Lumpy skin disease: Workshop on risk assessment and data collection for epidemiology, control and surveillance

Transcription

1 EVENT REPORT APPROVED: 20 November 2018 doi: /sp.efsa.2018.en-1520 Lumpy skin disease: Workshop on risk assessment and data collection for epidemiology, control and surveillance European Food Safety Authority Abstract The epidemics of lumpy skin disease in EU has been controlled mainly thanks to the coordinated control measures taken in the Balkan region, based above all on regional vaccination campaign. Since before the epidemics EFSA has been performing risk assessment on LSD to support the decision making process both for EC and also for the national authorities. Periodical meetings with representatives from affected and at risk countries have been organised by EFSA in order to commonly agree on type of data to collect and share by the national authorities to serve the risk assessment. This workshop aimed to update the data models used so far, to verify with the country representatives what kind of risk assessment EFSA can provide in the future that may be useful for better planning control and surveillance measures. European Food Safety Authority, 2018 Key words: lumpy skin disease, data collection, bovine, vaccination, surveillance Question number: EFSA-Q Correspondence: any enquires related to this output should be addressed to EFSA Supporting publication 2018:EN-1520

2 Disclaimer: The views or positions expressed in this publication do not necessarily represent in legal terms the official position of the European Food Safety Authority (EFSA). EFSA assumes no responsibility or liability for any errors or inaccuracies that may appear. Acknowledgements: EFSA wishes to thank: Paolo Calistri, Andy Haegeman, Simon Gubbins, Eyal Klement, Arjan Stegeman, Žaklin Acinger-Rogić, Aleksandar Nemet, Chrysoula Dile, Bafti Murati, Vanja Kondratenko, Tatjana Labus, and EFSA staff members: Sotiria-Eleni Antoniou, Alessandro Broglia, José Cortiñas Abrahantes, Nikolaus Kriz, Drago Marojevic, Gabriele Zancanaro. Suggested citation: EFSA (European Food Safety Authority), Lumpy skin disease: workshop on risk assessment and data collection for epidemiology, control and surveillance. EFSA Supporting publication 2018:EN pp. doi: /sp.efsa.2018.en-1520 ISSN: European Food Safety Authority, 2018 Reproduction is authorised provided the source is acknowledged. 2 EFSA Supporting publication 2018:EN-1520

3 Table of contents Abstract Introduction Workshop Update on situation in the different countries Inputs by scientists member of standing WG on LSD Mathematical model for LSD spread, vaccination and surveillance Analysis of vaccination effectiveness Diagnostic tests for LSD Scenarios for LSD surveillance SIGMA project Survey design and sample size theory and calculation Results of the questionnaire Action points Data collection Estimation of milk drop after vaccination Serological surveys and possible analysis Conclusions References EFSA Supporting publication 2018:EN-1520

4 1. Introduction The workshop on lumpy skin disease brought together scientists who are members of the standing working group on LSD of EFSA together with representatives from LSD affected and at risk countries in order to i) share the knowledge about LSD, ii) explain the analysis performed by EFSA and make them applicable to each country situation, iii) update the data models used so far for the data collection in view of the next EFSA outputs, iv) provide the participating countries with practical indications about how to do surveys for testing vaccination effectiveness, vaccine monitoring and surveillance for detection of the disease (Figure 1). Figure 1: Participants to the workshop. From the left: Drago Marojevic (EFSA), Bafti Murati (Kosovo*), Aleksandar Nemet (Bosnia Herzegovina), Tatjana Labus (Serbia), Zaklin Rogic Acinger (Croatia), Eyal Klement (Israel), Simon Gubbins (UK), Vanja Kondratneko (FYROM), Sotiria-Eleni Antoniou (EFSA), Chrysoula Dile (Greece), Arjan Stegeman (Netherlands), Alessandro Broglia (EFSA). 2. Workshop 2.1. Update on situation in the different countries Each representative from LSD affected or at risk countries gave an update about current situation on LSD both from the epidemiological and control status in particular about vaccination and surveillance, especially about control and surveillance activities in place where data are available and can be shared with EFSA to provide analysis useful to the country itself. No outbreaks have been reported in 2018 in the whole Balkan region. Bosnia Herzegovina has been performing preventive vaccination against LSD since 2017 in the southern areas of the country. Bosnia considered how to share data on cattle population and vaccination at municipality level. Croatia stopped vaccination in January 2018 and put in place a clinical, serological and virological surveillance, the data can be shared with EFSA. Compensation was provided to farmers following suspicion of adverse effects reported up to 15 days post vaccination. It was discussed that a robust study design is needed in order to demonstrate milk losses due to vaccination, EFSA can support in that. FYROM presented a plan performed for vaccination monitoring based on 284 paired samples serological tested. Seroconversion of up to 77% was reported. 4 EFSA Supporting publication 2018:EN-1520

5 Greece performed clinical surveillance in the high risk area (north, eastern Greece and island opposite Turkey) in with over 30 thousands visits, the data can be shared with EFSA. It was pointed out that immunisation of the population due to vaccination may be underestimated because the number of animals registered is higher than the existing ones, and the number of vaccinations registered is less than the actual number vaccinated animals due to the delay on registration of vaccination. The corrected vaccination coverage is currently around 70% at national level. In Montenegro the vaccination campaigns took place in 2016, 2017 and The 2018 vaccination campaign started in May. The vaccination coverage at animal level in 2018 is 77%, while it was close to 100% in Serbia is conducting the third year of vaccination against LSD, until now 80% of animals have been vaccinated. In 2019 there may be different approached for continuing the vaccination, i) complete population, ii) complete population in zone 1 (southern Serbia) + only new born calves> 6 months + imported animals, iii) new born calves> 6 months + imported animals in zone 1 and no vaccination in zone 2 (northern Serbia). 22 cases of side effects have been reported since 2016 and have been compensated; if possible data about this aspect can be shared with EFSA Inputs by scientists member of standing WG on LSD The inputs by the WG experts were about providing clarifications on the analysis done in the last reports issued by EFSA, i.e. on the spread model, on the vaccination effectiveness, on the surveillance planning according to the epidemiological and immune situation of each country and on diagnostics test. Each topic was followed by discussion mainly focused on: i) the importance of the results of the analysis carried out by EFSA for each of the country and ii) the tools that EFSA may develop and disseminate that can be of use for the countries Mathematical model for LSD spread, vaccination and surveillance Simon Gubbins presented the mathematical model used to i) analyse the outbreak data, ii) test the vaccination strategy, and iii) provide quantitative elements to plan the surveillance strategy The approach is a spatial model for transmission between herds to explore effect of distance between herds, seasonality and vaccination (EFSA, 2017 and 2018a). As pointed out in the respective previous publications: most LSD transmission occurs over short distances (<10 km) with appreciable probability of transmission over longer distances; there is a seasonal variation in force of infection associated with temperature; and vaccination (with a homologous live-attenuated vaccine) has a significant impact on spread. Regarding the vaccination policy the model was used to study how long and at what level of coverage and effectiveness vaccination should be carried out to lead to the elimination of the disease. The results presented in details in the last EFSA report (EFSA, 2018b) are displayed below in Table 1. Table 1: Probability of LSD elimination given different vaccination scenarios according to duration, coverage and effectiveness Scenario Coverage* VE 2 years 3 years 4 years 5 years Albania 50% 65% PERSIST PERSIST p=76% p=25% p=1% p=1% 90% 65% PERSIST p=22% p=2% p=1% Greece and Bulgaria (as single region) 70% 80% PERSIST p=17% 70% 95% PERSIST p=3% p=11% p=3% 5 EFSA Supporting publication 2018:EN-1520

6 90% 80% PERSIST p=14% p=1% 90% 95% p=3% p=2% Furthermore it was presented how the model was used to inform the most important elements for surveillance planning, namely i) the design prevalence for early detection of the disease assuming different delays at detection and ii) the design prevalence for demonstration of absence of disease, and iii) the buffer zone for risk based surveillance in certain radius from infected areas Finally, the gaps in the model were highlighted, mainly related to within herd spread. No data are available at animal level about follow up visits to outbreak herds meaning within herd spread cannot be estimated. As an alternative, the within-village spread from Albania could be explored. Because herds are clustered together within a village and often share grazing, the village can be considered as the epidemiological unit, with the spread estimated within each village. It was discussed also about the possibility of publishing the model code; this will be followed up Analysis of vaccination effectiveness Eyal Klement presented the analysis on vaccination effectiveness and the importance of which data to measure it. The vaccination effectiveness is the ability of a vaccine to protect animals from disease or infection and this is different from immunogenicity. In case of LSD there may be some correlation between protection conferred by the vaccine and Ab titre, but not complete (some seronegative animals may be protected from the infection, because cellular mediate immunity plays a major role), therefore it was discussed about the meaning and purpose of checking seroconversion after vaccination, which is still useful but can be better defined as vaccination monitoring and mainly give an idea about vaccination coverage. The analysis is based on the comparison between sick and healthy animals and vs vaccinated and non vaccinated and can be expressed as 1- risk ratio (risk in vaccinated group/ risk in non vaccinated group). I f data of vaccination and disease are available at animal level, the following data are necessary: Farm cow # Group/age/ other risk factors Vaccinated? (y/n) Vacc. date sick (y/n) date sick severe (y/n) In the current situation, disease data are not available at each animal level, so what has been used is an analysis at herd level, with the following. ID farm Vaccine Y/N Date of Vaccination LSD Y/N Suspicion date Other risk factors The results of such analysis are presented in previous EFSA reports (EFSA, 2018a) for FYROM, Serbia, Montenegro, Greece, Albania, Bulgaria. The overall conclusions of Eyal s presentations were: vaccine effectiveness overall in the region is about 80% for protection against clinical LSD infection It takes about 14 days for the vaccine to reach its full effectiveness Farming type might be a risk factor but the effect might also be the results of confounding by herd immunity Diagnostic tests for LSD Andy Haegeman from EURL on capripoxvirus gave an overview of the available diagnostic tools for LSD, mainly classical gel-based PCR assay, real time PCR assay, serological assays mainly ELISA and 6 EFSA Supporting publication 2018:EN-1520

7 immunoperoxidase monolayer assays. DIVA methods available are either PCR+RFLP or real time PCR assays, apart from sequencing methods. Some inhibition in DIVA real time PCR was experienced with DNA extracted from organ biopsy (e.g. skin, scabs), this issue was overcome by applying a 1/10 dilution of DNA, which is therefore recommended in the protocol. Nevertheless, for first line detection, the DIVA real-time in blood or swabs is not recommended, since vaccine viremia or shedding can be low and missed. The sensitivity of diagnostic tests to be used for active surveillance purposes was reported as below: Clinical detection in the first 3 weeks after infection: 67-75% PCR test of blood or skin: diagnostic sensitivity % in blood and % in tissues ELISA and IPMA: antibodies after 1 month Experimentally vaccinated or infected animals: ELISA: Se = 83%; Sp = 99.7% IPMA: Se = 100%; Sp = 100% Under field conditions: ELISA: Se = 59%; Sp = 99.7%; IPMA: Se = 53%; Sp = 100%. Although studies done in Serbia and FYROM showed ELISA Se around 75-80%. For checking the seroconversion after vaccination using serological tests it was recommended to sample not before than after 45 days post vaccination, although the producer claims a lag of 28 days for maximum seroconversion. It was reminded that EURL is available for providing support about molecular and serological diagnostics, proficiency testing, strain analysis (field and vaccine strains), and vaccine batch testing Scenarios for LSD surveillance Paolo Calistri explained the assessment of surveillance applied to different 4 scenarios as presented in the last EFSA report (EFSA, 2018b). For each of those the main aspects were discussed, namely where to carry out surveillance (e.g. risk areas), when (risk periods) and how (type of surveillance, type of tests, sample size, sampling frequency, target population). In details the following elements have been presented: The epidemiological situation such as the absence of infection (never occurred), current or past infection, the time since the last LSD occurrence, possible source of introduction or reemergence of the infection. The immunological status of the host population (as a result of vaccination or natural infection). The main surveillance objectives. The geographical area and the best time period of time for performing the surveillance activities, according to the selected objectives. The type of surveillance (active or passive). In this context: passive surveillance = the detection of the disease based on clinical suspicion by farmers or veterinarians active surveillance = the detection of the disease through surveillance activities actively performed by the official veterinarians (randomly or not, based on clinical, serological or virological testing) The target population of the surveillance activities and the criteria for its selection (census, random, targeted, based on the risk). 7 EFSA Supporting publication 2018:EN-1520

8 The parameters for the calculation of sample size (i.e. design prevalence). It was stressed the importance of keeping passive surveillance in place and the awareness at high level everywhere. Further details are available in the EFSA report (EFSA, 2018b) SIGMA project Gabriele Zancanaro from ALPHA Unit presented the SIGMA project, to make aware also the representatives from IPA countries about this activity promoted by ALPHA Unit of EFSA, which aims to harmonise the approach of data collection on animal diseases. The main points explained were about the main objectives of the SIGMA project and the resources available to be allocated to which actions in which country. Detailed information are available also at Survey design and sample size theory and calculation Josè Cortinhas from the AMU Unit of EFSA presented the general sampling principles, including sampling breakdown and type of survey samplings, how to plan a survey and sample size calculations. Furthermore he gave a demonstration about a practical use of a web application ( to calculate sample size for different designs, both for inferential purposes (e.g. RIBESS+ tool) and estimation of parameters (e.g. sampelator tool) including actual allocation, risk factors and selection of sample units. The manual for the sampelator tool can be found at this link: Results of the questionnaire Sotiria-Eleni Antoniou from ALPHA Unit presented the results of the EU Survey questionnaire which had been launched to the countries attending the workshop few weeks before. The scope of this questionnaire was to identify: a) the needs of the countries regarding the risk assessment activities of LSD and b) the available data on bovine population, LSD outbreaks, vaccination, side effects and laboratory results. Eight countries out of nine replied and they raised their needs for more support and better knowledge on risk assessment procedures and on designing surveillance activities. Given the fact that well designed risk assessments and surveillance programs by the countries will lead to the generation of better quality of data, it will be worthwhile if EFSA can intervene also at this stage by providing support to the Veterinary Authorities. To this end, training, manuals and guidelines will be usefully to be included also in the future activities of EFSA (see below). 8 EFSA Supporting publication 2018:EN-1520

9 Regarding the data needed for the next EFSA reports on LSD, the replies on the questionnaire and the discussion during the meeting provided with a clear idea of what kind of data are already available in each country. In particular for bovine population all the countries have detailed information of cattle even at animal level (date of birth, sex, etc.), although few ones have information about production type of the establishment, type of housing (indoor/outdoor activity), and none has information about level of biosecurity. Regarding vaccination all can provide information about the date of vaccination at animal level, but none of them record adverse effect of vaccine. Laboratory data are fully recorded by all countries enquired, including date of sampling and testing, type of sample, method used, results. Consequently, data model were revised and agreed together and they are presented in the next section Action points of this report Action points Here below the main action points decided at the workshop for the next steps of the risk assessment on LSD Data collection The action points decided at the workshop are mainly related to type of data to be collected for 2018 and 2019, see below the agreed data models. Data model for cattle population In blue the fields related to data at animal level, if possible to be collected and shared with EFSA. VARIABLE Animal ID Birth date sex species breed Mother ID Herd birth ID ATTRIBUTE Unique identifier animal The date of birth of the animal DD/MM/YYYY The sex of the animal M/F The species of the animal (bovine) The breed of the animal The individual identification code of the mother of each animal The identification code of the establishment of birth where each animal was born 9 EFSA Supporting publication 2018:EN-1520

10 Country birth Entry date Herd origin ID Exit date Holding/farm_ID country NUTS 3 Municipality Village/Town Longitude (X) of the holding Latitude (Y) of the holding Number of animals farmtype farmstructure pastureacc grazing The country where each animal was born The date of entry of each animal in the current establishment (e.g.: in case bought from another establishment) The identification code of the establishment of origin from where the animal came from (e.g. in case bought from another establishment) The date of exit of each animal from the establishment (e.g. in case of sale) Unique identifier for the farm or holding. Name of the country where the farm is located or belongs to. NUTS3 Area 1 where the farm or holding is located (Nomenclature of territorial units for statistics- NUTS - coding system valid only for EEA and Switzerland). Name (in Latin alphabet if possible) of the municipality where the farm is located or belongs to. If possible please provide a shapefile of this subdivision Name (in Latin alphabet if possible) of the town or village where the farm is located or belongs to. If possible please provide a shapefile of this subdivision Coordinate of the farm in decimal degree Coordinate of the farm in decimal degree Number of animals in the farm at the moment of the extraction. If data are provided per each single animal this is not applicable If available: Dairy, beef, reproduction, mixed If available: Commercial / non commercial If available: Indoor / outdoor If available: Yes, Individual / Yes, communal /No grazing Data model for vaccination (referred to 2018 campaign): If available, data on vaccination should be collected at animal level, by indicating the data of vaccination of each animal. If this is not possible, then the data should be collected at herd level by indicating the date of vaccination of the herd and the number of animals vaccinated (see field in blue in the table below). VARIABLE Animal ID holdingid Country* ATTRIBUTE Unique identifier animal (if data are recorded per each single animal) Unique identifier for the farm or holding. Name of the country where the farm is located or belongs to EFSA Supporting publication 2018:EN-1520

11 NUTS 3* Municipality* Village/Town* Longitude (X) of the holding* Latitude (Y) of the holding* Vaccination date Vaccine Name NUTS3 Area 2 where the farm or holding is located (Nomenclature of territorial units for statistics- NUTS - coding system valid only for EEA and Switzerland). Name (in Latin alphabet if possible) of the municipality where the farm is located or belongs to. If possible please provide a shapefile of this subdivision Name (in Latin alphabet if possible) of the town or village where the farm is located or belongs to. If possible please provide a shapefile of this subdivision Coordinate (longitude) of the farm in decimal degree Coordinate (latitude) of the farm in decimal degree Date of vaccination Name of the vaccine used (if available) Number of vaccinated animals in the farm. This N_vaccinated information is needed only if the data are collected at herd level *NOTE: This geographical information is the same as for the cattle population records, and it could be merged by using the holding ID. Nevertheless, since sometimes there are mistakes in the holding IDs between datasets, if it is possible it is better to report again the same geographical information Data model for surveillance: VARIABLE surveillance type objective sampleid animalid vaccinated Last_vacc Times_vacc holdingid Country* NUTS 3* Municipality* Village/Town* Longitude (X) of the holding* ATTRIBUTE Active / passive Early detection / demonstration of freedom/ vaccination monitoring ID of sample ID of single animal Y/N date of last vaccination Number of times vaccinated ID of the establishment (e.g. farm) Name of the country where the farm is located or belongs to. NUTS3 Area 3 where the farm or holding is located (Nomenclature of territorial units for statistics- NUTS - coding system valid only for EEA and Switzerland). Name (in Latin alphabet if possible) of the municipality where the farm is located or belongs to. If possible please provide a shapefile of this subdivision Name (in Latin alphabet if possible) of the town or village where the farm is located or belongs to. If possible please provide a shapefile of this subdivision Coordinate (longitude) of the farm in decimal degree EFSA Supporting publication 2018:EN-1520

12 Latitude (Y) of the holding* Coordinate (latitude) of the farm in decimal degree Sampling date The date when the sample was taken sample matrix Blood, serum, ocular swab, skin, nasal swab labtest PCR, ELISA, SNT, clinical visit test date The date when the lab test was done Result Pos, neg, unclear Result_info Negative, vaccine strain, field virus OD Optical density (for ELISA test) symptomfever (If available) Y/N/na symptommilkreduction (If available) Y/N/na symptomnodules (If available) Y/N/na Insurgence date (If available) Date of insurgence of symptoms *NOTE: This geographical information is the same as for the cattle population records, and it could be merged by using the holding ID. Nevertheless, since sometimes there are mistakes in the holding IDs between datasets, if it is possible it is better to report again the same geographical information Estimation of milk drop after vaccination As discussed during the workshop, the analysis of the possible milk drop as side effect of vaccination require a robust study done at animal level for a sufficient period of time in order to consider the fluctuations of milk production due to other reasons. The discussion brought to consider the following data to be collected: Random selection of at least 1000 herds, making sure that the date of vaccination is not the same from all herds, so to have a picture of milk production along several months, or along the year. The selected herds should be proportionally allocated from different counties/regions (representing the population size of each county) Data collected one month back before vaccination and 2 months after vaccination for each cow as below: Herd ID ID of farm or establishment Cow ID ID of animal Date calving Date of last calving Lactation group number of lactations done by the cow Date of last vaccination DD/MM/YYYY date of previous vaccination DD/MM/YYYY Vaccine type Type of vaccine used (commercial name) Date of milking DD/MM/YYYY of milking one month back before vaccination and 2 months after vaccination Daily frequency milking How many times the cow is milked per day Daily milk yield (Kg) Total daily production of milk in kg Metritis Y/N (if available) Ketosis Y/N (if available) other disease ID ID of the disease (if available) Serological surveys and possible analysis 12 EFSA Supporting publication 2018:EN-1520

13 In countries where serological surveys have been carried out (so far Croatia and FYROM) the following can be tested: Seroconversion after one or multiple vaccination: the hypothesis is whether the seroconversion is higher after one or two (or more than two) vaccinations, after controlling for the time between vaccination and sampling. The minimum necessary data to test that are like below: Sample ID Animal ID Holding ID Country Village/town Municipality LONG LAT date 1 st sample ELISA result first sampling OD 1 date 2 nd sample ELISA result second sampling OD 2 Date of vaccination 2017 Date of vaccination 2018 ID of sample ID of animal ID of farm or establishment Coordinate of farm Coordinate of farm DD/MM/YYYY Pos/neg Optical density first sampling DD/MM/YYYY Pos/neg Optical density second sampling DD/MM/YYYY DD/MM/YYYY 3. Conclusions The workshop was useful for the countries to be aware about the activities running or planned in the other countries and to get technical indications for surveillance planning. For EFSA the benefit of the report was to update the data models on the data collection that will serve the next outputs on LSD. Further bilateral meetings with each of the representatives of each country will follow, in order to deepen the technical discussion on the datasets available in each country. 4. References EFSA AHAW Panel (EFSA Panel on Animal Health and Welfare), Scientific Opinion on lumpy skin disease. EFSA Journal 2015;13(1):3986, 73 pp. doi: /j.efsa EFSA AHAW Panel (EFSA Panel on Animal Health and Welfare), Statement: Urgent advice on lumpy skin disease. EFSA Journal 2016;14(8):4573, 27 pp. doi: /j.efsa EFSA (European Food Safety Authority), Lumpy skin disease: I. Data collection and analysis. EFSA Journal,15, , doi: /tbed EFSA (European Food Safety Authority), 2018a. Lumpy skin disease II. Data collection and analysis. EFSA Journal 2018;16(2):5176, 33 pp; DOI: /j.efsa EFSA (European Food Safety Authority), Calistri P, DeClercq K, De Vleeschauwer A, Gubbins S, Klement E, Stegeman A, CortinasAbrahantes J, Antoniou S-E, Broglia A and Gogin A, 2018b. Scientific report on lumpy skin disease: scientific and technical assistance on control and surveillance activities. EFSA Journal 2018;16(10):5452, 46 pp EFSA Supporting publication 2018:EN-1520