tularaemia cutaneous anthrax) and are likely under-recognized because of a lack of clinical suspicion and widely available diagnostics.

    Specific treatments for individuals experiencing complications do exist, but availability of those biologicals and compounds that have been approved as therapies is limited.

  • Estimated level of under-reporting in humans

    Unknown since the diseases are not reportable.

    GAP: Diseases are not notifiable.

  • Likelihood of spread in humans

    Orthopoxviruses are potentially transmissible between persons (CDC).

    GAPS:

    Not known, few reports about man-to-man spread.

  • Impact on animal welfare and biodiversity

  • Both disease and prevention/control measures related

    Isolation and quarantine of new animals are useful prevention tactics.  

    Rodent exclusion and. Contact precautions (use of gloves, eye protection when manipulating symptomatic animals), and environmental remediation as well as vaccination may be useful for control.

    GAPS:

    Efficient and safe vaccines providing long lasting immunity are missing

    Large scale prevention and control programs in animals have not been systematically evaluated for efficacy or acceptability.

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

    OPXV infections cause a high degree of mortality and morbidity in a broad range of taxa, affecting animals as diverse as elephants, dormice and ant-eaters.  Outbreaks of MPXV and CPXV have repeatedly occurred in captive animal populations, often in such instances human illnesses occur.  The growing number of anecdotal reports of CPXV in peri-domestic rats raises concern for increased transmission to domestic species, particularly cats and cattle.

    GAPS:

    Prevalence in wildlife ruminants is unknown

    The impact of CPXV transmission to threatened or endangered native mammals has not yet been thoroughly explored. Presence of the virus in rats is of increasing concern.

  • Slaughter necessity according to EU rules or other regions

    Ewes and cows, which suffer loss of mammary function due to VV/BPXV, may have to be culled.  Cohorting, isolation and quarantine may be effective strategies.

  • Geographical distribution and spread

  • Current occurence/distribution

    VV/BPXVs are currently found in southern Brazil (Minas Gerais, Sao Paulo, Rio de janeiro, Espírito Santo States) and throughout south Asia (India, Pakistan). The range of CPXV extends throughout much of Eurasia (excluding Ireland). MPXV is naturally-occurring in heavily forested regions of West Africa and the Congo Basin.

    GAPS:

    The current prevalence of CPXV in rats in the EU is undefined.

  • Epizootic/endemic- if epidemic frequency of outbreaks

    Frequency of outbreaks is currently undefined. 

    VV/BPXV and CPXV infections rarely occur as individual sporadic cases, but rather emerge as focal outbreaks. Rarely occur as individual sporadic cases, but rather emerge as focal outbreaks.

    GAPS:

    Frequency of outbreaks /affected herds is not known in EU member states and worldwide.

    Currently undefined due to under-reporting. No information about subclinical infection. In clinically affected herds up to 80% morbidity.

  • Seasonality

    Undefined.

  • Speed of spatial spread during an outbreak

    Currently undefined, situationally dependent.

  • Transboundary potential of the disease

    Only with animal movements.

    CPXV: High, based on outbreak in the EU (2008/2009).

  • Seasonal cycle linked to climate

    Dry season - it is believed that the presence of thistles in areas where the animals are grazing favours outbreak and spread – basically things that can break the skin.

  • Distribution of disease or vector linked to climate

    No arthropod vector.

  • Outbreaks linked to extreme weather

    Virus more stable in dry conditions.

    GAP: No information from countries with extreme climate differences.

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

    No arthropod vector. Climate change may affect the distribution of disease via impact on reservoir or transmitting host habitats.

  • Route of Transmission

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

    Direct contact / infectious fomites. Always through broken skin. OPXV are not transmissible via respiratory routes. MPXV, on the other hand, can be transmitted via direct physical contact (as above) but also via inhalation of infectious materials or respiratory droplets, especially during the first three days after symptom onset, when ill persons are febrile but lacking in evident signs of rash.
  • Occasional mode of transmission

    Anthropozoonotic, from recently smallpox-vaccinated humans

  • Conditions that favour spread

    Previous outbreaks / Rough pasture / Housing / Over-crowding / intensive farming practises.

    GAPS:

    Conditions favouring virus transmission from one species to another remain poorly defined.

    Many risk factors remain unknown.

  • Detection and Immune response to infection

  • Mechanism of host response

    Animals, including humans, mount a specific cellular and humoral immune response after infection. The duration of the immunity is varied and repeated infections can occur for VV/BPXV (after an interval of years) and potentially for CPXV, but the symptoms of infection are generally mitigated with subsequent infections.

    GAP: Mechanism of protection not fully understood.

  • Immunological basis of diagnosis

    Detection of IgG response to whole virus.

    Antibody responses to old world Orthopox-viruses are broadly cross reactive. 

    GAP:

    • No robust or commercial antibody test;
    • Species specific immunological detection reagents are not available – pre-existing smallpox vaccination, for instance, can obscure diagnosis for OPXV.
  • Main means of prevention, detection and control

  • Sanitary measures

    Disinfection / steam cleaning required for food troughs, buildings etc. used with known affected animals. Appears to be effective.

    GAP:

    Obstacles for prevention and control of zoonotic poxviruses include, an absence of readily available diagnostic assays, lack of familiarity with human and animal clinical disease (among veterinarians and physicians), lack of vaccines and therapeutics to prevent virus acquisition/transmission, a current incomplete understanding of the burden and distribution of zoonotic poxviruses globally.

  • Mechanical and biological control

    Scabs contain millions of virus particles which, when they dry up and drop off the animal, will contaminate the environment. 

    Distribution of fomites contaminated with variola virus scabs (the agent of smallpox, a non-zoonotic orthopox virus) was a means of intentional and unintentional disease propagation during the smallpox era. Hygienic measures such as quarantine or isolation of symptomatic animals and use of personal protective equipment or restriction from work of symptomatic persons can be instituted to diminish the potential for continuing spread of orthopox viruses.

    GAP:

    Large scale prevention and control programs in animals have not been systematically evaluated for efficacy or acceptability.

  • Diagnostic tools

    Several LAMP techniques, a new mini array method able to simultaneously detect OPXV and PPV and an OPV ELISA detection have been recently published.

    GAPS:

    Missed or mistaken diagnosis constitutes a ground for reflection on the sometimes incapacitating consequences of the disease on certain categories of patients such as children and immunocompromised individuals and on public health in case of poxvirus zoonoses and other life-threatening cutaneous agents.

    Lack of translation of research results into commercial products for these neglected diseases.

  • Vaccines

    Human smallpox vaccines are based on VVs. Use of smallpox vaccine in persons at occupational risk for exposure to VV/BPXV or MPXV may be considered. Only one such vaccine, MVA (modified vaccinia Ankara) is currently licensed for use in the United States for persons with immune-compromise or other conditions for which use of non-highly attenuated vaccines are contra-indicated. 

    GAP: No vaccines are under development for specific use in animals.

  • Therapeutics

    None available commercially, but anti-virals have been tested successfully in the laboratory.

    GAP: No therapies are under development for specific use in animals and humans.

  • Biosecurity measures effective as a preventive measure

    Monkeypox is a select agent in the U.S.

  • Border/trade/movement control sufficient for control

    Not normally practised, but imports/exports are occasionally affected.

  • Prevention tools

    Prophylactic vaccination and sanitary / bio-security measures.

  • Surveillance

    No routine surveillance programmes in place.

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

    No country has eradicated the diseases. Prevention and control is normally a combination of vaccination and sanitary / bio-security measures. Recent gains in diagnostic and treatment capacity for OPXV infections engendered through bio-terror preparedness activities could be leveraged to combat the negative health, welfare and economic impacts of zoonotic OPXV including VV/BPXV, CPXV and MPXV.

  • Costs of above measures

    Costs of surveillance are relatively low (5 € per sample), but significant in times of low farm gate prices and in developing countries.

  • Disease information from the OIE

  • Disease notifiable to the OIE

    OPXV infections of domestic animals are not reportable to the OIE. Outbreaks of VV occur in southern Brazil annually during the summer months, causing substantial economic losses and stigma to affected farms. Reporting of BPXV outbreaks in south Asia is variable, but nosocomial human infections (19 probable cases over a 5-month period) were observed in a burn ward in Karachi in 2004-5. Instances of CPXV infection in domestic animals do occur in the EU. In 2008-09, at least 30 cases of pet-associated human CPXV infections were reported from France, Germany and the Netherlands. In general, however, there is likely to be under-reporting of the occurrence of zoonotic poxvirus infections worldwide as appropriate diagnostic assays are not readily available, and the stigma attached to producers and hunters due to contact with these agents is considerable. These are classic neglected zoonoses with considerable potential to cause significant, even life-threatening disease in humans and animals as well as profound negative impacts on agricultural productivity.

  • OIE disease card available

    No.

  • OIE Terrestrial Animal Health Code

    No.

  • OIE Terrestrial Manual

    No.

  • Socio-economic impact

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

    UNKNOWN: Numbers seldom reflect the real importance of the disease in the communities in which they occur. Poxvirus zoonoses fall into the category of neglected zoonoses with considerable potential to cause significant, even life-threatening, disease in humans and animals as well as profound negative impacts on agricultural productivity.

    GAP: The incidence is often unknown or greatly underestimated. Under-reporting leads to underestimating the true number of DALYs which can be averted by effective control.

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

    Unknown.

  • Direct impact (a) on production

    Although BPXV/VV is known to cause substantial economic losses in other regions (Brazil, India, Saudi Arabia, etc.). VV/BPXV primarily affects traditional dairy producers whose facilities are generally smaller and have fewer animals than those using automated machinery. Consequently, the spread of VV/BPXV may have a devastating impact on rural, artisanal dairies where production depends on a small number of cows or buffaloes.

    GAP: There are no published studies on the costs of OPXV diseases in the EU and worldwide.

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

    Unknown. Initial impact likely to be high due to scientific uncertainty and public perception (fear) of poxviruses.

    GAP: No cost benefit analysis available.

  • Indirect impact

    Significant losses in productivity occur when the ability of young animals to feed is negatively impacted either due to the development of mastitis in the adult (often following secondary infection) or oral pain or obstruction in the juvenile. Infections rarely occur as individual sporadic cases, but rather emerge as focal outbreaks, often affecting the majority of animals within a given herd resulting in significant curtailment of dairy production for an affected producer.

  • Trade implications

  • Impact on international trade/exports from the EU

    Australia exports large numbers of live sheep (several million each year) to Middle Eastern markets. In the past the presence of orf virus infected sheep has been a problem and has resulted in shipments being not accepted. In light of this potential trade barrier, all sheep for live export must be vaccinated against orf virus prior to export.

    GAP: Unknown. Initial impact likely high due to scientific uncertainty and public perception (fear) of poxviruses. Surveys are necessary.

  • Impact on EU intra-community trade

    Occasional. DG SANCO communication 12/02/2009 to CVOs: CPXV in humans associated with contact with pet rats from Czech Republic.

    GAP: Unknown. Initial impact likely high due to scientific uncertainty and public perception (fear) of poxviruses. Surveys are necessary.

  • Impact on national trade

    Occasional.

  • Main perceived obstacles for effective prevention and control

    No vaccine capable of providing sterile immunity for PPVs.

    Obstacles for prevention and control of zoonotic poxviruses include, an absence of readily available diagnostic assays, lack of familiarity with human and animal clinical disease (among veterinarians and physicians), lack of vaccines and therapeutics to prevent virus acquisition/transmission, current incomplete understanding of the burden and distribution of zoonotic poxviruses globally.

    GAP: Rodent reservoirs for CPXV (and VV) are undefined on the European continent impeding fundamental control measures.

  • Main perceived facilitators for effective prevention and control

    Recent gains in diagnostic and treatment capacity for orthopoxvirus infections engendered through bio-terror preparedness activities could be leveraged to combat the negative health, welfare and economic impacts of zoonotic orthopoxviruses including VV/BPXV, CPXV and MPXV.

Risk

  • Risks for outbreaks of VV/BPXV are greatest where traditional, non-mechanized diary production occurs, but instances of CPXV (which is endemic through much of Eurasia) have also been observed even on mechanized farms. The experience in the United States with zoonotic transmission of MPXV, which entered the country via imported exotic animals, underscores the importance of being prepared to manage a potentially catastrophic situation.

Main critical gaps

Conclusion

  • Orthopoxvirus-associated infections have had significant negative impacts on local production and have generated public health concerns for people who interact with the infected animals. Preparation includes having

  • Trained clinicians who can identify suspected cases of orthopoxvirus-associated illnesses in humans and animals,
  • Diagnostic testing capacity to rapidly identify a poxvirus-associated ethiology and identify the species of virus involved,
  • Implementation capacity for appropriate sanitary measures, which may include quarantine and vaccination, and 
  • Therapeutic treatments available for persons experiencing severe illness due to infection with any one of these agents.
  • Thoughtful and efficient use of resources may be necessary to ensure that issues related to the availability and development of safe vaccines and effective drugs are addressed.

Sources of information

  • Expert group composition

    Expert group members are included where permission has been given:

    Alessandra Scagliarini, Università di Bologna, Italy - [Leader]

    Colin McInnes, Moredun Research Institute, UK

    Andrew Mercer, University of Otago, New Zealand

    Giliane Trindade, University of Minas Gerais, Brazil

    Mathias Büttner, University of Leipzig, Germany

  • Reviewed by

    Project Management Board.

  • Date of submission by expert group

    April 2016

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