ASF Exit Strategy: Providing cumulative evidence of the absence of African swine fever virus circulation in wild boar populations using standard surveillance measures
2021; Wiley; Volume: 19; Issue: 3 Linguagem: Inglês
10.2903/j.efsa.2021.6419
ISSN1831-4732
AutoresSøren Saxmose Nielsen, Julio Álvarez, Dominique Bicout, Paolo Calistri, Klaus Depner, Julian Ashley Drewe, Bruno Garin‐Bastuji, José Luis Gonzales Rojas, Christian Gortázar, Mette Herskin, Virginie Michel, Miguel Ángel Miranda Chueca, Paolo Pasquali, Helen Clare Roberts, Liisa Sihvonen, H.A.M. Spoolder, Karl Ståhl, Antonio Velarde, Christoph Winckler, José Cortiñas Abrahantes, Sofie Dhollander, Corina Ivanciu, Alexandra Papanikolaou, Yves Van der Stede, Sandra Blome, Vittorio Gubertì, Federica Loi, Simon J. More, Edvīns Oļševskis, Hans‐Hermann Thulke, Arvo Viltrop,
Tópico(s)Viral Infections and Immunology Research
ResumoEFSA JournalVolume 19, Issue 3 e06419 Scientific OpinionOpen Access ASF Exit Strategy: Providing cumulative evidence of the absence of African swine fever virus circulation in wild boar populations using standard surveillance measures European Food Safety Authority (EFSA), Corresponding Author ahaw@efsa.europa.eu Correspondence:ahaw@efsa.europa.euSearch for more papers by this authorSøren Saxmose Nielsen, Search for more papers by this authorJulio Alvarez, Search for more papers by this authorDominique Joseph Bicout, Search for more papers by this authorPaolo Calistri, Search for more papers by this authorKlaus Depner, Search for more papers by this authorJulian Ashley Drewe, Search for more papers by this authorBruno Garin-Bastuji, Search for more papers by this authorJose Luis Gonzales Rojas, Search for more papers by this authorChristian Gortazar Schmidt, Search for more papers by this authorMette Herskin, Search for more papers by this authorVirginie Michel, Search for more papers by this authorMiguel Ángel Miranda Chueca, Search for more papers by this authorPaolo Pasquali, Search for more papers by this authorHelen Clare Roberts, Search for more papers by this authorLiisa Helena Sihvonen, Search for more papers by this authorHans Spoolder, Search for more papers by this authorKarl Stahl, Search for more papers by this authorAntonio Velarde, Search for more papers by this authorChristoph Winckler, Search for more papers by this authorJosé Cortiňas Abrahantes, Search for more papers by this authorSofie Dhollander, Search for more papers by this authorCorina Ivanciu, Search for more papers by this authorAlexandra Papanikolaou, Search for more papers by this authorYves Van der Stede, Search for more papers by this authorSandra Blome, Search for more papers by this authorVittorio Guberti, Search for more papers by this authorFederica Loi, Search for more papers by this authorSimon More, Search for more papers by this authorEdvins Olsevskis, Search for more papers by this authorHans Hermann Thulke, Search for more papers by this authorArvo Viltrop, Search for more papers by this author European Food Safety Authority (EFSA), Corresponding Author ahaw@efsa.europa.eu Correspondence:ahaw@efsa.europa.euSearch for more papers by this authorSøren Saxmose Nielsen, Search for more papers by this authorJulio Alvarez, Search for more papers by this authorDominique Joseph Bicout, Search for more papers by this authorPaolo Calistri, Search for more papers by this authorKlaus Depner, Search for more papers by this authorJulian Ashley Drewe, Search for more papers by this authorBruno Garin-Bastuji, Search for more papers by this authorJose Luis Gonzales Rojas, Search for more papers by this authorChristian Gortazar Schmidt, Search for more papers by this authorMette Herskin, Search for more papers by this authorVirginie Michel, Search for more papers by this authorMiguel Ángel Miranda Chueca, Search for more papers by this authorPaolo Pasquali, Search for more papers by this authorHelen Clare Roberts, Search for more papers by this authorLiisa Helena Sihvonen, Search for more papers by this authorHans Spoolder, Search for more papers by this authorKarl Stahl, Search for more papers by this authorAntonio Velarde, Search for more papers by this authorChristoph Winckler, Search for more papers by this authorJosé Cortiňas Abrahantes, Search for more papers by this authorSofie Dhollander, Search for more papers by this authorCorina Ivanciu, Search for more papers by this authorAlexandra Papanikolaou, Search for more papers by this authorYves Van der Stede, Search for more papers by this authorSandra Blome, Search for more papers by this authorVittorio Guberti, Search for more papers by this authorFederica Loi, Search for more papers by this authorSimon More, Search for more papers by this authorEdvins Olsevskis, Search for more papers by this authorHans Hermann Thulke, Search for more papers by this authorArvo Viltrop, Search for more papers by this author First published: 03 March 2021 https://doi.org/10.2903/j.efsa.2021.6419Citations: 1 Requestor: European Commission Question number: EFSA-Q-2020-00424 Panel members: Julio Alvarez, Dominique Joseph Bicout, Paolo Calistri, Klaus Depner, Julian Ashley Drewe, Bruno Garin-Bastuji, Jose Luis Gonzales Rojas, Christian Gortázar Schmidt, Mette Herskin, Virginie Michel, Miguel Ángel Miranda Chueca, Søren Saxmose Nielsen, Paolo Paquali, Helen Clare Roberts, Liisa Helena Sihvonen, Hans Spoolder, Karl Stahl, Antonio Velarde, Arvo Viltrop and Christoph Winckler. Declarations of interest: The declarations of interest of all scientific experts active in EFSA's work are available at https://ess.efsa.europa.eu/doi/doiweb/doisearch. Acknowledgements: The AHAW Panel wishes to thank the following for the support provided to this scientific output: the trainee Elisabeth Dorbek-Kolin and the ad-interim staff Cristina Rapagnà (AHAW team, ALPHA unit, EFSA). Amendment: Figure 24 was replaced following an editorial amendment. Adopted: 21 January 2021 Amended: 8 Mar 21 AboutSectionsPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Abstract EFSA assessed the role of seropositive wild boar in African swine fever (ASF) persistence. Surveillance data from Estonia and Latvia investigated with a generalised equation method demonstrated a significantly slower decline in seroprevalence in adult animals compared with subadults. The seroprevalence in adults, taking more than 24 months to approach zero after the last detection of ASFV circulation, would be a poor indicator to demonstrate the absence of virus circulation. A narrative literature review updated the knowledge on the mortality rate, the duration of protective immunity and maternal antibodies and transmission parameters. In addition, parameters potentially leading to prolonged virus circulation (persistence) in wild boar populations were reviewed. A stochastic explicit model was used to evaluate the dynamics of virus prevalence, seroprevalence and the number of carcasses attributed to ASF. Secondly, the impact of four scenarios on the duration of ASF virus (ASFV) persistence was evaluated with the model, namely a: (1) prolonged, lifelong infectious period, (2) reduction in the case-fatality rate and prolonged transient infectiousness; (3) change in duration of protective immunity and (4) change in the duration of protection from maternal antibodies. Only the lifelong infectious period scenario had an important prolonging effect on the persistence of ASF. Finally, the model tested the performance of different proposed surveillance strategies to provide evidence of the absence of virus circulation (Exit Strategy). A two-phase approach (Screening Phase, Confirmation Phase) was suggested for the Exit Strategy. The accuracy of the Exit Strategy increases with increasing numbers of carcasses collected and tested. The inclusion of active surveillance based on hunting has limited impact on the performance of the Exit Strategy compared with lengthening of the monitoring period. This performance improvement should be reasonably balanced against an unnecessary prolonged 'time free' with only a marginal gain in performance. Recommendations are provided for minimum monitoring periods leading to minimal failure rates of the Exit Strategy. The proposed Exit Strategy would fail with the presence of lifelong infectious wild boar. That said, it should be emphasised that the existence of such animals is speculative, based on current knowledge. Summary Term of Reference 1 (ToR 1) of the mandate of the European Commission requested EFSA to (1) clarify the risk factors possibly contributing to African swine fever (ASF) persistence in affected areas over a number of years in wild boar populations and (2) assess the role of seropositive wild boar in the context of ASF infection, and in particular in areas without evidence of recent virus circulation. The first subquestion of ToR 1 (ToR 1.1) was related to the role of seropositive wild boar in ASF persistence, and specifically how ASF seroprevalence in the adult and subadult wild boar population evolves after the last detection of a polymerase chain reaction (PCR)-positive sample. To address this question, surveillance data from Estonia, Latvia and Sardinia submitted to EFSA's data collection framework were investigated with a generalised equation method. The objective was to study the evolution of the seroprevalence in adult (≥ 1 year old) and subadult (< 1 year old) wild boar after the last detection of a PCR-positive sample in a given local administrative unit in Latvia and Estonia. The model demonstrated a more rapid decrease towards zero seroprevalence among subadult animals compared with adult animals subsequent to the last detection of a PCR-positive sample, both in Estonia and Latvia. The decline in seroprevalence in adult animals compared with subadults was much slower, taking more than 24 months to approach zero. For this reason, seroprevalence in adults is a poor indicator to demonstrate the absence of virus circulation. In Sardinia, a decline in virus and seroprevalence has been observed from 2015. In the Anglona-Gallura subregion of Sardinia, ASF appears to have faded out as no PCR-positive animals have been detected since 2015. Nonetheless, seropositive adult animals were detected as recently as January 2020. Although not explicitly mentioned in ToR 1, during initial discussions with the European Commission, it was queried whether current surveillance activities would be able to reliably detect the presence of clusters of virus when virus prevalence is very low. This became the second subquestion of ToR 1 (ToR 1.2). The disease freedom methodology which considers different risk for the sampled subgroups (hunted and found dead animals) was used to estimate the combined confidence in disease freedom. It was assumed that the risk of finding ASF in found dead animals is 60 times higher than in hunted animals. Based on Estonian data, the current sampling intensities were found to be insufficient to detect infection in many Estonian Local Administrative Unit 1 (LAU 1) regions, based on the assumption of 1% disease prevalence and homogenous geographical distribution of infected animals. Instead, it was concluded that intensive sampling would be required to demonstrate the absence of virus circulation based on mainly active surveillance (hunted animals). The collection of the number of samples required to achieve at least 95% confidence in freedom from infection would probably be unfeasible under field conditions. In this Opinion, a spatial-explicit stochastic model has been used to test different surveillance strategies, based on available surveillance tools and achievable sampling efforts. A previously documented spatially explicit stochastic model (Grimm et al., 2006, 2010; Grimm, 2020) was chosen (e.g. modelling infectious diseases in wild boar at http://www.ecoepi.eu/ASFWB) for this purpose. In addition to standard testing of wild boar hunted or found dead, the potential inclusion of serological testing of young wild boar as an indicator of freedom from infection was also considered. The third subquestion of ToR 1 requested an update of aspects of ASF epidemiology that are still subject to considerable scientific uncertainty (ToR 1.3), including the implications of these uncertainties for any conclusions drawn. This information is directly relevant to the stochastic models. In this context, a narrative literature review was conducted. Several relevant epidemiological attributes were identified including the mortality rate due to ASF, the duration of protective immunity and duration of maternal antibodies and transmission parameters. The true mortality caused by ASF at the population level is difficult to estimate due to the occurrence of non-ASF-related mortality, such as hunting. Recent estimates from Poland and Latvia attributed around 80% of the mortality in the wild boar population to ASF. The case-fatality rate due to ASF experimental infections of wild boar with ASFV genotype II strains is likely above 95%. The duration of protective immunity in animals recovering from ASF has not been well studied and is considered a knowledge gap. Recent studies have demonstrated a lack of protection even 4 months post-immunisation with attenuated ASFV strains. There was no clear correlation between protection and antibody levels. However, protection from clinical disease may still last for several months in animals recovering from the disease. Re-infection of these animals, however, cannot be excluded. The duration of maternal antibodies in piglets of sows surviving ASF is not known. According to the literature, the longest time that maternal antibodies against ASFV have been found in piglets is 7 weeks. However, true long-term studies are missing. Maternal antibodies against other pig diseases such as Classical Swine Fever virus and porcine parvovirus have been shown to last up to 2–4 months, and up to 6 months for Aujeszky's disease virus. In all cases, some individuals will show antibodies for prolonged periods. The transmission parameter estimates from experimental studies are dependent on the experimental setting and conditions. The use of differing humane endpoints (moment when euthanising the animals in animal experiments) is particularly relevant. The estimates from field studies are influenced by various factors that affect contact rates between animals, e.g. farm management. The point estimates for transmission parameters obtained in experimental conditions fall within a relatively narrow range (R0: 5.0–6.1). The parameters calculated based on field data are more variable, being lowest for ASFV genotype I in Sardinia (R0 ranging from 1.2 to 2.7) and highest for genotype II outbreaks in Russia (R0 ranging from 4.4 to 17.3). There are no experimental data on transmission of ASFV from infected carcasses to susceptible wild boar. The studies estimating R0 for wild boar are based on field data and incorporate the effect of all transmission routes. The transmission parameter estimates from field data are influenced by local conditions (e.g. population density and management of wild boar) and disease intervention measures, which all have an effect on contact rates between the animals and animal groups. The fourth subquestion of ToR 1 (ToR 1.4) was related to parameters that could potentially lead to prolonged virus circulation (persistence) in wild boar populations in an affected area. This subquestion was addressed through a narrative literature review. Firstly, possible hypotheses for persistence of ASFV in the environment were reviewed. African swine fever virus is known to be highly stable under a wide range of environmental conditions. Several modelling studies reported in the scientific literature demonstrated that more than half of all transmission events in wild boar populations are attributed to contact between live wild boar and infectious carcasses. The behaviour of wild boar towards dead conspecifics is likely to be one of avoidance, but with occasional contact of infectious material around dead animals. For this reason, carcass removal is considered an important control measure for ASF. Also, possible persistence of ASFV through biological and mechanical vectors was reviewed. Scavenger mammal and bird species represent a minor risk factor for spreading ASF in wild boar populations but may contribute to reducing local virus persistence by removing infected carcasses. Based on current knowledge, Ornithodoros spp., belonging to the Argasidae family of soft ticks, is the only tick genus that can be considered a competent vector that is able to replicate and transmit ASFV. Ticks of the O. erraticus complex are present in parts of the European, trans-Caucasus countries and Russian Federation territories and may be important in maintaining the local foci of the ASFV within traditional pig management systems. However, they do not play an active role in the geographic spread of ASFV. Furthermore, European wild boars rest above the ground rather than in protected burrows, thereby reducing the opportunity for Ornithodoros spp. infestation. Ticks of the O. erraticus complex have not been reported from central or northern Europe. ASFV DNA has been detected in some biting arthropods in outbreak farms in Lithuania and Romania. However, their potential role in the mechanical transmission in ASFV needs to be clarified. Specifically, conclusive evidence of their role in ASFV transmission will require consideration of virus isolation studies on arthropods caught on outbreak pig farms and laboratory experimental transmission studies; and to link this evidence with studies on arthropod foraging strategies and habitat use. Secondly, factors relating to wild boar that could possibly contribute to ASFV persistence were reviewed. The last decade of ASF in Europe has demonstrated that ASFV can persist in wild boar populations without re-infection from domestic pigs. Viral persistence in wild boar populations is influenced by both host and environmental factors. Direct transmission between live wild boar is primarily to other individuals within the same social group. Furthermore, habitat quality is important, and the presence of large, well-connected forests favours unrestricted wild boar movement and contact. At higher boar densities, there is increased potential for direct transmission because of increased within-group contacts, and indirect transmission through contact of wild boar with infected carcasses and contaminated environments. As wild boar density falls, viral persistence is likely to be facilitated by viral survival in infectious carcasses. There is no evidence of a population density threshold for spontaneous ASF fade-out. The potential role of surviving infectious animals in long-term transmission is still controversial. Although virus can be isolated from survivors for roughly 60–70 days following initial infection, there is no evidence of a major role for these long-term infectious animals in maintaining virus circulation from either field experience or long-term studies. Thirdly, the review focused on possible factors that are intrinsic characteristics of the virus that could contribute to virus persistence in wild boar populations. The ASFV strains in the current European epidemic belong to the p72 genotype II. These strains are usually highly virulent, inducing an acute form of ASF with a case-fatality rate approaching 95%, regardless of age, dose or route of administration. There have been several examples of naturally occurring, attenuated genotype II strains during the current epidemic, in Estonia and Latvia, but they appear to have disappeared from the wild boar populations, possibly due to their reduced ability to generate infectious carcasses. Circulation of genotype I in Europe is limited to Sardinia, following introduction in 1978. The genotype I strains circulating in Sardinia have always been associated with high virulence. In recent years, however, the virus was isolated from apparently healthy pigs. The presence of less virulent ASFV strains in Sardinia has never been confirmed, although the field observations are highly suggestive. Finally, human-induced factors that could lead to virus persistence were reviewed. Although the spread of ASF in wild boar populations can continue without re-infection from domestic pigs, there are some examples of spillover from domestic pigs to wild boar, such as introduction and spread into a country through indirect contacts with infected meat or products in Europe. The risk related to infected meat and products from domestic pigs and wild boar is often associated with illegal movements of such products or with small free-ranging backyard farms where animals are illegally fed with untreated food leftovers or catering waste. Human activity remains an important contributor to both ASF persistence and expansion in wild boar populations, including hunting activities with poor biosecurity. In the current epidemic, there have been multiple examples of long-distance translocations of infection, which could plausibly only be related to human activity. Term of Reference 2 (ToR 2) of the mandate requested EFSA to define pathway(s) to ASF freedom in relevant areas, in accordance with the Strategic approach to the management of African Swine Fever for the EU and recommend criteria for defining an area as free from ASF in wild boar. In this task, EFSA was asked to take account of the results of wild boar testing (in particular, antibody detection and virus identification). As a first step, a spatial-explicit stochastic model was used to simulate the spread of ASF in Estonia, based on surveillance data submitted to EFSA's data collection framework, generating the temporal dynamics of virus prevalence, seroprevalence and the number of carcasses attributed to ASF infection throughout the epidemic in the wild boar population at the scale of the local administrative unit 1 (LAU 1). The area covered by LAU 1 units varied between less than 1,000 and 5,000 km2. Throughout the ASF epidemic, a low virus prevalence was observed with a median of about 2% at the peak of epidemic (1–4% as central 50% interval), and the virus prevalence was very low during the 6 months prior to virus extinction in an LAU 1 region in Estonia (median virus prevalence below 0.5% with 0.1–2% as central 50% interval). The median seroprevalence in subadults declined to 0% within 1 year (9–18 months as central 50% interval) after local extinction of ASFV in an LAU 1 region in Estonia, whereas the same decline in adults took more than 3 years. The median number of wild boar dying because of ASF was around 150 carcasses per LAU 1 at the peak of epidemic (100–300 central 50% interval across runs and LAU 1 units) and 1 year before local extinction about 40 carcasses (10–150 central 50% interval across runs and LAU 1 units). As a second step, the model was used to test the impact of those attributes contributing to ASF epidemiology that could potentially contribute to prolonged virus circulation (persistence) in wild boar populations in an affected area. Specifically, four scenarios were evaluated, including: (1) the potential existence of wild boar with prolonged infectious period (carriers) (scenario 1); (2) a reduction in the case-fatality rate and a lengthened period of transient infectiousness among surviving animals (scenario 2); (3) a change in the duration of protective immunity among animals surviving ASFV infection (scenario 3); and a change in the duration of protection from maternal antibodies on the duration of virus circulation (scenario 4). In scenario 1, there was a more marked difference in the serological profile of subadult compared with adult animals with an increasing proportion of carriers involved. The seroprevalence in subadults was lower than in adults and the decline in seroprevalence much slower in the years prior to regional extinction, as the proportion of carriers increases. Furthermore, carcass numbers attributable to ASF were lower and the decline in carcass numbers much slower in the years prior to regional extinction, as the proportion of carriers increases. In scenario 2, variation in case-fatality alone did not substantially impact the duration of virus circulation, given transient infectiousness of about 1 week among surviving animals. There was an impact on duration of virus circulation when the duration of transient infectiousness among surviving animals was increased to 4 weeks, however, final fade-out was only marginally affected. For scenarios 3 and 4, the impact on duration of virus circulation was minimal. As a third step, the model was used to test the performance of different proposed surveillance strategies that could be implemented to provide evidence of the absence of virus circulation (Exit Strategy). To make sure the Exit Strategy would be feasible to implement in the field, different combinations of duration and intensity of existing surveillance tools (active surveillance based on hunting and passive surveillance based on wild boar found dead) were tested in several iterations of the stochastic model. For the active surveillance, only testing on the subadult wild boar was included in these iterations, as it was already shown that inclusion of serology of adult wild boar would be poor indicator to demonstrate the absence of virus circulation, since it would take up to 3 years before seropositive wild boar would disappear from the population after the virus was eliminated. After these first iterations of the stochastic model, which are reported in the External Scientific Report (Lange et al., 2021), it became evident that as a general principle, a two-phase approach (Screening Phase, Confirmation Phase) would be advisable for the Exit Strategy, based on knowledge of virological and serological prevalence profiles. Further model simulations evaluated different Exit Strategy options, which varied by surveillance options and intensity and the length of the monitoring period during each phase. Each option was assessed in terms of performance (failure rate, being the per cent of simulations for which it was falsely concluded that virus is absent) and 'time free' (the time lag between point of viral extinction and time when an exit decision is possible). It was demonstrated that the accuracy of the Exit Strategy approach to demonstrate freedom of ASFV circulation in a wild boar population increased with an increasing number of carcasses being routinely collected and tested. However, the Exit Strategy will only be feasible if the duration and intensity of the passive surveillance can be sustained under field conditions. To increase the feasibility of the Exit Strategy approach, a longer monitoring phase with routine surveillance effort (the Screening Phase) and a shorter monitoring phase with the maximum surveillance possible under field conditions (the Confirmation Phase) is proposed. Lengthening of the monitoring periods leads to an improvement in Exit Strategy performance; however, this performance improvement should be reasonably balanced against an unnecessary prolonged 'time free' with only a marginal gain in performance of the Exit Strategy. In general, the inclusion of active surveillance in the Exit Strategy has very limited impact on the performance compared with a lengthening the overall monitoring period. A declining seroprevalence in subadults can add information about the fade-out of the epidemic and trigger the decision to initiate the Exit Strategy, however including this surveillance activity during the Exit Strategy only marginally improves its performance. Furthermore, it was demonstrated by the model that the scenario based on a decreased case-fatality rate, with surviving animals having a longer (but still transient) period of infectivity, would not influence the outcomes of the Exit Strategy approach. In contrast, the proposed Exit Strategy would fail with the presence of lifelong infectious carrier animals. That said, it should be emphasised that the existence of such carriers is speculative, based on current knowledge. Assuming a higher natural mortality that is not caused by ASF or hunting in the model, reduced the probability of finding infected carcasses in an affected area and therefore reduced the performance of passive surveillance. This is due to the dilution effect for detecting infected carcasses by the increased proportions of carcasses of wild boar that died due to reasons other than ASF. Therefore, a more cautious approach may be advisable in those regions where the natural mortality rates are uncertain or known to be higher than the assumed 10% natural mortality that is not caused by ASF or hunting. Based on the model outcomes, several practical examples of an Exit Strategy, both for large affected areas and for smaller areas after a focal introduction of ASF were provided. 1 Introduction 1.1 Background and Terms of Reference as provided by the requestor 1.1.1 Background ASF is an infectious lethal disease affecting domestic pigs and wild boar. It can be transmitted via direct animal contact or via dissemination of contaminated food or equipment. This disease has serious economic implications for pig meat and related sectors, including indirect costs related to trade restrictions. The persistence of the disease in wild boar and the limited number of control measures available represents a challenge for the whole EU agricultural sector, in particular the pig farming industry. There is no vaccine or cure despite active ongoing research. From the beginning of 2014 until now, genotype II of ASF has been notified in Belgium, Bulgaria, the Czech Republic, Estonia, Greece, Latvia, Lithuania, Poland, Romania and Slovakia causing very serious concerns. The disease has also been reported in Belarus, Moldova, Serbia, Russia and Ukraine, which creates a constant risk for all the Member States that share a border with these third countries. In Italy (Sardinia only) genotype I of ASFV has been present since 1978 in domestic pigs and wild boar. The remainder of Italy remains free of the disease. The entire island is considered as part IV in terms of regionalisation, the only area in the EU subject to this type of restriction at present. Member States and the Commission are continuously
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