Parapox - available
Control ToolsDiagnostics availabilityDiagnostic test performed at academic institutions or in public health reference laboratories. No universal diagnostic test in use. GAP: Rapid (validated), point-of-care tests are not available. No universal diagnostic test in use when available, is mainly performed at academic institutions or in public health reference laboratories. GAP: Rapid (validated), point-of-care tests are not available. None. None. 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 parapoxviruses. 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. Better knowledge about PPV epidemiology will open the market for commercial diagnostics because negative testing for PPV infection will become a quality standard. GAP: 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. None available / Low requirement. A standard diagnostic test should be established to assess PPV associated disease across Europe. Developing a test(s) capable of distinguishing between the parapoxviruses and other agents causing vesicular disease in ruminants. Pen-side devices allowing veterinarians and physicians to rapidly distinguish PPV from other agents causing vesicular diseases in animals and life-threatening cutaneous zoonoses. GAP: specificity and sensitivity needs to be maximised against the library of virus strains from across Europe. An assessment of worldwide PPV strain variability will be important to develop acurate diagnostics test that can differentiate between endemic and imported isolates. This may also allow for regional differentiation and will enhance epidemiological efforts. Differential diagnosis will also require an understanding of variation present among other agents causing vesicular disease and how they differ genetically and biologically. Vaccines availabilityLive 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 grown Licenced in a minority of countries. GAP: there is no published information available on the level of usage of OV vaccines. There are few commercial vaccines against OV, with none having authorisation for use across the whole of 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: there is no published information available on the level of usage of orf virus vaccine in Europe. None. None. OV: Live fully virulent virus that causes disease and if used off-label can result in disease outbreaks in flocks. Current vaccines against orf are successful in reducing the severity of the disease but can disseminate the vaccine strain of the virus which can cause disease. No sterile immunity is induced. Vaccination considered being effective for 6 -12 months. There is considerable scope for improving the currently available. GAP: moderate if safety issues are dealt with.
National/Federal support underpins vaccine procurement and stockpiling in the United States.
There is a need to improve vaccines against OV since current vaccines are fully virulent live viruses. Iit is most likely that protective immunity to OV requires the stimulation of a cellular response. It cannot be predicted if this will be achieved most efficiently by a non-infectious subunit vaccine, an engineered attenuated OV, or some other means such as a vector containing the appropriate OV genes. For this reason it is important to pursue each of these lines of investigation. Deliver viral antigens in such a way as to stimulate a cell mediated Th 1 response, including the presentation of peptides on class 1 MHC. Most promising candidate is DNA vaccination. GAPS:
Pharmaceutical availabilityThere are no approved veterinary treatments for poxvirus-related infections. There are records of traditional or alternative remedies used for the treatment and prevention of OV infections in sheep and goats. Application of different oils (sesame and castor), the juice of Acra (Calotropis procera) and that of Thor (Euphorbia spp) have been used in India and in several African countries while Ilex aquifolium has been employed to cure and prevent ecthyma in the Netherlands and in France. The anti-orf virus activity of Cidofovir (HPMPC, CDV, Vistide®) was demonstrated in studies in vitro and ex vivo. In vivo, in experimentally infected lambs, it was shown that the topical application of cidofovir cream resulted in milder lesions that resolved more quickly than untreated lesions. Cidofovir also reduces the amount of viable virus found in the lesions and thus could be critical to reducing the incidence of disease on farms that have a persistent problem with orf. 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. Pharmaceuticals would be of greatest value in the event of an outbreak and or following an introduction event. The acceptability of using antivirals in food animals is unknown, but use of these compounds for humans, and high value animals (zoo animals) could be explored. Pharmaceuticals would be of greatest value in the event of an outbreak and or following an introduction event.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. See "Commercial potential for pharmaceuticals in Europe". New developments for diagnostic testsDiagnostic 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. GAP: specificity and sensitivity need to be maximised against the library of virus strains from across Europe and worldwide It will be important to developing accurate diagnostics test that can differentiate between endemic and imported isolates. Short term. Assay validation will likely require collaboration with a reference facility. Limited. Pen-side tests. Important for discrimination against other pathogens causing vesicular disease. GAPS:
This technology does not exist and would be difficult to develop.(CDC) New developments for vaccinesRequirement for a vaccine that does not cause disease in its own right. Multiple different approaches to vaccine development could be considered including live-attenuated virus vaccines, DNA vaccines, live recombinant vaccines. Long term(5 years with full market authorization).
Unknown and variable. Will depend on the approach selected. Requirement for a vaccine that does not cause disease in its own right. Multiple different approaches to vaccine development could be considered including, live-attenuated virus vaccines, DNA vaccines, live recombinant vaccines. New developments for pharmaceuticalsTesting of anti-virals / excipients / delivery mechanisms. GAPS:
2-3 years. Unknown. Robust animal infection model. Disease detailsDescription and characteristics.Family Poxviridae, subfamily Chordopoxvirinae. The genus Parapoxvirus (PPV) includes three members, bovine papular stomatitis virus (BPSV), pseudocowpox virus (PCPV) and orf virus (OV). GAPS:
Routine PPV diseases are normally self-limiting with low impact on individual animals, although lack of thrift is common leading to delayed finishing times. Occasional severe outbreaks occur leading to loss of teats or to fatalities. GAPS: little is known about prevalence of PPV severe disease. Nothing is known about risk factors associated with severe disease. Missing knowledge about the clinical and sub-clinical prevalence of PPV infections in cattle and small ruminants in EU member states. 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
All causing contagious skin infection. GAPS: Range of permissive hosts for interspecies recombination All the viral species infect humans, causing different diseases ranging from benign and self-limiting to severe (hospitalisation). Reports exist of atypical proliferating forms of giant OV in immunosuppressed and several reports of complicated forms also in immunocompetent individuals. GAPS: Nothing is known about risk factors associated with severe disease. Under-reported because it is seen as occupational hazard that normally is self-limiting. None. PPVs infect domestic and wild ruminants as well as wildlife species (e.g seal). GAP: a better understanding of the identity and distribution of reservoirs for poxvirus associated zoonotic agents. Description of infection & disease in natural hostsHighly transmissible (almost 100% morbidity on affected farms). PPVs infect via broken, scarified or otherwise damaged skin and replicates in epidermal cells following direct contact with infected animals or with contaminated fomites. PPVs 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.
PPVs 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. GAP: several aspects of virus genotype-associated pathology remain undefined and are currently under study. PPV progress from erythema to macule/papule/vesicle to pustule then scab usually around the mouth or nares of lambs, but also occasionally on the teats of nursing ewes or around the coronets. 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.
GAPS: Prevalence not known in EU member states. Possibility of mis-diagnosis with other pathogens causing vesicular disease in ruminants. The sub-clinical occurrence of PPV is largely however in context with diagnostic surveillance of notifiable diseases such as FMD, Bluetongue, BVD-Mucosal Disease and BHV-1 parapoxviruses (PPV) have been frequently detected in skin biopsies and swabs. The sub-clinical occurrence of PPV is largely unknown however in context with diagnostic surveillance of notifiable diseases such as FMD, Bluetongue, BVD-Mucosal Disease and BHV-1 parapoxviruses (PPV) have been frequently detected in skin biopsies and swabs.
Incubating period for PPV is generally from 3 to 4 days. GAP: possibility for PPVs subclinical infections in animals. The mortality rate of PPVs is usually less than 1% but secondary complications of OV can increase this rate to around 20 to 50%. 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. OV virus in wool remains infectious for at least one month. GAP: much is inferred from studies of vaccinia virus or ectromelia, but actual studies in reservoir, transmitting, or “end” hosts have been limited. Zoonotic potentialVirtually all PPV species are transmissible to humans. Human infections with orf, reindeerpox, sealpox and psuedocowpox have been recorded in recent years across Europe. In the UK, orf virus infections are the most common viral zoontic reported to the public health laboratory. One study conducted in New Zealand found a 4% annual OV incidence amongst workers directly involved in slaughtering sheep. 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. GAPS: Lack of epidemiological investigations. The incidence in humans is frequently unknown since the diseases are not notifiable this remains an assumption. Unknown since the diseases are not reportable. GAP: the diseases are not notifiable. The majority of PPVs are transmissible to man with disease considered an occupational hazard to farmers, shepherds, veterinarians, animal handlers, meat and wool processors and also associated with religious slaughter of animals. Increasing number of cases in children exposed to infected animals in an occupational setting or during recreation (source CDC). There is a high risk of contracting orf infection from handling pelts and wool, and that direct contact with current lesions was not required. GAPS: Currently PPV infections are considered an occupational risk of veterinarians and animal handlers, but cases occur in categories not considered at risk. Many risk factors are still unknown. PPVs cause painful lesions on the hands, fingers and face that respond poorly to treatment. The viruses can cause a systemic reaction sufficiently severe to require hospitalisation. Reports exist of atypical proliferating forms of giant orf in immunosuppressed and reports exist also for immunocompetent individuals. Further complications such as erythema multiform, bullous pemphigoid, swan-neck deformity and paresthesia and autoimmune blistering disorders have also been reported following OV infection. 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. PPVs human to human transmission is possible but usually limited to direct contacts. GAP: not known, few reports about man-to-man spread. Impact on animal welfare and biodiversityIsolation/quarantine of new animals are useful prevention tactics. GAPS:
Orf and PCPV have severe effects (high mortality) in semi domesticated reindeer and in muskox. GAP: prevalence in wildlife ruminants is unknown. Ewes and cows, which suffer loss of mammary function due to PPVs, VACV BPXV, may have to be culled. Cohorting, isolation and quarantine may be effective strategies.
Geographical distribution and spreadPPV-associated infectious diseases are found throughout the world. Recently it was reported that during the past three years 40% of the flocks in the USA have been infected with orf virus (source CDC). Frequency of outbreaks is currently undefined. PPV infections are endemic wherever sheep / goats / cattle are farmed. GAPS: frequency of outbreaks /affected herds is not known in the EU member states and worldwide. Frequency currently undefined due to undereporting. No information about subclinical infection. Particularly prevalent during lambing and nursing, but otherwise non-seasonal. GAP: seasonal cycle undefined. Appears to be very fast within a flock / herd. GAP: Undefined speed of spread. Only with animal movements. Dry season- it is believed that the presence of thistles etc in areas where the animals are grazing favours outbreak and spread – basically things that can break the skin. GAP: seasonal cycle undefined and under study. No arthropod vector. Virus more stable in dry conditions. GAP: no information from countries with extreme climate differences. No arthropod vector. GAP: climate change may affect the distribution of disease via impact on reservoir or transmitting host habitats. Route of TransmissionDirect contact / infectious fomites. Always through broken skin. PPVs are not transmissible via respiratory routes.
Previous outbreaks / Rough pasture / Housing / Over-crowding / intensive farming practises. GAP: conditions favouring virus transmission from one species to another remain poorly defined. Many risk factors remain unknown. Detection and Immune response to infectionVigorous humoral and cell-mediated response to infection. Neutralising anti-bodies not normally found. Colostrum from vaccinated / previously exposed ewes has no protective effect. GAP: mechanism of protection not fully understood. Detection of IgG response to whole virus. GAP: no robust or commercial antibody test available. Species specific immunological detection reagents are not available. Main means of prevention, detection and controlDisinfection / steam cleaning required for food troughs, buildings etc. used with known affected animals. Such methods appear to be effective. GAPS: 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. Scabs contain millions of virus particles which, when they dry up and drop off the animal, will contaminate the environment. 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. GAP: large scale prevention and control programs in animals have not been systematically evaluated for efficacy or acceptability. ELISAs and PCRs available. GAP: 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. Limited licenced vaccines available for PPVs. All vaccines are fully virulent live viruses that can themselves cause outbreaks of disease. GAP: no vaccines are under development for specific use in animals. None available commercially, but anti-virals have been tested successfully in vitro, ex vivo and in vivo experiments. GAP: no therapy is under development for specific use in animals and humans. Not using the vaccine on premises where there is no history of OV infection. Not normally used, but imports/exports are occasionally affected. Prophylactic vaccination and sanitary / bio-security measures. Not routine. No country has eradicated the diseases. Prevention and control is usually a combination of vaccination and sanitary / bio-security measures. Cost of surveillance: relatively low ~ 5 € per sample, but significant in times of low farm gate prices and in developing countries. Disease information from the OIENo. No. No reference. No reference. Socio-economic impactUNKNOWN: 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. Unknown. Parapoxvirus infections and in particular orf have a great economic impact to those rural communities that are predominantly reliant on livestock farming for their livelihood. OV is in the top twenty most important viral diseases of sheep and goats globally in terms of impact on the poor. Growth may be retarded in lambs affected with the mouth form of orf or with strawberry footrot. There may be a reduction in the reproductive performance of a flock if rams affected with the venereal form of orf become reluctant to mate. Lambing percentages may be reduced and/or the breeding season and lambing may be extended. Bottle feeding and the isolation of infected animals may also add to operating costs, reduction in milk production, extra veterinary costs are due to the usual occurrence of secondary infections on teats leading to mastitis. The reduction in milk production and the spread of these viruses could severely impact the economy. Reindeer infections cause important economic losses to indigenous people (Saami) in Northern Europe.. All of these factors can result in increased prices of milk, cheese, meat, hides and other products. GAP: there are no published studies on the costs of PPV diseases in the EU and worldwide. Unknown. Initial impact likely to be high due to scientific uncertainty and public perception (fear) of poxviruses. GAP: no cost benefit analysis available. Significant losses in productivity occur when the ability of young animals to feed is negatively impacted either by the development of mastitis in the adult (often following secondary infection) or by oral pain or by 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 implicationsAustralia 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: impact unknown. Initial impact likely to be high due to scientific uncertainty and public perception (fear) of poxviruses Questionnaires necessary. Occasionnal impact. GAP: impact unknown. Occasional impact. Main perceived obstacles for effective prevention and controlNo 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. Main perceived facilitators for effective prevention and controlVaccination / bio-security / sanitary measures to reduce the incidence, and therefore in the impact, of parapoxvirus associated disease. This will not only have benefits for the health and welfare of affected animals, but should also reduce the zoonotic impact on human health. There is a high and promising potential for improvement and standardization of parapoxvirus (PPV) infection diagnostics. Especially rapid and reliable diagnostic differentiation of PPV from high priority notifiable virus infections in cattle and small ruminants is urgently needed. Potential for developing therapeutic treatments for persons experiencing severe illness. ConclusionResearch in this field may lead to a reduction in the incidence, and therefore in the impact, of parapoxvirus associated disease. This will not only have benefits for the health and welfare of affected animals, but should also reduce the zoonotic impact on human health. There is a high and promising potential for improvement and standardization of parapoxvirus (PPV) infection diagnostics. Especially rapid and reliable diagnostic differentiation of PPV from high priority notifiable virus infections in cattle and small ruminants is urgently needed. 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. |
